ZINGIBER OFFICINALE EFFECT ON HELICOBACTER PYLORI INFECTION IN HUMAN; A SYSTEMATIC REVIEWHTML Full Text
ZINGIBER OFFICINALE EFFECT ON HELICOBACTER PYLORI INFECTION IN HUMAN; A SYSTEMATIC REVIEW
Vahid Mirzaee 1, Abdollah Jafarzadeh 2-5, Afshin Tahmasebi 1 and Shila Jalalpour * 2
Department of Internal Medicine 1, Department of Immunology, School of Medicine 3 Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Molecular Medicine Research Center 2, Immunology of Infectious Diseases Research Center 5, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Department of Immunology, School of Medicine 4, Kerman University of Medical Sciences, Kerman, Iran.
ABSTRACT: Helicobacter pylori (HP) as a non-invasive microbe, has been cloned in the stomach. The most important side effects of HP are inflammation, peptic ulcer (PU) and gastric cancer (GC). Control of inflammation, leads to preventing other HP side effects and antibiotic resistance, therefore it is important to use of natural anti-inflammatory compounds. In present study, review the effect of Zingiber officinale (Z. officinale) in controlling side effects of HP in human. Related articles were collected in Google Scholar, Pub Med, Science direct, Scientific Information Database and Scopus. For this purpose, using the terms pylori, Zingiber officinale and Ginger in the title of the all articles published to 2020. Based on search results, were absorbed 15 articles in Google Scholar, 10 articles in Pub Med, 1 articles in Science direct, 1 article in Scientific Information Database and 13 articles in Scopus. After removing the same articles, protocols and no English language articles, finally reviewed, 8 English-language articles and 1 Farsi language article. Regard to long-term treatment of HP and the multiple side effects of routine therapy and possible formation of antibiotic-resistant strains, it's necessary to use natural drugs with less side effects. The Z. officinale effects on HP such prevention, inhibitory proliferation and control of the side effects of HP colonization, and so economic efficiency and easy accessibility, have been identified as an appropriate candidate for treatment and prevention and of HP infection.
Helicobacter pylori, Infection, Ginger, Zingiber officinale
INTRODUCTION: HP has infected mankind in Africa continent since the early Stone Age 1. Prior to the twentieth century, the majority of the world’s population was infected with HP 2. The history of HP dates back to 1875 when the German scientists first found spiral bacteria in the lining of the human stomach 3.
Medical scientists know that HP was only cultured recently, in 20th century at Royal Perth Hospital in Western Australia, HP discovery by Prof. Robin Warren and Barry Marshall in 19th century 4, 5.
HP, is a Gram negative helix-shaped (not spirochaete), 0.5 µm diameter and about 3 µm long. It is microaerophilic; that is, it’s an anaerobic; (low oxygen concentration, requires). HP contains a hydrogenase enzyme. HP produces 3 important enzyme include urease, oxidase and catalase. HP can to form biofilms and convert from helix to a possibly viable but non-cultural coccoid form 3, 6. The coccoid form can adhere to gastric epithelial cells in-vitro condition, whose ecological niche is the human stomach which is also linked to severe gastritis-associated diseases 7, 8. HP infection is one of the prevalent bacterial infections involved about 50% of the population worldwide 9. Recurrence of HP infection after successful eradication is rare in developed countries and more frequent in developing countries 10. HP infection and prevalence in developed countries were reduced in younger patients (less than 20% but remaining still high (over 50%) in the elderly population. The incidence is stable in developing countries with a prevalence of 70-80%. The prevalence of HP in Iranians population is 54%, also observed that this prevalence was significantly different according to age and HP diagnostic method 9. HP colonization usually does not lead to disease, since 85% of infected people remain asymptomatic throughout life, but this infection is more common in developing countries compare to developed communities 9.
