Isochaihulactone protects PC12 cell against H(2)O(2) induced oxidative stress and exerts the potent anti-aging effects in D-galactose aging mouse model

• Published in: Acta pharmacologica Sinica Vol. 31; no. 12; p. 1532
• Main Authors: YU, Sung-Liang, LIN, Shih-bin, YU, Yung-luen, CHIEN, Min-hui, SU, Kuo-jung, LIN, Ching-Ju, WAY, Tzong-der, YIANG, Giou-Teng, LIN, Chai-Ching, CHAN, De-Chuan, HARN, Horng-Jyh, CHEN, Yi-Lin Sophia
• Format: Journal Article
• Language: English
• Published: United States 01.12.2010
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - chemistry; 4-Butyrolactone - pharmacology; Adenosine Diphosphate Ribose - metabolism; Aging, Premature - chemically induced; Aging, Premature - prevention & control; Animals; Antioxidants - chemistry; Antioxidants - pharmacology; Apoptosis - drug effects; Benzodioxoles - chemistry; Benzodioxoles - pharmacology; Bupleurum - chemistry; Cell Line, Tumor; Cell Survival - drug effects; Cyclooxygenase 2 - metabolism; Galactose; Glutathione Peroxidase - metabolism; Hydrogen Peroxide - pharmacology; Lipid Peroxidation - drug effects; Male; Malondialdehyde - metabolism; Mice; Mice, Inbred C57BL; NF-kappa B - metabolism; Oxidative Stress - drug effects; PC12 Cells; Rats; Reactive Oxygen Species - metabolism; Superoxide Dismutase - metabolism
• ISSN: 1745-7254
• DOI: 10.1038/aps.2010.152

to investigate the effect of isochaihulactone (also known as K8), a lignan compound of Bupleurum scorzonerifolium, on H(2)O(2)-induced cytotoxicity in neuronally differentiated PC12 cells (nPC12). 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. pretreatment with isochaihulactone (5-10 micromol/L) increased cell viability and decreased membrane damage, generation of reactive oxygen species and degradation of poly (ADP-ribose) polymerase in H(2)O(2)-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 mgxkg(-1)xd(-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. the results suggest that isochaihulactone exerts potent anti-aging effects against D-gal in mice possibly via antioxidative mechanisms.