Department of Laboratory Sciences, College of Sciences and Arts at Al-Rass, Qassim University, P.O. Box 53, Saudi Arabia
Received Date: October 11, 2016; Accepted Date: November 08, 2016; Published Date: November 10, 2016
Citation: Abdallah EM. Medicinal Plants with Antibacterial Properties Against Helicobacter pylori: A Brief Review 2016, 1:3
Helicobacter pylori (H. pylori) is one of the most common worldwide human infections. It is estimated over half of the Earth’s population are infected with this bacterium. This pathogen is a causative agent for many gastroduodenal diseases, peptic ulcers and gastric cancer. In recent years, emerging resistant to antibiotics limits their use in the treatment of this infection. As a result, many natural products have been studied to find new effective alternative drugs against difficult to treat H. pylori giving special attention to plants used traditionally for a long time against gastrointestinal disorders. This review presents the potential of many medicinal plants to serve as promising sources for new and alternative anti-H. pylori agents.
Medicinal plants; Anti-bacterial; Anti-H. pylori; Helicobacter pylori
According to the World Health Organization (WHO), upto 80% of the world’s population relies on the traditional medicine (Mostly from medicinal plants) for their primary health care needs . Meaning that, only 20% of the world’s population depends on Modern medicine (Mostly synthesized or semi-synthesized compounds). Moreover, up to 25% of the modern drugs are from plant origin, 11% of the essential and basic drugs are produced from plants and 60% of anti-tumor and anti-infectious drugs are initially from natural products . The use of medicinal plants to heal diseases which is known as phytotherapy is as old as the human being. Medicinal plants have acquired their therapeutic properties from its ability to reproduce numerous and renewable secondary metabolites known as phytochemical compounds, Plants used these phytochemicals as a defense mechanism against macroorganisms as well as micro-organisms . Recently, due to the constant emergence of resistant pathogens, almost all conventional antibiotics has been motivated the pharmaceutical companies to change their strategy and develop new antimicrobial drugs from medicinal plants . Although, the synthetic antibiotics are the dominant antimicrobial drugs. Within the last three decades, incidences of infectious diseases has increased dramatically, including old infections with properties as well as new infections and it is reported that about 30 new infectious agents has been recorded, 60% of them are zoonotic origin (spread between animals and human), among them are Helicobacter pylori which may cause Duodenal, gastric ulcer and stomach cancer . This review aimed to highlight some medicinal plants that recorded potential antibacterial activity against Helicobacter pylori that may be a candidate for use as a source of future effective drugs against this pathogen.
Helicobacter pylori infection
The human being has granted a complex normal flora ecosystem in many niches in the body, one of these niches is the gastrointestinal tract. The normal gastrointestinal microflora are stable in the normal individual and is essential for maintaining the eco-physiological balance in the gastrointestinal tract, and it was observed that there is an inverse relationship between the commensal microflora and the growth of H. pylori . Marshall and Warren were the first who isolated H. pylori in 1983 from the gastric epithelium and proved that this bacterium is the cause of the most gastroduodenal diseases, peptic ulcers and gastric cancer . H. pylori is one of the most genetically diverse bacterium, (Helicobacter: a spiral rod, pylori: gate keeper), it is a small, spiral (S-shaped) or curved gram-negative motile bacilli, microaerophilic, non-sporing and coccal transformation occurs when exposed to air for about two hours [8,9]. About 50% of the world inhabitants are infected with H. pylori, this percentage may reach 80% in some developing countries and 40% in the developed industrial countries, and this explains why scientists believe that the prevalence of H. pylori could be inversely correlated with the socioeconomic situation and hygiene . Ironically, in the developed industrialized countries there is a relatively high prevalence of gastric cancer, while the developing countries have low incidences of gastric cancer . The mechanism of acquisition and transmission of H. pylori are still unknown. However, it is believed that the primary means of transmission are fecal-oral and gastro-oral route from person to person, contaminated food or water or via some domestic animals .
