The effect of Hippophae rhamnoides on Hydroxychloroquine-Induced stomatitis in rats

Background: Stomatitis is the most common mucosal side effect associated with Hydroxychloroquine (HCQ). Hippophae Rhamnoides (HR) is known to contain several phytonutrients, including anti-inflammatory, and antioxidant properties. This study aimed whether HR can mitigate HCQ-induced oxidative stress and inflammation in rat cheek tissue and to corroborate biochemical findings with macroscopic and histopathological evaluations. Methods: Twenty four rats were used and split into four groups: healthy control group (HG), receiving HR alone, receiving HCQ alone, and receiving both HR and HCQ (HRHQ). The drugs were administered for 10 days, and at the end of the 10th day, the rats were euthanized with high dose of thiopental sodium anesthesia and the inner cheek tissues removed. Results: HR decreased malondialdehyde, and pro-inflammatory cytokine levels, which increased by HCQ, while it increased anti-oxidant levels, which decreased by HCQ. The inner cheek tissue was examined macroscopically for edema, hemorrhagic cracks, hyperemia and gray appearance that developed due to HCQ use, which were alleviated with HR. Histopathologically, epithelial necrosis, muscle degeneration, scar tissue, polymorphonuclear cell (PMNL) infiltration, haemorrhage and edema were observed in the HCQ group. In contrast, in the HRHQ group, epithelial necrosis, and muscle degeneration were normal, haemorrhage was absent, PMNL infiltration persisted in some-areas, and moderate capillary congestion and dilatation were observed. detected. Conclusion: The results indicate that HR may be a potential candidate for preventing and treating stomatitis associated with HCQ use. Translating these findings into clinical practice could support the safe and effective use of HR as a therapeutic agent. © The Author(s) 2026.