Different studies have been done in many countries, reported the prevalence of HP infection from <20% in European countries to more than 80% in some Eastern Mediterranean countries 9. HP prevalence is more than half in Africa, Asia Central/South America and East/South Europe and HP prevalence in countries with high GC is twofold higher than other country, in North America and Northern Europe, about 33% of adults population are infected 11. In developed countries, HP has highly outbreak in the immigrants population. It became evident that the bacterium was present in all human races, on all continents, although it was more common in developing countries and less common in western countries or affluent communities within countries 11. Side effects of HP colonization are classified at two groups of gastrointestinal and non-gastrointestinal: gastroduodenal diseases including chronic gastritis, PUs, gastric adenocarcinoma (Adenocarcinoma is the main type of gastric malignancy 12) and gastric lymphoma 7, 8, 13, 14 Fig. 1 and around 15%-20% of the infected individuals develop gastroduodenal diseases 15, 16, 17. Non gastrointestinal symptoms following HP colonization include: respiratory disorders, vascular, autoimmune antibodies, middle ear disorders, cardiovascular disease and iron-deficiency anemia and adenovirus and Tansylar ischemic heart disease 18, 19, 20. Persistent stomach infection with HP causes chronic mucosal inflammation (gastritis), which is widely recognized as an essential precursor to GC 21, Therefore preventing and controlling inflammation is important in controlling cancer 22, 23. A standard triple therapy (STT), including the proton pump inhibitor (PPI)/amoxicillin and clarithromycin or metronidazole, as proposed at the first Maastricht conference, was globally accepted as first-line HP eradication therapy.
The widespread use of antibiotics the success percent of HP eradication treatment can be reduced 24. Treatment of HP is hard today because of its high resistance to tronidazole and clarithromycin resistance rates are alarming although they vary among populations 25. Due to the spread of antibiotic resistance microorganisms in worldwide, anti-HP treatment is continuing to be a high challenge for physicians in clinical practice. The Real-world Practice & Expectation of Asia-Pacific Physicians and Patients in HP Eradication (REAP-HP) Survey demonstrated that the accepted minimal eradication rate of anti-HP regimen in HP-infected patients was 91% 26. Anti HP induced inflammation activity by natural products, usually relevant to mitogen-activate protein kinase pathway activation, suppression of nuclear factor-κB and inhibition of oxidative stress. Anti HP gastritis effects of herbal products, including apple peel polyphenol, carotenoids-rich algae, quercetin, tea product, apigenin, garlic and finger-root extract, have been documented 27.
Those herbal products have demonstrated high potential as pharmaceutical candidates for HP eradication and HP induced related gastric disorders prevention 27. The word “nutraceuticals” means the bioactive compounds that are found in foods, herbal products and dietary supplements. Therefore, nutraceuticals are those molecules/ plants which have health-promoting, disease-preventing medicinal properties 28. Since, Z. officinale has been introduced in Iranian traditional medicine as a herbal anti-inflammatory and according to the traditional treatment of gastrointestinal diseases, Z. officinale have potential effects in control of HP side effect 29. Z. officinale have anti-inflammatory, anti-oxidants and the anti-cancer effects and protection of the gastrointestinal tract and anti-ulcer on HP.
FIG. 1: EFFECT OF ZINGIBER OFFICINALE (GINGER) ON THE HUMAN GASTROINTESTINAL TRACS
The Z. officinale have been used to therapy of arthritis, asthma, catarrh, cramps, dementia, diabetes, gingivitis, hypertension, infectious diseases, nervous diseases, muscular aches, pains, rheumatism, sprains, sore throats, stroke, toothache, treat vomiting, nausea, dyspepsia, inflammation, indigestion, asthma, cough, palpitation, loss of appetite, constipation, common cold, stomachache, fever and influenza 30.
Considering the importance and prevalence of HP in higher than 50% of the population and the need for a natural drug with the ability to induce proper immune system to prevent the onset of HP, and also the need for therapy to inhibit bacterial proliferation and in particular inhibit the inflammation caused by the host to bacteria. The aim of present study was systematic review the effect of Z. officinale on controlling and preventing complications following colonization of HP in human.
METHODS: The current review was conducted in 2020 by reviewing all full-text articles published in English/Persian language on the effect of Zingiber officinale on HP. Articles were collected from international and national search websites of Google Scholar, Pub Med, Science Direct, Scientific Information Database, and Scopus. For this purpose, using the 3 terms "pylori", Zingiber officinale and "ginger" in the title of the articles.
RESULTS: Based on search results, 40 articles were identifier. 15 articles in Google Scholar, 10 articles in Pub Med, 1 article in Science direct, 1 article in Scientific Information Database and 13 articles in Scopus. After removing the same articles, protocols and no English language articles, finally reviewed, 9 articles such 8 English-language articles and 1 Farsi language article Fig. 2.
