Overview of the phytomedicine approaches against Helicobacter pylori

Table 1 Examples of clinical trials using herbal medicines

Herb	Study design	Sample	Experimental intervention	Control	Outcome	Difference between experimental and control group		Ref.
Garlic oil	Blind non-randomized trial	20 dyspeptic patients	275 mg garlic oil 3 times a day for 14 d	Same plus 20 mg omeprazole	Negative for histology and urease test	No	Symptom score (8.7 ± 1.70 vs 8.5 ± 1.51) and H. pylori density (2.0 ± 0.82 vs 2.1 ± 0.74) did not significantly changed	[111]
Fresh garlic or jalapeno peppers	Open non-randomized trial	12 healthy patients with H. pylori	10 cloves fresh garlic or 6 jalapeno peppers with 3 meals per test day	Bismuth subsalicylate with 3 meals per test day or no intervention	Reduction in urea breath test counts		Garlic and jalapeno add no effect (P > 0.8), but significant reduction after bismuth (P < 0.001)	[112]
Cinnamon	Blinding placebo-controlled	23 patients undergoing gastroscopy	40 mg cinnamon extract twice a day for 4 wk	Placebo	Reduction in urea breath test counts	No	Mean urea breath test reading (23.9 vs 25.9) did not significantly changed	[109]
Lycopene	Quasi-control trial	54 patients with H. pylori	Metronidazole 500 mg/bd, amoxicillin 1g/bd, omeprazole 20 mg/bd, bismuth 240 mg/bd, and lycopene 30 mg/daily	Metronidazole 500 mg/bd, Amoxicillin 1 g/bd, Omeprazole 20 mg/bd, Bismuth 240 mg/bd	Slight increased eradication rate with lycopene (no statistical difference) evaluated by urease rapid test	No statistical difference		[113]
Nigella sativa (N. sativa)	Randomized trial	88 dyspeptic patients	Triple therapy (TT: clarithromycin 500 mg twice daily, amoxicillin 1g twice daily, omeprazole 40 mg once daily) and 1, 2 or 3 g N. sativa	Clarithromycin 500 mg twice daily, amoxicillin 1g twice daily, omeprazole 40 mg once daily	2 g/d and TT no statistical difference 1 g/d and 3 g/d significantly less effective than TT by stool antigen test	No	Eradication rates with 2 g N. sativa and TT with no statistical difference; eradication rate with 1g or 3 g N. sativa was significantly less than that with TT (P < 0.05)	[89]
Green propolis	Non-randomized clinical trial	18 patients infected with H. pylori	20 drops of alcoholic preparation of Brazilian green propolis 3 times a day for 7 d	No	One patient negative for H. pylori 40 d after treatment	Not applicable		[108]
Glycyrrhizaglabra	Randomized double blind placebo controlled trial	107 patients infected with H. pylori	55 patients - 150 mg of GutGard (root extract of G. glabra) once daily for 60 d	52 patients - placebo once daily for 60 d	56% of patients receiving GutGard eradicate H. pylori vs 4% on placebo	Yes	A significant interaction effect between group and time (P = 0.00)	[88]
Chinese patent medicine wenweishu /yangweishu	Randomized, controlled and multicenter trial	642 patients infected with H. pylori	PCM plus wenweishu group (n = 196); and PCM plus yangweishu group (n = 224)	PCM group (n = 222, pantoprazole 40 mg twice a day, clarithromycin 500 mg twice a day, metronidazole 400 mg twice a day, for 7 d)	Higher healing rate in PCM plus wenweishu; Higher rates of symptom relief in PCM plus wenweishu and PCM plus yangweishu; Eradication rate between PMC group and PMC plus wenweishu or PMC plus yangweishu group was not significantly different (P = 0.108, 0.532, respectively)	Yes	Healing rate in PCM plus wenweishu groups was significantly higher than the rate in PCM group (P = 0.004) Symptom relief rates in PCM plus wenweishu groups and PCM plus yangweishu were significantly higher than the rate in PCM group (both P < 0.01)	[110]

PCM: Pantoprazole, clarithromycin, metronidazole; H. pylori: Helicobacter pylori.

Table 2 Herbal medicines tested against Helicobacter pylori

Herb	Study type	Result	Observation	Active principle	Mechanism of action	Ref.
