Phytochemicals in Helicobacter pylori Infections: What Are We Doing Now?

Abstract

In this critical review, plant sources used as effective antibacterial agents against Helicobacter pylori infections are carefully described. The main intrinsic bioactive molecules, responsible for the observed effects are also underlined and their corresponding modes of action specifically highlighted. In addition to traditional uses as herbal remedies, in vitro and in vivo studies focusing on plant extracts and isolated bioactive compounds with anti-H. pylori activity are also critically discussed. Lastly, special attention was also given to plant extracts with urease inhibitory effects, with emphasis on involved modes of action.

1. Introduction

Plant products, their enriched-derived extracts, and their isolated bioactive molecules have been increasingly studied due their renowned health attributes, largely used in folk medicine over centuries for multiple purposes [1,2,3,4,5,6,7,8,9]. Indeed, phytomedicine is garnering much attention among the medical and scientific communities [10,11,12]. Commercially available synthetic drugs have often been negatively pointed out due to their side effects and related toxicity [13]. In fact, the active molecules used in pharmaceutical formulation are formerly derived from bioactive molecules extracted from plants and other living organisms [14]. Also, a growing number of studies have progressively underlined the multiple bioactive properties conferred by plant formulations [15,16]. Specifically, the antimicrobial effects of multiple plant preparations have been progressively confirmed and supported by both in vitro and in vivo studies and clinical trials [17,18,19,20,21]. Thus, their lower costs, high effectiveness, bioavailability, bioefficacy, and few to no adverse effects have led to intensive research on this topic [22,23,24,25,26,27,28].

Among the various opportunistic infections, those caused by Helicobacter pylori, a human opportunistic pathogen, is attracting much attention [29]. In fact, it is widely recognized that this bacterium plays an important role in the etiology of peptic and gastric ulcers and even gastric cancers and gastric lymphomas [29]. About half of the worldwide population is colonized by this bacterium, but there are only about 20% who manifest clinical symptoms, which has been linked to the ability of some H. pylori strains to both adapt to host’s immunological responses and to support an ever-changing gastric environment [29]. Relatedly, increasing rates of antibiotic-resistant H. pylori strains have been found, and therefore, the search for new eradication strategies and effective antibiotic therapies has become an issue of crucial importance [30]. Hence, research effort is focused on exploring plants as sources of anti-H. pylori agents.

Based on these findings, the present report aims to provide an extensive overview of Helicobacter pylori infections, namely describing its involvement in triggering gastric cancer and the most common antimicrobials used in H. pylori eradication. Special attention is also given to medicinal plants and their corresponding extracts and isolated constituents used as anti-H. pylori agents and urease inhibitors. This review was performed by consulting the databases of PubMed, Web of Science, Embase, and Google Scholar (as a search engine); only full-text available articles were considered, and articles published from 2008 to 2018 were prioritized. The search strategy included the combination of following keywords: “Helicobacter pylori”, “anti-Helicobacter”, “medicinal plant”, “plant extract”, “essential oil”, “bioactive”, “phytochemical”, “antimicrobial”, and “eradication”.

2. Helicobacter pylori and Gastric Cancer

H. pylori infection has been implicated in the development of gastric cancer, a multifactorial disease and a leading cause of mortality. The risk factors for gastric cancer have been shown to include environmental factors and factors that influence host–pathogen interaction, as well as the complex interplay between these factors [31]. Modern lifestyle, high stress levels, smoking and excessive alcohol consumption, nutritional deficiencies, and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most relevant etiological environmental factors [32].

This bacterial infection has been linked to the initiation of chronic gastritis that could later lead to adenocarcinoma of the intestine [33]. However, several mechanisms have been proposed to represent the involvement of H. pylori infection in tumorigenesis. Several bacterial virulence factors, such as the cytotoxin-associated gene A (CagA) protein, present in the DNA insertion element Cag pathogenicity island (CagPAI), were found to be of prominent importance in carcinogenesis [34]. Likewise, bacterial peptidoglycan can be delivered into gastric epithelial cells, where it activates a phosphoinositide 3-kinase (PI3K)-Akt pathway leading to cell proliferation, migration, and prevention of apoptosis [35]. Furthermore, H. pylori-induced gastric inflammation involves the cyclooxygenase-2 (COX2)/prostaglandin E2 (PGE2) pathway and inflammatory marker interleukin 1β (IL-1β), which are important factors triggering chronic active gastritis and adenocarcinoma [31]. Studies have also shown that H. pylori infection-induced oxidative stress and DNA damage coupled with dysregulation of E-cadherin/β-catenin/p120 interactions also play critical roles in tumorigenesis [31]. Several environmental and dietary factors have also been suggested to modify H. pylori-induced adenocarcinoma [36]. Gastric adenocarcinoma is strongly influenced by dietary salt intake, with high salt intake aggravating tumorigenesis [37].

3. Antimicrobials for H. pylori Eradication

The success of H. pylori eradication markedly depends on the type and duration of treatment, patient compliance to therapy, and antibiotic resistance. For example, because it is difficult to achieve optimal eradication of H. pylori infection in patients with peptic ulcers, combinational regimens using two or three antibiotics in addition to a proton pump inhibitor or bismuth are often prescribed to achieve higher eradication rates and to prevent antibiotic resistance emergence [38,39]. These regimens, also known as triple therapies, have cure rates of around 85–90%. They are usually administered for a period of about 10–14 days, in which treatment regimens include the following: (A) bismuth subsalicylate, metronidazole, and tetracycline for 14 days; (B) omeprazole, amoxicillin, and clarithromycin for 10 days; and (C) lansoprazole, amoxicillin, and clarithromycin for either 10 or 14 days.

Unfortunately, the heightening of antimicrobial resistance has been associated with increases in the standard triple therapies failure to eradicate H. pylori infection [40]. Hence, research is focusing on developing potent and effective antibacterial regimens that will favor total eradication of the infection. Nonetheless, any eradication treatment comes with some degree of adverse effects, such as nausea, metallic taste, vomiting, skin rash, and diarrhea. Therefore, efforts are being channeled towards the development of effective treatments with few to no side effects.

In the Maastricht V/Florence Consensus Report, 43 experts from 24 countries provided recommendations on the basis of the best available evidence and relevance to the current therapeutic options of management of H. pylori infection in the various clinical scenarios [41].

4. Plant Extracts and Phytochemicals with Anti-Helicobacter pylori Activity

Considering that H. pylori infection has been associated with gastrointestinal diseases, including chronic gastritis, peptic ulcer, gastric carcinoma, and mucosa-associated lymphoid tissue lymphoma [42], and that, due to the widespread use of therapeutic agents for the eradication of this bacterium and associated-side effects, increasing rates of H. pylori strains with acquired resistance have been discovered. So, the urgent need for alternative has been rekindled and aided by the use of natural drugs [32].

Despite, the newly proposed and used tri-therapy regimens, the cost of acid suppressors and stomach protectors make it inaccessible to the majority of the population [43]. Naturally-derived drugs, including herbs, have been shown to display anti-H. pylori activities with minimal side effects, easy accessibility, and affordability [42,44]. In fact, many medicinal plants have been reported in the traditional management of gastrointestinal disorders. Many of these medicinal plants have gone through bioassays to assess their potency against H. pylori. Here, the anti-H. pylori activity of medicinal plants and isolated bioactive molecules is discussed [45].

Almost all plant parts have been tested for anti-H. pylori activity. Plant extract preparations include water (Table 1), essential oils (Table 2), or organic solvents, such as the following: ethanol (Table 3); methanol (Table 4); acetone (Table 5); chloroform (Table 6); petroleum ether (Table 7); methanol/water, ethanol/water, methanol/petroleum, and methanol/dichloromethane extracts (Table 8); and other plant extracts (Table 9).

Table 1. Plant aqueous extracts with anti-Helicobacter pylori activity.

