INTRODUCTION

Known as vishwabheshaja, “the universal medicine”, ginger (zingiber officinale) has been a panacea for digestive, respiratory, and circulatory disorders for thousands of years.1,2  Ginger’s versatility is found in ancient Ayurvedic texts, international cuisine, and a broad spectrum of home remedies. With today’s advent of scientific research, ginger’s therapeutic constituents are being isolated and tested against some of the most common diseases. Not only has it been scientifically proven to aid in digestion, ginger has also shown anti-inflammatory, anti-carcinogenic, and anti-oxidant properties. This paper gives a brief background of ginger, its traditional Ayurvedic use, and its effectiveness in clinical trials.

HISTORY

Ginger is a perennial lily, indigenous to tropical Asia, though it has never been found growing in the wild. Even though its exact botanical origins are unknown, it plays a large role in the ancient traditions of Ayurveda, Unani, and Chinese Medicine. The flowering plant reaches heights “of 3 to 4 feet, *with+ leaves growing 6 to

12 inches long…[Its] flowers are white with purple streaks and grow in spikes.” 3  The medicinal portion used is the rhizome, or horizontal, underground stem. This fleshy, aromatic, firm, fibrous, and plump portion of the plant is how it

propagates itself, through its many knobby portions, and not through its sterile flowers. Today it grows throughout the world in tropical

Botanical Drawing of Zingiber officinale

A Modern Herbal, Mrs. M. Grieve, Ginger.  http://www.botanical.com/botanical/mgmh/g/ginger13.htm

climates, its unique flavor finding its way into signature dishes worldwide. 4 ,5,6

Whereas Indian, Chinese, and other Asian cuisines have used ginger for thousands of years, its unique qualities made it attractive to Europeans more recently, as an important ingredient along the spice trade routes. Ginger ale was popular in 19th century pubs, while ginger’s use in everything from baked goods, to salad dressings,

to exotic dishes continues in the western world.7,8  As KP Khalsa says, in the Way of Ayurvedic Herbs, “*g+inger is a

multi-purpose spice, equally delicious in both sweet and savory dishes.” He also mentions that, though “*h+erbs and spices are typically not significant sources of nutrients in the diet…ginger has [a] relatively high calcium and iron content.”9  Its addition to meals may therefore not only add flavor and medicinal properties, but valuable nutrients too.

AYURVEDIC INTERPRETATION

In Ayurveda, ginger’s rasa (taste) is pungent and sweet, its virya (energy) heating, and its vipāka, (post- digestive effect) sweet. Even though it has a pungent and heating, it is tonifying, as a sweet vipāka implies. As Pole explains in Ayurvedic Medicine, this sweet vipāka leaves a cooling, lasting effect. Through its warm virya, it subdues vāta and kāpha, while increasing pitta, though it is often found counter-balanced in pitta-reducing

remedies. As the “universal medicine,” it affects all dhātus (tissues) and specifically the digestive, respiratory, and circulatory srotas (channels). 10,11,12, 13

The Ayurvedic actions of ginger, as described by Pole include: Āmanāśaka (Destroys toxins), Pācana (Digestive), Chardinigrahaṇa (Prevents nausea), Hikkānigrahaṇa (Stops hiccups), Agni dῑpana (Enkindles the digestive fire), Grāhῑ (Absorbs fluids from the intestines), Arśoghna (Removes piles), Śitapraśamana (Reduces feelings of cold), Rasāyana (Rejuvenative), Kāsaśvāsahara (Alleviates cough and breathing difficulties), and Vedanāsthāpana (Alleviates pain).14  Its therapeutic uses are also found throughout the Materia Medica of Ayurveda and the Sushrut Samhita, mostly in formulas treating varying complaints.

WESTERN INTERPRETATION

In western herbal terminology, it is described as a stimulant, diaphoretic, expectorant, carminative, anti- emetic, analgesic, sialagogue, appetizer, anti-flatulent, anti-tussive, antimicrobial, hypolipidemic, anti-oxidant, anti-spasmodic, anti-atherosclerotic, cardiotonic, circulatory stimulant, and emmenagogue. Its indications include

digestive upset of all kinds, including nausea, indigestion, vomiting, belching, abdominal pain, gas, colic, and motion sickness. It can also be used for respiratory conditions, rheumatism, osteoporosis, gout, colds, flu, laryngitis, arthritis, hemorrhoids, headaches, heart disease, gas, “cramps in the abdomen, including menstrual cramps due to cold”15, migraines, lumbago, fever, and its fresh juice can even be used for burns. 16,17,18,19,20  With such a long list of actions and indications, it is no wonder it is referred to as “the universal medicine”.

ĀRDRAKA & ŚUṆṬHI

Ginger has many names across cultures, and even within Ayurveda. Most commonly, the fresh form is recognized as ārdraka (moist), and the dry rhizome as either śuṇṭhi or nagara, meaning “dry.” 21  Traditional Chinese Medicine also creates a distinction between these two forms of the rhizome, calling fresh ginger shen   jiang and dry ginger gan jiang.22,23  Scientific research confirms the difference between the properties of fresh and dried ginger. As the “volatile and diaphoretic essential oils β-sesquipphellandrene and zingiberene decompose on drying…*t+he warming gingerol principle transforms into shogoals…making it more centrally heating”. 24  “Gingerols have been reported to be responsible for the characteristic taste” of ginger. 25    “The gingerols have analgesic, sedative, antipyretic, antibacterial and gastrointestinal tract motility effects.26  As the most numerous chemical constituents of ginger, both gingerols and shogoals are some of the most researched compounds of ginger.

In The Yoga of Herbs, authors Frawley and Lad mention that “*f+resh ginger is a better diaphoretic, better for colds, cough, vomiting and for deranged Vāta.”27  In both the Materia Medica of Ayurveda and the Sushrut Samhita, ārdraka is touted for promoting a “good voice,” curing vibandha (constipation), ānāha (obstruction to the movement of wind in the stomach), and śúla (colic pain). It is said to be an effective “appetizer, aphrodisiac and cardiac tonic.”28,29 It is also found as part of a treatment for acute conditions, such as earache. 30

Frawley and Lad also state that the drying action and increased heat of dry ginger makes it “a better stimulant and expectorant for reducing Kapha and increasing Agni.” Śunthi is found in many kapha-reducing remedies throughout the Materia Medica, often combined with marica (black pepper) and pippalῑ (long pepper).31 Together the three herbs, combined into powder in equal portions, are commonly called Trikaṭu Cūrṇa, a heating,

stimulating, and toxin-reducing rasāyana for Kapha.32

APPLICATIONS & RESEARCH

DIGESTIVE SYSTEM

Ginger “warms the digestive system, [and] increases agni and the secretion of digestive enzymes. Fresh ginger especially benefits rasadhātvagni (agni of the rasa dhatu) while dry ginger clears āma and is better for kledaka kapha aggravations.”33  As Pole suggests, the two forms of ginger play different roles in digestion, but both help to warm and stimulate the process. Many randomized controlled trials (RCT) were performed on people to examine ginger’s effect on digestion. It is said that “*a+bout 40% of patients with functional dyspepsia have abnormally delayed gastric emptying.” 34  Therefore, two RCTs were done to “evaluate the effects of ginger on gastric motility and emptying, abdominal symptoms, and hormones that influence motility in dyspepsia”. 35

Patients who suffered from functional dyspepsia ingested either three ginger capsules totaling 1.2g, or a placebo. Gastric emptying was more rapid and antral contractions were more numerous in the experimental group, but the ginger “had no impact on gastrointestinal symptoms or gut peptides.” 36  The same study was done previously on healthy, asymptomatic volunteers to test the gastrointestinal effects of ginger. Again, the 1.2g of ginger accelerated gastric emptying while stimulating antral contractions. 37  In another RCT, adult respiratory distress syndrome (ARDS) patients, who were dependent on mechanical ventilation and fed via nasogastric tube, “showed that gastric feed supplementation with [120mg] ginger extract might reduce delayed gastric emptying and help reduce the incidence of ventilator-associated pneumonia in ARDS.” 38

Pole also mentions ginger’s effectiveness in nausea for motion sickness, morning sickness in pregnancy, and post-operative nausea.39 Ginger as a remedy for motion sickness was evaluated in an RCT, where the experimental group was pre-treated with ginger at 1g and 2g before being subject to circular vection. The study showed that “ginger reduces nausea, tachygastric activity, and vasopressin release induced by circular vection,” while delaying their onset and shortening the recovery time afterwards.40 Another RCT, evaluating the effectiveness of ginger on motion sickness, was performed on “eighty naval cadets, unaccustomed to sailing in heavy seas”. 1g of “ginger root reduced the tendency to vomiting and cold sweating significantly better than placebo” and ingestion gave “remarkably fewer symptoms of nausea and vertigo,” though the latter “was not statistically significant.”41  One article explained that, “gingerols have been reported to be responsible for…many pharmacological activities including motion sickness”. They are thought to work directly “on the gastrointestinal tract rather than…on the central nervous system.”42

Studies show that ginger’s anti-emetic properties can benefit patients in a variety of circumstances. In a guide for pre-natal care from London, the authors referred to three RCTs that demonstrate the alleviation of  nausea and vomiting in pregnancy with the use of ginger. After taking 250 mg of ginger, four times a day, pregnant women displayed less severe nausea and fewer instances of vomiting over those in the control group. In another RCT mentioned in the report, patients ingesting 1 tbsp. of ginger syrup in 4 to 8 fluid oz., four times a day, showed a relief in nausea and less vomiting than those in the placebo group. 43 Ginger was also found to be effective in a review of RCTs concerning post-operative nausea and vomiting. The analysis demonstrated “that a fixed dose *of+ at least 1 g of ginger is more effective than placebo for the prevention of [24-hour] postoperative nausea and vomiting *PONV+.”44  In clinical trials for patients with Chemotherapy-induced nausea and vomiting (CINV), ginger again proved to be a valuable anti-emetic. “Ginger root powder was effective in reducing severity of acute and delayed CINV as additional therapy to ondensetron and dexamethasone in patients receiving high emetogenic chemotherapy”. 45  Thus, the ancient tradition of using ginger to reduce nausea by stimulating digestion has been proven successful in clinical trials.