Z. officinale Roscoe (Zingiberaceae family) that known as ginger, is indigenous to tropical southern China or India and Asia. The rhizomes of Z. officinale have a powerful aroma 31. Over 4000 years Z. officinale was used as a spice in food usage and as a home‑remedy for digestive problem and during pregnancy 32.
Compositional analysis has revealed the presence of carbohydrates, fats, vitamins, minerals, and extractable oleoresins 33. Z. officinale has been fractionated into at least 14 bioactive compounds, including -gingerol, -gingerol, -gingerol, -gingerol, -paradol, -shogaol, -shogaol, 1-dehydro--gingerdione, -ginger-dione, hexahydrocurcumin, tetrahydrocurcumin, gingerenone A, 1,7-bis-(4′ hydroxyl-3′ methoxy-phenyl)-5-methoxyhepthan-3-one, and methoxy-- gingerol 34. The myriad pharmacological effects are supposed to be due to the presence of volatile compounds like zingiberene, curcumene, farnesene, bisabolene, b-sesquiphellandrene, 1, 8-cineole, linalool, borneol, neral, and geraniol and the nonvolatile ones like shogaol, gingerols, zingerone and paradols. The other constituents include capsaicin, diarylheptanoids, ginger pro-tease, gingediol, galanolactone, gingesulfonic acid, galactosyl glycerols, gingerglycolipids, neral, and phytosterols 1.
FIG. 2: PRISMA FLOW DIAGRAM FOR GINGER EFFECT ON HELICOBACTER PYLORI INFECTION IN HUMANS
At least 115 component in fresh and powder Z. officinale have been identified the methanolic extracts of fresh Z. officinale rhizome has at least 31 gingerol related compounds 28. In fresh Z. officinale the amount of 6-shogaol, is very low but much higher after the steaming process. With significantly higher anticancer activities, 6-shogaol can serve as an agent for drug discovery. The compound structure modification can be performed based on its three key functional and reactive groups 35. Gingerols (GNs) (a volatile phenolic compound) have response to pungent taste of fresh Z. officinale rhizome, 6-gingerol is the main compound of the Z. officinale, and other gingerols such as 4, 8, 10 and 12-gingerol, are present in lower concentrations. These compounds are thermally labile and are transformed at high temperatures to shogaols (SGs), which impart a pungent and spicy-sweet fragrance 6-gingerol ((5S)- 5- hydroxy-1-(4-hydroxy- 3-methoxyphenyl) decan-3-one), 8-gingerol ((5S)-5-hydroxy-1-(4-hydroxy- 3- methoxyphenyl)dodecan-3-one), 10-gingerol((5S)-5-hydroxy-1-(4-hydroxy-3-methoxy-phenyl)tetradecan-3-one), 6-shogaol ((E)- 1- (4-hydroxy- 3 -methoxyphenyl)dec- 4- en-3-one), 8-shogaol ((E)- 1- (4-hydroxy- 3- methoxyphenyl) dodec-4-en-3-one) and 10-shogaol ((E)- 1- (4-hydroxy-3-methoxyphenyl) tetradec- 4- en-3-one) gingerol analogues are sensitive to temperature but shogaols which spicy taste is found in dried Z. officinale. Both shogaols and gingerols have biological activities, ranging from anti-microbial, anti-cancer, anti-oxidant, anti-inflammatory and anti-allergic 31.
Consumption of Z. officinale regularly leads to decreased pain levels in patients with rheumatoid arthritis or osteoarthritis along with improvements in their mobility 28, also usage Z. officinale has effective role in, gastritis, nausea, vomiting, dyspepsia, belching, bloating, epigastric discomfort, gastric ulcerations, indigestion, and scientific studies have validated the ethno medicinal uses 36.
