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.
OBJECTIVE
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).


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 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.


CONCLUSIONS
the results suggest that isochaihulactone exerts potent anti-aging effects against D-gal in mice possibly via antioxidative mechanisms.
Department of Clinical Laboratory Science and Medical Biotechnology, College of Medicine National Taiwan University, Taipei, Taiwan, China.
Sung-Liang
SL
YU
Shih-bin
SB
LIN
Yung-luen
YL
YU
Min-hui
MH
CHIEN
Kuo-jung
KJ
SU
Ching-Ju
CJ
LIN
Tzong-der
TD
WAY
Giou-Teng
GT
YIANG
Chai-Ching
CC
LIN
De-Chuan
DC
CHAN
Horng-Jyh
HJ
HARN
Yi-Lin Sophia
YL
CHEN
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D019588:Aging, Premature / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D052117:Benzodioxoles / Q000737:chemistry / Q000494:pharmacology*; D029972:Bupleurum / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005690:Galactose; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D052117:Benzodioxoles; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C512868:isochaihulactone; D000246:Adenosine Diphosphate Ribose; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D015107:4-Butyrolactone; D005690:Galactose