In addition to aiding in the general digestive process, it exhibits cholagogic effects, with its chief pungent principles, [6]-gingerol and [10]-gingerol, being most responsible. 46  While ginger stimulates bile production, it is also hepato-protective. A study using an aqueous ethanol extract of ginger concluded that it works either by preventing the decline of hepatic antioxidant status or due to its direct radical scavenging capacity.47  Another experiment compared the hepato-protective property of 6-gingerol against the standard drug silymarin, and found them to by comparable.48

Even though it is heating in virya, ginger has even been shown to be beneficial in the treatment of experimental ulcers. It stimulates defensive mucin (a constituent of mucous) production slightly more than the offensive acid-pepsin secretions. The isolated compound 6- gingesulphonic acid proved more effective in anti- ulcer activity than 6- gingerol and 6-shogaol, perhaps due to weaker pungency.49  A study on ulcer-induced rats “clearly demonstrated that aqueous extract of ginger was able to protect the gastric mucosa from stress-induced mucosal lesions and inhibits gastric acid secretion probably by blocking H+, K+-ATPase action, inhibiting growth of H. pylori and offering anti-oxidant protection against oxidative stress-induced gastric damage.” 50  Ginger also assists in the treatment of ulcers through antibacterial actions, as found by a Nigerian study:

Ginger’s antibacterial ‘power’ is effective against preventing numerous intestinal problems that take place as a result of the alteration of the intestinal flora. This is ideal to avoid the formation of ulcers by eliminating the Helicobacter pylori, a bacterium whose secretions of ammonia are responsible for many ulcers, especially those of the duodene, and for other stomach problems like gastritis, since the plant is able to neutralize the excess of gastric acid that is another of the causes that favours the formation of ulcers.51

ANTI-MICROBIAL

“Its gingerol-related components have been reported to possess antimicrobial and antifungal properties, as well as several pharmaceutical properties.” 52    The aforementioned Nigerian study demonstrated the effectiveness of the anti-bacterial properties of ginger against digestive pathogens. Various extracts, ranging from ethanolic to raw juice, to hot and cold water, exhibited varying effectiveness at different concentrations.  “*T+he cold-water extract of ginger inhibited both Escherichia coli and Salmonella typhi at all concentrations,” while the “ethanolic extract of ginger gave the widest zone of inhibition” against Salmonella typhi. In other studies referenced by the authors, “ginger extract and its pungent compounds demonstrated greater [than those of onion] antibacterial activity against a variety of bacterial species including Helicobacter pylori, Staphylococcus aureus, Pseudomonasaeruginosa and Escherichia coli, although mixed result is attributed to different ginger preparations and varying strength.”53 Pole confirms ginger’s antibacterial actions against Escherichia coli and adds its effectiveness against Shigella bacillus.54 

Ginger’s antimicrobial actions go beyond digestive pathogens. As some bacteria grow resistant to pharmaceuticals, such as Acinetobacter baumannii (XDRAB) has, scientific studies turn to ginger as a potential aid. When combined with tetracycline, four components of ginger, [6]-dehydrogingerdione, [10]-gingerol, [6]-shogaol and [6]-gingerol, exhibited antibacterial actions against XDRAB, and modulated resistance to the drug. Results of the experiment also showed that antioxidants within the compounds aided the antimicrobial actions. 55A research article in Phytotherapy Research sought to explore the anti-bacterial actions of ginger, and its isolated components, on oral pathogens related to periodontitis. Ethanol and n-hexane extracts of ginger showed anti- bacterial actions, while the isolated constituents [10]-gingerol and [12]-gingerol, also inhibited the growth of, and killed the three strains of bacteria in the experiment.56

ANTI-INFLAMMATORY

Ginger is gaining more and more recognition for its anti-inflammatory actions. While Ayurveda has long- touted its benefits, contemporary research studies are now proving which constituents are most responsible, and how they work.  From an Ayurvedic perspective, Pole states, “*d+ry ginger is used as an āma-clearing, śleṣaka kapha-reducing, toxin-digesting, anti-inflammatory in arthritis (āma-vāta) in many traditional ayurvedic formulas, e.g. triphala guggul, yograj guggul.” He goes on to mention that, “despite its ‘warm’ energy it also inhibits the activity of inflammatory prostaglandins.” 57

As a relative of turmeric, ginger shares many of its functions. One study found ginger’s active constituents to act much like turmeric’s in affecting inflammation, oxidative damage, and “fighting the ravages of aging and degenerative diseases.” It did so by influencing:

some endocrine gland functions, and signal pathways involved to mediate their actions. With some systems and adipose tissue, ginger and turmeric exert their actions through some/all of the following signals or molecular mechanisms: (1) through reduction of high levels of some hormones (as: T4, leptin) or interaction with hormone receptors; (2) by inhibition of cytokines/adipokine expression; (3) acting as a potent inhibitor of reactive oxygen species (ROS)- generating enzymes, which play an essential role between inflammation and progression of diseases; (4) mediation of their effects through the inhibition of signaling transcription factors; and/or (5) decrease the proliferative potent by down-regulation of antiapoptotic genes, which may suppress tumor promotion by blocking signal transduction pathways in the target cells. 58

Today, scientists look to some of the key enzymes within the body to understand the mechanism behind ginger’s anti-inflammatory properties. Actions from Cyclooxygenase-1 (COX-1) enzymes produce hormone-like prostaglandins that protect the digestive tract from acids and assist in essential blood clotting.  COX-2 enzymes play a direct role in the production of prostaglandins that protect the body after injury, creating inflammation.

Non-steroidal anti-inflammatory drugs (NSAIDS), such as aspirin and ibuprofen, are often used to both reduce inflammation, and the associated pain. By acting on COX-2 and often COX-1 enzymes, NSAIDS reduce the prostaglandins produced, and “may irritate the stomach’s lining and cause digestive upset, peptic ulcers, and bleeding in the digestive tract.” 59  One research paper summarized research on ginger, and what the findings have meant for pharmacology:

The original discovery of ginger’s inhibitory effects on prostaglandin biosynthesis in the early 1970s has been repeatedly confirmed. This discovery identified ginger as an herbal medicinal product that shares pharmacological properties with non-steroidal anti-inflammatory drugs. Ginger suppresses prostaglandin synthesis through inhibition of cyclooxygenase- 1 and cyclooxygenase-2. An important extension of this early work was the observation that ginger also suppresses leukotriene biosynthesis by inhibiting 5-lipoxygenase. This pharmacological property distinguishes ginger from nonsteroidal anti-inflammatory drugs. This discovery preceded the observation that dual inhibitors of cyclooxygenase and 5-lipoxygenase may have a better therapeutic profile and have fewer side effects than non-steroidal anti-inflammatory drugs. The characterization of the pharmacological properties of ginger entered a new phase with the discovery that a ginger extract (EV.EXT.77) derived from Zingiber officinale (family Zingiberaceae) and Alpina galanga (family Zingiberaceae) inhibits the induction of several genes involved in the inflammatory response. These include genes encoding cytokines, chemokines, and the inducible enzyme cyclooxygenase-2. This discovery provided the first evidence that ginger modulates biochemical pathways activated in chronic inflammation. Identification of the molecular targets of individual ginger constituents provides an opportunity to optimize and standardize ginger products with respect to their effects on specific biomarkers of inflammation.60

Many studies have since been done on the various components in ginger, examining the effectiveness on inflammation. In an in-vitro study of 6-shogaol, and 6-, 8-, and 10-gingerols, the compounds were evaluated for their antioxidant and anti-inflammatory efficacy. “6-Shogaol has exhibited the most potent antioxidant and anti- inflammatory properties which can be attributed to the presence of alpha,beta-unsaturated ketone moiety. The carbon chain length has also played a significant role in making 10-gingerol as the most potent among all the gingerols.”61  As some of the most-studied components of ginger, shogaols and gingerols do not act alone. A scientific study compared a “crude dichloromethane ginger extract, which also contained essential oils and more polar compounds”, to a compound containing only gingerols and their derivatives. The crude extract had significantly more anti-arthritic effects on arthritis-induced rats, reducing both joint inflammation and destruction. This research revealed that gingerols are more effective in treating arthritis when working synergistically with other components naturally found in ginger.62

Another scientific study used methanol extracts of ginger roots, to isolate the components, 10-gingerol, 8- shogaol and 10-shogaol. They inhibited cyclooxygenase-2, COX-2, but not COX-1. The report reiterates that the “inhibition of COX-1 is associated with gastrointestinal irritation,” and goes on to explain that “selective inhibition of COX-2 should help minimize this side effect.” 63  Thus, ginger’s use over common NSAIDS may have less side effects in the digestive tract.  The study involving the “standardized and highly concentrated extract of 2 ginger species, Zingiber officinale and Alpinia galanga (EV.EXT 77),” showed a “statistically significant” reduction of symptoms in patients with osteoarthritis (OA) of the knee. Since only “mild GI adverse events *occurred+ in the ginger extract group, it was concluded to have a “good safety profile.”64  In a smaller experiment, a limited number of patients used ginger compresses on their kidneys to manage the symptoms of osteoarthritis. They explained that “warmth penetrated through the entire self, activating deep relaxation, [and that] total relaxation of the self enabled release of tension and improved receptivity towards others. Additionally, interest in the outer world increased as the self felt more mobile and energized.” This alternative treatment to arthritis enabled them to overcome some of the other symptoms that many arthritis patients face, such as “psychological distress, social isolation and general inability to cope” as well as pain.65  In one study, 6-shogaol expressed its usual anti- inflammatory capabilities, but the study examined them within cells of the central nervous system. By mediating microglial activation, which results in neuronal cell death, “6-shogaol is an effective therapeutic agent for treating *and possibly preventing+ neurodegenerative diseases.”66  Ginger exhibits actions across a widespread spectrum of inflammatory conditions.

RESPIRATORY SYSTEM

Though not as many clinical research studies have examined ginger’s effects on the respiratory system, its use in Ayurveda for respiratory complaints is well known. As a kāsaśvāsahara, it is known for alleviating cough and breathing difficulties. As Pole also mentions, fresh ginger’s stimulating effects on peripheral circulation, vasodilation, and sweating may contribute to its ability to clear colds.  As the āma clears from the rasa and rakta, kapha-vāta coughs and colds are reduced. Combined with different herbs, ginger’s many actions can be tailored to the symptoms at hand. With cinnamon and lemongrass, it can induce sweating for a cold. For a high kapha-vata cough, vasa and pippali may be more helpful. As part of trikatu, it can also aid kapha respiratory complaints while accelerating slugglish digestion. 67

According to the Merck Manual of Medical Information, asthma is becoming more common, more serious, and is even resulting in more deaths annually. As explained in the Manual, “airways narrow –usually reversibly—in response to certain stimuli”. While one muscle layer spasms, another becomes inflamed, leading to the excessive production of mucous, which may further lead to an obstruction of the airway. 68    Recurring attacks over a long-period of time, may lead to airway remodeling, a “permanent narrowing of the bronchial tubes.”69

Ginger has been proven effective with asthma, as an anti-inflammatory, anti-hypersecretory, and even helping to repair the body after attack. Using an aqueous methanolic crude extract of ginger, one study found it to inhibit airway contraction through its anti-inflammatory properties.70  Perhaps it did this by reducing interleukin-1 secretion, as a German research paper found it to do, in human bronchial epithelial cells. The authors went on to propose “that distinct ginger compounds could be used as anti-inflammatory drugs in respiratory infections,” such as those in asthmatic patients.71  It can also repair the body after harmful inflammation. A Taiwanese study found that “inflammatory cytokines, which are produced by the bronchial epithelium after exposure to phthalate esters [ingredient in many plastics]…contribute to airway remodeling”. The research went on to demonstrate that “ginger reverses phthalate ester-mediated airway remodeling.”72  Research from South Korea proved [6]- Gingerol’s anti-hypersecretory abilities in relation to human airway epithelial cells.73  Thus, ginger can help reduce inflammation, secretions, and even long-term destruction related to asthma, and thus help in many stages of the disease.

ANTI-CARCINOGENIC

In cultured cell studies and experiments with animals, ginger’s pungent principles (gingerols, shogaols, paradols, and zingerone) have proven to possess anti-carcinogenic properties that may be both chemopreventive and chemotherapeutic. 74  These “cancer preventive activities are supposed to be mainly due to free radical scavenging, antioxidant pathways, alteration of gene expressions, and induction of apoptosis, all of which contribute towards decrease in tumor initiation, promotion, and progression.”75  6-Gingerol assisted the apoptic pathway in gastric cancer cells by enhancing the TRAIL-induced viability reduction of the cells. 6-Shogaol damaged microtubules of the cancer cells, halting their reproduction and thus reducing their ability to reproduce. 76 In breast cancer cells, 6-gingerol has been found to inhibit “cell adhesion, invasion, motility and activities”.