Ani-inflammatory Effect of Z. officinale on H. pylori: Z. officinale has ancient of use as an anti-inflammatory and many of its component have been demonstrated as having anti-inflammatory effect 37. Z. officinale can inhibit prostaglandin biosynthesis 38. Z. officinale has same pharmacological effect with non-steroidal anti-inflammatory drugs (NSAIDs) because Z. officinale suppresses prostaglandin synthesis by the limitation of cyclooxygenase and cyclooxygenase-1 39. Identification of the molecular targets of individual Z. officinale constituents creates an chance to optimize and standardize Z. officinale products with respect to their property on special biomarkers of inflammation 40. The anti-inflammatory effect of gingerols is thought to have importance in these problems. Z. officinale could be related to inhibition of leukotriene and prostaglandin synthesis 28. Previous studies carried out in the recent past indicate that inflammation plays a cardinal role in various pathophysiological processes and that it is mediated by TNF-a, NF-kb, i-NOS and COX-2, and increased generation of proinflammatory eisonaoids 41. Z. officinale and its compounds have been studied in detail for its anti-infammatory effects and studies have shown it to suppress synthesis of prostaglandin by inhibiting COX-1,-2 and inhibiting 5- LOX 42, 43. The 8-shogaol and 8-paradol have high avibility inhibitory effects on COX-2 activity in-vitro condition 44. Z. officinale and 8-shogaol and 8-paradol are also shown to decrease the levels of pro-infammatory cytokines and to reduce the elevated expression of NFkB 45.
Z. officinale extract inhibited the activity of COX-2, NF-kB and to inhibit the release of IL-1b, IL-6, IL-8, and TNF-a from LPS-stimulated human PBMCs in combating HP infection 36. Several experiments have been carried out to survey the anti-inflammatory effects of Z. officinale on animal models and cell cultures, and all have been able to confirm the anti-inflammatory property of Z. officinale 46, 47. Red Z. officinale (Z. officinale var. Rubra) was used an analgesic for arthritis pain. Color of the Z. officinale var. Rubra is purple because it contains anthocyanidins. Shimoda and et al., study anti-inflammatory activity of 40% ethanolic extract of red ginger extract. In an acetic acid-induced animal model, 10–100 mg/kg red ginger extract can inhibited the frequency of writhing and the enhancement in permeability of abdominal capillaries. Consumption with red ginger extract (10 mg/kg) significantly reduced footpad inflammation in animal model adjuvant arthritis model. Red ginger extract (3 and 10 mg/mL) significantly reduced PGE2 production and limited NO production at 100 mg/ml. 6-shogaol and gingerdiols inhibits NO production. Red dye fractions presumed to be proanthocyanidins also inhibited production of NO at 100 mg/ml. suppressive property of red ginger extract on inflammation, be involved inhibition activation of macrophage, - Shogaol, gingerdiols and proanthocyanidins were identified as constituents that inhibited NO production 47. Gaus and et al., study effects of the Z. officinale extract on prevention and eradication of infection in an animal model. Animals consume daily 100 mg/kg dose of Z. officinale extract for 3 weeks before being infected or 6 weeks being infected. Consume of Z. officinale extract significantly reduced HP load and lowered acute and chronic mucosal and sub-mucosal inflammation. So Z. officinale suppressed the activity of cyclooxygenase-2 and nuclear factor-kappaB transcriptional response in kBZ Jurkat cells, and significantly inhibited the release of tumor necrosis factor-alpha and IL-1 beta, -6, -8 from lipopolysaccharide-stimulated PBMCs with IC50 values of 3.89, 7.7, 8.5, and 8.37 mug/mL, respectively. These results suggest Z. officinale extracts may be helpful for development as compound to reduce HP-induced inflammation and as for GC chemoprevention 48.
In human and animals Cisplatin treatment causes vomiting and nausea 37 25, 50, 100 and 200 mg/kg oral doses of acetone/ ethanolic extracts of Z. officinale exhibited significantly protection, but aqueous extract has not ineffective against cisplatin emesis in and animals such rats 49 and dogs 50.
Anticancer effect of Z. officinale on H. pylori: GC is the fourth common cancer in men and the fifth common cancer in women 51 and is the third most common cause of death from cancer in the world 52, 53. From the first reports based on the role of HP with adenocarcinoma 54, 55, to recent studies, all confirmed the association between HP and adenocarcinoma 56, 57. Finally in 1994, the International Agency for Research on Cancer classified HP as a type I carcinogen bacterium 52.
