Saikosaponin D, a triterpene saponin from Bupleurum falcatum, restores circadian rhythm and attenuates hepatic fibrosis via Esr1-Per2 axis.

IF 1.3 3区 医学 Q3 CHEMISTRY, APPLIED Journal of Asian Natural Products Research Pub Date : 2025-04-09 DOI:10.1080/10286020.2025.2482068
Yu-Gang Fu, Jun-Min Wang, Si-Min Gu, Chong Chen, Yan-Ping Wang, Yi-Yuan Zheng, Yong Li
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Abstract

Hepatic fibrosis, a precursor to chronic liver diseases, is linked to circadian rhythm disruptions. This study investigates the anti-fibrotic effects of saikosaponin D (SSd) from Bupleurum falcatum L. and its regulation of circadian genes. Transcriptomic and single-cell analyses revealed circadian gene dysregulation, particularly Period 2 (Per2), in liver fibrosis and hepatic stellate cells. SSd upregulated Per2 transcription via estrogen receptor 1 (Esr1), as confirmed by siRNA, real-time quantitative polymerase chain reaction, and Western blot analyses. In vivo, SSd alleviated fibrosis and hepatitis, increasing Esr1 but not Per2 protein levels. These findings suggest SSd exerts anti-fibrotic effects by modulating Esr1-mediated Per2 transcription.

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柴胡皂苷D是一种来自柴胡的三萜皂苷,通过Esr1-Per2轴恢复昼夜节律并减轻肝纤维化。
肝纤维化是慢性肝病的前兆,与昼夜节律紊乱有关。本研究调查了柴胡中的柴胡皂苷 D(SSd)的抗纤维化作用及其对昼夜节律基因的调控。转录组和单细胞分析表明,肝纤维化和肝星状细胞中的昼夜节律基因失调,尤其是周期2(Per2)。经 siRNA、实时定量聚合酶链反应和 Western 印迹分析证实,SSd 通过雌激素受体 1(Esr1)上调 Per2 的转录。在体内,SSd 能减轻肝纤维化和肝炎,提高 Esr1 蛋白水平,但不能提高 Per2 蛋白水平。这些发现表明 SSd 通过调节 Esr1 介导的 Per2 转录发挥抗纤维化作用。
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来源期刊
CiteScore
3.20
自引率
5.90%
发文量
47
审稿时长
2.3 months
期刊介绍: The Journal of Asian Natural Products Research (JANPR) publishes chemical and pharmaceutical studies in the English language in the field of natural product research on Asian ethnic medicine. The journal publishes work from scientists in Asian countries, e.g. China, Japan, Korea and India, including contributions from other countries concerning natural products of Asia. The journal is chemistry-orientated. Major fields covered are: isolation and structural elucidation of natural constituents (including those for non-medical uses), synthesis and transformation (including biosynthesis and biotransformation) of natural products, pharmacognosy, and allied topics. Biological evaluation of crude extracts are acceptable only as supporting data for pure isolates with well-characterized structures. All published research articles in this journal have undergone rigorous peer review, based on initial editor screening and anonymized refereeing by at least two expert referees.
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