Neuronutritional enhancement of antioxidant defense system through Nrf2/HO1/NQO1 axis in fibromyalgia

Abstract

Fibromyalgia (FM) is a disorder characterized by chronic widespread musculoskeletal pain, and it is often accompanied by fatigue, sleep disturbance, and cognitive dysfunction. Although pathophysiology is multifactorial, increasing evidence highlights the pivotal role of oxidative stress and mitochondrial dysfunction in the development of this condition. In particular, the Nrf2/HO-1/NQO1 antioxidant axis plays a crucial role in counteracting oxidative damage and maintaining cellular homeostasis. Boswellia (BS) is a genus of plants in the Burseraceae family, which includes around twenty species found across sub-Saharan Africa, the Arabian Peninsula, and the Indian subcontinent. In Ayurvedic medicine, it has traditionally been used in the treatment of diabetes, fever, as well as certain cardiovascular, dermatological, and neurological conditions. Boswellic acids are thought to possess anti-inflammatory, anti-rheumatic, and pain-relieving properties. The purpose of this study was to investigate the beneficial effects of BS extract in a murine model of reserpine-induced FM. Following reserpine administration, markers of oxidative stress, neuroinflammation, and behavioral changes including mechanical allodynia, hyperalgesia, anxiety, and depression-like behaviors were significantly increased. Daily oral administration of BS at a dose of 100 mg/kg effectively restored these pathological changes. BS oral supplementation, by preventing microglia and astrocyte activation, as demonstrated by decreased GFAP and Iba-1 expression, BS decreased neurological inflammation and restored neurotransmitter levels such as norepinephrine, dopamine and serotonin. Futhermore, improved antioxidant defenses by increasing nuclear translocation of Nrf2 and subsequent expression of its downstream targets, HO-1 and NQO1, limiting lipid peroxidation and ROS production. According to behavioral tests, BS significantly reduced the emotional deficit and mechanical sensitivity linked to FM. Our findings indicate that BS integration has neuroprotective effects, acting on oxidative stress and neuroinflammation, and suggesting that it is a viable natural strategy for managing FM symptoms.