Species	Family	Parts	Anti-H. pylori Potency	Ref.
Acacia nilotica (L.) Delile	Leguminosae	Flowers	MIC = 8–64 μg/mL	[49]
Adhatoda vasica Nees	Acanthaceae	Whole plant	MIC = 16–512 μg/mL	[49]
Alepidea amatymbica Eckl. and Zeyh	Apiaceae	Roots/Rhizomes	IZD = 8.0 ± 8.2 mm	[50,51]
Amphipterygium adstringens (Schltdl.) Standl.	Anacardiaceae	Aerial parts	MIC = 62.5–125 µg/mL	[52]
Annona cherimola Mill.	Annonaceae	Leaves/Stem	MIC = 500 µg/mL	[52]
Artemisia ludoviciana Nutt. subsp. mexicana (Willd. ex Spreng.) Fernald	Compositae	Leaves/stems	MIC = 125 µg/mL	[52]
Bridelia micrantha (Hochst.) Baill.	Phyllanthaceae	Bark	IZD = 0–15 mm; MIC50 = 48–313 mg/mL; MIC90 = 78 ≥ 625 µg/mL	[53]
Buddleja perfoliata Kunth	Scrophulariaceae	Aerial parts	MIC = 500 µg/mL	[52]
Calandrinia ciliata (Ruiz and Pav.) DC. (cited as Calandrinia micrantha Schltdl.)	Portulacaceae	Leaves/Stems	MIC = 1000 µg/mL	[52]
Calotropis procera (Aiton) W.T. Aiton	Apocynaceae	Leaves	MIC = 16–256 μg/mL	[49]
		Flowers	MIC = 8–256 μg/mL	[49]
Campyloneurum amphostenon (Kunze ex Klotzsch) Fée	Polypodiaceae	Aerial parts	MIC = 1000 µg/mL	[52]
Casuarina equisetifolia L.	Casuarinaceae	Fruit	MIC = 128–1024 μg/mL	[49]
Chenopodium incisum Poir. (cited as Teloxys graveolens (Willd.) W. A. Weber)	Amaranthaceae	Aerial parts	MIC = 250 µg/mL	[52]
Cichorium intybus L.	Asteraceae	Root	IZD < 9 mm	[47]
Cinnamomum zeylanicum Blume	Lauraceae	Bark	IZD < 9 mm	[47]
Cistus laurifolius L.	Cistaceae	Flowers	MIC = 62.5–125 µg/mL	[54]
Citrus reticulata Blanco	Rutaceae	Fruit shell	MIC = 100 µg/mL	[55]
Cocculus hirsutus (L.) Diels.	Menispermaceae	Leaves	IZD = 22 mm (200–1000 μg/mL)	[56]
Combretum molle R. Br. Ex G. Don	Combretaceae	Bark	IZD = 2.7 ± 5.5 mm	[50,51]
Coriandrum sativum L.	Apiaceae	Seed	IZD = 9 mm; MIC = 1.25–5 mg/mL	[47]
Corydalis yanhusuo W.T. Wang	Papaveraceae	Stem	MIC = 100 µg/mL	[55]
Cuminum cyminum L.	Apiaceae	Seed	IZD < 9 mm	[47]
Cuphea aequipetala Cav.	Lythraceae	Aerial parts	MIC = 125 μg/mL	[57]
			MIC = 125 µg/mL	[52]
Cynara scolymus L.	Asteraceae	Leaves	IZD = 18 mm; MIC= 1.25–5 mg/mL	[47]
Cyrtocarpa procera Kunth	Anacardiaceae	Bark	MIC = 125 µg/mL	[58]
			MIC = 250 µg/mL	[52]
Desmos cochinchinensis Lour.	Annonaceae	Leaves	IZD = 10.0 ± 0.6 mm (240 µg/disc)	[59]
Dysphania ambrosioides (L.) Mosyakin and Clemants (cited as Teloxys ambrosioides (L.) W. A. Weber)	Amaranthaceae	Aerial parts	MIC = 1000 µg/mL	[52]
Elettaria cardamomum (L.) Maton.	Zingiberaceae	Seeds	IZD < 9 mm	[47]
Eryngium carlinae F. Delaroche	Apiaceae	Aerial parts	MIC = 1000 µg/mL	[52]
Eugenia caryophyllata Thunb	Myrtaceae	Flower	MIC = 60 µg/mL	[55]
Eupatorium petiolare Moc. ex DC.	Compositae	Aerial parts	MIC = 500 µg/mL	[52]
Fagoniaar abica L.	Zygophyllaceae	Whole plant	MIC = 16–256 μg/mL	[49]
Foeniculum vulgare Mill. var. dulce DC	Apiaceae	Seed	IZD < 9 mm; MIC = 5–10 mg/mL	[47]
Fritillaria thunbergii Miq.	Liliaceae	Stem	MIC = 40 µg/mL	[55]
Garcinia kola Heckel	Guttiferae	Seeds	IZD = 1.0 ± 2.6 mm	[50,51]
Geum iranicum Khatamsaz	Rosaceae	Root	IZD = 24–35 mm (100 µg/mL)	[60]
Gnaphalium canescens DC.	Compositae	Aerial parts	MIC = 500 µg/mL	[52]
Grindelia inuloides Willd.	Compositae	Aerial parts	MIC = 500 µg/mL	[52]
Hesperozygis marifolia Epling	Lamiaceae	Aerial parts	MIC = 1000 µg/mL	[52]
Heterotheca inuloides Cass.	Compositae	Aerial parts	MIC = 500 µg/mL	[52]
Juniperus communis L.	Cupressaceae	Berry	IZD < 9 mm	[47]
Larrea tridentata (Sessé and Moc. ex DC.) Coville	Zygophyllaceae	Aerial parts	MIC = 500 µg/mL	[52]
Ligusticum striatum DC (cited as Ligusticum chuanxiong Hort.)	Apiaceae	Root	MIC = 100 µg/mL	[55]
Lippia graveolens Kunth (cited as Lippia berlandieri Schauer)	Verbenaceae	Aerial parts	MIC = 1000 µg/mL	[52]
Ludwigia repens J. R. Forst.	Onagraceae	Aerial parts	MIC = 125 µg/mL	[52]
Machaeranthera riparia (Kunth) A.G. Jones	Compositae	Aerial parts	MIC = 1000 µg/mL	[52]
Machaeranthera tanacetifolia (Kunth) Nees	Compositae	Aerial parts	MIC = 1000 µg/mL	[52]
Mentha × piperita L.	Lamiaceae	Leaves	IZD < 9 mm	[47]
Mirabilis jalapa L.	Nyctaginaceae	Aerial parts	MIC = 250 µg/mL	[52]
Monarda citriodora var. austromontana (Epling) B. L. Turner (cited as Monarda austromontana Epling)	Lamiaceae	Aerial parts	MIC = 500 µg/mL	[52]
Olea europaea L.	Oleaceae	Leaves/Stem	MIC = 125 µg/mL	[52]
Origanum vulgare L.	Lamiaceae	Leaves	IZD = 25 mm; MIC = 0.6–2.5 mg/mL	[47]
Orthosiphon aristatus (Blume) Miq. (cited as Orthosiphon stamineus Benth)	Lamiaceae	Leaves	IZD = 9.0 ± 1.3 mm (240 µg/disc)	[59]
		Stem	IZD = 8.0 ± 0.1 mm (240 µg/disc)	[59]
Peumus boldus Mol.	Monimiaceae	Leaves	>1500 μg/mL	[61]
Plantago major L.	Plantaginaceae	Aerial parts	MIC = 1000 µg/mL	[52]
Priva grandiflora (Ortega) Moldenke	Verbenaceae	Aerial parts	MIC = 250 µg/mL	[52]
Prunus avium L.	Rosaceae	Peduncles	IZD = 9 mm; MIC = 5–10 mg/mL	[47]
Rosmarinus officinalis L.	Lamiaceae	Leaves	IZD < 9 mm	[47]
Ruta chalepensis L.	Rutaceae	Leaves	MIC = 1000 µg/mL	[52]
Salvia officinalis L.	Lamiaceae	Leaves	IZD = 10 mm; MIC = 1.25–10 mg/mL	[47]
Sclerocarya birrea A. Rich Hochst	Anacardiaceae	Stem bark	MIC = 0.16–2.5 mg/mL; IZD = 15.0 ± 2.7 mm	[50,51]
Tagetes lucida Cav.	Compositae	Aerial parts	MIC = 500 µg/mL	[52]
Tecoma stans (L.) Juss. ex Kunth	Bignoniaceae	Aerial parts	MIC = 1000 µg/mL	[52]
Terminalia catappa L.	Combretaceae	Aerial parts	MIC = 125 µg/mL	[62]
Terminalia chebula Retz	Combretaceae	Fruit	MIC = 125 mg/mL; MBC = 150 mg/mL	[63]
Thymus serpyllum L.	Lamiaceae	Aerial parts	IZD = 10 mm; MIC = 1.25–10 mg/mL	[47]
Tillandsia usneoides L.	Bromeliaceae	Aerial parts	MIC = 1000 µg/mL	[52]
Tinospora sagittata Gagnep.	Menispermaceae	Root	MIC = 100 µg/mL	[55]
Tithonia diversifolia (Hemsl.) A.G.	Compositae	Aerial parts	MIC = 500 µg/mL	[52]
Verbena carolina L.	Verbenaceae	Aerial parts	MIC = 62.5–125 µg/mL	[52]
Zingiber officinale Roscoe	Zingiberaceae	Rhizome	IZD = 9 mm; MIC = 2.5–5 mg/mL	[47]

MIC, minimal inhibitory concentration; IZD, inhibition zone diameter; MBC, minimal bactericidal concentration.

Table 2. Plant essential oils with anti-H. pylori activity.

Species	Family	Parts	Anti-H. pylori Potency	Ref.
Abies mariesii Mast. (cited as Abies maritima)	Pinaceae	Pine	IZD = 22 ± 2 mm (500 µg/disc)	[64]
			IZD = 14 ± 1 mm (500 µg/disc)	[64]
Allium sativum L.	Amaryllidaceae	Cloves	8–32 μg/mL	[65]
Artemisia dracunculus L.	Compositae	Tarragon	IZD = 7 ± 0 mm (500 µg/disc)	[64]
Carum carvi L.	Apiaceae	Caraway	IZD = 12 ± 0 mm (500 µg/disc)	[64]
Cinnamomum zeylanicum Blume	Lauraceae	Bark	MIC = 0.3 μL/mL; IZD = 24.8 mm	[66]
			IZD = 63 ± 0.5 mm (500 µg/disc)	[64]
			IZD = 45 ± 5 mm (500 µg/disc)	[64]
Cistus ladanifer L.	Cistaceae	Cistus	IZD = 8 ± 0 mm (500 µg/disc)	[64]
			IZD = 16 ± 1.5 mm (500 µg/disc)	[64]
Citrus aurantium L.	Rutaceae	Orange blossom	>88% inhibition (0.3 μL/mL)	[66]
			IZD = 12 ± 0 mm (500 µg/disc)	[64]
			IZD = 16 ± 0 mm (500 µg/disc)	[64]
Citrus limon (L.) Burm. f.	Rutaceae	Lemon	IZD = 16 ± 0 mm (500 µg/disc)	[64]
			IZD = 14 ± 10 mm (500 µg/disc)	[64]
Citrus paradise Macfad	Rutaceae	White grapefruit	IZD = 29 ± 2.5 mm (500 µg/disc)	[64]
			IZD = 17 mm (500 µg/disc)	[64]
		Grapefruit	IZD = 13 ± 0.5 mm (500 µg/disc)	[64]
		Tea tree	IZD = 9 ± 0 mm (500 µg/disc)	[64]
Cupressus sempervirens L.	Cupressaceae	Cypress	IZD = 19 ± 3.5 mm (500 µg/disc)	[64]
			IZD = 11 ± 10 mm (500 µg/disc)	[64]
Cymbopogon citratus (DC.) Stapf	Poaceae	Lemongrass	IZD = 32 ± 7 mm (500 µg/disc)	[64]
			IZD = 23 ± 0.05 mm (500 µg/disc)	[64]
Daucus carota L.	Apiaceae	Carrot seed	IZD = 8 ± 0.5 mm (500 µg/disc)	[64]
			IZD = 16 ± 1.5 mm (500 µg/disc)	[64]
Dittrichia viscosa (L.) Greuter subsp. revoluta	Asteraceae	Aerial parts	0.33 μL/mL *	[67]
Eucalyptus globulus L.	Myrtaceae	Eucalyptus	IZD = 10 ± 1 mm (500 µg/disc)	[64]
			IZD = 12 ± 10 mm (500 µg/disc)	[64]
Eugenia caryophyllus (Spreng.) Bullock and S. G. Harrison	Myrtaceae	Clove-bud	IZD = 13 ± 2.5 mm (500 µg/disc)	[64]
		Clove-leaf	IZD = 25 ± 5 mm (500 µg/disc)	[64]
Heracleum persicum L.	Apiaceae	Fruits	>88% inhibition (0.3 μL/mL)	[66]
Juniperus communis L.	Cupressaceae	Berry	IZD = 14 ± 0.5 mm (500 µg/disc)	[64]
			IZD = 10 ± 1 mm (500 µg/disc)	[64]
Leptospermum scoparium J. R. Forst and G. Forst	Myrtaceae	Manuka	IZD = 23 ± 3 mm (500 µg/disc)	[64]
Aloysia citriodora Palau (cited as Lippia citriodora)	Verbenaceae	Aerial parts	IZD = 29 ± 2 mm (500 µg/disc)	[64]
Matricaria chamomilla L. (cited as Matricaria recutita)	Compositae	Flowers	IZD = 7 ± 0 mm (500 µg/disc)	[64]
			IZD = 15 ± 10 mm (500 µg/disc)	[64]
Melaleuca alternifolia Cheel.	Myrtaceae	Tea tree	IZD = 9 ± 0.3 mm (500 µg/disc)	[64]
Ocimum basilicum L.	Lamiaceae	Aerial parts	IZD = 9 ± 0.3 mm (500 µg/disc)	[64]
			IZD = 8 ± 0.5 mm (500 µg/disc)	[64]
Origanum vulgare L.	Lamiaceae	Leaves	IZD = 19 ± 4 mm (500 µg/disc)	[64]
Pimpinella anisum L.	Apiaceae	Anise	IZD = 12 ± 10 mm (500 µg/disc)	[64]
Salvia sclarea L.	Lamiaceae	Aerial parts	IZD = 10 ± 2 mm (500 µg/disc)	[64]
			IZD = 10 ± 10 mm (500 µg/disc)	[64]
Salvia officinalis L.	Lamiaceae	Leaves	IZD = 7 ± 0 mm (500 µg/disc)	[64]
Sassafras officinale Siebold	Lauraceae	Aerial parts	IZD = 7 ± 0 mm (500 µg/disc)	[64]
Satureja montana L.	Lamiaceae	Savory	IZD = 25 ± 5 mm (500 µg/disc)	[64]
			IZD = 13 ± 5 mm (500 µg/disc)	[64]
Syzygium aromaticum (L.) Merr. and L. M. Perry	Myrtaceae	Buds	>88% inhibition (0.3 μL/mL)	[66]
Thymus vulgaris L.	Lamiaceae	Thyme	IZD = 15 ± 5 mm (500 µg/disc)	[64]
			IZD = 12 ± 10 mm (500 µg/disc)	[64]
Thymus zygis L.	Lamiaceae	Red thyme	IZD = 19 ± 0.5 mm (500 µg/disc)	[64]
Zataria multiflora Boiss.	Lamiaceae	Aerial parts	MIC = 0.3 μL/mL IZD = 23.6 mm	[66]

* Initial population of 8.52 ± 0.30 log10 colony forming unit (CFU)/mL reduced to 7.67 ± 0.22 log10CFU/mL; MIC, minimal inhibitory concentration; IZD, inhibition zone diameter.

