Potent Antioxidant and Anti-Inflammatory Metabolites of Pongamia pinnata Stems and Their Role in NF-κB and PI3K/AKT/mTOR Signaling Pathways Regulation in Irradiated Rats.

The objective of the work is to present a comprehensive analysis of the bioactive metabolites present in Pongamia pinnata (Pp) stems. The radioprotective properties of Pp against gamma radiation-induced inflammation in vivo were also clarified. A single acute dose of whole-body gamma radiation (7 Gy) was administered to the rats. For 10 days, the herbal extract was administered orally by gavage at doses of 300 and 1000 mg/kg. The irradiated group administered with Pp 70% ethanolic extract showed a significant reduction in testicular and renal oxidative stress markers, such as reduced glutathione and malondialdehyde. Pretreatment with Pp showed notable improvements in biomarkers (nuclear factor kappa B [NF-κB], phosphoinositide 3-kinases [PI3K], Akt, and mTOR) in testis and renal tissues. Both the incidence of sperm head abnormalities and the serum levels of urea and creatinine were markedly reduced in irradiated rats that had been pretreated with Pp herbal extract. The docking study concentrated on the ability of the herbal extract's most active metabolites, β-sitosterol, stigmasterol, betulinic acid, and ponganone XI, to bind to the NF-κB, PI3K, Akt, and mTOR target sites. Pp stem includes a variety of pharmacological properties that modulate the PI3K/Akt/mTOR pathway, including possible antioxidant and anti-inflammatory compounds.