Bavachin Induces Apoptosis through Mitochondrial Regulated ER Stress Pathway in HepG2 Cells
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- Yang Ying
- School of Chinese Medicine, Beijing University of Chinese Medicine Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine
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- Tang Xianglin
- Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine
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- Hao Feiran
- Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine
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- Ma Zengchun
- Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine
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- Wang Yuguang
- Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine
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- Wang Lili
- Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures
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- Gao Yue
- School of Chinese Medicine, Beijing University of Chinese Medicine Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine
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<p>As a traditional herbal medicine, the fruits of Psoralea corylifolia L. (Fructus Psoraleae (FP)) have been widely used for the treatment of various skin diseases for hundred years. Recently, the emerging FP-induced toxic effects, especially hepatotoxicity, in clinic are getting the public’s attention. However, its exact toxic components and mechanisms underlying remain unclear. Bavachin, one of flavonoids in FP, has been documented as a hepatotoxic substance, and the present study aimed to determine the toxicity caused by bavachin and the possible toxic mechanisms involved using human hepatocellular carcinoma (HepG2) cells. Our results showed that bavachin could significantly inhibited cell proliferation and trigger the endoplasmic reticulum (ER) stress in a dose dependent manner. Downregulating ER stress using tauroursodeoxycholic acid (TUDCA) obvious attenuated bavachin-triggerd cell apoptosis. Then, small interfering RNA (siRNA) knock-down of Mitofusion2 (Mfn2) resulted in a remarkable aggravation of ER stress through the inhibition of the phosphorylation of protein kinase B (Akt). Additionally, suppression of reactive oxygen species (ROS) by ROS Scavenger (N-acetyl-l-cystein (NAC)) also reduced bavachin-induced ER stress. Taken together, our study demonstrated that bavachin-induced ER stress caused cell apoptosis by Mfn2-Akt pathway, and that ROS may participate upstream in this mechanism. Here, we not only provide a new understanding of ROS/Mfn2/Akt pathway in bavachin-induced cytotoxicity via the ER stress, but also identify a new specific intervention to prevent FP-induced hepatotoxicity in the future.</p>
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 41 (2), 198-207, 2018
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679609986304
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- NII論文ID
- 130006329334
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 028787124
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- PubMed
- 29187671
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可