Table 3. Plant ethanolic extracts with anti-H. pylori activity.

Species	Family	Parts	Anti-H. pylori Potency	Ref.
Abrus cantoniensis Bge.	Leguminosae	Aerial parts	MIC = 40 µg/mL	[55]
Alepidea Amatymbica Eckl. and Zeyh	Apiaceae	Roots/rhizomes	IZD = 6.7 ± 6.7 mm	[50,51]
Amomum villosum Lour.	Zingiberaceae	Fruit	MIC = 100 µg/mL	[55]
Bixa orellana L.	Bixaceae	Seed	MIC ≤ 625–1250 μg/mL	[48]
Bupleurum chinense DC.	Apiaceae	Aerial parts	MIC = 60 µg/mL	[55]
Chamomilla recutita (L.) Rauschert	Compositae	Inflorescences	MIC ≤ 625 μg/mL	[48]
Cichorium intybus L.	Asteraceae	Root	IZD = 12 mm; MIC = 1.25–10 mg/mL	[47]
Cinnamomum zeylanicum Blume	Lauraceae	Bark	IZD = 20 mm; MIC = 1.25–5 mg/mL	[47]
Citrus reticulata Blanco	Rutaceae	Fruit shell	MIC = 60 µg/mL	[55]
Combretum molle R. Br. Ex G. Don	Combretaceae	Bark	IZD = 12.9 ± 4.7 mm	[50,51]
Convolvulus austro-aegyptiacu Abdallah and Saad	Convolvulaceae	Aerial parts	MIC = 100–200 µg/mL	[67]
Coriandrum sativum L.	Apiaceae	Seed	IZD = 12 mm; MIC = 5–10 mg/mL	[47]
Corydalis yanhusuo W.T. Wang	Papaveraceae	Stem	MIC = 60 µg/mL	[55]
Cuminum cyminum L.	Apiaceae	Seed	IZD = 14 mm; MIC= 0.075–0.6 mg/mL	[47]
Cynara scolymus L.	Asteraceae	Leaves	IZD = 25 mm; MIC = 0.15–0.6 mg/mL	[47]
Elettaria cardamomum (L.) Maton.	Zingiberaceae	Seed	IZD = 18 mm; MIC = 0.6–2.5 mg/mL	[47]
Eugenia caryophyllata Thunb	Myrtaceae	Flower	MIC = 40 µg/mL	[55]
Foeniculum vulgare Mill. var. dulce DC	Apiaceae	Seed	IZD < 9 mm	[47]
Fritillaria thunbergii Miq.	Liliaceae	Stem	MIC = 40 µg/mL	[55]
Garcinia kola Heckel	Guttiferae	Seeds	MIC = 0.63–5 mg/mL; IZD = 9.2 ± 7.2 mm	[50,51]
Hippophae rhamnoides L.	Elaeagnaceae	Leaves	MIC = 60 µg/mL	[55]
Ilex paraguariensis A. St.-Hil.	Aquifoliaceae	Green leaves	MIC ≤ 625–5000 μg/mL	[48]
		Roasted leaves	MIC ≤ 625–5000 μg/mL	[48]
Juniperus communis L.	Cupressaceae	Berry	IZD = 10 mm; MIC = 1.25–10 mg/mL	[47]
Ligusticum striatum DC (cited as Ligusticum chuanxiong)	Apiaceae	Root	MIC = 60 µg/mL	[55]
Lysimachia christinae Hance	Primulaceae	Whole plant	MIC = 100 µg/mL	[55]
Magnolia officinalis Rehd. et Wils.	Magnoliaceae	Bark	MIC = 60 µg/mL	[55]
Malva sylvestris L.	Malvaceae	Leaves and inflorescences	MIC ≤ 625–5000 μg/mL	[48]
Melia azedarach L. (cited as Melia toosendan)	Meliaceae	Fruit	MIC = 100 µg/mL	[55]
Mentha × piperita L.	Lamiaceae	Leaves	IZD < 9 mm	[47]
Piper longum L.	Piperaceae	Spike	MIC = 100 µg/mL	[55]
Prunus avium L.	Rosaceae	Peduncles	IZD = 10 mm; MIC = 1.25–10 mg/mL	[47]
Rosmarinus officinalis L.	Lamiaceae	Leaves	IZD = 20 mm; MIC = 1.25–10 mg/mL	[47]
Salvia officinalis L.	Lamiaceae	Leaves	IZD = 14 mm; MIC= 1.25–5 mg/mL	[47]
Saussurea costus (Falc.) Lipsch. (cited as Saussurea lappa)	Compositae	Root	MIC = 40 µg/mL	[55]
Schisandra chinensis Baill.	Schisandraceae	Fruit	MIC = 60 µg/mL	[55]
Sclerocarya birrea A. Rich Hochst	Anacardiaceae	Stem bark	IZD = 3.3 ± 5.0 mm	[50,51]
Thymus serpyllum L.	Lamiaceae	Aerial parts	IZD = 22 mm; MIC = 1.25–10 mg/mL	[47]
Tinospora sagittata Gagnep.	Menispermaceae	Aerial parts	MIC/MBC = 6250 μg/mL	[42]
Trigonella foenum-graecum L.	Leguminosae	Seed	MIC = 40 µg/mL	[55]
Zingiber officinale Roscoe	Zingiberaceae	Rhizome	IZD = 25 mm; MIC = 0.075–0.6 mg/mL	[47]

MIC, minimal inhibitory concentration; IZD, inhibition zone diameter.

Table 4. Plant methanolic extracts with anti-H. pylori activity.

