Stilbenes from Veratrum maackii Regel Protect against Ethanol-Induced DNA Damage in Mouse Cerebellum and Cerebral Cortex

Wu, Y; Li, S; Liu, J; Liu, X; Ruan, W; Lu, J; Liu, Y; Lawson, T; Shimoni, O; Lovejoy, DB; Walker, AK; Cong, Y; Shi, B

Stilbenes from Veratrum maackii Regel Protect against Ethanol-Induced DNA Damage in Mouse Cerebellum and Cerebral Cortex

Wu, Y Li, S Liu, J Liu, X Ruan, W Lu, J Liu, Y Lawson, T Shimoni, O

Lovejoy, DB Walker, AK Cong, Y Shi, B

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Publication Type:: Journal Article
Citation:: ACS Chemical Neuroscience, 2018, 9 (7), pp. 1616 - 1624
Issue Date:: 2018-07-18

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Field	Value	Language
dc.contributor.author	Wu, Y	en_US
dc.contributor.author	Li, S	en_US
dc.contributor.author	Liu, J	en_US
dc.contributor.author	Liu, X	en_US
dc.contributor.author	Ruan, W	en_US
dc.contributor.author	Lu, J	en_US
dc.contributor.author	Liu, Y	en_US
dc.contributor.author	Lawson, T	en_US
dc.contributor.author	Shimoni, O https://orcid.org/0000-0001-8822-1024	en_US
dc.contributor.author	Lovejoy, DB	en_US
dc.contributor.author	Walker, AK	en_US
dc.contributor.author	Cong, Y	en_US
dc.contributor.author	Shi, B	en_US
dc.date.issued	2018-07-18	en_US
dc.identifier.citation	ACS Chemical Neuroscience, 2018, 9 (7), pp. 1616 - 1624	en_US
dc.identifier.uri	http://hdl.handle.net/10453/131017
dc.description.abstract	© Copyright 2018 American Chemical Society. 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 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.	en_US
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1101258
dc.relation.ispartof	ACS Chemical Neuroscience	en_US
dc.relation.isbasedon	10.1021/acschemneuro.8b00006	en_US
dc.subject.mesh	Cerebellum	en_US
dc.subject.mesh	Cerebral Cortex	en_US
dc.subject.mesh	Neurons	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Veratrum	en_US
dc.subject.mesh	DNA Damage	en_US
dc.subject.mesh	Alcohol-Related Disorders	en_US
dc.subject.mesh	Ethanol	en_US
dc.subject.mesh	Stilbenes	en_US
dc.subject.mesh	Central Nervous System Depressants	en_US
dc.subject.mesh	Plant Extracts	en_US
dc.subject.mesh	Protective Agents	en_US
dc.subject.mesh	Phototherapy	en_US
dc.subject.mesh	Random Allocation	en_US
dc.subject.mesh	Molecular Structure	en_US
dc.subject.mesh	Male	en_US
dc.title	Stilbenes from Veratrum maackii Regel Protect against Ethanol-Induced DNA Damage in Mouse Cerebellum and Cerebral Cortex	en_US
dc.type	Journal Article
utslib.citation.volume	7	en_US
utslib.citation.volume	9	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	0304 Medicinal and Biomolecular Chemistry	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
utslib.copyright.status	closed_access
pubs.issue	7	en_US
pubs.publication-status	Published	en_US
pubs.volume	9	en_US

Abstract:

© Copyright 2018 American Chemical Society. 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 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.

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http://hdl.handle.net/10453/131017