Garlic	In vivo clinical trial	No improved eradication (consult Table 1)	NA	NA	NA	[111,112]
Pelargonium sidoides roots (eps) 7630	In vitro using AGS cells and in situ using biopsies	Inhibit H. pylori growth and cell adhesion	South African herbal remedy	NA	Anti-adhesive activity	[114,115]
Cranberry juice	In vitro using immobilized human mucus and erythrocytes	Inhibit H. pylori cell adhesion	NA	NA	Anti-adhesive activity (sialic acid-specific adhesion)	[116,117]
Oregano and cranberry	In vitro agar difusion assay	Inhibition zones on agar plate	NA	Phenolic compounds	Urease inhibition; disruption of energy production inhibiting proline dehydrogenase at the plasma membrane	[93]
Magnolia officinalis Rehd. Et Wils. (Magnoliaceae) and Cassia obtusifolia L. (Leguminosae)	Compounds tested against Jack bean urease	Inhibit urease	Chinese medicinal herbs	Hydroxamic acids, phosphoramidates, urea derivatives, quinones, and heterocyclic compounds	Inhibit urease	[118]
Camellia sinensis	In vitro test against H. pylori, urease activity assay	Inhibit urease; reduction of H. pylori population	Tea leaves	Polyphenolic compounds and catechin contents (epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate)	Inhibit urease	[94]
Apple peel polyphenols	Compounds tested against Jack bean urease; in vitro test against H. pylori; in vitro test using hela cells; in vivo test using C57BL6/J mice	Inhibit urease; prevented vacuolation in hela cells; antiadhesive effect; anti-inflammatory effect	NA	Polyphenols	Inhibit urease; anti-adhesive activity	[78,95]
Calophyllum brasiliense Camb. (Clusiaceae)	In vitro disk diffusion; in vivo using Wistar rats infected with H. pylori	Dose-dependent reduction of ulcerated area; decreased number of urease-positive animals; partial anti-H. pylori inhibition	Large tree widely distributed in Latin America known in Brazil as "guanandi"	Mixture of chromanone acids	Inhibit urease; modulation of endogenous antioxidant systems	[86,87]
Mouriri elliptica Martius (Melastomataceae)	In vivo Swiss albino mice and male Wistar albino rats animal	Gastric protective action without antisecretory effect; anti-H. pylori action	Brazilian fruit-bearing plant of known as “coroa-de-frade”	Acid derivatives, acylglycoflavonoids and condensed tannins	Inhibit NO production by macrophages; stimulating proliferation factors (PCNA), COX-2	[119]
Hancornia speciosa Gomez (Mangaba)	In vivo Swiss albino mice and male Wistar albino rats animal	Antiulcer activity	Medium-sized tree (3–10 m) from central Brazil, known as “mangaba”, “mangabeira” or “mangava”	Polymeric proanthocyanidins	Increase pH and decrease acid output of gastric juice, stimulate mucus synthesis and produce antisecretory effect	[120]
Byrsonima fagifolia Nied. (Malpighiaceae)	In vivo Swiss albino mice and male Wistar albino rats animal In vitro disc diffusion technique	Gastric protective action; anti-inflammatory effect; anti-H. pylori action	Brazilian herb known as "murici" or "murici-do-mato"	Phenolic compounds, flavonoids, gallic acid derivatives	Antioxidant properties	[97]
Alchornea triplinervia	In vivo mouse model	Antisecretory property; anti-H. pylori effect; gastroprotective action	Medicinal plant from Brazil	Flavonoids	Antisecretory action, increase of gastric mucosa prostaglandin E(2) levels	[96]
Amphipterygium adstringens (Schltdl.) Standl. (Anacardiaceae)	In vitro killing assay	Exhibits potent dose-dependent anti-H. pylori activity	Mexican folk medicine	Anacardic acids mixture	NA	[121]
Extract of Japanese rice also	In vivo Mongolian gerbil model	Anti-H. pylori activity; anti-inflammatory effect	NA	NA	NA	[122]
16 Mexican plants1	In vitro broth microdilution method	Anti-H. pylori activity	Mexican folk medicine	NA	NA	[123]
Bacopa monniera	In vitro broth microdilution method	Anti-H. pylori activity	In Ayurveda, (ancient medicine of India) known as medhya rasayana or "brahmi"	NA	Augmentation of defensive mucosal: mucin secretion, life span of mucosal cells, and gastric antioxidant	[124]