Species	Family	Parts	Anti-H. pylori Potency	Ref.
Acacia nilotica (L.) Delile	Leguminosae	Leaves	MIC = 8–128 μg/mL	[49]
		Flowers	MIC = 8–64 μg/mL	[49]
Acanthus montanus (Nees) T. Anders	Acanthaceae	Leaves stalk	IZD = 6–22 mm (25µg/disc)	[68]
Achillea millefolium L.	Compositae	Aerial parts	MIC = 1.56–100 µg/mL	[69]
Adhatoda vasica Nees	Acanthaceae	Whole plant	MIC = 64–512 μg/mL	[49]
Aframomum pruinosum Gagnepain	Zingiberaceae	Seed	MIC = 128 μg/mL	[70]
Ageratum conyzoides L.	Compositae	Whole plant	IZD = 6–22 mm (25 µg/disc); MIC = 63–1000 µg/mL; MBC = 195–12,500 µg/mL	[68]
Alchemilla fissa Günther and Schummel	Rosaceae	Aerial parts	MIC = 4–32 μg/mL	[71]
Alchemilla glabra Neygenf.	Rosaceae	Aerial parts	MIC = 4–32 μg/mL	[71]
Alchemilla monticola Opiz	Rosaceae	Aerial parts	MIC = 4–32 μg/mL	[71]
Alchemilla viridiflora Rothm.	Rosaceae	Aerial parts	MIC = 4–16 μg/mL	[71]
Alchornea triplinervia (Spreng.) Müll.Arg.	Euphorbiaceae	Aerial parts	MIC = 250 µg/mL	[72]
Alepidea amatymbica Eckl. and Zeyh	Apiaceae	Roots/rhizomes	IZD = 6.1 ± 6.4 mm	[50,51]
Alpinia galanga (L.) Willd. (cited as Languas galanga)	Zingiberaceae	Tuber	IZD = 21.5 ± 1.9 mm (240 µg/disc)	[59]
Amphipterygium adstringens (Schltdl.) Standl.	Anacardiaceae	Aerial parts	MIC = 250 µg/mL	[52]
Anoda cristata (L.) Schltdl.	Malvaceae	Leaves/stem	MIC = 500 µg/mL	[52]
Artemisia ludoviciana Nutt. subsp. mexicana (Willd. ex Spreng.) Fernald	Compositae	Leaves/stem	MIC = 250 µg/mL	[52]
Aulotandria kamerunensis (Loes)	Zingiberaceae	Rhizome	IZD = 16–22 mm (25 µg/disc)	[68]
Bidens pilosa L.	Compositae	Leaves	MIC = 128–512 μg/mL	[73]
Bryophyllum pinnatum (Lam.) Kurz	Crassulaceae	Leaves	MIC = 32 μg/mL; MBC = 256 μg/mL	[74]
Calandrinia ciliata (Ruiz and Pav.) DC. (cited as Calandrinia micrantha)	Portulacaceae	Leaves/Stem	MIC = 250 µg/mL	[52]
Calophyllum brasiliense Cambess.	Clusiaceae	Bark	MIC = 31 µg/mL; IZD = 7–8 mm (62.5–1000 µg/disc)	[75]
Calotropis gigantea (L.) W.T. Aiton	Apocynaceae	Leaves	IZD = 9.8 ±1.2 mm (240 µg/disc)	[59]
Calotropis procera W.T. Aiton	Apocynaceae	Flowers	MIC = 64–256 μg/mL	[49]
Capsella bursa-pastoris (L.) Medik.	Brassicaceae	Aerial parts	MIC = 62.5 µg/mL	[52]
Carum carvi L.	Apiaceae	Seeds	MIC = 100 µg/mL	[69]
Casuarina equisetifolia L.	Casuarinaceae	Fruit	MIC = 128–512 μg/mL	[49]
Centella asiatica (L.) Urb.	Apiaceae	Whole plant	IZD = 13.0 ± 0.9 mm (240 µg/disc)	[59]
Chenopodium incisum Poir. (cited as Teloxys graveolens)	Amaranthaceae	Aerial parts	MIC = 62.5 µg/mL	[52]
Chromolaena odorata (L.) R.M. King and H. Rob.	Asteraceae	Leaves	IZD = 25.3 ± 1.6 mm (240 µg/disc)	[59]
Cistus laurifolius L.	Cistaceae	Flowers	MIC = 62.5–125 µg/mL	[54]
Colubrina asiatica (L.) Brongn.	Rhamnaceae	Leaves	IZD = 16.3 ± 2.1 mm (240 µg/disc)	[59]
Combretum molle R. Br. Ex G. Don	Combretaceae	Bark	IZD = 13.1 ± 5.3 mm	[50,51]
Cosmos caudatus Kunth	Asteraceae	Leaves	IZD = 23.0 ± 0.9 mm (240 µg/disc)	[59]
Cuminum cyminum L.	Apiaceae	Seed	MIC = 100 µg/mL	[69]
Curcuma longa L.	Zingiberaceae	Rhizome	MIC = 12.5–100 µg/mL	[69]
Curcuma longa L./Zingiber officinale L.	Zingiberaceae	Rhizome	MIC = 3.125–100 µg/mL	[69]
Cymbopogon citratus (DC.) Stapf	Poaceae	Aerial parts	MIC = 31.2 µg/mL	[52]
		Stem	IZD = 28.5 ± 1.5 mm (240 µg/disc)	[59]
Cyrtocarpa procera Kunth	Anacardiaceae	Bark	MIC = 62.5 µg/mL	[58]
Derris trifoliata Lour.	Leguminosae	Stem	IZD = 47.0 ± 0.9 mm (240 µg/disc)	[59]
			IZD = 8.5 ± 1.0 mm (240 µg/disc)	[59]
Dysphania ambrosioides (L.) Mosyakin and Clemants (cited as Teloxys ambrosioides)	Amaranthaceae	Aerial parts	MIC = 250–500 µg/mL	[52]
Elettaria cardamomum (L.) Maton.	Zingiberaceae	Seed	MIC = 3.125-100 µg/mL	[69]
Emilia coccinea (Sims) G. Don	Compositae	Whole plant	IZD = 6–22 mm (25 µg/disc)	[68]
Eryngium carlinae F. Delaroche	Apiaceae	Aerial parts	MIC = 31.2 µg/mL	[52]
Eryngium foetidium L.	Apiaceae	Whole plant	IZD = 6–18 mm (25 µg/disc)	[68]
		Leaves	MIC = 64–512 μg/mL	[73]
Eucalyptus torelliana F. Muell.	Myrtaceae	Stem bark	MIC = 12.5–200 µg/mL	[76]
Eupatorium petiolare Moc. ex DC.	Compositae	Aerial parts	MIC = 125 µg/mL	[52]
Euphorbia hirta L.	Euphorbiaceae	Whole plant	IZD = 6–18 mm (25 µg/disc)	[68]
Euphorbia umbellata (Pax) Bruyns	Euphorbiaceae	Bark	44.6% inhibition (256 μg/mL)	[77]
Fagoniaar abica L.	Zygophyllaceae	Whole plant	MIC = 32–256 μg/mL	[49]
Ficus deltoidea Jack	Moraceae	Leaves	IZD = 12.0 ± 0.6 mm (240 µg/disc)	[59]
Foeniculum vulgare Mill. var. dulce DC	Apiaceae	Seeds	MIC = 50–100 µg/mL	[69]
Garcinia kola Heckel	Guttiferae	Seeds	IZD = 7.1 ± 5.8 mm	[50,51]
Galinsoga ciliata (Raf.) S. F. Blake	Compositae	Leaves	MIC = 128–512 μg/mL	[73]
Gentiana lutea L.	Gentianaceae	Root	MIC = 3.125–100 µg/mL	[69]
Ginkgo biloba L.	Ginkgoaceae	Leaves	MIC = 100 µg/mL	[69]
Glycyrrhiza glabra L.	Leguminosae	Root	IDZ = 19 mm (10 mg/mL)	[78]
Gnaphalium canescens DC.	Compositae	Aerial parts	MIC = 62.5 µg/mL	[52]
Grindelia inuloides Willd.	Compositae	Aerial parts	MIC = 62.5 µg/mL	[52]
Haplopappus spinulosus (Pursh) DC.	Compositae		MIC = 125 µg/mL	[52]
Hesperozygis marifolia Epling	Lamiaceae	Aerial parts	MIC = 62.5 µg/mL	[52]
Heterotheca inuloides Cass.	Compositae	Aerial parts	MIC = 31.25 µg/mL	[52]
Hibiscus rosa-sinensis L.	Malvaceae	Stem	IZD = 13.7 ± 1.2 mm (240 µg/disc)	[59]
		Leaves	IZD = 14.3 ± 1.0 mm (240 µg/disc)	[59]
Hippocratea celastroides HBK	Hippocrateace	Root bark	MIC = 31.25–125 μg/mL	[79]
		Leaves	MIC = 7.81–31.25 μg/mL	[79]
		Stem	MIC = 7.81–15.63 μg/mL	[79]
Hydrastis canadensis L.	Ranunculaceae	Rhizome	MIC = 0.78–50 µg/mL	[80]
Illicium verum Hook. f.	Schisandraceae	Fruit	MIC = 50–100 µg/mL	[69]
Jatropha podagrica Hook.	Euphorbiaceae	Leaves	IZD = 8.0 ± 0.7 mm (240 µg/disc)	[59]
		Stem	IZD = 9.2 ± 0.8 mm (240 µg/disc)	[59]
		Root	IZD = 34.0 ± 2.5 mm (240 µg/disc)	[59]
Juniperus communis L.	Cupressaceae	Berry	MIC = 25–100 µg/mL	[69]
Kaempferia galanga L.	Zingiberaceae	Leaves	IZD = 46.0±0.1 mm (240 µg/disc)	[59]
		Tuber	IZD = 11.0 ± 0.6 mm (240 µg/disc)	[59]
Larrea tridentata (Sessé and Moc. ex DC.) Coville	Zygophyllaceae	Aerial parts	MIC = 62.5 µg/mL	[52]
Laurus nobilis L.	Lauraceae	Leaves	MIC = 50–100 µg/mL	[69]
Lavandula angustifolia Mill.	Lamiaceae	Flower	MIC = 100–1000 µg/mL	[69]
Limnocharis flava (L.) Buchenau	Alismataceae	Leaves	IZD = 11.0 ±1.1 mm (240 µg/disc)	[59]
Lippia graveolens Kunth (cited as Lippia berlandieri)	Verbenaceae	Aerial parts	MIC = 31.2 µg/mL	[52]
Lithraea molleoides (Vell.) Engl.	Anacardiaceae	Aerial parts	MIC = 18–125 μg/mL	[81]
Ludwigia repens J. R. Forst.	Onagraceae	Aerial parts	MIC = 500 µg/mL	[52]
Lycopodium cernua (L.) Pic. Serm	Lycopodiaceae	Whole plant	IZD = 16–22 mm (25 µg/disc; MIC = 63–250 µg/mL; MBC = 195–12500 µg/mL	[68]
Machaeranthera parviflora A. Gray	Compositae	Aerial parts	MIC = 31.2 µg/mL	[52]
Machaeranthera riparia (Kunth) A.G. Jones	Compositae	Aerial parts	MIC = 62.5 µg/mL	[52]
Machaeranthera tanacetifolia (Kunth) Nees	Compositae	Aerial parts	MIC = 125 µg/mL	[52]
Marantodes pumilum (Blume) Kuntze (cited as Labisia pumila)	Primulaceae	Root	IZD = 8.0 ±0.5 mm (240 µg/disc)	[59]
Marrubium vulgare L.	Lamiaceae	Leaves/stem	MIC = 31.2 µg/mL	[52]
Melastoma malabathricum L. (blue variety)	Melastomataceae	Leaves	IZD = 25.7 ± 0.8 mm (240 µg/disc)	[59]
		Stem	IZD = 18.0 ±0.6 mm (240 µg/disc)	[59]
Melissa officinalis L.	Lamiaceae	Leaves	MIC = 100 ≥ 100 µg/mL	[69]
Mentha × piperita L.	Lamiaceae	Leaves	MIC = 25–100 µg/mL	[69]
		Leaves/Stem	MIC = 500 µg/mL	[52]
Mimosa pudica L.	Leguminosae	Whole plant	IZD = 14.2 ± 1.9 mm (240 µg/disc)	[59]
Mitrasacme indica Wight (cited as Mitrasacme alsinoides)	Loganiaceae	Leaves	IZD = 13.3 ± 2.3 mm (240 µg/disc)	[59]
Monarda citriodora var. austromontana (Epling) B. L. Turner. (cited as Monarda austromontana)	Lamiaceae	Aerial parts	MIC = 125 µg/mL	[52]
Moussonia deppeana (Schltdl. and Cham.) Klotzsch ex Hanst.	Gesneriaceae	Leaves/stem	MIC = 15.6 µg/mL	[52]
Myristica fragrans Houtt.	Myristicaceae	Seed	MIC = 3.125–25 µg/mL	[69]
Neptunia oleracea Lour.	Leguminosae	Leaves	IZD = 28.3 ± 4.1 mm (240 µg/disc)	[59]
Ocimum basilicum L.	Lamiaceae	Aerial parts	MIC = 31.2 µg/mL	[52]
Origanum majorana L.	Lamiaceae	Aerial parts	MIC = 50–100 µg/mL	[69]
Origanum vulgare L.	Lamiaceae	Leaves	MIC = 100 ≥ 100 µg/mL	[69]
Orthosiphon aristatus (Blume) Miq. (cited as Orthosiphon stamineus)	Lamiaceae	Leaves	IZD = 22.0 ± 2.4 mm (240 µg/disc)	[59]
		Stem	IZD = 16.0 ± 0.9 mm (240 µg/disc)	[59]
Paeonia × suffruticosa Andrews	Paeoniaceae	Root Cortex	IZD = 17 ± 0.08 mm (1 mg/disc)	[82]
Parkia speciosa Hassk.	Leguminosae	Seed	IZD = 18.0 ± 0.1 mm (240 µg/disc)	[59]
Passiflora edulis Sims (cited as Passiflora incarnata)	Passifloraceae	Aerial parts	MIC = 50–100 µg/mL	[69]
Persicaria minor (Huds.) Opiz (cited as Polygonum minus)	Polygonaceae	Leaves	IZD = 15.5 ± 1.1 mm (240 µg/disc)	[59]
Petroselinum crispum (Mill.) Fuss	Apiaceae	Aerial parts	MIC = 100 ≥ 100 µg/mL	[69]
Phaeomeria imperialis (Roscoe) Lindl.	Zingiberaceae	Flowers	IZD = 16.3 ± 1.4 mm (240 µg/disc)	[59]
Phyllanthus niruri L.	Phyllanthaceae	Whole plant	IZD = 29.7 ± 1.4 mm (240 µg/disc)	[59]
Piper betle L.	Piperaceae	Leaves	IZD = 23.5 ± 0.8 mm (240 µg/disc)	[59]
Plantago major L.	Plantaginaceae	Aerial parts	MIC = 250 µg/mL	[52]
Plectranthus amboinicus (Lour.) Spreng.	Lamiaceae	Aerial parts	MIC = 31.2 µg/mL	[52]
Pluchea indica (L.) Less.	Compositae	Leaves	IZD = 23.0 ± 1.3 mm (240 µg/disc)	[59]
Poliomintha longiflora A. Gray	Lamiaceae	Leaves/stem	MIC = 250 µg/mL	[52]
Priva grandiflora (Ortega) Moldenke	Verbenaceae	Aerial parts	MIC = 500 µg/mL	[52]
Psidium guajava L.	Myrtaceae	Leaves	IZD = 33.0 ± 2.3 mm (240 µg/disc)	[59]
Quercus rugosa Née	Fagaceae	Leaves	MIC = 125 µg/mL	[52]
Rosmarinus officinalis L.	Lamiaceae	Leaves	MIC = 12.5–100 µg/mL	[69]
Ruta chalepensis L.	Rutaceae	Leaves	MIC = 62.5 µg/mL	[52]
Salvia officinalis L.	Lamiaceae	Leaves	MIC = 25–100 µg/mL	[69]
Sanguinaria canadensis L.	Papaveraceae	Rhizome	MIC = 12.5–50 µg/mL	[80]
Scleria woodii var. ornata (Cherm.) J. Schultze-Motel (cited as Scleria striatonux)	Cyperaceae	Root	IZD = 6–30 mm (25 µg/disc); MIC = 63–1000 µg/mL; MBC = 195–12,500 µg/mL	[68]
Scleria verrucossa (Wild)	Cyperaceae	Root	IZD = 4–20 mm (25 µg/disc)	[68]
Sclerocarya birrea A. Rich Hochst	Anacardiaceae	Stem bark	IZD = 3.0 ± 4.4 mm	[50,51]
			IZD = 17.3 ± 1.6 mm (240 µg/disc)	[59]
Solanum torvum Sw.	Solanaceae	Seed	IZD = 12.3 ± 0.8 mm (240 µg/disc)	[59]
Stachys setifera C. A. Mey.	Lamiaceae	Aerial parts	IZD = 38.3 mm (8 mg/disc)	[83]
Tagetes lucida Cav.	Compositae	Aerial parts	MIC = 500 µg/mL	[52]
Tanacetum partshenium (L.) Sch. Bip.	Compositae		MIC = 62.5 µg/mL	[52]
Tapeinochilos ananassae (Hassk.) K. Schum.	Costaceae	Rhizome	IZD = 6–18 mm (25 µg/disc)	[68]
Tecoma stans (L.) Juss. ex Kunth	Bignoniaceae	Aerial parts	MIC = 500 µg/mL	[52]
Tillandsia usneoides L.	Bromeliaceae	Aerial parts	MIC = 125 µg/mL	[52]
Tinospora sinensis (Lour.) Merr. (cited as Tinospora cordifolia)	Menispermaceae	Stem	IZD = 13.7 ± 2.7 mm (240 µg/disc)	[59]
Tithonia diversifolia (Hemsl.) A.G.	Compositae	Aerial parts	MIC = 62.5 µg/mL	[52]
Verbena carolina L.	Verbenaceae	Aerial parts	MIC = 500–1000 µg/mL	[52]
Zingiber officinale Roscoe	Zingiberaceae	Rhizome	MIC = 6.25–50 µg/mL	[69]
			IZD = 19.7 ± 1.5 mm (240 µg/disc)	[59]

MIC, minimal inhibitory concentration; MBC, minimal bactericidal concentration; IZD, inhibition zone diameter.