The rate of inhibition was dose-dependent, increasing as the concentration of ginger compounds increased.77  In  an experiment from the National University of Singapore, the isolated constituents, 6-, 8- and 10-shogaol, were shown to “have an inhibitory effect on induced breast cancer cell invasion,” without creating cytotoxic  conditions.78  One study explained the method by which ginger reduced the incidence of liver neoplasms and “the risk of subsequent carcinoma”. In liver cancer cells, NF-κB is constitutively activated and…blocking NFκB activation with ginger resulted in suppressed production of *inflammatory markers+ NFκB and TNF-α. This is in line with findings that many of the pathways that mediate adaptive survival strategies in cancer cells are under the transcriptional control of NFκB. Thus, the ginger extract may have a chemotherapeutic effect in the treatment of liver cancer. 79

Researchers from the University of Minnesota referenced many experiments comparing the effectiveness of gingerols and shogaols in cancer inhibition. As the two constituents are those most prevalent in ginger, they were predominantly examined, although other components were also evaluated. With effectiveness varying with the compound, the constituents were successful against a broad spectrum of cancer cells, including human lung, leukemia, skin, ovarian, and colon cancer cells, as well as mouse skin and lung cancer cells.80

CARDIOVASCULAR SYSTEM

Ginger’s many actions show widespread potential in cardiovascular disease as well. In one study, ginger’s ability to increase body temperature was scientifically examined. It was found that gingerols and shogaols activated transient receptor potential vanilloid subtype 1 (TRPV1), which detects and regulates body temperature. The pungent constituents also increased adrenaline secretion, which heats the body.81  Describing it as a śitapraśamana, Ayurveda has known of its ability to reduce feelings of cold. Pole explains that, Ayurvedically, “*d+ry ginger may be of benefit in cardiac disorders due to increasing circulation and potential blood-thinning properties when used at a high dosage”.82  In combination with the herbs arjuna and guggulu, it treats congestive heart conditions and poor circulation.83

An article from the International Journal of Cardiology, explains, “*h+uman trials have been few and generally used a low dose with inconclusive results, however dosages of 5g or more demonstrated significant anti- platelet activity…Should *more human trials+…prove positive, ginger has the potential to offer not only a cheaper natural alternative to conventional agents but one with significantly lower side effects.”84  In an in-vitro  experiment comparing synthetic gingerols with aspirin, the gingerols and related analogues inhibited human platelet activation at the same potency, or greater than that of aspirin, depending on the analogue.85

Using an orally-administered, aqueous extract of ginger with rats, high doses of the extract (500mg/kg) lowered prostaglandin, thromboxane (blood-clotting substances), and cholesterol levels. “These results suggest that ginger could be used as a cholesterol-lowering, antithrombotic and anti-inflammatory agent.”86  In another study, test rabbits were fed cholesterol for 75 days, and thus were induced with atherosclerosis. After ingesting experimental doses of air dried ginger powder, at 0.1g/kg of body weight, for 75 days, atheroma was reduced by half. Evidence of anti-oxidation was evident in decreased lipid peroxidation, and an increase in fibrinolytic activity meant that wound-healing capabilities also increased. “However, ginger did not lower blood lipids to any significant extent. This distinct protection from the development of atherosclerosis by ginger is probably because of its free radical scavenging, prostaglandin inhibitory and fibri properties.”87

DOSAGES

CONCLUSION

Ginger’s versatility expands in all directions. As a seasoning, it spans continents, finding its way through Thai, Indian, Chinese, and other Asian cuisines, and into western baked goods, ales, and sauces. As a supplement, it provides valuable minerals, bridging the gap between diet and medicine. Therapeutically, it works on many conditions, operating synergistically to bring balance through various modalities. Many of the Ayurvedic uses and terms associated with ginger are being proven in today’s laboratories and clinical trials.

Its aid in digestion is widespread, working to initiate (agni dῑpana) and stimulate (pācana) the process, prevent nausea and vomiting (chardinigrahaṇa), treat ulcers, and inhibit harmful bacteria and fungi. It does all this while stimulating, and protecting the liver. It also simultaneously aids in inflammatory and cancerous conditions.  By affecting hormone processes, and other biochemical pathways, harmful gene expression, reactive oxygen species, and free-radical scavenging (āmanāśaka), it reduces inflammation and carcinogenic activity at the same time.

This simultaneously allows it to be a preventative, pain reliever (vedanāsthāpana), and rasāyana to damaged tissues. The remarkable thing about ginger is that these tissues can range from an arthritic and degenerated joint, to an obstructed airway, to an organ recovering from cancer. As if that was not enough, ginger also enhances cardiovascular health. In a modern-day, mostly sedentary society, with more and more high cholesterol and heart related diseases, ginger’s assistance is more than welcome. As a food with a long-history of use throughout the world, its harmful side effects are minimal, especially when compared to many pharmaceuticals. In a gavage safety assessment of ginger, rats were given excessive amounts of ginger, (2000mg/kg), but displayed no harmful abnormalities or mortalities, except for a slight decrease in weight of the testes.103  Though its dosage varies according to use, author, mode of extraction, and research study, it is still relatively safe, even if taken in excess.

Thus, ginger has proven to be the vishwabheshaja, “the universal medicine”, not only through time in ancient medical systems, but also through modern-day clinical and experimental research for some of today’s most common diseases.

ABSTRACTS OF ARTICLES CITED 

(in order of citation)

R.K. Goel, and K. Sairam. “Anti-Ulcer Drugs from Indigenous Sources with Emphasis on Musa Sapientum, Tamrabhasma, Asparagus Racemosus, and Zingiber Officinale,” Indian Journal of Pharmacology 34 (2002): 100-110.

Sula, Parinamasula and Amlapitta are clinical entities recognized by ayurveda, akin to peptic ulcer and functional dyspepsia. Many indigenous drugs have been advocated in ayurveda for treatment of dyspepsia. Our laboratory has been engaged in screening of various indigenous herbal and metallic drugs for their potential use in peptic ulcer diseases, taking lead from Ayurveda and have reported anti-ulcer and ulcerhealing properties of Tectona grandis (lapachol), Rhamnus procumbens (kaempferol), Rhamnus triquerta (emodin), Withania somnifera (acylsteryl glycoside), Shilajit (fulvic acid and carboxymethoxybiphenyl), Datura fastuosa (withafastuosin E), Fluggea microcarpa and Aegle marmelos (pyrano- and iso- coumarins) etc., along with their mechanism of action. The present article includes the detailed exploration of ulcer protective and healing effects of unripe plantain banana, tambrabhasma and Asparagus racemosus on various models of experimental gastroduodenal ulceration and patients with peptic ulcer. Their effects on mucin secretion, mucosal cell shedding, cell proliferation, anti-oxidant activity, glycoproteins, and PG synthesis have been reported. Clinical trials of these drugs for evaluating their potential ulcer healing effects in peptic ulcer patients have been done. Their potential ulcer protective effects both, experimental and clinical seemed to be due to their predominant effects on various mucosal defensive factors rather than on the offensive acid-pepsin secretion. Thus, the above herbal / herbo-mineral drugs do have potential usefulness for treatment of peptic ulcer diseases.

NC Azu, and RA Onyeagba, “Antimicrobial Properties Of Extracts Of Allium cepa (Onions) And Zingiber officinale (Ginger) On Escherichia coli, Salmonella typhi And Bacillus subtilis.” The Internet Journal of Tropical Medicine 3.2 (2007). http://www.ispub.com/journal/the-internet-journal-of-tropical-medicine/v… number-2/antimicrobial-properties-of-extracts-of-allium-cepa-onions-and-zingiber-officinale-ginger-on- escherichia-coli-salmonella-typhi-and-bacillus-subtilis.html

The antimicrobial properties of various extracts of Allium cepa (onions) and Zingiber officinale (ginger) against Escherichia coli, Salmonella typhi and Bacillus subtilis that are common cause of gastrointestinal tract infections were investigated using the cup-plate diffusion method. The result obtained revealed that ethanolic extract of ginger gave the widest zone of inhibition against two out of the three test organisms at the concentration of 0.8gml-1. However, Escherichia coli and Salmonella typhi were more sensitive to the extract of onion bulbs compared to Bacillus subtilis which was predominantly resistant. It was also observed that the solvent of extraction and its varying concentrations affected the sensitivity of two of the test organisms to the plant materials. The minimum inhibitory concentration (MIC) of ginger extracts on the test organisms ranged from 0.1gml-1 – 0.2gml-1, showing that ginger was more effective and produced remarkable inhibitory effect on the two out of the three test organisms when compared to the onion extracts. This investigation indicates that, though both plants had antimicrobial activities on the two gram negative test organisms but not effective on the gram positive test organism, ginger had more inhibitory effect thus confirming their use in folk medicine.

Seng-Kee Chuau, et.al, “Effect of Ginger on Gastric Motility and Symptoms of Functional Dyspepsia,” World Journal of Gastroenterology 17.1 (2011):105-110.

AIM: To evaluate the effects of ginger on gastric motility and emptying, abdominal symptoms, and hormones that influence motility in dyspepsia.

METHODS: Eleven patients with functional dyspepsia were studied twice in a randomized double-blind manner. After an 8-h fast, the patients ingested three capsules that contained ginger (total 1.2 g) or placebo, followed after 1 h by 500 mL low-nutrient soup. Antral area, fundus area and diameter, and the frequency of antral contractions were measured using ultrasound at frequent intervals, and the gastric half-emptying time was calculated from the change in antral area. Gastrointestinal sensations and appetite were scored using visual analog questionnaires, and blood was taken for measurement of plasma glucagon-like peptide-1 (GLP-1), motilin and ghrelin concentrations, at intervals throughout the study.

RESULTS: Gastric emptying was more rapid after ginger than placebo [median (range) half-emptying time 12.3 (8.5- 17.0) min after ginger, 16.1 (8.3-22.6) min after placebo, P ≤ 0.05+. There was a trend for more antral contractions (P = 0.06), but fundus dimensions and gastrointestinal symptoms did not differ, nor did serum concentrations of GLP-1, motilin and ghrelin.

CONCLUSION: Ginger stimulated gastric emptying and antral contractions in patients with functional dyspepsia, but had no impact on gastrointestinal symptoms or gut peptides.

SK Chuau, et al., “Effect of Ginger on Gastric Emptying and Motility in Healthy Humans,” European Journal of Gastroenterology and Hepatology 20.5 (2008):436-440.

OBJECTIVE:

Ginger has been reported to improve upper gastrointestinal symptoms. Little information about the effects of ginger on gastric motor function, exists, however. Our aim was to investigate the effects of ginger on gastric emptying, antral motility, proximal gastric dimensions, and postprandial symptoms.

METHODS:

Twenty-four healthy volunteers were studied twice in a randomized double-blind manner. After an 8 h fast, the volunteers ingested three ginger capsules (total 1200 mg) or placebo, followed after 1 h by 500 ml low-nutrient soup. Antral area, fundus area and diameter, and the frequency of antral contractions were measured using ultrasound at frequent intervals over 90 min, and the gastric half-emptying time was calculated from the change in antral area. Gastrointestinal sensations and appetite were scored using visual analog questionnaires. Data are expressed in terms of mean+/-standard error.

RESULTS:

Antral area decreased more rapidly (P<0.001) and the gastric half-emptying time was less after ginger than placebo ingestion (13.1+/-1.1 vs. 26.7+/-3.1 min, P<0.01), whereas the frequency of antral contractions was greater (P<0.005). Fundus dimensions did not differ, and there was no significant difference in any gastrointestinal symptoms.

CONCLUSION:

Ginger accelerates gastric emptying and stimulates antral contractions in healthy volunteers. These effects could potentially be beneficial in symptomatic patient groups.

M. Mokhtari, et al., “Ginger extract reduces delayed gastric emptying and nosocomial pneumonia in adult respiratory distress syndrome patients hospitalized in an intensive care unit,” Journal of Critical Care 25.4 (2010):647-650.

PURPOSE:

The purpose of this study was to evaluate the effect of ginger extract on delayed gastric emptying, developing ventilator-associated pneumonia, and clinical outcomes in adult respiratory distress syndrome (ARDS).

