2. Academic Validation
  3. Rehmannioside D ameliorates hepatocyte apoptosis and liver fibrosis by suppressing Sirt7/p53 axis

Rehmannioside D ameliorates hepatocyte apoptosis and liver fibrosis by suppressing Sirt7/p53 axis

  • J Ethnopharmacol. 2026 Feb 28:357:120863. doi: 10.1016/j.jep.2025.120863.
Yue Liang 1,  Tian-Yu Cheng 1,  Jia-Ying Pu 1,  Gao-Feng Chen 1,  Wei Liu 1,  Yong-Ping Mu 1,  Hua Zhang 1,  Jia-Mei Chen 2,  Ping Liu 3
Affiliations

Affiliations

  • 1 Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 2 Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: [email protected].
  • 3 Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: [email protected].
PMID: 41224087 DOI: 10.1016/j.jep.2025.120863
Abstract

Ethnopharmacological relevance: The traditional Chinese herb Rehmannia glutinosa (Gaertn.) DC. is an extensively employed to manage liver diseases. Rehmannioside D (RD), a major bioactive constituent of Rehmannia glutinosa (Gaertn.) DC, exhibits significant anti-apoptotic properties. Nevertheless, its efficacy and underlying mechanisms against hepatic fibrosis remain poorly defined.

Aim of the study: To evaluate the pharmacological effects of RD on liver fibrosis and elucidate its underlying mechanisms of action.

Materials and methods: In vivo, the therapeutic efficacy of RD was evaluated in two classical liver fibrosis models: CCl4-treated mice and DMN-exposed rats. In vitro, RD's impact on hepatocyte Apoptosis and the contribution of Sirtuin 7 (SIRT7) were investigated in H2O2-injured AML12 cells, using a selective SIRT7 Inhibitor.

Results: RD treatment demonstrated a systematic reduction in hepatic injury, inflammation, and Collagen deposition in vivo fibrosis models. RNA-sequencing analysis revealed that the therapeutic effects of RD was closely related to suppression of the p53 signaling pathway and cellular Apoptosis. Similarly, RD significantly alleviated hepatocyte Apoptosis in fibrotic livers, and this anti-apoptotic effect was mediated through the SIRT7/p53 signaling axis. In vitro, RD alleviated H2O2-induced Apoptosis in AML12 cells, however, this protective effect was partially abrogated by pharmacological inhibition of SIRT7.

Conclusion: Collectively, these findings indicated that RD attenuates hepatic fibrosis by upregulating SIRT7 expression, thereby inhibiting acetyl-p53-mediated hepatocyte Apoptosis. Collectively, our findings establish RD as a promising anti-fibrotic agent and identify the SIRT7/p53 axis as its key mechanistic conduit.

Keywords

Apoptosis; Liver fibrosis; Rehmannioside D; Sirt7; p53.

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