TY - JOUR
T1 - Stilbenes from Veratrum maackii Regel protect against ethanol-induced DNA damage in mouse cerebellum and cerebral cortex
AU - Wu, Yantong
AU - Li, Shasha
AU - Liu, Jinjin
AU - Liu, Xiping
AU - Ruan, Weimin
AU - Lu, Jengwei
AU - Liu, Yong
AU - Lawson, Tom
AU - Shimoni, Olga
AU - Lovejoy, David B.
AU - Walker, Adam K.
AU - Cong, Yue
AU - Shi, Bingyang
PY - 2018/7/18
Y1 - 2018/7/18
N2 - Ethanol is a principle ingredient of alcoholic beverages with potential neurotoxicity and genotoxicity, and the ethanol-associated oxidative DNA damage in the central nervous system is well documented. Natural source compounds may offer new options to protect the brain against ethanol-induced genotoxicity. Veratrum maackii Regel is a toxic rangeland plant linked to teratogenicity which is also used in traditional Chinese medicine as 'Lilu' and is reported to contain a family of compounds called stilbenes that can have positive biological activity. In this study, nine stilbenes were isolated from the aerial parts of V. maackii Regel and their structures were identified as cis-mulberroside A (1), resveratrol-4, 3′-O-β-D-diglucopyranoside (2), mulberroside A (3), gentifolin K (4), resveratrol-3, 5-O-β- D-diglucopyranoside (5), oxyresveratrol- 4'-O-β-D-glucopyranoside (6), oxyresveratrol-3-O- β-D -glucopyranoside (7), oxyresveratrol (8) and resveratrol (9) using ESI-MS and NMR techniques. The total concentration of extracted compounds 2-9 was 2.04 mg/g, suggesting that V. maackii Regel is a novel viable source of these compounds. In an in vivo comet assay, compounds 1∼9 were observed to decrease the DNA damage in mouse cerebellum and cerebral cortex caused by acute ethanol administration. Histological observation also revealed decreased brain injury in mice administered with compounds 1~9 after acute ethanol administration. The protective effects of compound 6 were associated with increasing T-SOD and GSH-PX activities and a decrease in NO and MDA concentrations. These findings suggest that these compounds are potent inhibitors of ethanol-induced brain injury possibly via the inhibition of oxidative stress and may be valuable leads for future therapeutic development.
AB - Ethanol is a principle ingredient of alcoholic beverages with potential neurotoxicity and genotoxicity, and the ethanol-associated oxidative DNA damage in the central nervous system is well documented. Natural source compounds may offer new options to protect the brain against ethanol-induced genotoxicity. Veratrum maackii Regel is a toxic rangeland plant linked to teratogenicity which is also used in traditional Chinese medicine as 'Lilu' and is reported to contain a family of compounds called stilbenes that can have positive biological activity. In this study, nine stilbenes were isolated from the aerial parts of V. maackii Regel and their structures were identified as cis-mulberroside A (1), resveratrol-4, 3′-O-β-D-diglucopyranoside (2), mulberroside A (3), gentifolin K (4), resveratrol-3, 5-O-β- D-diglucopyranoside (5), oxyresveratrol- 4'-O-β-D-glucopyranoside (6), oxyresveratrol-3-O- β-D -glucopyranoside (7), oxyresveratrol (8) and resveratrol (9) using ESI-MS and NMR techniques. The total concentration of extracted compounds 2-9 was 2.04 mg/g, suggesting that V. maackii Regel is a novel viable source of these compounds. In an in vivo comet assay, compounds 1∼9 were observed to decrease the DNA damage in mouse cerebellum and cerebral cortex caused by acute ethanol administration. Histological observation also revealed decreased brain injury in mice administered with compounds 1~9 after acute ethanol administration. The protective effects of compound 6 were associated with increasing T-SOD and GSH-PX activities and a decrease in NO and MDA concentrations. These findings suggest that these compounds are potent inhibitors of ethanol-induced brain injury possibly via the inhibition of oxidative stress and may be valuable leads for future therapeutic development.
KW - Veratrum maackii Regel
KW - stilbenes
KW - DNA damage
KW - oxidative stress
KW - oxyresveratrol-4′-O-β-D-glucoside
KW - ethanol
KW - cerebellum
KW - cerebral cortex
UR - http://www.scopus.com/inward/record.url?scp=85046530740&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/nhmrc/1111611
UR - http://purl.org/au-research/grants/nhmrc/1101258
U2 - 10.1021/acschemneuro.8b00006
DO - 10.1021/acschemneuro.8b00006
M3 - Article
C2 - 29708326
AN - SCOPUS:85046530740
SN - 1948-7193
VL - 9
SP - 1616
EP - 1624
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
IS - 7
ER -