Abstract -Helicobacter pylori is a class 1 carcinogen that requires targeted therapeutic strategy. A number of drugs including proton pump inhibitors, antibiotics and antiprotozoals are available for the treatment of Helicobacter pylori infections like chronic gastric irritation, gastro duodenal ulcers and low grade gastric mucosa associated lymphoid tissue lymphoma. Clinical evaluation of these drugs has shown the incidence of relapses, side effects and drug interactions. Multi drug resistance to Helicobacter pylori has been the main reason for treatment failure. This has been the rationale for the development of new anti-Helicobacter pylori drugs and search for novel molecules has been extended to medicinal herbs that offer better protection, decreased relapse and undevelopment of resistance towards bacteria. The present article reviews the medicinal herbs from global perspective for their anti-Helicobacter pylori activity and active compounds from the plants responsible for this activity. We have highlighted some of the important plants and their active constituents reported for their anti-Helicobacter pylori activity. Ancient system of medicine (Ayurvedic and Unani) supported by modern science is necessary to isolate, characterize and standardize the active constituents from herbal sources for anti-Helicobacter pylori activity.
Health Organization has categorized H. pylori as a class 1 carcinogen. 5 Eradication of the organism has been shown to result in ulcer healing, prevention of peptic ulcer reoccurrence and may also reduce the prevalence of gastric cancer in high-risk populations. 6 Many clinical trails involving patients with gastric and duodenal ulcers show that curing the infection is associated with a significant reduction in ulcer reoccurrence rates. [7][8] Since 1984 physicians prescribing triple therapy to treat H. pylori infections which includes three options.
First option includes the combination of proton pump inhibitor (PPI), clarithromycin and ampicillin. Second option includes PPI, clarithromycin and metronidazole. Third option includes bismuth subsalicylate, metronidazole and tetracycline, but the cure rate from standard triple therapy has been low as 50%. 9-10 However, eradication by the triple therapy is not always successful and acquisition by H. pylori resistance to antibiotics could present a serious problem that may reduce treatment efficiency. 11 Quadruple therapy, where three antibiotics are taken alongside the PPI, has also been used in cases where triple therapy has not been successful. But the success rate was only 67%. 12 Many strains of H. pylori are now developing resistance to commonly used antibiotics. H. pylory acquires resistance by mutations to all the antibiotics used in the treatment regimens. The mechanism of resistance involves point mutations which are transmitted vertically, however transformation may be possible if two strains are present simultaneously in the stomach. Drug efflux proteins also can contribute to natural insensitivity to antibiotics and to emerging antibiotic resistance. Efflux pump gene hef A of H. pylori play an important role in multidrug resistance. Global resistance of H. pylori to metronidazole, clarithromycin, amoxicillin and tetracycline was also reported. One person may have more than one strain of H. pylori. Here the antibiotics may kill one strain, but not the other. [13][14] Furthermore, undesirable side effects of the drugs and the significant cost of combination therapy require the
elicobacter pylori (H. pylori), a Gram -negative 1984 by Marshall et al, is one of the most common chronic bacterial pathogens in humans. 1 Approximately 50% of people in the world are infected with it, and its prevalence is significantly higher in developing countries than in developed countries. 2 Once a person is infected, the organism can live in the stomach indefinitely and may not cause clinical illness. It is still not clear how H.pylori are transmitted or why some people infected with bacteria become sick and others do not. 3 H. pylori infection is an important etiologic impetus usually leading to chronic gastritis, gastroduodenal ulcer and low grade gastric mucosa associated lymphoid tissue lymphoma.
Epidemiological data shows that a high H. pylori infection rate is related to the high incidence of gastric cancer and gastric adenocarcinoma. 4 World H spiral bacterium which was first detected in I.
II.
Current Treatment Regimens As phytomedicine has proved to be an untapped treasure for the discovery of lead compounds to cure gastrointestinal disorders. Hence several studies have been aimed to evaluate the anti-helicobacter pylori activity of medicinal herbs. 15 To the best of our knowledge, there is no extensive global view on exploring medicinal plants for anti-helicobacter pylori activity. List of medicinal herbs with anti-Helicobacter pylori activity including their source and active extracts are given in table 1.