Z. officinale are applied by various compounds, including vanilloids, 6-paradol, 6-gingerol, Shogaols, zingerone, Galanals A and Galanals B 58, 59 Galanals A and Galanals B are strong induction of apoptosis in Jurkat cells human T 58. Anticarcinogenic properties of Z. officinale to be mediated by various pathways 60. Z. officinale reported to has anti colon cancer activity 61. Gingerols, kill ovarian cancer cells by inducing autophagocytosis and apoptosis 62. In ovarian cancer, pro-inflammatory state has been important contributing factor. Z. officinale, reduced inflammatory mediator such IL-8, vascular endothelial growth factor and prostaglandin E2 in the ovarian cancer cells 62. Mixed treatment with TNF and 6-shogaol-related to induces apoptosis in type of cancer cells such breast carcinoma MDA-MB-231 cells, renal carcinoma Caki cells and glioma U118MG cells, but not in normal mesangial cells and normal mouse kidney cells. 6-Shogaol also can reduce cytochrome c and mitochondrial membrane potential released from mitochondria to cytosol via Bax activation. 6-Shogaol also resulted down-regulation of c-FLIP(L) expression at the posttranslational levels 63. Gingerol inhibited human colorectal cancer 61.
The effects of aquatic extract of Z. officinale on Brest cancer in mice shown, cancer significantly inhibited 62. Tumor development are multistep processes contains metabolic changes and genetic 63. A cytostatic/ cytotoxic effect, mediated by apoptosis, was found for 6-paradol and 6-gingerol in promyelocytic leukemia HL-60 cells 64 and also for 4 diarylheptanoids and 2 shogaols 28. 6-gingerol, 6-shogaol, 6-paradol, have potential effect for treatment and prevention of non-small cell lung carcinoma, among this compounds, 6-gingerols has most effective in inhibition the proliferation of non-small cell lung carcinoma 60. Z. officinale and its constituents are also helpful against pancreatic cancer 65. Whole Z. officinale extract or its constituents, inhibited induced death of pancreatic cancer 66. Z. officinale limitation of leukotriene A4 hydrolase activity and this properties resulted to prevention of colorectal cancer. In human colorectal cancer cells treatment with Z. officinale reduction of cell viability and induce apoptosis by the increased ATF3 expression via activating ATF3 promoter 67. In-vitro condition studies revealed that Z. officinale components are efficient against liver cancer. 6-shogaol induce apoptotic of Mahlavu hepatoma cells by an oxidative stress-mediated caspasedependent mechanism 68.
The major components of Z. officinale, 6-gingerol and 6-shogaol, have anti-invasive property against hepatoma cells. In animal model, Z. officinale by reducing lipid peroxidation and scavenging the free radical formation, inhibited hepatocarcinogenesis 69. An ethanol Z. officinale extract significantly protected effect against the development of skin tumors in mouse. Inhibition of 12-O-tetradecanoylphorbol-13-acetate-caused induction of cyclooxygenase (COX), epidermal ornithine decarboxylase and lipoxygenase activities 28, 70.
Antimicrobial Effect of Z. officinale on H. pylori: Antibiotic resistance is developing worldwide and consider as an important offender in the failure of antibiotic treatment. Consumption of antibiotics against microbes is effective treatment method but also causes side effects. Z. officinale having broad range of antimicrobial activity against both Gram+ and Gram- bacteria and fungi 71, 72. Continuous consumption of Z. officinale reduced multiplication of colon bacteria. These micro-organisms fermented of undigested carbohydrates causing flatulence which can be counteract with Z. officinale 73. Z. officinale and its constituents have a vital play in the limited of microorganisms growth or act as antimicrobial agents 74. Z. officinale rhizome contains constituents which have antibacterial / antifungal effects. The shogaol and gingerol are identified as high active antimicrobial agents 75. 10-Gingerol from Z. officinale has antimicrobial activity against a pathogenic microorganisms including Gram+ and Gram- bacteria and the Candida albicans 76. Various studies demonstrated time-dependent anthelmintic activity of crude aqueous extract of dried Z. officinale and crude powder (1–3 g/kg) in animal models infected with mixed species of gastrointestinal nematodes are reported 77. Z. officinale inhibits Aspergillus sp., a carcinogenic organism 78. 6-, 8-, and 10-gingerol have antimicrobial activity 78. 10-gingerol and 8-gingerol were active (MIC 25–50 μg/ml) exhibiting toward Mycobacterium avium and Mycobacterium tuberculosis H37Rv. Besides 12-gingerol and 6-gingerol have antimicrobial activity against periodontal bacteria 79. Thus, Z. officinale can provide protection effect against fungal and bacterial pathogens 28.
