Isochaihulactone protects PC12 cell against H2O2 induced oxidative stress and exerts the potent anti- aging effects in D-galactose aging mouse model

Aim： To investigate the effect of isochaihulactone （also known as K8）, a lignan compound of Bupleurum scorzonerifolium, on H2O2- induced cytotoxicity in neuronally differentiated PC12 cells （nPC12）. Methods： Viability of neuronal PC12 cells was measured using MTT assay. Protein expression was determined by Western blot. Apoptotic cells was determined using TUNEL assay. D-galactose aging mice were used as a model system to study the anti-oxidant effects of isochaihulactone in vivo. Results： Pretreatment with isochaihulactone （5-10 μmol/L） increased cell viability and decreased membrane damage, generation of reactive oxygen species and degradation of poly （ADP-ribose） polymerase in H2O2-treated nPC12 cells and also decreased the expression of cyclooxygenase-2, via downregulation of NF-kappaB, resulting in a decrease in lipid peroxidation. The results suggest that isochaihulactone is a potential antioxidant agent. In a murine aging model, in which chronic systemic exposure to D-galactose （D-gal） causes the acceleration of senescence, administration of isochaihulactone （10 mg.kg^-1·d^-1, sc） for 7 weeks concomitant with D-gal injection significantly increased superoxide dismutase and glutathione peroxidase activities and decreased the MDA level in plasma. Furthermore, H＆E staining to quantify cell death within hippocampus showed that percentage of pyknotic nuclei in the D-gal-treated mice were much higher than in control. Conclusion： The results suggest that isochaihulactone exerts potent anti-aging effects against D-gal in mice possibly via antioxidative mechanisms.