The insolubility of non-polar extracts makes it very difficult for the investigators to be used in an aqueous medium during the study of anti-Helicobacter pylori activity. 26 Water or alcohol (methanol/ethanol) are used mainly for a large number of crude extract preparations. 27 The type of solvent used may have an effect on the nature of the compounds extracted and the resulting bioactivity of the extract. 28 To estimate the value of each extract therefore, several factors, including the rate of extraction, the quantity extracted (yield), the diversity of compounds extracted, the diversity of inhibitory compounds extracted, the ease of subsequent handling of the extracts, toxicity of the solvent in the bioassays and the potential health hazards of the extractants have to be evaluated. In many research works, methanol/ethanol is used for alkaloid extraction; acetone for flavonoids and steroids; hexane, diethyl ether and chloroform for fat soluble oils, wax, lipids and esters. Dichloromethane for terpenoids, ethylacetate for esters, ethanol may be used for sterols, poly phenols, tannins and water for water soluble components like glycosides, polysaccharides, polypeptides and lectins. 29 Hundreds of plants with antimicrobial compounds have been reported. However, very few of these studies have reported the in vivo anti-Helicobacter pylori activity of these compounds. It is very important to know whether these compounds will still maintain their maximum activity in the gastric mucus niche of H. pylori. Anti-Helicobacter pylori compounds from plants and their mechanism of action are given in table 2.
Curcumin, biologically active poly phenolic from Curcuma longa has recently been shown to arrest H. pylori growth. The anti-Helicobacter pylori activity of curcumin against 65 clinical isolates of H. pylori in vitro was examined. Minimum inhibitory concentration ranging from 5-50 µg/ml, showing its effectiveness against H. pylori growth in vitro irrespective of genetic makeup of strains. Curcumin showed immense therapeutic potential against H.pylori infection as it was highly effective in eradication of H.pylori from infected mice as well as restoration of H.pylori induced gastric damage.
Curcuma longa extract was the most efficient in killing the seven strains of H.pylori within 15 minutes followed by chilli and ginger. [46][47][48] Mallotus phillipinesis is (Lam) Muell. Exhibited the most potent bactericidal activity against H.pylori which completely killed the bacteria at the concentration of 15.6-31.2 µg/ml. 16 There is no evidence of in vivo effectiveness of this plant. Antibacterial activity of Allium sativum L(garlic) against H.pylori is well documented (40 µg/ml) and resistance has not been reported.The synergistic action of garlic and omeprazole against H.pylori was also reported.
Thiosulfinates play an important role in the antibiotic activity of garlic. Further clinical evaluation seems warranted. [49][50][51] A mixture of tannic acid and n-propyl gallate can limit the gastric mucosa deterioration induced by H.pylori infection and vac A administration, suggest that vac A inhibition plays a role in this protective activity. So, polyphenols from plant sources may contribute to limit the pathological outcomes of H.pylori infection. 52 Successive extracts of Sapindus mukorossi and Rheum emodi inhibited the growth of 30 resistant clinical isolates of H.pylori in vitro and in vivo studies and there was no acquired resistance against these herbal extracts even after ten consecutive passages. 53 The evidence summarized above tentatively suggests possible benefits from some herbal sources with anti-Helicobacter pylori activity. Herbal science, Ayurvedic knowledge supported by modern science is required to standardize the plant extracts and to isolate, characterize and standardize the active constituents from plant sources for anti-Helicobacter pylori activity.
Extensive investigations and large scale well designed clinical trails are required to provide more conclusive proof to explore medicinal herbs for anti-Helicobacter pylori activity.
Table1 : Medicinal herbs having anti-Helicobacter pylori activity (global perspective).