MATERIALS AND METHODS:

Thirty-two ARDS patients who were dependent on mechanical ventilation and fed via nasogastric tube were studied. After enrollment, patients were randomized to 2 groups. The control group received 1 g of coconut oil as placebo, and the study group received 120 mg of ginger extract. The amount of feeding tolerated at the first 48 hours of feeding, amount of feeding tolerated during the entire study period, nosocomial pneumonia, number of intensive care unit (ICU)-free days, number of ventilator-free days, and mortality were evaluated during 21 days of intervention.

RESULTS:

There was a significant difference between the ginger group and the control group in the amount of feeding tolerated at the first 48 hours of enteral feeding (51% vs 57%, P < .005). There was a trend toward a decrease in pneumonia in the ginger group (P = .07). The overall in-ICU mortality was 15.6%, with no significant difference in the 2 groups. The number of ventilator-free days and that of ICU-free days were lower in the control group compared with the ginger group (P = .04 and P = .02).

CONCLUSION:

This study showed that gastric feed supplementation with ginger extract might reduce delayed gastric emptying and help reduce the incidence of ventilator-associated pneumonia in ARDS.

Owyang Chung, et al., “Effects of ginger on motion sickness and gastric slow-wave dysrhytmias induced by circular vection,” American Journal of Physiology 284.3 (2003):G481-G489.

Ginger has long been used as an alternative medication to prevent motion sickness. The mechanism of its action, however, is unknown. We hypothesize that ginger ameliorates the nausea associated with motion sickness by preventing the development of gastric dysrhythmias and the elevation of plasma vasopressin. Thirteen volunteers with a history of motion sickness underwent circular vection, during which nausea (scored 0–3, i.e., none to severe), electrogastrographic recordings, and plasma vasopressin levels were assessed with or without ginger pretreatment in a crossover-design, double-blind, randomized placebo-controlled study. Circular vection induced a maximal nausea score of 2.5 ± 0.2 and increased tachygastric activity and plasma vasopressin. Pretreatment with ginger (1,000 and 2,000 mg) reduced the nausea, tachygastria, and plasma vasopressin. Ginger also prolonged the latency before nausea onset and shortened the recovery time after vection cessation. Intravenous vasopressin infusion at 0.1 and 0.2 U/min induced nausea and increased bradygastric activity; ginger pretreatment (2,000 mg) affected neither. Ginger effectively reduces nausea, tachygastric activity, and vasopressin release induced by  circular vection. In this manner, ginger may act as a novel agent in the prevention and treatment of motion sickness.

Torben Brask, et al., “Ginger Root Against Seasickness: A Conctrolled Trial on the Open Sea,” Acta Oto- laryngologica 105.1-2 (1988):45-49.

In a double-blind randomized placebo trial, the effect of the powdered rhizome of ginger (Zingiber officinale) was tested on seasickness. Eighty naval cadets, unaccustomed to sailing in heavy seas reported during voyages on the high seas, symptoms of seasickness every hour for 4 consecutive hours after ingestion of 1 g of the drug or placebo. Ginger root reduced the tendency to vomiting and cold sweating significantly better than placebo did (p<0.05). With regard to vomiting, a modified Protection Index (PI)=72% was calculated. Remarkably fewer symptoms of nausea and vertigo were reported after ginger root ingestion, but the difference was not statistically significant. For all symptom categories, PI=38% was calculated.

N Chaiyakunapruk, et al., “The efficacy of ginger for the prevention of postoperative nausea and vomiting: a meta- analysis,” American Journal of Obstetrics and Gynecology 194.1 (2006):95-99.

OBJECTIVE: The aim of this study was to specifically determine the impact of a fixed dose of ginger administration, compared with placebo, on the 24-hour postoperative nausea and vomiting.

STUDY DESIGN: The design was a systematic review and metaanalysis of trials revealed by searches. Randomized controlled trials comparing ginger with placebo to prevent postoperative nausea and vomiting and postoperative vomiting from Medline, IPA, CINAHL, Cochrane CENTRAL, HealthStar, Current Contents, bibliographies of retrieved articles, contact of authors, and experts in the field. Two reviewers selected studies for inclusion and independently extracted data.

RESULTS: Five randomized trials including a total of 363 patients were pooled for analysis of preventing postoperative nausea and vomiting and postoperative vomiting. The summary relative risks of ginger for postoperative nausea and vomiting and postoperative vomiting were 0.69 (95% confidence interval 0.54 to 0.89) and 0.61 (95% confidence interval 0.45 to 0.84), respectively. Only one side effect, abdominal discomfort, was reported.

CONCLUSIONS: This meta-analysis demonstrates that a fixed dose at least 1 g of ginger is more effective than placebo for the prevention of postoperative nausea and vomiting and postoperative vomiting. Use of ginger is an effective means for reducing postoperative nausea and vomiting.

Y.K. Gupta, et al., “Anti-emetic effect of ginger powder versus placebo as an add-on therapy in children and young adults receiving high emetogenic chemotherapy,” Pediatric Blood & Cancer 56.2 (2011):234-238.

PURPOSE:

Chemotherapy-induced nausea and vomiting (CINV) are major adverse effects of chemotherapy. Ginger has been used in postoperative and pregnancy-induced nausea and vomiting. Data on its utility in reducing CINV in children and young adults are lacking.

PATIENTS AND METHODS:

Sixty chemotherapy cycles of cisplatin/doxorubicin in bone sarcoma patients were randomized to ginger root powder capsules or placebo capsules as an additional antiemetic to ondensetron and dexamethasone in a double- blind design. Acute CINV was defined as nausea and vomiting occurring within 24 hr of start of chemotherapy (days 1-4) and delayed CINV  as that occurring  after 24 hr of completion of chemotherapy (days 5-10). CINV was evaluated as per Edmonton’s Symptom Assessment Scale and National Cancer Institute criteria respectively.

RESULTS:

Acute moderate to severe nausea was observed in 28/30 (93.3%) cycles in control group as compared to 15/27 (55.6%) cycles in experimental group (P = 0.003). Acute moderate to severe vomiting was significantly more in the control group compared to the experimental group [23/30 (76.7%) vs. 9/27 (33.33%) respectively (P= 0.002)]. Delayed moderate to severe nausea was observed in 22/30 (73.3%) cycles in the control group as compared to 7/27 (25.9%) in the experimental group (P < 0.001). Delayed moderate to severe vomiting was significantly more in the control group compared to the experimental group [14/30 (46.67%) vs. 4/27 (14.81%) (P = 0.022)].

CONCLUSION:

Ginger root powder was effective in reducing severity of acute and delayed CINV as additional therapy to ondensetron and dexamethasone in patients receiving high emetogenic chemotherapy.

T Chisaka, et al., “Cholagogic effect of ginger and its active constituents,” Journal of ethnopharmacology 13.2 (1985):217-25.

The effect of bile secretion in rats was examined in order to clarify the stomachic action of ginger and also to investigate its active constituents. The results showed that mainly the acetone extracts of ginger, which contain essential oils and pungent principles, caused an increase in the bile secretion. Further analyses for the active constituents of the acetone extracts through column chromatography indicated that [6]-gingerol and [10]-gingerol, which are the pungent principles, are mainly responsible for the cholagogic effect of ginger.

T.A. Ajith, et al., “Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status,” Food and Chemical Toxicology 45.11 (2007): 2267-2272.

A large number of  xenobiotics are reported to be potentially hepatotoxic. Free radicals generated from the xenobiotic metabolism can induce lesions of the liver and react with the basic cellular constituents – proteins, lipids, RNA and DNA. Hepatoprotective activity of aqueous ethanol extract of Zingiber officinale was evaluated against single dose of acetaminophen-induced (3 g/kg, p.o.) acute hepatotoxicity in rat. Aqueous extract of Z. officinale significantly protected the hepatotoxicity as evident from the activities of serum transaminase and alkaline phosphatase (ALP). Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and ALP activities were significantly (p < 0.01) elevated in the acetaminophen alone treated animals. Antioxidant status in liver such as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase and glutathione-S-transferase (GST), a phase II enzyme, and levels of reduced glutathione (GSH) were declined significantly (p < 0.01) in the acetaminophen alone treated animals (control group). Hepatic lipid peroxidation was enhanced significantly (p < 0.01) in the control group. Administration of single dose of aqueous extract of Z. officinale (200 and 400 mg/kg, p.o.) prior to acetaminophen significantly declines the activities of serum transaminases and ALP. Further the hepatic antioxidant status was enhanced in the Z. officinale plus acetaminophen treated group than the control group. The results of the present study concluded that the hepatoprotective effect of aqueous ethanol extract of Z. officinale against acetaminophen-induced acute toxicity is mediated either by preventing the decline of hepatic antioxidant status or due to its direct radical scavenging capacity.

Suresh Kumar, et al., “6-gingerol, an active ingredient of ginger, protects acetaminophen-induced hepatotoxicity in mice,” Journal of Chinese integrative medicine 9.11 (2011):1264-1269.

To investigate the hepatoprotective efficacy of 6-gingerol against acetaminophen-induced hepatotoxicity in mice. Mice were injected with a single dose of acetaminophen (900 mg/kg) to induce hepatotoxicity, while 6-gingerol (30 mg/kg) or the standard drug silymarin (25 mg/kg) was given 30 min after the acetaminophen administration. The mice were sacrificed 4 h after acetaminophen injection to determine the activities of liver marker enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), total bilirubin in serum, and lipid peroxidation and antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase and glutathione) in liver homogenate. The treatment of 6-gingerol and silymarin to acetaminophen-induced hepatotoxicity showed significant hepatoprotective effect by lowering the hepatic marker enzymes (AST, ALT, and ALP) and total bilirubin in serum (P<0.05). In addition, 6-gingerol and silymarin treatment prevented the elevation of hepatic malondialdehyde formation and the depletion of antioxidant status in the liver of acetaminophen-intoxicated mice (P<0.05). The results evidently demonstrate that 6-gingerol has promising hepatoprotective effect which is comparable to the standard drug silymarin.

Harish Nayaka Mysore Annaiah, et al., “Gastroprotective Effect of Ginger Rhizome (Zingiber Officinale) Extract:   Role of Gallic Acid and Cinnamic Acid in H+, K+-ATPase/H. pylori Inhibition and Anti-Oxidative Mechanism,” Evidence –Based Complementary and Alternative Medicine 2011. (2011): 249487.

Zinger officinale has been used as a traditional source against gastric disturbances from time immemorial. The ulcer-preventive properties of aqueous extract of ginger rhizome (GRAE) belonging to the family Zingiberaceae is reported in the present study. GRAE at 200 mg kg−1 b.w. protected up to 86% and 77% for the swim stress-/ethanol stress-induced ulcers with an ulcer index (UI) of 50 ± 4.0/46 ± 4.0, respectively, similar to that of lansoprazole (80%) at 30 mg kg−1 b.w. Increased H+,  K+-ATPase activity  and thiobarbituric acid reactive substances (TBARS) were observed in ulcer-induced rats, while GRAE fed rats showed normalized levels and GRAE also normalized depleted/amplified anti-oxidant enzymes in swim stress and ethanol stress-induced animals. Gastric mucin damage was recovered up to 77% and 74% in swim stress and ethanol stress, respectively after GRAE treatment. GRAE also inhibited the growth  of  H.  pylori  with MIC  of 300 ±  38 μg and also possessed  reducing  power, free radical −1 scavenging ability with an IC50 of 6.8 ± 0.4 μg mL gallic acid equivalent (GAE). DNA protection up to 90% at 0.4 μg was also observed. Toxicity studies indicated no lethal effects in rats fed up to 5 g kg−1 b.w. Compositional analysis favored by determination of the efficacy of individual phenolic acids towards their potential ulcer-preventive ability revealed that between cinnamic (50%) and gallic (46%) phenolic acids, cinnamic acid appear to contribute to better H+, K+-ATPase and Helicobacter pylori inhibitory activity, while gallic acid contributes significantly to anti-oxidant activity.