Z. officinale possesses anthelmintic effects against human pathogens 1. Multiple studies demonstrated that Z. officinale and several of its phytochemical components possess antibacterial effects on both drug-resistant and sensitive bacteria 80, 81, 82. Effect of Z. officinale and its constituents on the growth of oral microbial associated with periodontitis. It was observed that the ethanol and n-hexane extracts of Z. officinale exhibited antibacterial activities activity-guided fractionated studies were also performed and it was observed that 10-gingerol and 12-gingerol effectively limited the growth of these oral pathogens at a MIC range of 6–30 mg/ml and a MBC range of 4–20 mg/ml 1.
Today, there is a requirement for an antimicrobial agents with charactristics safe effective and economical. Z. officinale has inhibitory effect on several of the oral microbes. Giriraju and Yunus demonstrated antimicrobial effect of 10% Z. officinale extract against C. albicans, S. mutans and E. faecalis by using MIC (serial broth dilution) and Agar disk diffusion test. 10% ethanolic Z. officinale extract showed: (a) highest inhibition zone against C. albicans, E. faecalis and S. mutans were 14, 11 and 8 mm respectively. (b) MIC again S. mutans, E. faecalis and C. albicans were 1.25%, 2.5%, and 2.5% respectively. 10% ethanolic Z. officinale extract has antimicrobial effect against this pathogens microbe 83. Ewnetu et al., estimated antimicrobial effects of Z. officinale rhizome powder and Ethiopian honeys extracts on Staphylococcus aureus, Klebsiella pneumoniae (R), Escherichia coli (R) and Escherichia coli (ATCC 25922). Broth and agar diffusion and media method were done to determine susceptibility of resistant clinical strains and standard strains isolates using honey/ Z. officinale mixtures. Honey- Z. officinale powder extract mixtures produced the highest inhibitory zone (25.62 mm ± 2.55) in comparison to the consumption of honeys (21.63 mm ± 3.30) or Z. officinale extracts (19.23 mm ± 3.42) individually. The ranges of inhibitions produced by honey- Z. officinale extract mixtures on susceptible test organisms (26–30 mm) and resistant strains (range: 19–27 mm) were higher compared to 7–22mm and 0–14mm by standard antibiotic discs. MIC of mixture of honeys- Z. officinale extracts were 6.25% (0.625 v/mL) on the susceptible bacteria compared to 75% for resistant clinical isolates. MBC of honey- Z. officinale extracts was 12.5% for all the test organisms. According their result honey- Z. officinale powder extract have antibacterial effect agents the drug resistant bacteria 30.
Dehghan and et al., studied the effect of ethanol, ether and water some herbal extracts on HP strains isolated from the patients, by the agar diffusion. Considered water extracts for their antibacterial effects, turmeric had the most anti HP efficacy (mean of inhibitory growth zone diameter 21.5 mm). Z. officinale, clove and cardamom were respectively placed thereafter. Among ethanol extracts, Z. officinale with diameter mean of 19.7 mm showed the most effective as compare with turmeric and clove. Ether extracts of the mentioned plants had anti HP effects (Mean of inhibitory growth zone diameter were 19, 13, 11.1 and 10.5 mm respectively 84.
HP is the primary agent associated with dyspepsia, gastric, PU and colon cancer, Mahady and et al., study alcoholic extract of Z. officinale and, 6-,8-, 10-gingerol and 6-shogoal, against 19 HP strains including 5 HP CagA+ strains. Their result show the antimicrobial effect of methanol extract of Z. officinale against all HP strains with a MIC range of 6.25–50 μg/ml. the gingerols fraction was active and limited the growth of all HP strains with an MIC range of 0.78-12.5 μg/ml and has significant activity against the HP CagA+ strains. Gingerols of Z. officinale extract, inhibit the growth of HP CagA+ 85. Kahald and et al., studied the antimicrobial activity of Z. officinale syrup against HP on fifty volunteers (2 gr Z. officinale/ 3 months) they demonstrated level of antibody against HP were decreased to be nearly up normal values 86.
Nanjundaiah and et al., studied the ulcer-preventive effect of aqueous extract of Z. officinale (AEZ). AEZ at 200 mg/kg b.w. protected 77% and 86% for the ethanol stress and swim stress induced ulcers with an ulcer index of 50 ± 4.0 ± 4.0/46 respectively. Gastric mucin damaged rat was recovered up to 77% and 74% in swim stress and ethanol stress, respectively after AEZ treatment. AEZ also limited the growth of HP with MIC of 300 ± 38 μg and also possessed reducing power, free radical scavenging ability with an IC50 of 6.8 ± 0.4 μgmL−1 gallic acid equivalent (GAE). DNA protection was observed up to 90% at 0.4 μg.
