PMID- 28522909 OWN - NLM STAT- MEDLINE DCOM- 20180516 LR - 20220408 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 23 IP - 16 DP - 2017 Apr 28 TI - In vitro and in vivo antioxidative and hepatoprotective activity of aqueous extract of Cortex Dictamni. PG - 2912-2927 LID - 10.3748/wjg.v23.i16.2912 [doi] AB - AIM: To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract (CDAE) in carbon tetrachloride (CCl(4))-induced liver damage in rats. METHODS: The in vitro antioxidant effect of CDAE was investigated using alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), beta-carotene bleaching, reducing power, and thiobarbituric acid reactive substance assays. A linoleic acid system, including ferric thiocyanate (FTC) and thiobarbituric acid (TBA) assays, was used to evaluate the inhibition of lipid peroxidation. The in vivo hepatoprotective and antioxidant effects of CDAE against CCl(4)-induced liver damage were evaluated in Sprague-Dawley rats. Silymarin was used as a positive control. Liver damage was assessed by determining hepatic histopathology and liver marker enzymes in serum. Enzyme and non-enzyme antioxidant levels and lipid peroxide content were measured in the liver. Cytochrome P450 2E1 (CYP2E1) protein expression was measured via immunohistochemical staining. Nuclear factor E2-related factor (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinine oxidoreductase 1 (NQO1), and gamma-glutamylcysteine synthetase catalytic subunit (gamma-GCSc) protein expression was measured by Western blot. RESULTS: Our results showed that CDAE exhibited a strong antioxidant activity in vitro. CDAE scavenged DPPH and ABTS radicals in a dose-dependent manner. CDAE inhibited lipid peroxidation with a lipid peroxide inhibition rate of 40.6% +/- 5.2%. In the FTC and TBA assays, CDAE significantly inhibited lipid peroxidation (P < 0.01). In vivo histopathological studies indicated that CCl(4)-induced liver injury was alleviated following CDAE treatment in rats of both sexes. CDAE (160 and 320 mg/kg) significantly prevented CCl(4)-induced elevations of alkaline phosphatase, glutamate pyruvate transaminase, aspartate aminotransferase, and total bilirubin levels in rats of both sexes (P < 0.05, 0.01, or 0.001). Moreover, CDAE restored the decreased activities of hepatic antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, as well as non-enzyme antioxidant glutathione, which were induced by CCl(4) treatment. CDAE significantly suppressed the up-regulation of CYP2E1 and promoted Nrf2, HO-1, NQO1, and gamma-GCSc protein expression. CONCLUSION: CDAE exhibits good antioxidant performance in vitro, with marked radical-scavenging and anti-lipid peroxidation activities. CDAE is effective in preventing CCl(4)-induced hepatic damage in rats of both sexes. The hepatoprotective activity of CDAE may be attributable to its antioxidant activity, which may involve Keap1-Nrf2-mediated antioxidant regulation. FAU - Li, Lin AU - Li L AD - Lin Li, Yun-Feng Zhou, Yan-Lin Li, Li-Li Wang, Yang Xu, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. FAU - Zhou, Yun-Feng AU - Zhou YF AD - Lin Li, Yun-Feng Zhou, Yan-Lin Li, Li-Li Wang, Yang Xu, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. FAU - Li, Yan-Lin AU - Li YL AD - Lin Li, Yun-Feng Zhou, Yan-Lin Li, Li-Li Wang, Yang Xu, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. FAU - Wang, Li-Li AU - Wang LL AD - Lin Li, Yun-Feng Zhou, Yan-Lin Li, Li-Li Wang, Yang Xu, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. FAU - Arai, Hiderori AU - Arai H AD - Lin Li, Yun-Feng Zhou, Yan-Lin Li, Li-Li Wang, Yang Xu, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. FAU - Xu, Yang AU - Xu Y AD - Lin Li, Yun-Feng Zhou, Yan-Lin Li, Li-Li Wang, Yang Xu, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (Antioxidants) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, rat) RN - 0 (Plant Extracts) RN - 0 (Silymarin) RN - CL2T97X0V0 (Carbon Tetrachloride) RN - EC 1.14.13.- (Cytochrome P-450 CYP2E1) RN - EC 1.14.14.18 (Heme Oxygenase (Decyclizing)) RN - EC 1.14.14.18 (Hmox1 protein, rat) RN - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone)) RN - EC 1.6.5.2 (NQO1 protein, rat) RN - EC 6.3.2.2 (Glutamate-Cysteine Ligase) SB - IM MH - Animals MH - Antioxidants/isolation & purification/*pharmacology MH - Carbon Tetrachloride MH - Chemical and Drug Induced Liver Injury/metabolism/pathology/*prevention & control MH - Cytochrome P-450 CYP2E1/metabolism MH - Cytoprotection MH - Dictamnus/*chemistry MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Glutamate-Cysteine Ligase/metabolism MH - Heme Oxygenase (Decyclizing)/metabolism MH - Lipid Peroxidation/drug effects MH - Liver/*drug effects/metabolism/pathology MH - Male MH - NAD(P)H Dehydrogenase (Quinone)/metabolism MH - NF-E2-Related Factor 2/metabolism MH - Oxidative Stress/*drug effects MH - Phytotherapy MH - Plant Extracts/isolation & purification/*pharmacology MH - Plants, Medicinal MH - Rats, Sprague-Dawley MH - Silymarin/pharmacology MH - Time Factors PMC - PMC5413786 OTO - NOTNLM OT - Antioxidant activity OT - Carbon tetrachloride OT - Cortex Dictamni OT - Hepatoprotective OT - Nrf2 COIS- Conflict-of-interest statement: The authors declare no financial conflict of interest. EDAT- 2017/05/20 06:00 MHDA- 2018/05/17 06:00 PMCR- 2017/04/28 CRDT- 2017/05/20 06:00 PHST- 2017/01/11 00:00 [received] PHST- 2017/02/28 00:00 [revised] PHST- 2017/03/15 00:00 [accepted] PHST- 2017/05/20 06:00 [entrez] PHST- 2017/05/20 06:00 [pubmed] PHST- 2018/05/17 06:00 [medline] PHST- 2017/04/28 00:00 [pmc-release] AID - 10.3748/wjg.v23.i16.2912 [doi] PST - ppublish SO - World J Gastroenterol. 2017 Apr 28;23(16):2912-2927. doi: 10.3748/wjg.v23.i16.2912.