Antipyretic activity of Phanera strychnifolia stem extract in yeast-induced febrile rats: A plasma metabolomics study.

ETHNOPHARMACOLOGICAL RELEVANCE: Phanera strychnifolia is a medicinal plant species distributed in Thailand and the Malay Peninsula. Its stem has been traditionally used for detoxification and reducing fever.

AIM OF THE STUDY: This study aimed to evaluate the antipyretic activity of P. strychnifolia stem extract and to elucidate fever associated metabolic alterations using an integrated pharmacological and metabolomics approach.

MATERIAL AND

METHODS

Antipyretic effects were evaluated in male Wistar rats with baker's yeast-induced fever. Animals were orally administered P. strychnifolia stem extract at doses of 100, 250, and 500 mg/kg, with paracetamol used as a reference drug. Rectal temperature was monitored for 6 h post-treatment. Untargeted plasma metabolomics was performed using LC-MS/MS, and multivariate analyses were applied to characterize fever- and treatment-associated metabolic changes.

RESULTS

Phanera strychnifolia stem extract, containing astilbin (9.0% w/w), produced a significant, dose-dependent reduction in rectal temperature; the highest dose (500 mg/kg) showed the most pronounced antipyretic effect, with a response approaching that of paracetamol without inducing hypothermia. Metabolomic analysis revealed that fever induction caused pronounced, system-wide metabolic reprogramming involving energy metabolism, lipid signaling, amino acid utilization, and cellular stress-related pathways. Exploratory PCA and PLS-DA visualizations suggested separation between pyretic and normal metabolic profiles, with partial overlap among some treatment groups. Paracetamol and P. strychnifolia treatment showed a partial movement of metabolic profiles toward the non-pyretic group, particularly at the higher extract dose.

CONCLUSION

Phanera strychnifolia stem extract exhibited significant antipyretic activity and was associated with partial modulation of fever-associated metabolic alterations in a yeast-induced fever model. The findings provide scientific evidence supporting its traditional use in fever management.