M Park, et al., “Antibacterial activity of *10+-gingerol and [12]-gingerol isolated from ginger rhizome against periodontal bacteria,” Phytotherapy Research 22. (2008): 1446–1449.

Ginger (Zingiber officinale Roscoe) has been used widely as a food spice and an herbal medicine. In particular, its gingerol-related components have been reported to possess antimicrobial and antifungal properties, as well as several pharmaceutical properties. However, the effective ginger constituents that inhibit the growth of oral bacteria associated with periodontitis in the human oral cavity have not been elucidated. This study revealed that the ethanol and n-hexane extracts of ginger exhibited antibacterial activities against three anaerobic Gram- negative bacteria, Porphyromonas gingivalis ATCC 53978, Porphyromonas endodontalis ATCC 35406 and Prevotella intermedia ATCC 25611, causing periodontal diseases. Thereafter, five ginger constituents were isolated by a preparative high-performance liquid chromatographic method from the active silica-gel column chromatography fractions, elucidated their structures by nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry and their antibacterial activity evaluated. In conclusion, two highly alkylated gingerols, [10]-gingerol and [12]-gingerol effectively inhibited the growth of these oral pathogens at a minimum inhibitory concentration (MIC) range of 6–30 µg/mL. These ginger compounds also killed the oral pathogens at a minimum bactericidal concentration (MBC) range of 4–20 µg/mL, but not the other ginger compounds 5-acetoxy-[6]-gingerol, 3,5- diacetoxy-[6]-gingerdiol and galanolactone.

CY Chen, et al., “Zingiber officinale (ginger) compounds have tetracycline-resistance modifying effects against clinical extensively drug-resistant Acinetobacter baumannii,” Phytotherapy Research 24.12 (2010):1825- 30.

Extensively drug-resistant Acinetobacter baumannii (XDRAB) is a growing and serious nosocomial infection worldwide, such that developing new agents against it is critical. The antimicrobial activities of the rhizomes from Zingiber officinale, known as ginger, have not been proven in clinical bacterial isolates with extensive drug- resistance. This study aimed to investigate the effects of four known components of ginger, [6]- dehydrogingerdione, [10]-gingerol, [6]-shogaol and [6]-gingerol, against clinical XDRAB.  All these compounds showed antibacterial effects against XDRAB. Combined with tetracycline, they showed good resistance modifying effects to modulate tetracycline resistance. Using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method, these four ginger compounds demonstrated antioxidant properties, which were inhibited by MnO₂, an oxidant without antibacterial effects. After the antioxidant property was blocked, their antimicrobial effects were abolished significantly. These results indicate that ginger compounds have antioxidant effects that partially contribute to their antimicrobial activity and are candidates for use in the treatment of infections with XDRAB.

RA Al-Essa RA, et al., “Physiological and therapeutical roles of ginger and turmeric on endocrine functions,” The American Journal of Chinese Medicine 39.2 (2011): 215-31.

The natural product ginger (Zingiber officinale) has active constituents gingerol, Shogaol and Zerumbone, while turmeric (Curcuma longa) contains three active major curcuminoids, namely, curcumin, demethoxycurcumin, and bisdemethoxycurcumin. They have the same scientific classification and are reported to have anti-inflammatory and many therapeutic effects. This article reviews the physiological and therapeutic effects of ginger and turm eric on some endocrine gland functions, and signal pathways involved to mediate their actions. With some systems and adipose tissue, ginger and turmeric exert their actions through some/all of the following signals or molecular mechanisms: (1) through reduction of high levels of some hormones (as: T4, leptin) or interaction with hormone receptors; (2) by inhibition of cytokines/adipokine expression; (3) acting as a potent inhibitor of reactive oxygen species (ROS)-generating enzymes, which play an essential role between inflammation and progression of diseases;

(4) mediation of their effects through the inhibition of signaling transcription factors; and/or (5) decrease the proliferative potent by down-regulation of antiapoptotic genes, which may suppress tumor promotion by blocking signal transduction pathways in the target cells. These multiple mechanisms of protection against inflammation and oxidative damage make ginger and curcumin particularly promising natural agents in fighting the ravages of aging and degenerative diseases, and need to be paid more attention by studies.

Carmelita G. Frondoza, et al., “Ginger—An Herbal Medicinal Product with Broad Anti-Inflammatory Actions,”

Journal of Medicinal Food 8.2 (2005):125-132.

The anti-inflammatory properties of ginger have been known and valued for centuries. During the past 25 years, many laboratories have provided scientific support for the long-held belief that ginger contains constituents with antiinflammatory properties. The original discovery of ginger’s inhibitory effects on prostaglandin biosynthesis in the early 1970s has been repeatedly confirmed. This discovery identified ginger as an herbal medicinal product that shares pharmacological properties with non-steroidal anti-inflammatory drugs. Ginger suppresses prostaglandin synthesis through inhibition of cyclooxygenase- 1 and cyclooxygenase-2. An important extension of this early work was the observation that ginger also suppresses leukotriene biosynthesis by inhibiting 5-lipoxygenase. This pharmacological property distinguishes ginger from nonsteroidal anti-inflammatory drugs. This discovery preceded the observation that dual inhibitors of cyclooxygenase and 5-lipoxygenase may have a better therapeutic profile and have fewer side effects than non-steroidal anti-inflammatory drugs. The characterization of the pharmacological properties of ginger entered a new phase with the discovery that a ginger extract (EV.EXT.77) derived from Zingiber officinale (family Zingiberaceae) and Alpina galanga (family Zingiberaceae) inhibits the induction of several genes involved in the inflammatory response. These include genes encoding cytokines, chemokines, and the inducible enzyme cyclooxygenase-2. This discovery provided the first evidence that ginger modulates biochemical pathways activated in chronic inflammation. Identification of the molecular targets of individual ginger constituents provides an opportunity to optimize and standardize ginger products with respect to their effects on specific biomarkers of inflammation. Such preparations will be useful for studies in experimental animals and humans.

MK Balijepalli, et al., “Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]- gingerol and [6]-shogaol,” Journal of ethnopharmacology 127.2 (2010): 515-20.

ETHNOPHARMACOLOGICAL    RELEVANCE:

Zingiber officinale Rosc. (Zingiberaceae) has been traditionally used in Ayurvedic, Chinese and Tibb-Unani herbal medicines for the treatment of various illnesses that involve inflammation and which are caused by oxidative stress. Although gingerols and shogaols are the major bioactive compounds present in Zingiber officinale, their molecular mechanisms of actions and the relationship between their structural features and the activity have not been well studied.

AIM OF THE STUDY:

The aim of the present study was to examine and compare the antioxidant and anti-inflammatory activities of gingerols and their natural analogues to determine their structure-activity relationship and molecular mechanisms. MATERIALS AND METHODS:

The in vitro activities of the compounds [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol were evaluated for scavenging of 1,1-diphenyl-2-picyrlhydrazyl (DPPH), superoxide and hydroxyl radicals, inhibition of N-formyl- methionyl-leucyl-phenylalanine (f-MLP) induced reactive oxygen species (ROS) production in human polymorphonuclear neutrophils (PMN), inhibition of lipopolysaccharide induced nitrite and prostaglandin E(2) production in RAW 264.7 cells.

RESULTS:

In the antioxidant activity assay, [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol exhibited substantial scavenging activities with IC(50) values of 26.3, 19.47, 10.47 and 8.05 microM against DPPH radical, IC(50) values of 4.05, 2.5, 1.68 and 0.85 microM against superoxide radical and IC(50) values of 4.62, 1.97, 1.35 and 0.72 microM against hydroxyl radical, respectively. The free radical scavenging activity of these compounds also enhanced with increasing concentration (P<0.05). On the other hand, all the compounds at a concentration of 6 microM have significantly inhibited (P<0.05) f-MLP-stimulated oxidative burst in PMN. In addition, production of inflammatory mediators (NO and PGE(2)) has been inhibited significantly (P<0.05) and dose-dependently.

CONCLUSIONS:

6-Shogaol has exhibited the most potent antioxidant and anti-inflammatory properties which can be attributed to the presence of alpha,beta-unsaturated ketone moiety. The carbon chain length has also played a significant role in making 10-gingerol as the most potent among all the gingerols. This study justifies the use of dry ginger in traditional systems of medicine.

Jennifer B. Frye, et al., “Comparative Effects of Two Gingerol-Containing Zingiber officinale Extracts on Experimental Rheumatoid Arthritis,” Journal of Natural Products 72.3 (2009): 403-407.

Ginger (Zingiber officinale) supplements are being promoted for arthritis treatment in western societies based on ginger’s traditional use as an anti-inflammatory in Chinese and Ayurvedic medicine. However, scientific evidence of ginger’s antiarthritic effects is sparse, and its bioactive joint-protective components have not been identified. Therefore, the ability of a well-characterized crude ginger extract to inhibit joint swelling in an animal model of rheumatoid arthritis, streptococcal cell wall (SCW)-induced arthritis, was compared to that of a fraction containing only gingerols and their derivatives. Both extracts were efficacious in preventing joint inflammation. However, the crude dichloromethane extract, which also contained essential oils and more polar compounds, was more efficacious (when normalized to gingerol content) in preventing both joint inflammation and destruction. In conclusion, these data document a very significant joint-protective effect of these ginger samples, and suggest that non-gingerol components are bioactive and can enhance the antiarthritic effects of the more widely studied gingerols.

Wenkui Li, et al. “Cyclooxygenase-2 inhibitors in ginger (Zingiber officinale),” Fitoterapia 82.1 (2011):38-43.

Ginger roots have been used to treat inflammation and have been reported to inhibit cyclooxygenase (COX). Ultrafiltration liquid chromatography mass spectrometry was used to screen a chloroform partition of a methanol extract of ginger roots for COX-2 ligands, and 10-gingerol, 12-gingerol, 8-shogaol, 10-shogaol, 6-gingerdione, 8- gingerdione, 10-gingerdione, 6-dehydro-10-gingerol, 6-paradol, and 8-paradol bound to the enzyme active site. Purified 10-gingerol, 8-shogaol and 10-shogaol inhibited COX-2 with IC50 values of 32 μM, 17.5 μM and 7.5 μM, respectively. No inhibition of COX-1 was detected. Therefore, 10-gingerol, 8-shogaol and 10-shogaol inhibit COX-2 but not COX-1, which can explain, in part, anti-inflammatory properties of ginger.

RD Altman, et al. “Effects of a ginger extract on knee pain in patients with osteoarthritis,” Arthritis and rheumatism

44.11 (2001): 2531-8.

OBJECTIVE:

To evaluate the efficacy and safety of a standardized and highly concentrated extract of 2 ginger species, Zingiber officinale and Alpinia galanga (EV.EXT 77), in patients with osteoarthritis (OA) of the knee.

METHODS:

Two hundred sixty-one patients with OA of the knee and moderate-to-severe pain were enrolled in a randomized, double-blind, placebo-controlled, multicenter, parallel-group, 6-week study. After washout, patients received ginger extract or placebo twice daily, with acetaminophen allowed as rescue medication. The primary efficacy variable was the proportion of responders experiencing a reduction in “knee pain on standing,” using an intent-to-treat analysis. A responder was defined by a reduction in pain of > or = 15 mm on a visual analog scale.