Treatment of Helicobacter pylori
In recent years, resistance to antibiotic therapy has dramatically increased while the ability to develop new antibiotics has decreased and the supply of new effective antibiotics expected to diminish in the future . H. pylori, like other bacterial pathogens, has readily developed resistance to the antibiotics. Besides, it is difficult to treat pathogen, since the Sensitivity pattern of H. pylori to antibiotics in vitro differs from that in vivo due to the effects of the conditions into mucous epithelium cells of the stomach . H. pylori characterized by a very high frequency of mutation (10-5-10-8) which are much larger than any other bacteria . Since the discovery of H. pylori and consider it as a serious etiological agent of chronic gastritis and peptic ulcer, antibiotics such as amoxicillin, clarithromycin and tinidazole considered effective drugs . Recently, as this pathogen is able to withstand to the single antibiotic therapy, a new strategy was invented to eradicate this infection. Accordingly, the triple therapy was invented, which is based on a combination of antibiotics, Bismuth sub-citrate and proton pump inhibitors, but this therapy is efficient for only 80% of patients and sometimes there is a possibility that the risk of infection returns after completion of the treatment . Accordingly, the effectiveness of the commonly used therapies has been increasingly compromised by the rapid emerging of new resistant strains of H. pylori. Herein, medicinal plants could be a good alternative source of new anti-H. pylori drugs, or it could be used in synergy to alter the mode of action of the antibiotics and re-strengthened the common antibiotics that used against H. pylori.
Medicinal plants and Helicobacter pylori
There is a growing need to find new medications to be used against H. pylori, due to the widespread of this bacterium, its serious pathogenicity and emerging of many resistant strains. In literature, many plants and herbs revealed significant antibacterial activity against H. pylori as shown in (Table 1).
|Plant name||Family||Part used||Extract||Method used||Activity||Reference|
|Aerial parts||Methanol||MIC*||50 µg/mL||Mahady et al. (2005)|
|Rosaceae||indefinite||Aqueous||MIC||1:256 µg/ml||Li et al. (2013)|
|Fresh cloves of the garlic pulp||Aqueous extract||MIC MBC||2-5 mg/ml
|Cellini et al. (1996)|
|Alpiniaspeciosa K. Schum.||Zingiberaceae||Root||Ethanol extract||CD**
|Wang and Huang (2005)|
|Anisomelesindica(L.) Kuntze||Lamiaceae||Leaves and stem||Ethanol extract||CD
|Wang and Huang (2005|
|AnnonacherimolaMill.||Annonaceae||Leaves/stem||Methanol extract||MIC||˂15.6 µg/ml||Castillo-Juárez et al. (2009)|
(Willd. Ex Spreng) Fernald
|Asteraceae||Leaves/stem||Aqueous extract||MIC||125 µg/ml||Castillo-Juárez et al. (2009)|
|Bixaorellana L.||Bixaceae||seeds||96% ethanol||DD***||7-10 mm||Cogo et al. ( 2010)|
|Wang and Huang (2005|
|ByrsonimacrassaNied.||Malpighiaceae||Leaves||Methaanol and chloroform extract||MIC||1024 µg/ml||Bonacorsi et al. (2009)|
|CarumcarviL.||Apiaceae||Fruit||Methanol, di-ethyl ether and petroleum benzene||DD
