Cytokine Modulation and Antioxidant Defense Restoration by Jateorhiza macrantha (Menispermaceae) Leaf Extracts Mitigate CFA‐Induced Hypernociception, Inflammation, and Pyrexia in Rats

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Abstract
Jateorhiza macrantha (Menispermaceae) is used in folk medicine in Africa for gastrointestinal and inflammatory disorders. However, its efficacy against inflammatory pain and associated neuro‐oxidative stress remains uncharacterized. This study evaluated the antihypernociceptive, anti‐inflammatory, and antipyretic properties of J. macrantha aqueous (AEJM) and methanolic (MEJM) leaf extracts in a rat model of complete Freund′s adjuvant (CFA)–induced persistent inflammation. Chronic inflammatory pain was induced in male Wistar rats by intraplantar injection of CFA (50 μ L). The test extracts were administered orally (100–400 mg/kg) for 14 days. Mechanical, cold, and thermal nociception were evaluated using Von Frey filaments, acetone test, and hot‐plate assay, respectively. Paw edema and rectal temperature were monitored to assess anti‐inflammatory and antipyretic effects. Serum levels of TNF‐ α , IL‐1 β , and IL‐6 were quantified, whereas oxidative stress markers (MDA, CAT, SOD, and GSH) were measured in brain and spinal cord tissues. Moreover, qualitative phytochemical profiling was performed. AEJM and MEJM significantly ( p < 0.05– p < 0.001) reduced paw edema and fever, increased paw withdrawal thresholds and thermal latencies. These improvements correlated with a significant downregulation of serum TNF‐ α , IL‐1 β , and IL‐6. Furthermore, both extracts significantly lowered MDA levels and increased antioxidant defenses (SOD, CAT, and GSH) in the brain and spinal cord. Notably, AEJM restored the locomotor performance compared with diclofenac. Phytochemical analysis showed flavonoids, saponins, steroids and tannins. AEJM and MEJM exert noteworthy anti‐inflammatory, antihypernociceptive, and antipyretic effects mediated through the concurrent suppression of proinflammatory cytokines and reinforcement of central antioxidant systems. These scientifically validate its traditional use.

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