RESULTS:

In the 247 evaluable patients, the percentage of responders experiencing a reduction in knee pain on standing was superior in the ginger extract group compared with the control group (63% versus 50%; P = 0.048). Analysis of the secondary efficacy variables revealed a consistently greater response in the ginger extract group compared with the control group, when analyzing mean values: reduction in knee pain on standing (24.5 mm versus 16.4 mm; P = 0.005), reduction in knee pain after walking 50 feet (15.1 mm versus 8.7 mm; P = 0.016), and reduction in the Western Ontario and McMaster Universities osteoarthritis composite index (12.9 mm versus 9.0 mm; P = 0.087). Change in global status and reduction in intake of rescue medication were numerically greater in the ginger extract group. Change in quality of life was equal in the 2 groups. Patients receiving ginger extract experienced more gastrointestinal (GI) adverse events than did the placebo group (59 patients versus 21 patients). GI adverse events were mostly mild.

CONCLUSION:

A highly purified and standardized ginger extract had a statistically significant effect on reducing symptoms of OA of the knee. This effect was moderate. There was a good safety profile, with mostly mild GI adverse events in the ginger extract group.

T. Therkleson, “Ginger compress therapy for adults with osteoarthritis,” Journal of Advanced Nursing 66. (2010): 2225–2233.

AIM:

This paper is a report of a study to explicate the phenomenon of ginger compresses for people with osteoarthritis. BACKGROUND:

Osteoarthritis is claimed to be the leading cause of musculoskeletal pain and disability in Western society. Management ideally  combines  non-pharmacological  strategies,  including complementary therapies  and  pain- relieving medication. Ginger has been applied externally for over a thousand years in China to manage arthritis symptoms.

METHOD:

Husserlian phenomenological methodology was used and the data were collected in 2007. Ten purposively selected adults who had suffered osteoarthritis for at least a year kept daily diaries and made drawings, and follow-up interviews and telephone conversations were conducted.

FINDINGS:

Seven themes were identified in the data: (1) Meditative-like stillness and relaxation of thoughts; (2) Constant penetrating warmth throughout the body; (3) Positive change in outlook; (4) Increased energy and interest in the world; (5) Deeply relaxed state that progressed to a gradual shift in pain and increased interest in others; (6) Increased suppleness within the body and (7) More comfortable, flexible joint mobility. The essential experience of ginger compresses exposed the unique qualities of heat, stimulation, anti-inflammation and analgesia.

CONCLUSION:

Nurses could consider this therapy as part of a holistic treatment for people with osteoarthritis symptoms. Controlled research is needed with larger numbers of older people to explore further the effects of the ginger compress therapy.

SY Kim, et al. “6-Shogaol, a ginger product, modulates neuroinflammation: A new approach to neuroprotection,”

Neuropharmacology 63.2 (2012): 211-23.

Inflammatory processes in the central nervous system play an important role in a number of neurodegenerative diseases mediated by microglial activation, which results in neuronal cell death. Microglia act in immune surveillance and host defense while resting. When activated, they can be deleterious to neurons, even resulting in neurodegeneration. Therefore, the inhibition of microglial activation is considered a useful strategy in searching for neuroprotective agents. In this study, we investigated the effects of 6-shogaol, a pungent agent from Zingiber officinale Roscoe, on microglia activation in BV-2 and primary microglial cell cultures. 6-Shogaol significantly inhibited the release of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS). The effect was better than that of 6-gingerol, wogonin, or N-monomethyl-l-arginine, agents previously reported to inhibit nitric oxide. 6-Shogaol exerted its anti-inflammatory effects by inhibiting the production of prostaglandin E(2) (PGE(2)) and proinflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and by downregulating cyclooxygenase-2 (COX-2), p38 mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-κB) expression. In addition, 6-shogaol suppressed the microglial activation induced by LPS both in primary cortical neuron-glia culture and in an in vivo neuroinflammatory model. Moreover, 6-shogaol showed significant neuroprotective effects in vivo in transient global ischemia via the inhibition of microglia. These results suggest that 6-shogaol is an effective therapeutic agent for treating neurodegenerative diseases.

MN Ghayur, et al. “Ginger attenuates acetylcholine-induced contraction and Ca2+ signalling in murine airway smooth muscle cells,” Canadian Journal of Physiology and Pharmacology 86.5 (2008):264-71.

Asthma is a chronic disease characterized by inflammation and hypersensitivity of airway smooth muscle cells (ASMCs) to different spasmogens. The past decade has seen increased use of herbal treatments for many chronic illnesses. Ginger (Zingiber officinale) is a common food plant that has been used for centuries in treating respiratory illnesses. In this study, we report the effect of its 70% aqueous methanolic crude extract (Zo.Cr) on acetylcholine (ACh)-induced airway contraction and Ca(2+) signalling in ASMCs using mouse lung slices. Airway contraction and Ca(2+) signalling, recorded via confocal microscopy, were induced with ACh, either alone or after pretreatment of slices with Zo.Cr and (or) verapamil, a standard Ca(2+) channel blocker. ACh (10 micromol/L) stimulated airway contraction, seen as decreased airway diameter, and also stimulated Ca(2+) transients (sharp rise in [Ca(2+)]i) and oscillations in ASMCs, seen as increased fluo-4-induced fluorescence intensity. When Zo.Cr (0.3-1.0 mg/mL) was given 30 min before ACh administration, the ACh-induced airway contraction and Ca(2+) signalling were significantly reduced. Similarly, verapamil (1 micromol/L) also inhibited agonist-induced airway contraction and Ca(2+) signalling,  indicating  a  similarity  in  the  modes  of  action.  When  Zo.Cr (0.3  mg/mL)  and verapamil  (1 micromol/L) were given together before ACh, the degree of inhibition was the same as that observed when each of these blockers was given alone, indicating absence of any additional inhibitory mechanism in the extract. In Ca(2+) – free solution, both Zo.Cr and verapamil, when given separately, inhibited Ca(2+) (10 mmol/L)-induced increase in fluorescence and airway contraction. This shows that ginger inhibits airway contraction and associated Ca(2+) signalling, possibly via blockade of plasma membrane Ca(2+) channels, thus reiterating the effectiveness of this age-old herb in treating respiratory illnesses.

JA Podlogar, and EJ Verspohl. “Antiinflammatory effects of ginger and some of its components in human bronchial epithelial (BEAS-2B) cells,” Phytotherapy Research 26.3 (2012): 333-6.

The proinflammatory chemokine interleukin-8 is increased in asthmatic patients. Traditionally, ginger is used as an antiinflammatory drug. An extract and several compounds of Zingiber officinale (ginger) were tested in human bronchial epithelial cells (BEAS-2B cells) with respect to their effect on lipopolysaccharide (LPS)-induced secretion of the proinflammatory chemokine interleukin 8 (IL-8) and RANTES (regulated upon activation, normal T-cell expressed and secreted). An oily extract of ginger rhizome with > 25% total pungent compounds, ginger volatile oil, ar-curcumene and α-pinene reduced the LPS-induced IL-8 secretion (measured by a specific enzyme-linked immunosorbent assay), whereas a spissum extract, the pungents [6]-gingerol and its metabolite [6]-shogaol, and the terpenoids citral and β-phellandrene showed no effect. The LPS-induced slight increase of RANTES was reduced by volatile oil, ar-curcumene and α-pinene. There was no effect of LPS on TNF-α. Our results suggest that distinct ginger compounds could be used as antiinflammatory drugs in respiratory infections.

MS Huang, et al. “Ginger suppresses phthalate ester-induced airway remodeling,” Journal of Agricultural and Food Chemistry 59.7 (2011) 3429-38.

This study has two novel findings: it is not only the first to demonstrate inflammatory cytokines, which are produced by the bronchial epithelium after exposure to phthalate esters and contribute to airway remodeling by increasing human bronchial smooth muscle cells (BSMC) migration and proliferation, but it is also the first to reveal that ginger reverses phthalate ester-mediated airway remodeling. Human bronchial epithelial cell lines BEAS-2B and HBE135-E6E7 (HBE) were treated with butylbenzyl phthalate (BBP), bis(2-ethylhexyl) phthalate (BEHP), dibutyl phthalate (DBP), and diethyl phthalate (DEP), and the conditioned medium (CM) was harvested and then added to BSMC. Cultures of BSMC with BBP-, BEHP-, DBP-, and DEP-BEAS-2B-CM and DEP-HBE-CM increased BSMC proliferation and migration, which are major features in asthma remodeling. Exposure of BEAS-2B and HBE to DBP caused epithelial cells to produce inflammatory cytokines IL-8 and RANTES, which subsequently induced BSMC proliferation and migration. Depleting both IL-8 and RANTES completely reversed the effect of DBP-BEAS-2B-CM and DBP-HBE-CM-mediated BSMC proliferation and migration, suggesting this effect is a synergistic influence of IL- 8 and RANTES. Moreover, [6]-shogaol, [6]-gingerol, [8]-gingerol, and [10]-gingerol, which are major bioactive compounds present in Zingiber officinale , suppress phthalate ester-mediated airway remodeling. This study suggests that ginger is capable of preventing phthalate ester-associated asthma.

JH Bae, et al., “*6+-Gingerol suppresses interleukin-1 beta-induced MUC5AC gene expression in human airway epithelial cells,” American Journal of Rhinology & Allergy 23.4 (2009): 385-91.

BACKGROUND:

[6]-Gingerol is a major  active component of ginger and a natural polyphenol compound. The present study investigated whether [6]-gingerol suppresses interleukin (IL)-1 beta-induced MUC5AC gene expression in human airway epithelial cells and, if so, examined whether the suppression of MUC5AC gene expression is mediated via the mitogen-activated protein kinase (MAPK) signal transduction pathway.

METHODS:

MUC5AC mRNA and protein were measured using reverse transcription-polymerase chain reaction (PCR), real-time PCR, and Western blot analysis in cultured NCI-H292 human airway epithelial cells. Extracellular signal-regulated kinase (ERK) and p38 MAPK protein levels were analyzed by Western blot.

RESULTS:

Expression of MUC5AC mRNA increased in NCI-H292 cells upon treatment with 10 ng/mL of IL-1 beta for 24 hours. When the cells were pretreated with 10 microM of [6]-gingerol, expression of IL-1 beta-induced MUC5AC mRNA and protein was significantly suppressed. Suppression of IL-1 beta-induced MUC5AC mRNA was also observed in cells pretreated with ERK- or p38 MAPK-specific inhibitors, suggesting that [6]-gingerol-mediated suppression of IL- 1 beta-induced MUC5AC mRNA operated via the ERK- and p38 MAPK-dependent pathways.

CONCLUSIONS:

[6]-Gingerol suppresses IL-1 beta -induced MUC5AC gene expression in human airway epithelial cells via the ERK- and p38 MAPK-dependent pathways; therefore, [6]-gingerol may be considered a possible anti-hypersecretory agent.

JK Kundu, et al., “Ginger-derived phenolic substances with cancer preventive and therapeutic potential,” Forum of Nutrition 61. (2009): 182-92.

Ginger, the rhizomes of Zingiber officinale Roscoe (Zingiberaceae), has widely been used as a spice and condiment in different societies. Besides its food-additive functions, ginger has a long history of medicinal use for  the treatment of a variety of human ailments including common colds, fever, rheumatic disorders, gastrointestinal complications, motion sickness, diabetes, cancer, etc. Ginger contains several nonvolatile pungent principles viz. gingerols, shogaols, paradols and zingerone, which account for many of its health beneficial effects. Studies conducted in cultured cells as well as in experimental animals revealed that these pungent phenolics possess anticarcinogenic properties. This chapter summarizes updated information on chemopreventive and chemotherapeutic effects of ginger-derived phenolic substances and their underlying mechanisms.

MS Baliga, et al., “Update on the chemopreventive effects of ginger and its phytochemicals,” Critical Reviews in Food Science and Nutrition 51.6 (2011): 499-523.