Table 5. Plant acetone extracts with anti-H. pylori activity.

Species	Family	Parts	Anti-H. pylori Potency	Ref.
Acacia nilotica (L.) Delile	Leguminosae	Leaves	MIC = 8–128 μg/mL	[49]
		Flowers	MIC = 4–64 μg/mL	[49]
Adhatoda vasica Nees	Acanthaceae	Whole plant	MIC = 16–512 μg/mL	[49]
Alepidea Amatymbica Eckl. and Zeyh	Apiaceae	Roots/Rhizomes	IZD = 7.0 ± 6.5 mm	[50,51]
Bridelia micrantha (Hochst.) Baill.	Phyllanthaceae	Bark	IZD = 16–23 mm	[53]
Calotropis procera W.T. Aiton	Apocynaceae	Leaves	MIC = 32–256 μg/mL	[49]
		Flowers	MIC = 8–128 μg/mL	[49]
Casuarina equisetifolia L.	Casuarinaceae	Fruit	MIC = 128.0–1024 μg/mL	[49]
Cocculus hirsutus (L.) Diels.	Menispermaceae	Leaves	IZD = 22–24 mm (200–1000 μg/mL)	[56]
Combretum molle R. Br. Ex G. Don *	Combretaceae	Bark	MIC50 = 0.08–1.25 mg/mL; IZD = 10.7 ± 4.7 mm;	[50,51]
Desmostachya bipinnata (L.) Stapf.	Gramineae	Whole plant	MIC = 1.3 mg/mL	[84]
Fagoniaar abica L.	Zygophyllaceae	Whole plant	MIC = 16–128 μg/mL	[49]
Garcinia kola Heckel	Guttiferae	Seeds	IZD = 8.8 ± 5.2 mm	[50,51]
Sclerocarya birrea A. Rich Hochst *	Anacardiaceae	Stem bark	MIC50 = 0.06–1.25 mg/mL; IZD = 14.7 ± 2.5 mm	[50,51]

* Exhibited remarkable bactericidal activity against H. pylori, killing more than 50% of the strains within 18 h at 4× MIC and led to complete elimnation within 24 h; MIC, minimal inhibitory concentration; MIC₅₀, minimal inhibitory concentration required to inhibit 50% of cells growth; IZD, inhibition zone diameter.

Table 6. Plant chloroform extracts with anti-H. pylori activity.

Species	Family	Parts	Anti-H. pylori Potency	Ref.
Calotropis gigantea (L.) W.T. Aiton	Apocynaceae	Leaves	IZD = 14.0 ± 0. 9 mm (240 µg/disc)	[59]
Cedrus libani A. Rich	Pinaceae	Cones	MIC = 31.2 µg/mL	[54]
Centaurea solstitialis L.	Asteraceae	Aerial parts	MIC = 1.95 µg/mL	[54]
Centella asiatica (L.) Urb.	Apiaceae	Whole plant	IZD = 8.2 ± 0.4 mm (240 µg/disc)	[59]
Chromolaena odorata (L.) R.M. King and H. Rob.	Asteraceae	Leaves	IZD = 27.5 ± 1.0 mm (240 µg/disc)	[59]
Cistus laurifolius L.	Cistaceae	Flowers	MIC = 1.95 µg/mL	[54]
Colubrina asiatica (L.) Brongn.	Rhamnaceae	Leaves	IZD = 10.0 ± 0.9 mm (240 µg/disc)	[59]
Cosmos caudatus Kunth	Asteraceae	Leaves	IZD = 11.7 ± 0.5 mm (240 µg/disc)	[59]
Cymbopogon citratus (DC.) Stapf	Poaceae	Stem	IZD = 18.0 ± 1.4 mm (240 µg/disc)	[59]
Derris trifoliata Lour.	Leguminosae	Stem	IZD = 47.0 ± 1.7 mm (240 µg/disc); MIC50 = 2 mg/mL MIC90 = 4 mg/L	[59]
			IZD = 38.0 ± 1.0 mm (240 µg/disc)	[59]
Desmos cochinchinensis Lour.	Annonaceae	Leaves	IZD = 30.0 ± 2.1 mm (240 µg/disc)	[59]
Desmostachya bipinnata (L.) Stapf.	Gramineae	Whole plant	MIC = 5 mg/mL	[84]
Eucalyptus camaldulensis Dehnh	Myrtaceae	Stem bark	MIC = 25–100 µg/mL	[76]
		Leaves	MIC = 50 µg/mL	[76]
Eucalyptus torelliana F. Muell.	Myrtaceae	Leaves	MIC = 25–400 µg/mL	[76]
		Stem bark	MIC = 50–100 µg/mL	[76]
Ficus deltoidea Jack	Moraceae	Leaves	IZD = 10.0 ± 0.6 mm (240 µg/disc)	[59]
Heterotheca inuloides Cass.	Compositae	Leaves	IZD = 11.2 ± 1.2 mm (240 µg/disc)	[59]
		Stem	IZD = 9.6 ± 0.6 mm (240 µg/disc)	[59]
Hypericum perforatum L.	Hypericaceae	Aerial parts	MIC = 7.8–31.2 µg/mL	[54]
Jatropha podagrica Hook.	Euphorbiaceae	Leaves	IZD = 10.0 ± 0.5 mm (240 µg/disc)	[59]
		Root	IZD = 42.0 ± 0.5 mm (240 µg/disc)	[59]
Kaempferia galanga L.	Zingiberaceae	Leaves	IZD = 66.0 ± 0.1 mm (240 µg/disc)	[59]
		Tuber	IZD = 18.3 ± 1.0 mm (240 µg/disc)	[59]
Alpinia galanga (L.) Willd. (cited as Languas galanga)	Zingiberaceae	Tuber	IZD = 24.2 ± 1.6 mm (240 µg/disc)	[59]
Limnocharis flava (L.) Buchenau	Alismataceae	Leaves	IZD = 14.0 ± 0.6 mm (240 µg/disc)	[59]
Melastoma malabathricum L. (blue variety)	Melastomataceae	Leaves	IZD = 22.2 ± 1.3 mm (240 µg/disc)	[59]
		Stem	IZD = 7.2 ± 0.4 mm (240 µg/disc)	[59]
Mimosa pudica L.	Leguminosae	Whole plant	IZD = 8.8 ± 1.6 mm (240 µg/disc)	[59]
Mitrasacme indica Wight (cited as Mitrasacme alsinoides)	Loganiaceae	Leaves	IZD = 9.5 ± 1.1 mm (240 µg/disc)	[59]
Momordica charantia L.	Cucurbitaceae	Fruits	MIC = 31.2–125 µg/mL	[54]
Neptunia oleracea Lour.	Leguminosae	Leaves	IZD = 10.7 ± 2.0 mm (240 µg/disc)	[59]
Orthosiphon aristatus (Blume) Miq. (cited as Orthosiphon stamineus)	Lamiaceae	Leaves	IZD = 18.3 ± 2.2 mm (240 µg/disc)	[59]
		Stem	IZD = 11.3 ± 1.0 mm (240 µg/disc)	[59]
Paeonia × suffruticosa Andrews	Paeoniaceae	Root Cortex	IZD = 23.9–26.7 mm (1–10 mg/disc)	[82]
Parkia speciosa Hassk.	Leguminosae	Seed	IZD = 26.0 ± 0.6 mm (240 µg/disc)	[59]
Phaeomeria imperialis (Roscoe) Lindl.	Zingiberaceae	Flowers	IZD = 14.0 ± 0.6 mm (240 µg/disc)	[59]
Phyllanthus niruri L.	Phyllanthaceae	Whole plant	IZD = 9.8 ± 0.8 mm (240 µg/disc)	[59]
Piper betle L.	Piperaceae	Leaves	IZD = 25.8 ± 0.8 mm (240 µg/disc)	[59]
Pluchea indica (L.) Less.	Compositae	Leaves	IZD = 11.0 ± 0.6 mm (240 µg/disc)	[59]
Persicaria minor (Huds.) Opiz (cited as Polygonum minus)	Polygonaceae	Leaves	IZD = 12.3 ± 0.8 mm (240 µg/disc)	[59]
Psidium guajava L.	Myrtaceae	Leaves	IZD = 10.0 ± 0.6 mm (240 µg/disc)	[59]
Sambucus ebulus	Adoxaceae	Aerial parts	MIC = 31.2 µg/mL	[54]
Sesbania grandiflora (L.) Pers.	Leguminosae	Leaves	IZD = 8.8 ± 1.1 mm (240 µg/disc)	[59]
Solanum torvum Sw.	Solanaceae	Seed	IZD = 8.7 ± 0.0 mm (240 µg/disc)	[59]
Tinospora sinensis (Lour.) Merr. (cited as Tinospora cordifolia)	Menispermaceae	Stem	IZD = 19.2 ± 5 mm (240 µg/disc)	[59]
Zingiber officinale Roscoe	Zingiberaceae	Rhizome	IZD = 41.5 ± 7.0 mm (240 µg/disc)	[59]

MIC, minimal inhibitory concentration; MIC₅₀ and MIC₉₀, minimal inhibitory concentration required to inhibit 50% and 90% of cells growth, respectively; IZD, inhibition zone diameter.

Table 7. Plant petroleum ether extracts with anti-H. pylori activity.