|Nariman et al. (2009)|
|ChamomillarecutitaL.||Asteraceae||Inflorescence||96% ethanol||DD||10-11 mm||Cogo et al. ( 2010)|
|CistuslaurifoliusL.||Cistaceae||Flowers||Chloroform fraction||MIC||1.95 µg/ml||Yesilada et al. (1999)|
|Rhizome||Aqueous||MIC||˂1:512 µg/ml||Li et al. (2013)|
|CupheaaequipetalaCav.||Lythraceae||Aerial parts||Aqueous extract||MIC||125 µg/ml||Castillo-Juárez et al. (2009)|
|Curcuma amadaRoxb.||Zingiberaceae||Rhizome||70% ethanol||MBC****||31.2-62.5 µg/ml||Zaidi et al. (2009)|
|Eugenia caryophyllataThumb.||Myrtaceae||Flowers||Aqueous||MIC||1: 256 µg/ml||Li et al. (2013)|
|FoeniculumvulgareMill.||Apiaceae(Umbelliferae)||Seeds||Methanol||MIC||50 µg/mL||Mahady et al (2005)|
|Guaiacum coulteriA.Gray||Zygophyllaceae||Bark||Methanol extract||MIC||≤15.6 µg/ml||Castillo-Juárez et al. (2009)|
|indefinite||Aqueous||MIC||1:512||Li et al. (2013)|
|Ilex paraguariensisA. St.-Hil.||Aquifoliaceae||Leaves||96% ethanol||DD||9-10 mm||Cogo et al. ( 2010)|
|LudwigiarepensJ.R.Forst.||Onagraceae||Aerial parts||Aqueous extract||MIC||125 µg/ml||Castillo-Juárez et al. (2009)|
|Euphorbiaceae||Powder covering fruits||70% ethanol||MBC||15.6-31.2 µg/ml||Zaidi et al. (2009)|
|MalvasylvestrisL.||Malvaceae||inflorescence and leaves||96% ethanol||DD||8-10 mm||Cogo et al. ( 2010)|
|MenthapiperitaL.||Lamiaceae||Leaves/stem||Aqueous extract||MIC||˂250 µg/ml||Castillo-Juárez et al. (2009)|
|Moussoniadeppeana (Schltdl. & Cham.) Klotzsch ex Hanst.||Gesneriaceae||Leaves/stem||Methanol extract||MIC||15.6 µg/ml||Castillo-Juárez et al. (2009)|
|70% ethanol Methanol||MBC MIC||31.2-125 µg/ml 12.5 µg/mL||Zaidi et al. (2009) Mahady et al (2005)|
|Aerial parts||Methanol||MIC||50 µg/mL||Mahady et al (2005)|
|Paederiascandens(Lour.) Merr.||Rubiaceae||Whole plant||Ethanol extract||CD
|Wang and Huang (2005)|
|PassifloraincarnataL.||Passifloraceae||Aerial parts||Methanol||MIC||50 µg/mL||Mahady et al (2005)|
|Persea Americana Mill.||Lauraceae||Leaves||Methanol extract||MIC||≤7.5 µg/ml||Castillo-Juárez et al. (2009)|
|Wang and Huang (2005|
|PsoraleacorylifoliaL.||Papilionaceae||Seeds||70% ethanol||MBC||31.2-62.5 µg/ml||Zaidi et al. (2009)|
|Pteleopsissuberosa Engl. et Diels||Combretaceae||Bark||Methanol extract||MIC||31.25-250 µg/ml||Germanò et al. (1998)|
|PunicagranatumL.||Punicaceae||Peel of fruit||methanol extracts||DD||27.96 ± 0.97 mm||Moghaddam (2011)|
|Sumac||Aqueous||MIC||˂1:512 µg/ml||Li et al. (2013)|
|RosmarinusofficinalisL.||Lamiaceae||Leaves||Methanol||MIC||25 µg/mL||Mahady et al (2005)|
|TerminaliaspinosaEngl.||Combretaceae||Young branches||Crude extract||MIC||62.5-500 µg/ml||Fabry et al. (1996)|
|Fruit||Methanol, di-ethyl ether and petroleum benzene||DD
|Nariman et al. (2009)|
|Xanthium brasilicumL.||Asteraceae||Aerial parts||Methanol, di-ethyl ether and petroleum benzene||DD
|Nariman et al. (2009)|
|ZingiberofficinaleRoscoe||Zingiberaceae||Rhizome||Methanol||MIC||25 µg/mL||Mahady et al. (2005)|
Table 1: Medicinal plants having anti-Helicobacter pylori activity (*MIC: Minimum Inhibitory Concentration Test, **CD: Cup-Plate Diffusion Test, ***DD: Disk Diffusion Test, ****MBC: Minimum Bactericidal Concentration Test).
