In Vivo and In Silico Evaluation of Antipyretic, Anti-inflammatory, and Analgesic Potential of Trichodesma indicum Root Extract

Abstract

Trichodesma indicum (L.) (family Boraginaceae) is a medicinal plant widely used in Ayurvedic and traditional medicine. However, comparative evidence regarding the pharmacological activities of its solvent-dependent root extracts and their underlying molecular mechanisms remains limited. This study investigated the antipyretic, anti-inflammatory, and analgesic activities of ethanolic root extract (ERETI) and chloroformic root extract (CRETI) in adult Wistar albino rats. Molecular docking was also performed to assess the interactions of selected phytochemicals with lipoxygenase (PDB ID: 2ESN) and cyclooxygenase-2 (COX-2; PDB ID: 1CX2). In the carrageenan-induced paw edema model, ERETI exhibited significant anti-inflammatory activity, achieving maximum inhibition of 44.44% at 200 mg/kg three hours after carrageenan administration. This finding suggests potential inhibition of inflammatory mediators involved in the later phase of inflammation. In the brewer’s yeast-induced hyperalgesia model, ERETI produced a maximum analgesic effect of 75.00% at 100 mg/kg after three hours, indicating a potentially non-linear dose-response relationship. In the brewer’s yeast-induced pyrexia model, ERETI demonstrated pronounced antipyretic activity, achieving 100.00% fever reduction at 400 mg/kg four hours after treatment and restoring rectal temperature to baseline levels. Overall, ERETI demonstrated greater pharmacological efficacy than CRETI across the evaluated models, suggesting that ethanol-extractable constituents may contribute substantially to these effects. Molecular docking using HDOCK revealed favorable predicted binding of lupeol to lipoxygenase, with a docking score of −248.40 and confidence score of 0.8774. Eugenol exhibited a docking score of −128.83 against COX-2, with reported interactions involving Tyr385 and His386. These findings highlight the pharmacological potential of T. indicum roots and identify lupeol and eugenol as promising candidates for further investigation. Comprehensive phytochemical analysis, toxicity assessment, and experimental validation are required to confirm their mechanisms and therapeutic relevance.