Species	Family	Parts	Anti-H. pylori Potency	Ref.
Calotropis gigantea (L.) W.T. Aiton	Apocynaceae	Leaves	IZD = 13.2 ± 0.8 mm (240 µg/disc)	[59]
Centella asiatica (L.) Urb.	Apiaceae	Whole plant	IZD = 8.5 ± 0.6 mm (240 µg/disc)	[59]
Chromolaena odorata (L.) R.M. King and H. Rob.	Asteraceae	Leaves	IZD = 20.3 ± 1.4 mm (240 µg/disc)	[59]
Colubrina asiatica (L.) Brongn.	Rhamnaceae	Leaves	IZD = 11.0 ± 0.9 mm (240 µg/disc)	[59]
Cosmos caudatus Kunth	Asteraceae	Leaves	IZD = 16.0 ± 0.6 mm (240 µg/disc)	[59]
Cymbopogon citratus (DC.) Stapf	Poaceae	Stem	IZD = 29.5 ± 1.5 mm (240 µg/disc)	[59]
Derris trifoliata Lour.	Leguminosae	Stem	IZD = 42.0 ± 0.9 mm (240 µg/disc); MIC50 = 1 mg/mL; MIC90 = 2 mg/L	[59]
			IZD = 42.0 ± 1.0 mm (240 µg/disc)	[59]
Desmostachya bipinnata (L.) Stapf.	Gramineae	Whole plant	MIC = 1.5 mg/mL	[84]
Ficus deltoidea Jack	Moraceae	Leaves	IZD = 8.0 ± 0.1 mm (240 µg/disc)	[59]
Heterotheca inuloides Cass.	Compositae	Leaves	IZD = 11.5 ± 1.1 mm (240 µg/disc)	[59]
		Stem	IZD = 13.2 ± 0.1 mm (240 µg/disc)	[59]
Jatropha podagrica Hook.	Euphorbiaceae	Leaves	IZD = 13.0 ± 1.1 mm (240 µg/disc)	[59]
		Stem	IZD = 15.5 ± 1.4 mm (240 µg/disc)	[59]
		Root	IZD = 47.3 ± 3.1 mm (240 µg/disc)	[59]
Kaempferia galanga L.	Zingiberaceae	Leaves	IZD = 62.0 ± 0.1 mm (240 µg/disc)	[59]
		Tuber	IZD = 18.3 ± 1.0 mm (240 µg/disc)	[59]
Alpinia galanga (L.) Willd. (cited as Languas galanga)	Zingiberaceae	Tuber	IZD = 39.3 ± 2.1 mm (240 µg/disc)	[59]
Limnocharis flava (L.) Buchenau	Alismataceae	Leaves	IZD = 24.0 ± 0.6 mm (240 µg/disc)	[59]
Melastoma malabathricum L. (blue variety)	Melastomataceae	Leaves	IZD = 14.0 ± 2.3 mm (240 µg/disc)	[59]
		Stem	IZD = 10.5 ± 0.8 mm (240 µg/disc)	[59]
Mimosa pudica L.	Leguminosae	Whole plant	IZD = 8.5 ± 0.6 mm (240 µg/disc)	[59]
Mitrasacme indica Wight (cited as Mitrasacme alsinoides R. Br.)	Loganiaceae	Leaves	IZD = 11.0 ± 0.6 mm (240 µg/disc)	[59]
Neptunia oleracea Lour.	Leguminosae	Leaves	IZD = 10.5 ± 0.8 mm (240 µg/disc)	[59]
Orthosiphon aristatus (Blume) Miq. (cited as Orthosiphon stamineus)	Lamiaceae	Leaves	IZD = 17.7 ± 2.8 mm (240 µg/disc)	[59]
		Stems	IZD = 12.7 ± 0.5 mm (240 µg/disc)	[59]
Parkia speciosa Hassk.	Leguminosae	Seeds	IZD = 10.5 ± 0.8 mm (240 µg/disc)	[59]
Pereskia sacharosa Griseb.	Cactaceae	Leaves	IZD = 13.3 ± 0.5 mm (240 µg/disc)	[59]
Etlingera elatior (Jack) R.M.Sm. (cited as Phaeomeria imperialis)	Zingiberaceae	Flowers	IZD = 18.0 ± 1.1 mm (240 µg/disc)	[59]
Phyllanthus niruri L.	Phyllanthaceae	Whole plant	IZD = 14.0 ± 1.6 mm (240 µg/disc)	[59]
Piper betle L.	Piperaceae	Leaves	IZD = 54.2 ± 0.8 mm (240 µg/disc)	[59]
Pluchea indica (L.) Less.	Compositae	Leaves	IZD = 13.7 ± 1.9 mm (240 µg/disc)	[59]
Persicaria minor (Huds.) Opiz (cited as Polygonum minus)	Polygonaceae	Leaves	IZD = 15.5 ± 0.6 mm (240 µg/disc)	[59]
Psidium guajava L.	Myrtaceae	Leaves	IZD = 8.5 ± 0.8 mm (240 µg/disc)	[59]
Sesbania grandiflora (L.) Pers.	Leguminosae	Leaves	IZD = 10.8 ± 1.0 mm (240 µg/disc)	[59]
Solanum torvum Sw.	Solanaceae	Seeds	IZD = 11.0 ± 0.9 mm (240 µg/disc)	[59]
Tinospora sinensis (Lour.) Merr. (cited as Tinospora cordifolia)	Menispermaceae	Stems	IZD = 10.7 ± 0.8 mm (240 µg/disc)	[59]
Zingiber officinale Roscoe	Zingiberaceae	Rhizome	IZD = 33.3 ± 1.6 mm (240 µg/disc)	[59]

MIC, minimal inhibitory concentration; MIC₅₀, minimal inhibitory concentration required to inhibit 50% of cells growth; IZD, inhibition zone diameter.

Table 8. Plant methanol/water, ethanol/water, methanol/petroleum, and methanol/dichloromethane extracts with anti-H. pylori activity.

Species	Family	Parts	Anti-H. pylori Potency	Ref.
Methanol/Water (70:30, v/v)
Acacia seyal Delile	Leguminoseae	Stem	MIC = 20 mg/mL	[84]
		Leaves	MIC = 20 mg/mL	[84]
Alhagi maurorum Medik.	Leguminoseae	Whole plant	MIC = 0.79 mg/mL	[84]
Bidens bipinnata L.	Compositae	Whole plant	MIC = 25 mg/mL	[84]
Capparis spinose L.	Capparaceae	Aerial parts	MIC = 10 mg/mL	[84]
Casimiroa edulis Llave and Lex	Rutaceae	Unripe fruit	MIC = 20 mg/mL	[84]
Centaurea alexandrina Delile	Compositae	Whole plant	MIC = 80 mg/mL	[84]
Centaurea pelia DC.	Compositae	ND	MIC = 0.625–5 mg/mL	[85]
Centaurea thessala Hausskn. ssp. drakiensis (Freyn and Sint.) Georg	Compositae	ND	MIC = 0.625–5 mg/mL	[85]
Cerastium candidisimum L.	Caryophyllaceae	ND	MIC = 0.625–2.5 mg/mL	[85]
Chamomilla recutita (L.) Rauschert	Compositae	ND	MIC = 0.625–2.5 mg/mL	[85]
Cleome africana Botsch.	Cleomaceae	Whole plant	MIC = 0.158 mg/mL	[84]
Conyza albida Willd. ex Spreng.	Asteraceae	ND	MIC = 0.625–2.5 mg/mL	[85]
Conyza bonariensis (L.) Cronquist.	Asteraceae	ND	MIC = 0.625–2.5 mg/mL	[85]
Cota palaestina Reut. ex Unger and Kotschy (cited as Anthemis melanolepis)	Compositae	ND	MIC = 0.625–2.5 mg/mL	[85]
Desmostachya bipinnata (L.) Stapf.	Gramineae	Whole plant	MIC = 0.040 mg/mL	[84]
Diplotaxis acris (Forssk.) Boiss.	Cruciferae	Whole plant	MIC = 10 mg/mL	[84]
Dittrichia viscosa (L.) Greuter subsp. revoluta	Asteraceae	ND	MIC = 0.625–2.5 mg/mL	[85]
Euphorbia retusa Forssk.	Euphorbiaceae		MIC = 2.5 mg/mL	[84]
Glossostemon brugueiri Desf.	Sterculiaceae	Root	MIC = 10 mg/mL	[84]
		Leaves	MIC = 25 mg/mL	[84]
Hamada elegans (Bunge) Botsch.	Chenopodiaceae	Whole plant	MIC = 10 mg/mL	[84]
Haplophyllum tuberculatum (Forssk.) A. Juss.	Rutaceae	Whole plant	MIC = 1.58 mg/mL	[84]
Lythrum salicaria L.*	Lythraceae	Aerial parts	IZD = 17 ± 0.08 mm (500 mg/mL)	[86]
Marrubium vulgare L.	Lamiaceae	Whole plant	MIC = 0.251 mg/mL	[84]
Ocimum basilicum L.	Lamiaceae	Aerial parts	MIC = 0.625–5 mg/mL	[85]
Origanum dictamnus L.	Lamiaceae	Aerial parts	MIC = 0.625–5 mg/mL	[85]
Origanum majorana L.	Lamiaceae	Aerial parts	MIC = 0.625–5 mg/mL	[85]
Origanum vulgare L.	Lamiaceae	Leaves	MIC = 0.625–2.5 mg/mL	[85]
Schouwia thebaica Webb.	Brassicaceae	Whole plant	MIC = 25 mg/mL	[84]
Sisymbrium irio L.	Brassicaceae	Whole plant	MIC = 0.074 mg/mL	[84]
Stachys alopecuros (L.) Benth.	Lamiaceae	Aerial parts	MIC = 0.625–2.5 mg/mL	[85]
Thymbra capitata (L.) Cav. (cited as Thymus capitatus)	Lamiaceae	Whole plant	MIC = 12.5 mg/mL	[84]
Trifolium alexandrinum L.	Leguminosae	Whole plant	MIC = 25 mg/mL	[84]
Ethanol/Water (70:30, v/v)
Calophyllum brasiliense Cambess.	Clusiaceae	Bark	MIC = 31 µg/mL; IZD = 8–14 mm (62.5–1000 µg/disc)	[75]
Cocculus hirsutus (L.) Diels.	Menispermaceae	Leaves	IZD = 26 mm (200–1000 μg/mL)	[56]
Fridericia chica (Bonpl.) L. G. Lohmann (cited as Arrabidaea chica)	Bignoniaceae	Fresh leaves	12.5	[87]
Hancornia speciosa Gomez	Apocynaceae	Bark	MIC = 125 µg/mL	[88]
Methanol/Petroleum (1:1)
Carum bulbocastanum (L.) Koch.	Apiaceae	Fruit	MIC = 31.25–250 µg/mL	[46]
Carum carvi L.	Apiaceae	Fruit	MIC = 31.25–125 µg/mL	[46]
Glycyrrhiza glabra Linn	Leguminosae	Root	MIC = 15.6–250 µg/mL	[46]
Mentha longifolia (L). Huds.	Lamiaceae	Aerial parts	MIC = 31.25–125 µg/mL	[46]
Salvia limbata C. A. Mey.	Lamiaceae	Aerial parts	MIC = 125–250 µg/mL	[46]
Salvia sclarea L.	Lamiaceae	Aerial parts	MIC = 125–500 µg/mL	[46]
Trachyspermum ammi (L.) Sprague (cited as Trachyspermum copticum)	Apiaceae	Aerial parts	MIC = 31.25–250 µg/mL	[46,89]
Xanthium strumarium subsp. brasilicum (Vell.) O. Bolòs and Vigo (cited as Xanthium brasilicum)	Compositae	Aerial parts	MIC = 31.25–250 µg/mL	[46,89]
Ziziphora clinopodioides Lam.	Lamiaceae	Aerial parts	MIC = 31.25–125 µg/mL	[46]
Methanol/Dichloromethan
Cyrtocarpa procera Kunth	Anacardiaceae	Bark	MIC = 62.5 µg/mL	[58]

* Methanol/water (80:20, v/v); ND, not defined; MIC, minimal inhibitory concentration; IZD, inhibition zone diameter.

