A <i>Scd1</i>-mediated metabolic alteration participates in liver responses to low-dose bavachin

Pan Shen; Zhi-Jie Bai; Lei Zhou; Ning-Ning Wang; Zhe-Xin Ni; De-Zhi Sun; Cong-Shu Huang; Yang-Yi Hu; Cheng-Rong Xiao; Wei Zhou; Bo-Li Zhang; Yue Gao

doi:10.1016/j.jpha.2023.03.010

Volume 13 Issue 7

Jul. 2023

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Article Navigation > Journal of Pharmaceutical Analysis > 2023 > 13(7): 806-816

Pan Shen, Zhi-Jie Bai, Lei Zhou, Ning-Ning Wang, Zhe-Xin Ni, De-Zhi Sun, Cong-Shu Huang, Yang-Yi Hu, Cheng-Rong Xiao, Wei Zhou, Bo-Li Zhang, Yue Gao. A Scd1-mediated metabolic alteration participates in liver responses to low-dose bavachin[J]. Journal of Pharmaceutical Analysis, 2023, 13(7): 806-816. doi: 10.1016/j.jpha.2023.03.010

Citation:

Pan Shen, Zhi-Jie Bai, Lei Zhou, Ning-Ning Wang, Zhe-Xin Ni, De-Zhi Sun, Cong-Shu Huang, Yang-Yi Hu, Cheng-Rong Xiao, Wei Zhou, Bo-Li Zhang, Yue Gao. A Scd1-mediated metabolic alteration participates in liver responses to low-dose bavachin[J]. Journal of Pharmaceutical Analysis, 2023, 13(7): 806-816. doi: 10.1016/j.jpha.2023.03.010

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A Scd1-mediated metabolic alteration participates in liver responses to low-dose bavachin

doi: 10.1016/j.jpha.2023.03.010

a. Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, China;
b. State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China

Funds:

This work was supported by the National Natural Science Foundation of China (Grant Nos.: 82192910 and 82192911) and the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine (Grant No.: ZYYCXTD-D-202207).

Received Date: Nov. 30, 2022
Accepted Date: Mar. 27, 2023
Rev Recd Date: Mar. 24, 2023
Publish Date: Apr. 05, 2023

Abstract

Abstract

Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs, such as bavachin (BV) in Fructus Psoraleae, has a prolonged latency to overt drug-induced liver injury in the clinic. Several studies have described BV-induced liver damage and underlying toxicity mechanisms, but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level, and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase, making it much harder for early recognition of hepatotoxicity. Here, we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests, but found subtle steatosis in BV-treated hepatocytes. We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver. Among these, the hepa3 subtype suffered from a vast alteration in lipid metabolism, which was characterized by enhanced expression of apolipoproteins, carboxylesterases, and stearoyl-CoA desaturase 1 (Scd1). In particular, increased Scd1 promoted monounsaturated fatty acids (MUFAs) synthesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids (PUFAs) generation, which participates in the initiation of ferroptosis. Additionally, we demonstrated that multiple intrinsic transcription factors, including Srebf1 and Hnf4a, and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes. Collectively, our study deciphered the features of hepatocytes in response to BV insult, decoded the underlying molecular mechanisms, and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.
- Bavachin,
- Hepatotoxicity,
- Scd1,
- Lipid metabolism,
- Single-cell RNA-Seq

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References(72)

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