Hibiscus sabdariffa protects against fibromyalgia by modulating the neuroinflammation–oxidative stress–microRNA axis

Fibromyalgia (FM) is a chronic syndrome characterized by widespread pain, fatigue, cognitive dysfunction and neuropsychiatric disturbances, associated with dysregulated oxidative stress and neuroinflammation. Emerging evidence suggests that microRNAs guiding these pathways, including miR-145-5p and miR-451a, may play a central role in FM pathogenesis. However, currently available pharmacological therapies provide limited efficacy and are frequently associated with adverse effects. Therefore, the present study investigated whether the methanolic extract of Hibiscus sabdariffa (MeOH-Exs), a polyphenol rich extract with known antioxidant and anti-inflammatory properties, alleviates reserpine (Res)-induced FM in rats through modulation of the neuroinflammation–oxidative stress–microRNA axis. FM was induced by Res (1 mg/kg, s.c., for three days), followed by 28-day treatment with MeOH-Exs (25 or 50 mg/kg, p.o.) compared with the standard drug Neurontin (Neu). Behavioral assessments, serum hydrogen peroxide, brain serotonin, peripheral expression of miR-145-5p and miR-451a, and spinal cord inflammatory and histopathological alterations were evaluated. MeOH-Exs significantly improved hyperalgesia, depressive- and anxiety-like behaviors, locomotion, and cognition relative to the Res group. The 50 mg/kg dose exerted the most pronounced effects, restoring expression of miR-145-5p and miR-451a, reducing oxidative stress, and elevating brain serotonin levels. Histological and immunohistochemical analyses confirmed attenuation of spinal cord inflammation and neuronal degeneration, caspase 3 expression and TNF-α immunoreactivity with effects comparable to or greater than Neu. Collectively, these findings indicate that Hibiscus sabdariffa may ameliorate FM – like menifistations by targeting an integrated biochemical pathway linking oxidative stress, neuroinflammation, apoptosis, microRNA dysregulation and spinal cord histopathological alterations. While the precise molecular mechanisms require further investigation, MeOH-Exs demonstrates a promising multi-target neuroprotective profile and may represent a potential complementary preclinical therapeutic candidate for FM.