| Exploring Medicinal Plants for Anti-Helicobacter Pylori Activity | ||||
| Botanical name | Source | Part used | Extract | Reference |
| South Asian Herbs | ||||
| Mallotus phillipinesis | Pakistan | covering fruit | Aqueous ethanol (70%) | 16,17,18 |
| Curcuma amada Roxb. | Pakistan | rhizome | ||
| Myristica fragrans Houtt. | Pakistan | seed | ||
| Psoralea corylifolia | Pakistan | seed | ||
| Glycyrrhiza glabra L | India,Srilanka | root | ||
| Terminalia chebula | Pakistan | fruit | ||
| Curcuma longa L | India | rhizome | ||
| Cuminum cyminum | Srilanka | seed | ||
| Coccinia grandis | India | leaves | Ethanol | |
| Terminalia arjuna | India | bark | Methanol | |
| East Asian Herbs | ||||
| Rhizoma coptidis | China | rhizome | Aqueous | 19,20 |
| Radix scutellariae | China | root | ||
| Radix isatidis Asasarum sieboldi | China Korea | root root | Methanol | |
| Lindera strychifolia | Korea | root | ||
| Angelica tenuissima | Korea | root | ||
| Alpinia oxyphylla | Korea | fruit | ||
| American Herbs | ||||
| Zingiber officinale | USA | rhizome | Methanol | 21 |
| Rosmarinus officinalis | USA | rosemary leaf | ||
| Foeniculum vulgare | USA | seed | ||
| Nigella sativa | USA | seed | ||
| African Herbs | ||||
| Terminalia spinosa | East Africa | young branches | Aqueous | 22 |
| Harrisonia abyssinica | East Africa | root | ||
| Ximenia caffra | East Africa | root | ||
| Azadirachta indica | East Africa | leaves, stem bark | ||
| Combretum molle | South Africa | stem bark | Acetone | 23 |
| Sclerocarya birrea | South Africa | stem bark | ||
| Carica papaya | Nigeria | leaf | Aqueous& ethanol | 24 |
| Morinda lucida | Nigeria | leaf | ||
| Octimum gratissimum Phyllanthus amarus | Nigeria Nigeria | leaf leaf | ||
| Brazelian Herbs | ||||
| Bixa orellana L | Brazil | seed | Aqueous ethanol (96%) | 25 |
| Chamonilla recutita L | Brazil | inflorescence | ||
| Ilex paraguariensis A | Brazil | green leaves | ||
| Malva sylvestris L | Brazil | inflorescence & leaves | ||
| Exploring Medicinal Plants for Anti-Helicobacter Pylori Activity | |||||
| Compound name | Examples | Mechanism of action | reference | ||
| Quinones | Quinones,idebenone,duroquinone, | ||||
| menadione,juglone,coenzyme Q 1 | |||||
| Flavones, flavonoids | Quercetin, catechins, myristin, rutin | ||||
| and flavonols | |||||
| Phenolics | and | Catechol, pyrogallol, curcumin | |||
| polyphenols | |||||
| Tannins | Polymeric phenols, hydrolysable tannins | ||||
| 7-hydroxy-4-methyl | coumarin, | 6,7- | |||
| Coumarins | |||||
| Terpenoids | and | ||||
| essential oils | |||||
| Alkaloids | |||||
| Lectins and poly | |||||
| peptides | |||||
Antimicrobial and antioxidant activities of coumarins from the roots of Ferulago campestris (Apiaceae). Molecules 2009. 14 p. .
Helicobacter pylori eradication: are there alternatives to antibiotics. Altern Med Rev 2001. 6 (4) p. .
Allium ampeloprasum (elephant garlic) and Allium cepa (onion), garlic compounds and commercial garlic supplement products. Phytotherapy Res 1991. 5 p. . (Antimicrobial effect of Allium sativum L (garlic))
Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984. 1 p. .
Bussing A Induction of apoptosis by the mistletoe lectins: A review on the mechanism of cytotoxicity References Références Referencias 2012 May mediated by Viscum album. Apoptosis 1996. 1 p. .
Ndip RN Aqueous and organic extracts of selected South African medicinal plants possesss antimicrobial activity against drug resistant strains of Helicobacter pylori inhibition and bactericidal potential. Int J Mol Sci 2011. 12 (9) p. .
Cowan MM Plant products as Antimicrobial agents. Clin Microbiol Rev 1999. 12 p. .
Northfield TC Helicobacterpylori infection. Lancet 1997. 349 p. .
Immune subversion by Helicobacterpylori. Trends Immunol 2005. 26 p. .
Guidelines for management of Helicobacter pylori infection. Am J Gastroenterology 1998. 93 p. .
Iori V A Curcumin based 1-week triple therapy for eradication of Helicobacter pylori infection: something to learn from failure. Helicobacter 2007. 12 p. .
