#terpinolene

Diabetes induced oxidative stress impairs hepatic function, contributing to peripheral nerve injury. Growing evidence indicates that overactivation of NOX4 brings metabolic derangements in hepatic tissue, which concomitantly alter thermal behavior in experimental rats. This study investigated the hepatoprotective and antinociceptive effects of terpinolene in streptozotocin (STZ)-induced DPN rats. Male SD rats were made diabetic with STZ (55 mg/kg, b.w. i.p) prepared in 0.1 M citrate buffer (pH 4.5). After six weeks, diabetic animals were treated daily with terpinolene at doses of 12.5, 25, and 50 mg/kg for four weeks. Diabetic control rats exhibited a significant decrease in the levels of endogenous antioxidants (enzymic and non-enzymic), along with elevated lipid peroxidation products and transaminase (AST, ALT) activities, indicating severe hepatic dysfunction. An alteration in thermal behavior was observed in diabetic control rats. Oral administration of terpinolene dose-dependently improved hepatic antioxidant status and reduced lipid peroxidation markers. Histological examination revealed that terpinolene restored the architecture of hepatic tissue, and the effect was more pronounced at 50mg/kg b.w than the other two doses. Further in silico analysis revealed a strong binding interaction between terpinolene and NOX4 with a binding energy of -5.2 kcal/mol. This indicates that terpinolene effectively inhibits NOX4-mediated oxidative stress in the hepatic tissue and ameliorates thermal nociception in DPN rats. The efficacy of terpinolene was comparable to the standard drug, α-lipoic acid.