Propolis	In vitro test against H. pylori Test against Recombinant protein (peptide deformylase)	Anti-H. pylori activity	Resinous hive product collected by honeybees	Phenolic compounds, mainly Caffeic acid phenethyl ester (CAPE)	CAPE is a competitive inhibitor of H. pylori peptide deformylase	[107,125]
Gosyuyu (Wu-Chu-Yu) and Psoralen (extract from Psoralea corylifolia)	In vitro test against H. pylori	Anti-H. pylori activity	Chinese herbal medicine, namely “buguzhi”	Alkyl methyl quinolone alkaloids	NA	[126]
Amu-ru 7, a	In vitro test against H. pyloriIn vivo Mongolian gerbil	Anti-H. pylori activity Did not cure Mongolian gerbil, but colonization rate diminish	Mongolian folk medicine	Alkyl methyl quinolone alkaloids Rhei rhizome is the most effective component	Inhibited biofilm formation by H. pylori partial inhibition of urease	[127]
Agrimonia eupatoria, Hydrastis canadensis, Filipendula ulmaria, and Salvia officinalis	In vitro test against H. pylori	Anti-H. pylori activity	Western herbal medicine	NA	NA	[128]
Curcumin diferuloylmethane	In vitro test against H. pyloriIn vitro using AGS cells In vivo C57BL/6 mice and Male Sprague-Dawley rats	In vitro anti-H. pylori activity; effective in eradication of H. pylori from infected mice and in restoration of H. pylori-induced gastric damage	The major yellow pigment present in the rhizome of turmeric (the perennial herb Curcuma longa)	Diferuloylmethane	Suppressing secretion of metalloproteinases 3 and 9 by gastric cells noncompetitive inhibitor of H. pylori shikimate dehydrogenase, among others decrease nuclear factor-kB (NF-κB) p65	[76,106,129]
Nigella sativa (Ranunculaceae)	In vivo adult patients	Administrated with omeprazole had a eradication rate similar to triple therapy (consult Table 1)	Grows in the Middle East, Eastern Europe, and Eastern and Middle Asia	Thymoquinone, dihydrothymoquinone and terpenes	Disrupting the lipid structure of the cell membrane	[89]
Methanol extract of the leaf of Allium ascalonicum	In vitro test against H. pylori	Anti-H. pylori activity	Known as garlic	Alkaloids, cardiac glycosides and saponins	Decrease urease activity	[130]
Leaves of Piper carpunya Ruiz and Pav. (syn Piper lenticellosum C.D.C.) (Piperaceae)	In vitro test against H. pyloriIn vitro against rat peritoneal leukocytes	Anti-inflammatory; anti-ulcer action	Widely used in folk medicine in tropical and subtropical South American	Flavonoids	Inhibition of H+, K+-ATPase activity	[98,99]
Apium graveolens seeds	In vitro test against H. pylori	Anti-H. pylori activity	Used in Ayurvedic medicine	Compound with anti-Helicobacter activity, an asymmetric phthalide dimer	Induces morphologic changes in H. pylori and inhibits protein and DNA synthesis	[131]
Davilla elliptica and Davilla nitida	In vivo Swiss albino mice and male Wistar albino rats animal In vitro disc diffusion technique	Anti-H. pylori activity; gastric protection action	Brazil folk medicine	Phenolic acid derivatives, acylglycoflavonoids, and condensed tannins	Stimulats moderate levels of H2O2, trigger moderation of the oxidative burst and consequently the immune response	[132]
Resveratrol	In vitro test against H. pyloriIn vitro using MKN-45 cells	Inhibit urease, anti-inflammatory and anti-cancer activity cardioprotective and neuroprotective properties	highly abundant in red grapes	Polyphenol	Modulation of interleukin (IL)-6, NF-κB, and mitogen-activated protein kinases; modulatory effects on H. pylori-induced IL-8 secretion, reactive oxygen species production, and morphological changes	[102,103,133, 134-136]
Anisomeles indica	In vitro test against H. pyloriIn vitro using AGS cells	Anti-H. pylori activity; anti-inflammatory properties	From Southeast Asia and Australia	Ovatodiolide	Attenuated the inflammatory response by decreasing NF-κB activation and IL-8 secretion, inhibit lipopolysaccharide-induced inflammation in macrophages (including the secretion of the pro-inflammatory cytokine tumor necrosis factor-α, and nitric oxide (NO) production, and protein expressions of inducible NO synthase and cyclooxygenase-2 (COX-2)	[75]