Stobberingh E Antibacterial effect of garlic and omeprazole on Helicobacter pylori. J Antimicrobial Chemotherapy 1999. 43 p. .
Eloff JN Which extractant should used for the screening and isolation of antimicrobial components from plants. J Ethanopharmacol 1998b. 60 p. .
Yang Bai Screening test for anti-Helicobacter pylori activity of traditional Chinese herbal medicines. W J Gastroenter 2010. 16 (44) p. .
Chadwich LR Invitro susceptibility of Helicobacter pylori to botonical extracts used traditionally for the treatment of gastrointestinal disorders. Phytother Res 2005. 19 (11) p. .
Polter JD Helicobacter pylori-in vitro susceptibility to garlic (Allium sativum) extracts. Nutr Cancer 1997. 27 p. .
Ahn YJ Antibacterial activity of oriental medicinal plants extracts toward Helicobacter pylori. Agri Chem Biotechnol 2003. 46 (3) p. .
Helicobacterpylori infection. Semin Gastrointest Dis 1997. 8 p. .
The effects of tannin rich plants on parasitic nematodes in ruminates. Trends Parsitol 2006. 22 p. .
McGaw LJ The biological activity and chemistry of the Southren African Combretaceae. J Ethanopharmacol 2008. 119 p. .
A comprehensive review of the natural history of Helicobacter pylori infection in children. Arch Med Res 2000. 31 p. .
Antibacterial activity of hydrilysable tannins derived from medicinal plants against Helicobacter pylori. Microbiol Immunol 2004. 48 p. .
Tsuneo T In-vitro and in vivo activities of Tea catechins against Helicobacter pylori. Antimicrobia Agents Chemother 1999. 43 p. .
Helicobacter pylori activity of plant extracts traditionally used for the treatment of gastrointestinal disorders. Brazilian J Microbiol 2010. 41 p. .
Befrits R Concordance of Helicobacter pylori strains within families. J Clin Microb 2003. 41 (12) p. .
NIH consenses conference Helicobacterpylori in peptic ulcer disease. Jamaica 1994. 272 p. .
Flavonoids with anti-Helicobacter pylori activity from Citus laurifolius leaves. J Ethanopharmacol 2006. 108 p. .
Corthesy-Jheulaz IE Essential oils as components of a diet-based approach to management of Helicobacter pylori. Antimicrob Agents Chemoth 2003. 47 p. .
Poogunran D In-vitro antimicrobial activity of Coccinia grandis on ulcer producing Helicobacter pylori. Euro J App Sci 2011. 3 (3) p. .
Polyphenols reduce gastritis induced by Helicobacter pylori infection or vac A toxin administration in mice. Antimicro agents Chemotherapy 2006. 50 (7) p. .
Antimicribial activity of curcumin against Indian Helicobacter pylori and also during mice infection. Antimicrobial agents and Chemotherapy 2009. 53 (4) p. .
Scalbert A Antimicribial properties of tannins. Phytochemistry 1991. 30 p. .
Bactericidal activity of medicinal plants, employed for the treatment of gastrointestinal ailments against Helicobacter pylori. J Ethanopharmacol 2009. 2005. 121 (47) p. . (W J Gastroenter)
Idebenone acts against growth of Helicobacter pylori by inhibiting its respiration. Antimicrob Agents Chemother 2006. 50 p. .
Omonigbehin EA The effect of some Nigerian local herbs on Helicobacter pylori. Afri J Clin Exp Microbiol 2003. 4 (2) p. .
Important role of melanin as protector against free radicals in skin. SOFWJ 2007. 133 p. .
Inactivation of red beet ?-glycon synthase by native and oxidized phenolic compounds. Phytochemistry 1987. 26 p. .
Ansorg R Activity of East African medicinal plants against Helicobacter pylori. Chemotherapy 1996. 42 (5) p. .
Screening of anti-helicobacter pylori herbs deriving from Taiwanese folk medicinal plants. FEMS-Immunol Med Microbiol 2005. 43 p. .
Singhania SS Exploring of antimicrobial activity of Triphala Mashian Ayurvedic formulation. Evid based Complem Alter Med 2008. 5 p. .
Derim H Comparison of short and long term treatment protocols and the results of second-line quadrupole therapy in children with Helicobacter pylori infection. J Gastroenterol 2008. 43 p. .