Table 9. Plant cyclohexane, dichloromethane, ethyl acetate, n-Butanol, n-Hexane, and other extracts with anti-H. pylori activity.

Species	Family	Parts	Anti-H. pylori Potency	Ref.
Cyclohexane
Alchemilla fissa Günther and Schummel	Rosaceae	Aerial parts	MIC = 64–256 μg/mL	[71]
Alchemilla glabra Neygenf.	Rosaceae	Aerial parts	MIC = 64–256 μg/mL	[71]
Alchemilla monticola Opiz	Rosaceae	Aerial parts	MIC = 8–64 μg/mL	[71]
Alchemilla viridiflora Rothm.	Rosaceae	Aerial parts	MIC = 64–256 μg/mL	[71]
Dichloromethane
Alchemilla fissa Günther and Schummel	Rosaceae	Aerial parts	MIC = 64–256 μg/mL	[71]
Alchemilla glabra Neygenf.	Rosaceae	Aerial parts	MIC = 64–256 μg/mL	[71]
Alchemilla monticola Opiz	Rosaceae	Aerial parts	MIC = 16–64 μg/mL	[71]
Alchemilla viridiflora Rothm.	Rosaceae	Aerial parts	MIC = 16–128 μg/mL	[71]
Calophyllum brasiliense Cambess.	Clusiaceae	Bark	MIC = 125 µg/mL; IZD = 7–10 mm (62.5–1000 µg/disc)	[75]
Cyrtocarpa procera Kunth	Anacardiaceae	Bark	MIC = 15.6 µg/mL	[58]
Ethyl acetate
Alepidea Amatymbica Eckl. and Zeyh	Apiaceae	Roots/rhizomes	IZD = 8.5 ± 4.8 mm	[50,51]
Bidens pilosa L.	Compositae	Leaves	MIC = 128–512 μg/mL	[73]
Bridelia micrantha (Hochst.) Baill.	Phyllanthaceae	Bark	IZD = 12–20 mm; MIC50 = 4.8–156 µg/mL; MIC90 = 4.8–2500 µg/mL	[53]
Calophyllum brasiliense Cambess.	Clusiaceae	Bark	MIC = 125 µg/mL; IZD = 7–8 mm (62.5–1000 µg/disc)	[75]
Combretum molle R. Br. Ex G. Don	Combretaceae	Bark	IZD =10.7 ± 4.7 mm	[50,51]
Desmostachya bipinnata (L.) Stapf.	Gramineae	Whole plant	MIC = 0.79 mg/mL	[84]
Eryngium foetidium (Linn)	Apiaceae	Leaves	MIC = 128–512 μg/mL	[73]
Garcinia kola Heckel	Guttiferae	Seeds	IZD = 5.1 ± 4.6 mm	[50,51]
Galinsoga ciliata (Raf.) S. F. Blake	Compositae	Leaves	MIC = 128–512 μg/mL	[73]
Geranium wilfordii Maxim	Geraniaceae	Aerial parts	MIC = 30 µg/mL	[90]
Paeonia × suffruticosa Andrews	Paeoniaceae	Root Cortex	IZD = 14.1–19.9 mm (1–10 mg/disc)	[82]
Physalis alkekengi L. var. franchetii (Mast.) Makino	Solanaceae	Aerial parts	MIC = 500 μg/mL	[91]
Sclerocarya birrea A. Rich Hochst	Anacardiaceae	Stem bark	IZD = 13.2 ± 2.8 mm	[50,51]
n-Butanol
Centaurea solstitialis L. subsp. solstitialis	Asteraceae	Aerial parts	MIC = 31.2 µg/mL	[54]
Cistus laurifolius L.	Cistaceae	Flowers	MIC = 62.5–125 µg/mL	[54]
Hypericum perforatum L.	Hypericaceae	Aerial parts	MIC = 15.6–31.2 µg/mL	[54]
Momordica charantia L.	Cucurbitaceae	Fruits	MIC = 62.5 µg/mL	[54]
n-Hexane
Calophylum brasiliense Cambess.	Clusiaceae	Bark	IZD = 7–14 mm (100–400 μg/disc)	[92]
			IZD =7–8 mm (62.5–1000 µg/disc)	[75]
			IZD = 14 mm (400 mg/mL) MIC = 31 µg/mL	[75]
Cyrtocarpa procera Kunth	Anacardiaceae	Bark	MIC = 7.81 µg/mL	[58]
Eucalyptus camaldulensis Dehnh	Myrtaceae	Stem bark	MIC = 25–200 µg/mL	[76]
		Leaves	MIC = 50 µg/mL	[76]
Eucalyptus torelliana F. Muell.	Myrtaceae	Leaves	MIC = 25–50 µg/mL	[76]
		Stem bark	MIC = 25–200 µg/mL	[76]
Mitrella kentii (Bl.) Miq	Annonaceae	Bark	MIC = 125 μg/mL	[93]
Paeonia × suffruticosa Andrews	Paeoniaceae	Root Cortex	IZD = 29.9–31.3 mm (1–10 mg/disc)	[82]
Others
Camellia sinensis (L.) Kuntze	Theaceae	Young shoots	IZD = 22.5 mm (20–60 μg/disc) MBC = 4 mg/mL	[94]
			IZD = 18 mm (20–60 μg/disc) MBC = 5.5 mg/mL	[94]
Chenopodium ambrosioides L.	Amaranthaceae	Aerial parts	MIC = 16 mg/L *	[95]

* 1 and 2 × MIC completely inhibited H. pylori growth at 24 h; MIC, minimal inhibitory concentration; MIC₅₀, minimal inhibitory concentration required to inhibit 50% of cells growth; MBC, minimal bactericidal concentration; IZD, inhibition zone diameter.

The susceptibility of H. pylori isolates and strains to 543 extracts from 246 plant species was tested by disc diffusion, agar diffusion, agar dilution, and broth microdilution assays. Activity ranged from 1.56–100,000 µg/mL for minimal inhibitory concentration (MIC) and 7–42 mm for inhibition zone diameters (IZDs). However, disparities were observed among the methods used and the tested concentrations: some extracts were tested at very high concentrations (100,000 µg/mL) that might have resulted in biased conclusions. Though many plants (246 species) showed anti-H. pylori activity in vitro, very few have been screened for activity in animal models.

Organic extracts of Carum carvi, Xanthium brasilicum, and Trachyspermum copticum have demonstrated antibacterial activity against 10 clinical isolates of H. pylori [46]. In addition, ethanolic extracts of Cuminum cyminum and propolis exhibited significant in vitro inhibitory effect against H. pylori and, therefore, could be considered a valuable support in the treatment of infection, even contributing to the development of new and safer agents for inclusion in anti-H. pylori therapy regimens [47]. Some popular plant species used in Brazilian cuisine and folk medicine in the treatment of gastrointestinal disorders were also investigated for their antibacterial effects, among which Bixa orellana, Chamomilla recutita, Ilex paraguariensis, and Malva sylvestris were the most effective against H. pylori [48].

Bioactive plant compounds were also tested for their anti-H. pylori potency (Table 10), namely those isolated from the Allium sativum (cloves), Convolvulus austro-aegyptiacu (aerial parts), Glycyrrhiza glabra (roots), Hydrastis canadensis (rhizomes), Sanguinaria canadensis (rhizomes), and Tinospora sagittata (aerial parts) species. Berberine, a benzylisoquinoline alkaloid, isolated from Hydrastis canadensis, revealed the lowest MIC value (0.78 μg/mL), being therefore considered the most effective bioactive compound, followed by diallyl tetrasulfide (3–6 μg/mL), allicin (4 μg/mL), and palmatine (3.12–6.25 μg/mL) isolated from Allium sativum and Tinospora sagittate, respectively.

Table 10. Bioactive compounds with anti-H. pylori activity.

Plant Species	Bioactive Compounds	Anti-H. pylori Potency (MIC)	Ref.
Allium sativum L. (cloves)	Allicin (garlic poder)	4 μg/mL	[96]
	Allicin	6 μg/mL	[96]
	Diallyl disulfide	100–200 μg/mL	[96]
	Diallyl tetrasulfide	3–6 μg/mL	[96]
Convolvulus austro-aegyptiacu Abdallah and Saad (aerial parts)	Scopoletin	50–200 µg/mL	[67]
	Scopolin	50–100 µg/mL	[67]
Glycyrrhiza glabra L. (roots)	Licoricidin	6.25–12.5 µg/mL	[78]
	Licoisoflavone	6.25 µg/mL	[78]
	Fuscaxanthone I	15.2–122.0 μM	[97]
	Beta-Mangostin	18.3–147.3 μM	[97]
	Fuscaxanthone A	16.3–131.2 μM	[97]
	Cowanin	16.3–130.6 μM	[97]
	Cowaxanthone	4.6–152.3 μg/mL	[97]
	Alpha-Mangostin	19.0–76.1 μM	[97]
	Cowanol	15.7–126.4 μM	[97]
	Isojacareubin	23.9 μM	[97]
	Fuscaxanthone G	16.3–130.6 μM	[97]
	Nigrolineabiphenyl B	56.5–226.3 μM	[97]
	1,3,5,6-Tetrahydroxyxanthone	29.9–240.3 μM	[97]
	Vokensiflavone	14.4–115.7 μM	[97]
	Morelloflavone	14.0–112.3 μM	[97]
Hydrastis canadensis L. (rhizomes)	Berberine	0.78–25 µg/mL	[80]
	β-Hydrastine	25–100 µg/mL	[80]
Sanguinaria canadensis L. (rhizomes)	Sanguinarine	6.25–50 µg/mL	[80]
	Chelerythrine	25–100 µg/mL	[80]
	Protopine	25 ≥ 100 µg/mL	[80]
Tinospora sagittata Gagnep. (aerial parts)	Palmatine	3.12–6.25 μg/mL	[42]

MIC, minimal inhibitory concentration.

5. In Vivo Findings

H. pylori colonization is increasingly being associated with a heightened risk of developing upper gastrointestinal tract diseases. Despite many plant extracts having demonstrated a prominent H. pylori inhibition capacity in culture, it is of crucial importance to assess their in vivo efficacy, because it is pivotal to ascertain their effective antibacterial potency. However, a relatively low number of medicinal plants have been investigated to date for in vivo activity, as discussed below.

Paeonia lactiflora root extract (100 µg/mL) showed a complete inhibition of H. pylori colonization (4–5 × 10⁵ colony forming unit (CFU)), being the antibacterial potential equivalent to of ampicillin used as positive control (10 µg/mL) (2–4 × 10⁵ CFU) [98]. Time course viability experiments were also performed in simulated gastric environments to assess the anti-H. pylori activity of garlic (Allium sativum) oil (16 and 32 µg/mL). A rapid anti-H. pylori action in artificial gastric juice was found. Nevertheless, the anti-H. pylori activity displayed by garlic oil was noticeably affected by food materials and mucin, despite the fact that a substantial activity remained under simulated gastric conditions [65]. Also, H. pylori-inoculated Swiss mice receiving 125, 250, or 500 mg/kg of Bryophyllum pinnutum or ciprofloxacin (500 mg/kg) for 7 days, showed a significant reduction of H. pylori colonization on gastric tissue from 100% to 17%. In addition, the highest B. pinnatum extract tested (85.91 ± 52.91 CFU) and standard drug ciprofloxacin (25.74 ± 16.15 CFU) also reduced significantly (p < 0.05) the bacterial load of gastric mucosa as compared with untreated infected mice (11883 ± 1831 CFU) [74]. On the other hand, Eryngium foetidum methanol extract (381.9 ± 239.5 CFU) and positive control ciprofloxacin (248 ± 153.2 CFU) significantly reduced the bacterial load in gastric mucosa at the same dose (500 mg/kg) compared with untreated and inoculated mice (14350 ± 690 CFU) [73].

