Natural supplements effectively suppress Helicobacter pylori colonization and improve gastric antioxidant and antiinflammatory responses in an indomethacin-induced ulcer model
Microbial pathogenesis, vol.213, pp.108320, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 213
- Publication Date: 2026
- Doi Number: 10.1016/j.micpath.2026.108320
- Journal Name: Microbial pathogenesis
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, Environment Index, MEDLINE
- Page Numbers: pp.108320
- Keywords: H. pylori, HIF-1α, IL-10, IL-1β, Indomethacin, Oxidative stress
- Kütahya Health Sciences University Affiliated: Yes
Abstract
BACKGROUND: The coexistence of Helicobacter pylori (H. pylori) infection and use of non-steroidal anti-inflammatory drugs (NSAIDs) is very common in clinics and they act together to worsen the gastric damage. The growing resistance to antibiotics and the side effects of the eradication regimens support the use of multi-target supportive strategies. The study aimed to determine the antibacterial, antibiofilm, antioxidant, and anti-inflammatory effects of three natural supplements as well as their effect on HIF-1α and TGF-β expression in a rat model of indomethacin-induced H. pylori gastric ulcer. METHODS: The in vitro anti-H. pylori activity of the two formulations (Nitro-plus and Sunset) was evaluated by determining the minimum inhibitory concentration (MIC) and using resazurin microdilution methods, along with antibiofilm assays conducted in 96-well plates. The experiment was carried out on female Wistar rats, which were allocated to six groups: healthy control, indomethacin-induced ulcer, H. pylori + gastritis ulcer, gastritis ulcer + natural supplements, H. pylori + gastritis ulcer + natural supplements, and H. pylori + gastritis ulcer + standard triple therapy. Indomethacin (5 mg/kg) was the agent used for inducing ulcers, and the presence of H. pylori was determined by testing for fecal antigen and urease. After a 30-day period of different treatments, the gastric tissues were assessed for the following parameters: urease activity, bacterial load (CFU/g), IL-1β and IL-10 levels (ELISA), HIF-1α and TGF-β expression (qPCR), as well as total antioxidant status (TAS) and total oxidant status (TOS) measurements, malondialdehyde (MDA), catalase (CAT), and glutathione (GSH) levels, and histopathology. RESULTS: Nitro-plus and Sunset presented notable anti-H. pylori activities (MIC 2.2 and 0.406 mg/mL without resazurin) and also antibiofilm activities, with the inhibition of biofilm biomass being ∼58 % and ∼47 %, respectively. In vivo, natural supplements, in decreasing the gastric burden of H. pylori, reducing the urease activity, lowering the levels of IL-1β and HIF-1α, and raising the level of IL-10 as compared to the untreated H. pylori + ulcer group, had effects comparable to triple therapy in several parameters. The TOS and MDA levels were lowered while the TAS, CAT and GSH levels were increased, thus the histological scores were also improved due to the attenuation of inflammation, neutrophil activation, and bacterial colonization. CONCLUSION: The use of multi-component natural supplements that addressed bacterial load, biofilm formation, oxidative stress, inflammatory cytokines and hypoxia-related pathways reduced the effects of indomethacin and H. pylori in causing gastric damage and made the supplements a good candidate for adjunctive support in standard eradication regimens. The clinical trials should be controlled and conducted to confirm the translational relevance.