The rhizomes of Zingiber officinale Roscoe (Zingiberaceae), commonly known as ginger, is one of the most widely used spice and condiment. It is also an integral part of many traditional medicines and has been extensively used in Chinese, Ayurvedic, Tibb-Unani, Srilankan, Arabic, and African traditional medicines, since antiquity, for many unrelated human ailments including common colds, fever, sore throats, vomiting, motion sickness, gastrointestinal complications, indigestion, constipation, arthritis, rheumatism, sprains, muscular aches, pains, cramps, hypertension, dementia, fever, infectious diseases, and helminthiasis. The putative active compounds are nonvolatile pungent principles, namely gingerols, shogaols, paradols, and zingerone. These compounds are some of the extensively studied phytochemicals and account for the antioxidant, anti-inflammatory, antiemetic, and gastroprotective activities. A number of preclinical investigations with a wide variety of assay systems and carcinogens have shown that ginger and its compounds possess chemopreventive and antineoplastic effects. A number of mechanisms have been observed to be involved in the chemopreventive effects of ginger. The cancer preventive activities of ginger are supposed to be mainly due to free radical scavenging, antioxidant pathways, alteration of gene expressions, and induction of apoptosis, all of which contribute towards decrease in tumor initiation, promotion, and progression. This review provides concise information from preclinical studies with both cell culture models and relevant animal studies by focusing on the mechanisms responsible for the chemopreventive action. The conclusion describes directions for future research to establish its activity and utility as a human cancer preventive and therapeutic drug. The above-mentioned mechanisms of ginger seem to be promising for cancer prevention; however, further clinical studies are warranted to assess the efficacy and safety of ginger.

T Ando, et al., “Ginger ingredients reduce viability of gastric cancer cells via distinct mechanisms,” Biochemical and Biophysical Chemical Research Communications 362.1 (2007):218-23.

Ginger has been used throughout the world as spice, food and traditional herb. We found that 6-gingerol, a phenolic alkanone isolated from ginger, enhanced the TRAIL-induced viability reduction of gastric cancer cells while 6-gingerol alone affected viability only slightly. 6-Gingerol facilitated TRAIL-induced apoptosis by increasing TRAIL- induced caspase-3/7 activation. 6-Gingerol was shown to down-regulate the expression of cIAP1, which suppresses caspase-3/7 activity, by inhibiting TRAIL-induced NF-kappaB activation. As 6-shogaol has a chemical structure similar to 6-gingerol, we also assessed the effect of 6-shogaol on the viability of gastric cancer cells. Unlike 6- gingerol, 6-shogaol alone reduced the viability of gastric cancer cells. 6-Shogaol was shown to damage microtubules and induce mitotic arrest. These findings indicate for the first time that in gastric cancer cells, 6- gingerol enhances TRAIL-induced viability reduction by inhibiting TRAIL-induced NF-kappaB activation while 6- shogaol alone reduces viability by damaging microtubules.

Nam E Kang, et al., “[6]-Gingerol inhibits metastasis of MDA-MB-231 human breast cancer cells,” The Journal of Nutritional Biochemistry 19.5 (2008): 313-319.

Gingerol (Zingiber officinale Roscoe, Zingiberaceae) is one of the most frequently and heavily consumed dietary condiments throughout the world. The oleoresin from rhizomes of ginger contains [6]-gingerol (1-*4′-hydroxy-3′- methoxyphenyl]-5-hydroxy-3-decanone) and its homologs which are pungent ingredients that have been found to possess many interesting pharmacological and physiological activities, such as anti-inflammatory, antihepatotoxic and cardiotonic effects. However, the effects of [6]-gingerol on metastatic processes in breast cancer cells are not currently well known. Therefore, in this study, we examined the effects of [6]-gingerol on adhesion, invasion, motility, activity and the amount of MMP-2 or -9 in the MDA-MB-231 human breast cancer cell line. We cultured MDA-MB-231 cells in the presence of various concentrations of [6]-gingerol (0, 2.5, 5 and 10 μM). *6+-Gingerol had no effect on cell adhesion up to 5 μM, but resulted in a 16% reduction at 10 μM. Treatment of MDA-MB-231 cells with increasing concentrations of [6]-gingerol led to a concentration-dependent decrease in cell migration and motility. The activities of MMP-2 or MMP-9 in MDA-MB-231 cells were decreased by treatment with [6]-gingerol and occurred in a dose-dependent manner. The amount of MMP-2 protein was decreased in a dose-dependent manner, although there was no change in the MMP-9 protein levels following treatment with [6]-gingerol. MMP-2 and MMP-9 mRNA expression were decreased by [6]-gingerol treatment. In conclusion, we have shown that [6]- gingerol inhibits cell adhesion, invasion, motility and activities of MMP-2 and MMP-9 in MDA-MB-231 human breast cancer cell lines.

E-H Chew, et al., “6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via blockade of nuclear factor-κB activation,” British Journal of Pharmacology 161.8 (2010):1763-1777.

BACKGROUND AND PURPOSE

Shogaols are reported to possess anti-inflammatory and anticancer activities. However, the antimetastatic potential of shogaols remains unexplored. This study was performed to assess the effects of shogaols against breast cancer cell invasion and to investigate the underlying mechanisms.

EXPERIMENTAL APPROACH

The anti-invasive effect of a series of shogaols was initially evaluated on MDA-MB-231 breast cancer cells using the matrigel invasion assay. The suppressive effects of 6-shogaol on phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-9 (MMP-9) gelatinolytic activity and nuclear factor-κB (NF-κB) activation were further determined.

KEY RESULTS

Shogaols (6-, 8- and 10-shogaol) inhibited PMA-stimulated MDA-MB-231 cell invasion with an accompanying decrease in MMP-9 secretion. 6-Shogaol was identified to display the greatest anti-invasive effect in association with a dose-dependent reduction in MMP-9 gene activation, protein expression and secretion. The NF-κB transcriptional activity was decreased by 6-shogaol; an effect mediated by inhibition of IκB phosphorylation and degradation that subsequently led to suppression of NF-κB p65 phosphorylation and nuclear translocation. In addition, 6-shogaol was found to inhibit JNK activation with no resulting reduction in activator protein-1 transcriptional activity. By using specific inhibitors, it was demonstrated that ERK and NF-κB signalling, but not JNK and p38 signalling, were involved in PMA-stimulated MMP-9 activation.

CONCLUSIONS AND IMPLICATIONS

6-Shogaol is a potent inhibitor of MDA-MB-231 cell invasion, and the molecular mechanism involves at least in part the down-regulation of MMP-9 transcription by targeting the NF-κB activation cascade. This class of naturally occurring small molecules thus have potential for clinical use as antimetastatic treatments.

Srijit Das, et al., “Ginger Extract (Zingiber Officinale) has Anti-Cancer and Anti-Inflammatory Effects on Ethionine- Induced Hepatoma Rats,” Clinics 63.6 (2008):807-813.

OBJECTIVE

To evaluate the effect of ginger extract on the expression of NFκB and TNF-α in liver cancer-induced rats. METHODS

Male Wistar rats were randomly divided into 5 groups based on diet: i) control (given normal rat chow), ii) olive oil,

iii) ginger extract (100mg/kg body weight), iv) choline-deficient diet + 0.1% ethionine to induce liver cancer and v) choline-deficient diet + ginger extract (100mg/kg body weight). Tissue samples obtained at eight weeks were fixed with formalin and embedded in paraffin wax, followed by immunohistochemistry staining for NFκB and TNF-α. RESULTS

The expression of NFκB was detected in the choline-deficient diet group, with 88.3 ± 1.83% of samples showing positive staining, while in the choline-deficient diet supplemented with ginger group, the expression of NFκB was significantly reduced, to 32.35 ± 1.34% (p<0.05). In the choline-deficient diet group, 83.3 ± 4.52% of samples showed positive staining of TNF-α, which was significantly reduced to 7.94 ± 1.32% (p<0.05) when treated with ginger. There was a significant correlation demonstrated between NFκB and TNF-α in the choline-deficient diet group but not in the choline-deficient diet treated with ginger extract group.

CONCLUSION

In conclusion, ginger extract significantly reduced the elevated expression of NFκB and TNF-α in rats with liver cancer. Ginger may act as an anti-cancer and anti-inflammatory agent by inactivating NFκB through the suppression of the pro-inflammatory TNF-α.

Ann M. Bode, et al. “[6]-Gingerol Suppresses Colon Cancer Growth by Targeting Leukotriene A4 Hydrolase,” Cancer Research 69.13 (2009):5584-91.

[6]-Gingerol, a natural component of ginger, exhibits anti-inflammatory and antitumorigenic activities. Despite its potential efficacy in cancer, the mechanism by which [6]-gingerol exerts its chemopreventive effects remains elusive. The leukotriene A4 hydrolase (LTA4H) protein is regarded as a relevant target for cancer therapy. Our in silico prediction using a reverse-docking approach revealed that LTA4H might be a potential target of [6]-gingerol. We supported our prediction by showing that [6]-gingerol suppresses anchorage-independent cancer cell growth by inhibiting LTA4H activity in HCT116 colorectal cancer cells. We showed that [6]-gingerol effectively suppressed tumor growth in vivo in nude mice, an effect that was mediated by inhibition of LTA4H activity. Collectively, these findings indicate a crucial role of LTA4H in cancer and also support the anticancer efficacy of [6]-gingerol targeting of LTA4H for the prevention of colorectal cancer.

K. Kobata, “A nonpungent component of steamed ginger–[10]-shogaol–increases adrenaline secretion via the activation of TRPV1,” Nutritional Neuroscience 9.3-4 (2006):169-78.

We investigated the components of ginger that are involved in increasing body temperature. Gingerols ([6,8,10]- gingerols) and shogaols ([6,8,10]-shogaols) having different alkyl carbon chain lengths were targeted. All the gingerols and shogaols increased intracellular calcium concentration in rat transient receptor potential vanilloid subtype 1 (TRPV1)-expressing HEK293 cells via TRPV1. In this regard, the shogaols were more potent than the gingerols. Aversive responses were induced by [6]-, [10]-gingerol, and [6]-shogaol (5 mmol/l) in rats when these compounds were applied to the eye; however, no response was observed in response to [10]-shogaol (5 and 10 mmol/l). [10]-Shogaol induced nociceptive responses via TRPV1 in rats following its subcutaneous injection into the hindpaw; the pungent compound capsaicin (CAP) and [6]-shogaol were observed to have similar effects. Moreover, adrenal catecholamine secretion, which influences energy consumption, was promoted in rats in response to [6]- and [10]-gingerols and [6]- and [10]-shogaols (1.6 micromol/kg, i.v.). [10]-Shogaol-induced adrenaline secretion was inhibited by administration of capsazepine, a TRPV1 antagonist. In conclusion, gingerols and shogaols activated TRPV1 and increased adrenaline secretion. Interestingly, [10]-shogaol is the only nonpungent compound among the gingerols and shogaols, suggesting its usefulness as a functional ingredient in food.

MY Henein, and R. Nicoll, “Ginger (Zingiber officinale Roscoe): a hot remedy for cardiovascular disease?”

International Journal of Cardiology 131.3 (2009):408-9.

Ginger is now exciting considerable interest for its potential to treat many aspects of cardiovascular disease. This letter reviews the more recent trials, which suggest that ginger shows considerable anti-inflammatory, antioxidant, anti-platelet, hypotensive and hypolipidemic effect in in vitro and animal studies. Human trials have been few and generally used a low dose with inconclusive results, however dosages of 5 g or more demonstrated significant anti- platelet activity. More human trials are needed using an appropriate dosage of a standardised extract. Should these prove positive, ginger has the potential to offer not only a cheaper natural alternative to conventional agents but one with significantly lower side effects.

