Inflammation underlies the pathophysiology of numerous chronic non-communicable diseases, and plant-derived agents acting through complementary phytochemical mechanisms remain an active area of anti-inflammatory drug discovery. This study comparatively evaluated the anti-inflammatory activity of methanolic leaf extracts of Zygophyllum coccineum (Zygophyllaceae) and Heliotropium indicum (Boraginaceae) against carrageenan-induced acute paw oedema and cotton pellet-induced chronic granuloma in Wistar rats, benchmarked against diclofenac sodium (10 mg/kg). Soxhlet extraction yielded 12.40% w/w (Z. coccineum) and 10.80% w/w (H. indicum); phytochemical screening identified a flavonoid-saponin-triterpenoid-rich profile in Z. coccineum and an alkaloid-flavonoid-rich profile in H. indicum. Both extracts were non-toxic at the OECD 423 limit dose of 2000 mg/kg, supporting selection of 200 and 400 mg/kg (Z. coccineum) and 400 mg/kg (H. indicum) for the main study. In the carrageenan model, Z. coccineum (400 mg/kg) produced 57.32% inhibition of paw oedema at 3 h, Z. coccineum (200 mg/kg) 39.02%, and H. indicum (400 mg/kg) 50.00%, against 71.95% for diclofenac. In the cotton pellet model, the corresponding inhibitions were 37.80%, 24.39% and 31.71%, against 53.66% for diclofenac. Both extracts showed dose-dependent, statistically significant activity (p < 0.05-0.001) across models, with Z. coccineum consistently more potent than H. indicum, and both extracts retaining a greater proportion of their acute activity into the chronic phase than diclofenac, consistent with a multi-target mechanism of action.
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