Glycyrrhiza glabra	In vitro test against H. pyloriIn vitro using AGS cells In vivo adult patients	Anti-H. pylori activity; anti-inflammatory properties (consult Table 1)	Legume known as licorice from southern Europe and parts of Asia	Flavenoid, main component glycyrrhetinic acid	Inhibition H. pylori of DNA gyrase, protein synthesis and dihydrofolate reductase enzyme; anti-inflammatory activity likely through inhibition of COX and lipoxygenase pathways	[88,100]
Cistus laurifolius	In vitro test against H. pylori	Anti-H. pylori activity	Folk medicine in Anatolia	Flavenoid, most active is quercetin 3-methyl ether (isorhamnetin)	NA	[137]
Sclerocarya birrea	In vitro test against H. pylori	Anti-H. pylori activity	Medicinal plant used by Zulus, Vhavendas, Xhosas and Sothos of South Africa	Essential oils: terpinen-4-ol (35.83%), pyrrolidine (32.15%), aromadendrene (13.63%) and α-gurjunene (8.77%)	NA	[138]
Phyllanthus urinaria	In vitro test against H. pyloriIn vitro using AGS cells	Anti-H. pylori activity; anti-inflammatory properties	Tropical and subtropical countries (Taiwan)	Phyllanthin, phyltetralin, trimethyl-3,4-dehydrochebulate, methyl gallate, rhamnocitrin, methyl brevifolincarboxylate, β-sitosterol-3-O-β-d-glucopyranoside, quercitrin and rutin	Inhibits AGS cells adhesion and invasion; decreases NF-κB activation and IL-8 secretion	[139,140]
Artemisia douglasiana Besser (Asteraceae)	In vitro test against H. pylori	Anti-H. pylori activity	Folk medicine in Argentina known as "matico"	Dehydroleucodine, a sesquiterpene lactone of the guaianolide type	Potent inhibitors of the transcription factor NF-κB	[141,142]
Geranium wilfordii	In vitro test against H. pylori	Anti-H. pylori activity	Herb from China	Corilagin (1), and 1,2,3,6-tetra-O-galloyl-β-D-glucose	NA	[143]
HZJW, composed of 12 medicinal herbs	In vitro test against H. pyloriIn vivo Balb/c mice	Anti-H. pylori activity; reduction of ulcerative lesion; eradicate H. pylori in mice	Chinese herbal formula composed of 12 herbs listed in (91)	Protoberberine alkaloids palmatine, coptisine and aporphine alkaloid of magnoflorine	NA	[91]
Cratoxylum arborescens (Vahl) Blume	In vitro test against H. pyloriIn vivo Balb/c mice	Anti-H. pylori activity, anti-inflammatory activity; reduced ulcer area, higher mucus content	Asian herbal medicine	α-mangostin (AM), is a prenylated xanthone	Anti-COX-2 and anti-NO activities	[144]
Chenopodium ambrosioides L. And Adina pilulifera. Chenopodium ambrosioides L.	In vitro test against H. pylori	Anti-H. pylori activity	Jinghua Weikang Capsule (Chinese patent drug for peptic ulcer	NA	NA	[145]
Momordica cochinchinensis Springer (Cucurbitaceae)	In vivo mice	Gastroprotective effect		Momordica saponin I	NA	[146]
Sangre de grado (Croton lecheleri and Croton palanostigma)	In vitro test against H. pyloriIn vivo C57BL/6 mice	Anti-H. pylori activity No bactericidal effect in mice	Sangre de grado is a red, viscous latex from the cortex of trees used in Peruvian medicine	NA	Mice with higher hepatic metallothionein levels	[147]
Polygonum tinctorium Lour	In vitro test against H. pyloriIn vivo Mongolian gerbil	Anti-H. pylori activity; anti-inflammatory effect; decreased bacterial load in Mongolian gerbil	Known as indigo	Tryptanthrin and kaempferol (flavenoid)	Inhibition of nitric oxide production, and the transcription of cyclooxygenase	[80]
Artocarpus obtusus Jarret	In vitro test against H. pyloriIn vivo Mongolian gerbil	Anti-H. pylori activity; gastroprotective effect; increased mucus content	Endemic species of Borneo known as “pala tupai”	Pyranocycloartobiloxanthone A, a xanthone	Free radical scavenging effect, induction of HSP70, via anti-apoptotic property (down regulate bax gene), inhibits Cox-2 enzyme	[148]
Punica granatum and Juglans regia	In vitro test against H. pylori	Anti-H. pylori activity	Iranian plants	NA	NA	[149]

¹Castella tortuosa, Amphipterygium adstringens, Ibervillea sonorae, Pscalium decompositum, Krameria erecta, Selaginella lepidophylla, Pimpinella anisum, Marrubium vulgare, Ambrosia confertiflora, Couterea latiflora, Byophyllum pinnatum, Tecoma stans linnaeus, Kohleria deppena, Jatropha cuneata, Chenopodium ambrosoides, and Taxodium macronatum. NA: Not applicable; H. pylori: Helicobacter pylori.