AJ Ammit, et al. “Gingerols and related analogues inhibit arachidonic acid-induced human platelet serotonin release and aggregation,” Thrombosis Research 103.5 (2001):387-97.

Gingerols, the active components of ginger (the rhizome of Zingiber officinale, Roscoe), represent a potential new class of platelet activation inhibitors. In this study, we examined the ability of a series of synthetic gingerols and related phenylalkanol analogues (G1-G7) to inhibit human platelet activation, compared to aspirin, by measuring their effects on arachidonic acid (AA)-induced platelet serotonin release and aggregation in vitro. The IC(50) for inhibition of AA-induced (at EC(50)=0.75 mM) serotonin release by aspirin was 23.4+/-3.6 microM. Gingerols and related analogues (G1-G7) inhibited the AA-induced platelet release reaction in a similar dose range as aspirin, with IC(50) values between 45.3 and 82.6 microM. G1-G7 were also effective inhibitors of AA-induced human platelet aggregation. Maximum inhibitory (IC(max)) values of 10.5+/-3.9 and 10.4+/-3.2 microM for G3 and G4, respectively, were approximately 2-fold greater than aspirin (IC(max)=6.0+/-1.0 microM). The remaining gingerols and related analogues maximally inhibited AA-induced platelet aggregation at approximately 20-25 microM. The mechanism underlying inhibition of the AA-induced platelet release reaction and aggregation by G1-G7 may be via an effect on cyclooxygenase (COX) activity in platelets because representative gingerols and related analogues (G3- G6) potently inhibited COX activity in rat basophilic leukemia (RBL-2H3) cells. These results provide a basis for the design of more potent synthetic gingerol analogues, with similar potencies to aspirin, as platelet  activation inhibitors with potential value in cardiovascular disease.

KK Al-Qattan, et al., “The use of ginger (Zingiber officinale Rosc.) as a potential anti-inflammatory and antithrombotic agent,” Prostaglandins, Leukotrienes, and Essential Fatty Acids 67.6 (2002):475-8.

The effect of an aqueous extract of ginger (Zingiber officinale) on serum cholesterol and triglyceride levels as well as platelet thromboxane-B(2) and prostaglandin-E(2) production was examined. A raw aqueous extract of ginger was administered daily for a period of 4 weeks, either orally or intraperitoneally (IP) to rats. Fasting blood serum was investigated for thromboxane-B(2), prostaglandin-E(2), cholesterol and triglycerides. A low dose of ginger (50 mg/kg) administered either orally or IP did not produce any significant reduction in the serum thromboxane-B(2) levels when compared to saline-treated animals. However, ginger administered orally caused significant changes in the serum PGE(2) at this dose. High doses of ginger (500 mg/kg) were significantly effective in lowering serum PGE(2) when given either orally or IP. However, TXB(2) levels were significantly lower in rats given 500 mg/kg ginger orally but not IP. A significant reduction in serum cholesterol was observed when a higher dose of ginger (500 mg/kg) was administered. At a low dose of ginger (50 mg/kg), a significant reduction in the serum cholesterol was observed only when ginger was administered IP. No significant changes in serum triglyceride levels were observed upon administration of either the low or high dose of ginger. These results suggest that ginger could be used as an cholesterol-lowering, antithrombotic and anti-inflammatory agent.

A. Bordia, et al., “Protective effect of ginger, Zingiber officinale Rosc on experimental atherosclerosis in rabbits,”

Indian Journal of Experimental Biology 42.7 (2004):736-8.

The effects of air dried ginger powder (0.1g/kg body weight, po, for 75 days) were studied on experimentally induced atherosclerosis in rabbits by cholesterol feeding (0.3g/kg body weight, po). Cholesterol feeding for 75 days lead to distinct development of atheroma in the aorta and coronary arteriesof the rabbits and this was significantly inhibited by about 50% following ginger administration. There was distinct decrease in lipid peroxidation and enhancement of fibrinolytic activity in ginger treated animals. However, ginger did not lower blood lipidsto any significant extent. This distinct protection from the development of atherosclerosis by ginger is probably because of its free radical scavanging, prostaglandin inhibitory and fibri properties.

Yuhao Li, et al., “A 35-day gavage safety assessment of ginger in rats.” Regulatory Toxicology and Pharmacology 54.2 (2009):118-123.

Ginger (Zingiber officinale Roscoe, Zingiberacae) is one of the most commonly used spices around the world and a traditional medicinal plant that has been widely used in Chinese, Ayurvedic and Unani-Tibb medicines for several thousand years. However, there was still lack of systemic safety evaluation. We conducted a 35-day toxicity study on ginger in rats. Both male and female rats were daily treated with ginger powder at the dosages of 500, 1000 and 2000 mg/kg body weight by a gavage method for 35 days. The results demonstrated that this chronic administration of ginger was not associated with any mortalities and abnormalities in general conditions, behavior, growth, and food and water consumption. Except for dose-related decrease in serum lactate dehydrogenase activity in males, ginger treatment induced similar hematological and blood biochemical parameters to those of controlled animals. In general, ginger treatment caused no overt organ abnormality. Only at a very high dose (2000 mg/kg), ginger led to slightly reduced absolute and relative weights of testes (by 14.4% and 11.5%, respectively). This study provides a new understanding of the toxicological properties of ginger.

ENDNOTES

1 Sebastian Pole, Ayurvedic Medicine (Philadelphia, PA: Elsevier, 2006) 183.

2 David Frawley, and Vasant Lad, The Yoga of Herbs (Twin Lakes, WI: Lotus Press, 1992) 122.

3 John Lust, The Herb Book (New York: Benedict Lust Publications, 2005) 205, 514.

4 Ibid, p205, 514.

5 Karta Purkh Singh Khalsa, and Michael Tierra The Way of Ayurvedic Herbs (Twin Lakes, WI: Lotus Press, 2008) 136, 138.

6 R.K. Goel and K. Sairam. “Anti-Ulcer Drugs from Indigenous Sources with Emphasis on Musa Sapientum, Tamrabhasma, Asparagus Racemosus, and Zingiber Officinale,” Indian Journal of Pharmacology 34 (2002): 100-

110.

7 Karta Purkh Singh Khalsa, and Michael Tierra The Way of Ayurvedic Herbs (Twin Lakes, WI: Lotus Press, 2008) 136, 138.

8 John Lust, The Herb Book (New York: Benedict Lust Publications, 2005) 514-515.

9 Karta Purkh Singh Khalsa and Michael Tierra, The Way of Ayurvedic Herbs (Twin Lakes, WI: Lotus Press, 2008) 138.

10 Sebastian Pole, Ayurvedic Medicine (Philadelphia, PA: Elsevier, 2006) 183.

11 David Frawley, and Vasant Lad, The Yoga of Herbs (Twin Lakes, WI: Lotus Press, 1992) 121.

12 Vaidya Bhagwan Dash, Materia Medica of Ayurveda (New Delhi: Concept Publishing, 1980) 35, ch.2, v.54.

13Kaviraj Kunia Lal Bhishagratna, ed. The Sushruta Samhita. Vol.I (Calcutta, self, 1907) 510, ch. XLVI.

14 Sebastian Pole, Ayurvedic Medicine (Philadelphia, PA: Elsevier, 2006) 183.

15 David Frawley, and Vasant Lad, The Yoga of Herbs (Twin Lakes, WI: Lotus Press, 1992) 122.

16 Karta Purkh Singh Khalsa and Michael Tierra, The Way of Ayurvedic Herbs (Twin Lakes, WI: Lotus Press, 2008) 136.

17 Michael Tierra, The Way of Herbs (Santa Cruz, CA: Unity Press, 1980) 70.

18 David Frawley and Vasant Lad, The Yoga of Herbs (Twin Lakes, WI: Lotus Press, 1992) 121-122.

19 Daniel P. Reid, Chinese Herbal Medicine (Boston: Shambhala Publications, Inc., 1986) 116.

20 Victoria Zak, 20,000 Secrets of Tea (New York: Dell Publishing, 1999) 131-132.

21 David Frawley and Vasant Lad, The Yoga of Herbs (Twin Lakes, WI: Lotus Press, 1992) 121. 22 Daniel P. Reid, Chinese Herbal Medicine (Boston: Shambhala Publications, Inc., 1986) 116. 23 David Frawley and Vasant Lad, The Yoga of Herbs (Twin Lakes, WI: Lotus Press, 1992) 121. 24 Sebastian Pole, Ayurvedic Medicine (Philadelphia, PA: Elsevier, 2006) 183.

25 R.K. Goel and K. Sairam. “Anti-Ulcer Drugs from Indigenous Sources with Emphasis on Musa Sapientum, Tamrabhasma, Asparagus Racemosus, and Zingiber Officinale,” Indian Journal of Pharmacology 34 (2002): 100- 110.

26NC Azu and RA Onyeagba, “Antimicrobial Properties Of Extracts Of Allium cepa (Onions) And Zingiber officinale

(Ginger) On Escherichia coli, Salmonella typhi And Bacillus subtilis.” The Internet Journal of Tropical Medicine 3.2 (2007).        http://www.ispub.com/journal/the-internet-journal-of-tropical-medicine/volume-3-number- 2/antimicrobial-properties-of-extracts-of-allium-cepa-onions-and-zingiber-officinale-ginger-on-escherichia-coli- salmonella-typhi-and-bacillus-subtilis.html

27 David Frawley and Vasant Lad, The Yoga of Herbs (Twin Lakes, WI: Lotus Press, 1992) 122.

28 Vaidya Bhagwan Dash, Materia Medica of Ayurveda (New Delhi: Concept Publishing, 1980) ch.2, v.54.

29 Kaviraj Kunia Lal Bhishagratna, ed. Sushruta Samhita, vol.II, 311, ch.V, verse 34.

30 Ibid, vol.II, 311, ch.V, verse 34.

31 Vaidya Bhagwan Dash, Materia Medica of Ayurveda (New Delhi: Concept Publishing, 1980) ch.2, v.63; ch.8, v.9; ch.27, v.11-13.

32 Sebastian Pole, Ayurvedic Medicine (Philadelphia, PA: Elsevier, 2006) 302.

33 Ibid p183.

34 Seng-Kee Chuau, et.al, “Effect of Ginger on Gastric Motility and Symptoms of Functional Dyspepsia,” World Journal of Gastroenterology 17.1 (2011):105-110.

35 Ibid p105-110.

36 Ibid p105-110.

37 SK Chuau, et al., “Effect of Ginger on Gastric Emptying and Motility in Healthy Humans,” European Journal of Gastroenterology and Hepatology 20.5 (2008):436-440.

38 M. Mokhtari, et al., “Ginger extract reduces delayed gastric emptying and nosocomial pneumonia in adult

respiratory distress syndrome patients hospitalized in an intensive care unit,” Journal of Critical Care 25.4 (2010):647-650.

39 Sebastian Pole, Ayurvedic Medicine (Philadelphia, PA: Elsevier, 2006) 183.

40 Owyang Chung, et al., “Effects of ginger on motion sickness and gastric slow-wave dysrhytmias induced by circular vection,” American Journal of Physiology 284.3 (2003):G481-G489.

41 Torben Brask, et al., “Ginger Root Against Seasickness: A Conctrolled Trial on the Open Sea,” Acta Oto-

laryngologica 105.1-2 (1988):45-49.

42 R.K. Goel and K. Sairam. “Anti-Ulcer Drugs from Indigenous Sources with Emphasis on Musa Sapientum,

Tamrabhasma, Asparagus Racemosus, and Zingiber Officinale,” Indian Journal of Pharmacology 34 (2002): 100- 110.

43“NICE Clinical Guidelines, No. 62,” Antenatal Care: Routine Care for the Healthy Pregnant Woman. London:

National Collaborating Centre for Women’s and Children’s Health (UK), RCOG Press, 2008.

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