Glucagon-like peptide-1 agonist and Quercetin improve skeletal muscle performance and pain threshold in male rats with fibromyalgia via activating the Nrf2/HO1/NQO1 pathway.

Short title: Liraglutide and Quercetin improve muscle performance and pain in FM.AbstractBackground: Chronic fatigue and musculoskeletal pain, compromising the quality of life, are hallmarks of fibromyalgia (FM). Yet, there is no proven treatment for these health issues associated with FM. Nuclear factor erythroid 2-related factor 2 (Nrf2) agonists reduce pain. As well, they enhance muscle activity. Nevertheless, little information is available on how Liraglutide and Quercetin, Nrf2 agonists, impact FM patients' motor functions and pain. Objective: The current research explored how Liraglutide and Quercetin might affect pain threshold and muscular function in FM rats. Methods: Four groups including 24 male Wistar rats were equally distributed as Control, FM, FM + Liraglutide and FM + Quercetin. We evaluated the body weight, mechanical pain pressure threshold, skeletal muscle contractions, serum substance P and glucose, muscle tissue catalase, malondialdehyde, and gene expression of Nrf2, NAD(P)H: quinone oxidoreductase 1 (NQO1) and hemoxygenase1 (HO1). Results: Liraglutide and Quercetin substantially enhanced the muscle performance, and pain threshold, via enhancing the antioxidant activity through upregulation of Nrf2, HO1 and NQO1 genes. Conclusion: Liraglutide and Quercetin comparably showed favorable efficacy on the motor dysfunctions and pain associated with FM.