Hippocratea celastroides hydroethanolic root-bark extract, a widely used plant against gastric and intestinal infections, also showed anti-H. pylori efficacy in naturally infected dogs. In a study of 18 experimental dogs treated with a dose of 93.5–500 mg/kg of H. celastroides extract in weight and 19 infected dogs receiving amoxicillin–clarithromycin–omeprazole (control treatment), the results showed effectiveness of 33.3 and 55% in the experimental and control groups, respectively [99].

On the other hand, Ye et al. [95], aiming to investigate the in vivo bactericidal effects of Chenopodium ambrosioides L. against H. pylori, randomly assigned H. pylori-infected mice into plant extract group, triple therapy control (lansoprazole, metronidazole, and clarithromycin), blank control, and H. pylori control groups. The obtained eradication ratios, determined by rapid urease tests (RUTs) and histopathology, were, respectively, 60% (6/10) using RUT and 50% (5/10) using histopathology for the test group and both 70% (7/10) for the control group. In addition, the histopathologic evaluation revealed a massive bacterial colonization on the gastric mucosa surface and slight mononuclear cells infiltration after H. pylori inoculation, but no obvious inflammation or other pathologic changes in gastric mucosa were stated between the C. ambrosioides-treated mice and the standard therapy.

Tinospora sagittata and its main component, palmatine, showed in vitro bactericidal effects on H pylori strains, with both MIC and minimal bactericidal concentration (MBC) values of 6250 μg/mL, whereas palmatine’s MIC value against H. pylori SCYA201401 was 6.25 μg/mL and against H. pylori SS1 was 3.12 μg/mL. The time-kill kinetic study evidenced a dose-dependent and progressive decline in the numbers of viable bacteria up to 40 h. H. pylori-infected mice treated with extract, palmatine, or control therapy (omeprazole, clarithromycin, and amoxicillin), presented eradication ratios of, respectively, 80%, 50%, and 70%. The anti-H. pylori activity found in T. sagittata extracts and its major constituent, palmatine, both in culture and animal models, clearly highlights the antibacterial potential of this plant in the treatment of both infected humans and animals [42].

Total alkaloids fraction activity (TASA) of Sophora alopecuroides L., widely used in herbal remedies against stomach-associated diseases, were also investigated on 120 H. pylori-infected BALB/c mice mouse gastritis. A total of 100 infected mice were randomly assigned into 10 treatment groups: group I (normal saline); group II (bismuth pectin); group III (omeprazole); group IV (TASA 2 mg/day); group V (TASA 4 mg/day); group VI (TASA 5 mg/day); group VII (TASA + bismuth pectin); group VIII (TASA + omeprazole); group IX (bismuth pectin + clarithromycin + metronidazole); and group X (omeprazole + clarithromycin + metronidazole). The mice were sacrificed 4 weeks after treatment. Real-time PCR was used to detect 16sDNA of H. pylori to test both the colonization and mice clearance of bacteria of each treatment. Hematoxylin and eosin staining and immunostaining of mice gastric mucosa were also used to observe the general inflammation and related factors: IL-8, COX2, and nuclear factor-kappa B (NF-κB) expression changed after treatments. TASA combined with omeprazole or bismuth pectin showed promising antimicrobial activity against H. pylori, as well as conventional triple therapy. Indeed, hematoxylin and eosin staining and immune-staining of mice gastric mucosa evidenced that the inflammation on mice gastric mucosal membrane were also clearly relieved in TASA combined treatments and conventional triple therapy compared with normal saline-treated mice. Accordingly, from immunohistochemistry results, H. pylori-induced IL-8, COX2, and NF-κB were consistently suppressed in the seventh, eighth, ninth, and tenth groups to a certain extent [100].

Pastene et al. [101] investigated the inhibitory effects of a standardized apple peel polyphenol-rich extract (Malus pumila Mill., cited as Malus domestica) against H. pylori infection and vacuolating bacterial toxin (VacA)-induced vacuolation and found that the preparation significantly prevented vacuolation in HeLa cells with an IC₅₀ value of 390 μg gallic acid equivalents (GAE)/mL and an in vitro anti-adhesive effect against H. pylori. A significant inhibition was also stated with 20–60% reduction of H. pylori attachment at concentrations between 0.250 and 5 mg GAE/mL. In a short-term infection model (C57BL6/J mice), doses of 150 and 300 mg/kg/day showed an inhibitory effect on H. pylori attachment. Orally administered apple peel polyphenols also showed an anti-inflammatory effect on H. pylori-associated gastritis, lowering malondialdehyde levels and gastritis scores.

Kim et al. [102] investigated the GutGard™ ability (a flavonoid rich, Glycyrrhiza glabra root extract) to inhibit H. pylori growth both in Mongolian gerbils and C57BL/6 mouse models. Infected male Mongolian gerbils were orally treated once daily 6 times/week for 8 weeks with 15, 30, and 60 mg/kg GutGard™. Bacterial identification in the biopsy samples of gastric mucosa, via urease, catalase, and ELISA, as well as immunohistochemistry revealed a dose-dependent inhibition of H. pylori colonization in gastric mucosa by GutGard™. As well, the administration of 25 mg/kg GutGard™ in H. pylori-infected C57BL/6 mice significantly reduced H. pylori colonization in gastric mucosa, suggesting its usefulness in H. pylori infection prevention.

Calophyllum brasiliense stem bark preparations are popular remedies for the treatment of chronic ulcers. A current report evidenced gastroprotective, gastric acid inhibitory properties and anti-H. pylori activity in culture (MIC = 31 µg/mL) [75]. Hydroethanolic (50, 100, and 200 mg/kg) and dichloromethane (100 and 200 mg/kg) fractions-treated Wistar rats ulcerated by acetic acid and inoculated with H. pylori, showed a marked delay in ulcer healing and reduced the ulcerated area in a dose-dependent manner [75]. While the dichloromethane fraction, at 200 mg/kg, increased PGE2 levels, both the hydroethanolic and dichloromethane fractions decreased the number of urease-positive animals, as confirmed by the reduction of the H. pylori presence in histopathological analysis. This aspect suggests that the antiulcer activity of C. brasiliense is partly linked with its anti-H. pylori efficacy [75]. Also, phenolic-rich oregano (Origanum vulgare) and cranberry (Vaccinium macrocarpon) extracts showed a prominent ability to inhibit H. pylori through urease inhibition and disruption of energy production by inhibition of proline dehydrogenase at the plasma membrane [103].

6. Urease Inhibition

The current therapies are challenged by the considerable number of emerging H. pylori-resistant strains. This fact has driven the need for alternative anti-H. pylori therapies that ideally should have good stability and low toxicity and to be able to inhibit urease activity [62]. It has been shown that H. pylori urease activity is crucial in bacterial survival and pathogenesis [104].

The inhibitory potency of some anti-H. pylori medicinal plants has been reported [62] and even investigated by some authors in the involved mechanisms of antibacterial action of those plant products [63].

Table 11 briefly shows the studied plant extracts with prominent anti-urease activity. Amin et al. [49] demonstrated that the methanolic and acetone extracts of some medicinal plants were able to inhibit urease activity. In fact, Acacia nilotica flower methanol and acetone extracts evidenced anti-H. pylori activity, being MIC values of 8–64 μg/mL and 4–64 μg/mL, respectively. Both extracts inhibited urease activity at 8.2–88.2% and 9.2–86.6%. Calotropis procera leaf and flower methanol and acetone extracts, with MIC values of 16–256 μg/mL, 32–256 μg/mL, and 8–128 μg/mL also displayed urease inhibitory effects, being, respectively, 12.2–48.2% and 7.2–58.2% for leaf and 9.3–68.2% for flower acetone extracts [49]. While A. nilotica extract exerted a competitive inhibition, that of C. procera extract displayed a mixed type of inhibition [49]. In addition, Casuarina equisetifolia fruit methanol extract, with MIC values varying from 128–512 μg/mL, also displayed 12.2–86.2% inhibition of urease activity [49].

Table 11. Urease inhibitory potential of plant extracts.

Plant Species	Parts	Extraction Solvent	Concentration Tested	Urease Inhibition	Ref.
Acacia nilotica (L.) Delile	Leaves	Methanol	8–128 μg/mL	8.21–88.21%	[49]
	Flowers	Acetone	8–128 μg/mL	9.20–86.56%	[49]
Calotropis procera (Aiton) W.T. Aiton	Leaves	Methanol	16–256 μg/mL	12.23–48.22%	[49]
	Leaves	Acetone	32–256 μg/mL	7.23–58.21%	[49]
	Flowers	Acetone	8–128 μg/mL	9.33–68.21%	[49]
Camellia sinensis (L.) Kuntze	Young shoots	Methanol: water (62.5:37.5 v/v) non-fermented extract	2.5 mg/mL	100% Ure A and B	[94]
		Methanol: water (62.5:37.5 v/v)) semifermented extract	3.5 mg/mL	100% Ure A and B	[94]
Casuarina equisetifolia L.	Fruit	Methanol	128–512 μg/mL	12.21–86.21%	[49]
Chamomilla recutita (L.) Rauschert	Flowers	Olive oil	31.25–250 mg/mL	Inhibited urease production	[105]
Euphorbia umbellata (Pax) Bruyns	Bark	Methanol	1024 μg/mL	78.6%	[77]
Peumus boldus Mol.	Leaves	Water		IC50 = 23.4 μg GAE/mL	[61]
Teminalia chebula Retz	Fruit	Water	1–2.5 mg/mL	Inhibited urease activity	[63]

IC50, 50% inhibitory concentration. GAE, gallic acid equivalents.

In another study, Camellia sinensis young non-fermented and semi-fermented shoot extracts, presented inhibition zone diameter (IZD) and MBC of, respectively, 22.5 mm at 20–60 μg/disk and 4 mg/mL, and 18 mm at 20–60 μg/disk and 5.5 mg/mL. They both inhibited Ure A and Ure B subunits production at 2.5 and 3.5 mg/mL [94]. Also, the Chamomilla recutita flower extract, which inhibited H. pylori growth at an MIC₉₀ value of 125 mg/mL and a MIC₅₀ value of 62.5 mg/mL, was able to inhibit the urease production [105]. In the same line, the methanol fraction of Euphorbia umbellata bark extract inhibited both H. pylori growth (44.6% inhibition) at 256 μg/mL and urease activity (78.6% inhibition) at 1024 μg/mL [77]. Moreover, the Peumus boldus flower aqueous extract showed anti-adherent activity against H. pylori and inhibited urease activity with an IC₅₀ value of 23.4 μg GAE/mL [61]. The aqueous extract of Teminalia chebula fruit showed activity with MIC and MBC values of 125 mg/mL and 150 mg/mL, respectively, and inhibited H. pylori urease activity at a concentration of 1–2.5 mg/mL [63].

7. Conclusions and Future Perspectives

Overall, the report suggests that the studied plant extracts possess anti-H. pylori activity, strengthening the claims made by traditional medicine practitioners about their putative anti-ulcerative properties. However, very few of them were investigated for efficacy in animal models or the ability to inhibit urease activity. Further studies are warranted for efficacy studies in animal models, elucidation of effective modes of action (including urease inhibition), and clinical trials in human being.