Natural alternatives for the treatment of Helicobacter pylori and gastric ulcers

Abstract

Helicobacter pylori is one of the most resilient human pathogens, infecting over half of the global population and is causative of the onset of gastric ulcers. Current H. pylori treatment methods are losing efficacy, as H. pylori rapidly gains resistance to antibiotics. Alternative treatments, such as natural products, is thus essential. Numerous medicinal plants are used traditionally in South Africa to treat gastric ulcers. Honey and propolis have been noted to elicit anti-ulcer and anti-H. pylori effects. Investigation into southern African natural products in this context, however, has been sorely neglected. This study aimed to investigate the antimicrobial activity of various Southern African derived natural products against both H. pylori and probiotic bacteria that occur naturally in the gut microbiome, as well as to investigate the combination of select natural products with probiotics against H. pylori. Based on the ethnobotanical evidence, 21 Southern African medicinal plants used traditionally for treating gastric ulcers were collected. Their antimicrobial activity was assessed against five clinical H. pylori strains, and in combination with each of three Lactobacillus probiotic strains (Lactobacillus acidophilus ATCC 314, Lactobacillus casei ATCC 334, and Lactobacillus rhamnosus ATCC 7469), using the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) microdilution assays. Noteworthy activity was observed against at least one H. pylori strain for 12 plant species. The lowest mean MICs were from Carissa edulis Vahl (0.18 mg/mL) Chironia baccifera L. (0.20 mg/mL), Sansevieria hyacinthodes (L.) Druce (0.26 mg/mL) and Dodonaea viscosa Jacq. (0.30 mg/mL). Aqueous extracts were combined with each of three probiotic Lactobacillus species and showed increased antimicrobial activity compared with the extracts alone for most combinations. Lactobacillus acidophilus combined with either Protea repens (L.) L, Carpobrotus edulis (L.) L.Bolus or Warburgia salutaris (Bertol.f.) Chiov. had the best anti-H. pylori activity (mean MBCs of 0.10 mg/mL for each combination). A selection of South African propolis samples was collected (51 samples) as well as three Brazilian propolis samples, which served as gold standard comparators. Ethanolic extracts were prepared, and the microdilution broth assay used to assess antimicrobial activity against three clinical H. pylori strains. Anti-H. pylori activity less than or equal to that of Brazilian propolis extracts was observed for 27 of the sample extracts. Using ultra performance liquid x chromatography-mass spectrometry, the compounds pinocembrin, 3-O-acetylpinobanksin, and pinobanksin, were revealed to be the most abundant in the most active propolis samples. Toxicity of the plant and propolis extracts was assessed using the brine shrimp lethality assay. Only four organic and one aqueous plant extract(s) were considered toxic. No propolis extracts were considered toxic. A selection of South African honeys was collected (76 variants) as well as Manuka honey, which served as a gold standard comparator. An agar dilution assay was employed to determine the antimicrobial activity of honey against three clinical H. pylori strains and in combination with each of the three Lactobacillus species. A third of the investigated honey variants showed anti-H. pylori activity better than or equal to that of Manuka honey (8.33% v/v) against at least one strain, including honey with citrus, fynbos and buchu floral sources. Combinations of honey and each of three Lactobacillus species showed increased anti-H. pylori activity for 82.50% of honey variants compared with that of the honey alone. Combinations of honey with L. rhamnosus showed the best anti-H. pylori activity for 12 honey variants (4.17% v/v for each combination). Combinations of honey and L. casei showed the greatest increase in anti-H. pylori activity. A positive correlation between the anti-H. pylori activity and the concentration of hydrogen peroxide in honey was observed (R2 = 0.76). These results highlight the potential of natural products for inhibiting H. pylori growth and their role in the traditional management of ulcers, as well as the potential benefit of including probiotics as potentiators of the anti-H. pylori activity.