Toxicity studies indicated there was no lethal effects of Z. officinale in rats fed until 5g/k b.w. study on ulcer-preventive of cinnamic and gallic phenolic acids, cinnamic acid appear to contribute to better H+, K+-ATPase and HP inhibitory activity, while gallic acid contributes significantly to anti-oxidant activity 87. Attari and et al., studied gastro- protective effect of Z. officinale in HP+ patients, they studied 15 HP+ patients. Patients consume 3 gr/daily Z. officinale powder as three 1-gr tablets for 4-weeks. They demonstrated Z. officinale consumption accompanied by significant HP eradication rate of 53.3% (P = 0.019) 88. Azadia, and et al., studied inhibitory effects of the mixture of cinnamon and Z. officinale on cagA expression of HP. They demonstrated the synergetic effect of cinnamon/ Z. officinale as anti HP compared to the Tetracycline 30 μg and shown there are significant decrease in the expression of the cagA after exposure to the extract mixture in comparison of the ureC reference gene (p < 0.05) 89.
Some in-vitro condition studies have shown the effectiveness of Z. officinale and cinnamon extracts against HP. Ahmed and et al., demonstrated the efficacy of Z. officinale and cinnamon preparations as components of dual or triple omeprazole-based HP eradication regimens in patients with HP-associated functional dyspepsia. HP status was tested using the non-invasive stool antigen test before and 4 weeks after eradication therapy. Following 14-day therapy, significantly higher eradication rates were obtained with dual Z. officinale/omeprazole and triple cinnamon/Z. officinale/omeprazole regimens compared to dual cinnamon/omeprazole regimen (70% and 80% versus 50%, p≤0.05). All eradication regimens lowered dyspeptic symptoms 90.
Gastrointestinal Effects of Z. officinale on H. pylori: PU is a major health problem worldwide in both males and females having several factors triggering its effect including food ingredients, stress, HP, and drugs. In traditional system of medicine, herbal has anti-ulcer effect in various ways, but usually their mechanism is not understood 91. Z. officinale and its constituents increasing mucin secretion and with this mechanism prevent the PU findings demonstrated anti-ulcerative effects of Z. officinale in experimental GU models 92. 6-gingerol and 6-shogaol suppressed gastric contraction in situ, with 6-shogaol having more intensive 93. It was shown that acetone, 50% ethanolic extracts of Z. officinale (100–500 mg/kg) and Z. officinale juice (2–4 ml/kg) reversed cisplatin induced delay in gastric emptying in animal model when given orally 49. Z. officinale has gastric motility effect. In animal model Z. officinale can stimulate bile secretion, trypsin, intestinal lipase, chymotrypsin, amylase, maltase and sucrase activities, 6 gingerol and 10 gingerol are responsible for this activity 66. Recently findings explain the traditional use of Z. officinale as a digestive supplementary. Z. officinale utilized in alleviating symptoms of vomiting and nausea 94. But its mechanism remains unknown. However, there are several proposed mechanisms. The antiemetic effect components in Z. officinale, are contains shogaols, gingerols and galanolactone 95.
Based on in-vitro and animal models studies, demonstrated that Z. officinale extract has anti-serotoninergic and 5-HT3 receptor antagonism effects, this compound have an important role in vomiting and postoperative nausea 96. The role of Z. officinale as an antiemetic component attributed to its carminative effect, which led to break up and exit intestinal gas. This idea was improved by the results of a trial study in which healthy people demonstrated Z. officinale stimulated antral contractions accelerated gastric emptying 97.
