Hepatoprotective Effect of Pericarpium zanthoxyli Extract Is Mediated via Antagonism of Oxidative Stress

Sang Mi Park; Jae Kwang Kim; Eun Ok Kim; Kyung Hwan Jegal; Dae Hwa Jung; Sang Gon Lee; Il Je Cho; SeungMo Kim; Sung Hui Byun; Sae-Kwang Ku; Chung A Park; Chul Won Lee; Won G An; Sang Chan Kim; Rongjie Zhao

doi:10.1155/2020/6761842

Hepatoprotective Effect of Pericarpium zanthoxyli Extract Is Mediated via Antagonism of Oxidative Stress

Evid Based Complement Alternat Med. 2020 Jul 9:2020:6761842. doi: 10.1155/2020/6761842. eCollection 2020.

Authors

Affiliations

¹ College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
² HaniBio Co. Ltd., Gyeongsan 38540, Republic of Korea.
³ Kabsan Korean Hospital, Seoul 06362, Republic of Korea.
⁴ Research Institute for Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
⁵ School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
⁶ Department of Psychopharmacology, Qiqihar Medical University, Qiqihar 161006, China.

Abstract

Pericarpium zanthoxyli has been extensively used in traditional Oriental medicine to treat gastric disorders and has anti-inflammatory and antioxidative activities. Therefore, the present study examined a possible hepatoprotective effect of a P. zanthoxyli extract (PZE) and investigated the underlying molecular mechanisms. We employed an in vitro model of arachidonic acid (AA) + iron-induced hepatocyte damage and an in vivo model of CCl₄-induced liver injury to assess the effects of PZE and evaluated the relevant molecular targets using biochemical assays, flow cytometry analysis, Western blot, and histopathological analysis. The PZE inhibited AA + iron-induced hepatotoxicity in HepG2 cells, improved mitochondrial dysfunction, and reversed an increase in the cellular H₂O₂ production and a decrease in the reduced GSH levels induced by AA + iron. Treatment with either 30 or 100 μg/ml PZE significantly increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) protein, and the latter dose also increased the antioxidant response element- (ARE-) driven luciferase activity and enhanced the protein expressions of glutamate-cysteine ligase catalytic subunit and NAD(P)H:quinone oxidoreductase 1. In addition, treatment with 100 μg/ml PZE for 3 or 6 h increased the phosphorylation rates of Nrf2 and the extracellular signal-regulated kinase. In the in vivo experiment, oral treatment with both 100 and 300 mg/kg PZE inhibited the plasma aspartate aminotransferase activity, and the latter also inhibited the plasma alanine aminotransferase activity. In addition, both doses of PZE ameliorated the parenchymal degeneration and necrosis in the liver induced by CCl₄ administration, which was associated with reduced expressions of cleaved caspase-3, cleaved poly (ADP-ribose) polymerase, nitrotyrosine, and 4-hydroxynonenal by PZE. These findings suggest that PZE has protective effects against hepatotoxicity both in vitro and in vivo, which are mainly mediated via its antioxidant activity.