There are numerous plants showed anti-H. pylori activity, in this brief review, up to 41 plant species are reported to have potential anti-H. pylori activity, although these are not all plants studied worldwide and a comprehensive study is required to cover all plants screened against H. pylori. Based on the literature gathered in this review, it was reported that, among 7 different plant species used in Brazilian traditional medicine against gastrointestinal disorders, 4 of them (Bixa orellana, Chamomilla recutita, Ilex paraguariensis and Malva sylvestris) showed different degrees of anti-H. pylori activity . Up to 53 plants used in Mexican traditional medicine for gastrointestinal disorders were screened for their antibacterial effects against H. pylori, 7 of them have shown significant activity, namely, Artemisia ludoviciana subsp. mexicana, Cuphea aequipetala, Ludwigia repens, Mentha piperita, Persea americana, Annona cherimola, Guaiacum coulteri, and Moussonia deppeana . Another study on 50 commonly used traditional medicinal plants from Pakistan were evaluated for their bactericidal effect against H. pylori, the most potent bactericidal activity was exhibited by 4 plant species, which were Curcuma amada, Mallotus phillipinesis, Myrisctica fragrans and Psoralea corylifolia . 20 Iranian plant species were tested for their efficacy against H. pylori clinical isolates, 10 of them showed varied degrees of anti-H. pylori activity, but the highest activity showed with Carum carvi, Xanthium brasilicum and Trachyspermum copticum . 40 Chinese herbs prescribed in the traditional medicine were studied for their anti-H. pylori activity, 5 of them possess higher potent activity, namely Agrimonia pilosa, Coptis chinensis, Eugenia caryophyllata Houttuynia cordata and Rhus chinensis . 50 Taiwanese medicinal plants were examined for anti-H. pylori activity, five of them demonstrated strong activity which were; Paederia scandens, Plumbago zeylanica, Anisomeles indica, Bombax malabaricum and Alpinia speciosa . In the USA, 24 plant species brought from different countries including the USA were screened in vitro against 15 strains of H. pylori, 7 plants considered as the most active anti-H. pylori, which were; Myristica fragrans, Zingiber officinale, Rosmarinus officinalis, Achillea millefolium, Foeniculum vulgare, Passiflora incarnate and Origanum majorana . Moreover, many traditional plants from different regions were screened for anti-H. pylori activity and some of them showed potential effect, such as; Terminalia spinosa from east Africa , Pteleopsis suberosa from Mali , Byrsonima crassa from Brazil , Punica granatum From Iran , Cistus laurifolius from turkey  and garlic extract (Allium sativum) . Since most of these screened plants have a long history of traditional uses against gastrointestinal disorders and some of them revealed anti-H. pylori comparable to antibiotics that are currently losing their efficacy against H. pylori due to emerging of resistant strains; Hence, the isolation of different potent compounds from the most active plant extracts is encouraging. Also, as shown in (Table 1), the in vitro studies for anti-H. pylori activity of medicinal plants are still lacking the standardization that would allow for the meaningful comparison and understanding the activity. Some studies used cup-plat or disc diffusion tests, others employed MIC or MBC or both. The data collected from these methods should allow other researchers to compare these results. Besides, the above-mentioned methods are known as basic methods (disc diffusion and agar or broth dilution), further deep antimicrobial studies must be implemented to support these findings such as time-kill method and flow cytofluorometric method which provides important information about the nature of the antibacterial compounds and their interactions in the prokaryotic cells .
As reviewed in this paper, it is obviously, there are numerous traditional plants potentially valuable sources of novel anti-H. pylori agents. However, most reports are on crud extracts, which gives general evaluation on the potency of these plants as anti-H. pylori agents but do not provide enough data on the complexity of these natural products to serve as drugs as well as the in vivo clinical studies. Accordingly, plants mentioned in this review could become the starting material for more integrated bioassay studies, such as fractionation to determine the active ingredients, understanding the mode of action of these plant extracts or compounds, low toxicity, cumulative effects and possible side effects as well as other significant pharmacological actions which could be beneficial for future drug development against Helicobacter pylori.