Contrary to these results, in one randomized crossover trial study of 16 healthy person, that consume Z. officinale (1 gr/orally), they had no effect on gastric emptying 98. However, it's clear that nausea and vomiting during pregnancy reduced in most pregnant women 99. Overall consumption of dietary supplements in pregnant women appears to be low, but Z. officinale is usually recommended to prevent nausea 100. Several clinical trials study demonstrated that Z. officinale consumption is safe and effective manner to control vomiting and nausea pregnancy women 101. Z. officinale may also increase the conversion of cholesterol into bile acids by increasing the activity of hepatic cholesterol-7-α-hydroxylase, the rate limiting enzyme of bile acid biosynthesis 102. Z. officinale increases the production of stomach acid thereby interfering with antacids, H2 antagonists or proton pump inhibitors and sucralfate. Interestingly, shogaol, specially (6)-gingerol, has demonstrated inhibitory intestinal motility in intravenous preparations and facilitatory gastrointestinal motility in oral preparations. A number of animal models studies have shown hypo-cholesterolemic action of Z. officinale and Z. officinale extracts by reduce lipid peroxidation and increased fibrinolytic activity. Z. officinale decreased levels of triglycerides, total cholesterol, LDL-cholesterol, very low-density-lipoprotein-cholesterol and increased levels in high-density-lipoprotein-cholesterol 103. According recent study, air-dried Z. officinale powder (100 mg/kg oral in daily) fed to rabbits with experimentally induced atherosclerosis for 75/days, inhibited atherosclerotic changes in the aorta and coronary arteries by a proximally 50% 104.
DISCUSSION AND CONCLUSION: Herbal in traditional medicinal system since ancient time have been used as a source of medicine therapy 105. The WHO has described traditional medicine therapy as inexpensive way to achieve total people and has encouraged the rational use of herbal based traditional medicines by member states 106. The WHO estimates that about 80% of the population are user of herbal medicine to treat various illnesses as means of primary healthcare 107. The therapeutic application of herbs has been considered for their bioactive effects since ancient times 108, 109, the WHO has called on Member States to make rational use of herbs 30. Unsuitable consumption of antimicrobial drug resulted in the development of resistant pathogenic microorganism's like anti-microbial resistant bacteria. The increasing antibiotic resistance in bacteria scientific focus on plants derived antimicrobial agents Traditional medicine therapy has become a type of supplementary natural therapy for multiple antibiotic resistant bacterial.
HP treatment is based on the consume of antibiotics and proton pump inhibitors that may due to the problems surrounding the consume of antibiotics and the side effects of anti-inflammatory agents 110. Antibiotic therapy failure may arise upon of other factors i.e. the drug sensitivity to diet, such pH (tetracycline has high activity at a low pH and amoxicillin has high activity at a neutral pH) 27. Herbal medicine supplementary therapy is still the mainstay of nearly 75% to 80% of the whole world population, commonly in developing countries, for primary treatment because of better cultural acceptability, better compatibility with the human body and fewer side effects. However, the last few years have seen a major increase in their use in the developed world 111. The failed treatment and eradication success for HP infection are, largely due to the rapid emergence of antibiotic resistant strains 112. Antibiotic resistance is a constantly changing phenomenon, according to prevalence studies, the prevalence of antibiotic resistance in HP strains varies considerably across countries, and this difference even across regions of one country 112 HP. Antimicrobial resistance is assessed by HP culture and antimicrobial susceptibility testing. Molecular method such resistance-associated mutations HP strains and genetic identification of HP and is an efficient way to replace of HP culture. Surveillance of antibiotic resistance by laboratory methods is necessary to inform physicians in their choice of therapy method for management of HP infection 112.
Z. officinale has been used to treat various gastrointestinal ailments. Due to its abundance, safety and low cost, Z. officinale remains a species with tremendous potential and countless possibilities for further investigation. The pharmacological activities of Z. officinale depended to the various phytochemicals. With regard to certain pharmacological effects (antibacterial and antiemetic effects against motion sickness and chemotherapy-induced nausea in humans), contradictory results are seen and this may be possibly due to the variation in the phytochemicals in the Z. officinale used.
The eating of Z. officinale in human health has been demonstrated since ancient times and they provide a useful natural source of new therapeutics.
ACKNOWLEDGEMENT: The authors of the article thank the Rafsanjan University of Medical Sciences for the support of this research project.
CONFLICTS OF INTEREST: The authors have no conflicts of interest to declare.
Financial Discloser: The authors declared that Rafsanjan University of Medical Sciences support of this research with the code number 97066.
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How to cite this article:
Mirzaee V, Jafarzadeh A, Tahmasebi A and Jalalpour S: Zingiber officinale effect on Helicobacter pylori infection in human; a systematic review. Int J Pharm Sci & Res 2020; 11(7): 3047-59. doi: 10.13040/IJPSR.0975-8232.11(7).3047-59.
All © 2013 are reserved by the International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
V. Mirzaee, A. Jafarzadeh, A. Tahmasebi and S. Jalalpour *
Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
18 October 2019
04 February 2020
04 March 2020
01 July 2020