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Peer-reviewedCC BY 4.0Frontiers in Pharmacology

Kurarinol A from Sophora flavescens suppresses hepatic stellate cell activation via the TLR4/MyD88/NF-κB pathway

  • Xing-Jun Chen1,2,3
  • Qian Wang1,2,3
  • Mu-Zhen Wang1,2,3
  • Xu Zhang1,2,3
  • Shang-Gao Liao1,2,3
  • Zhu Zeng1,2,3
  • Xiao-Peng Li4
  • Lihui Wang5
  • Bo Tu1,2,3
  • Yan Lin1,2,3
5 affiliations
  1. 1State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine and School of Pharmaceutical Sciences, Guizhou Medical University
  2. 2Engineering Research Center for the Prevention and Treatment of Chronic Diseases by Authentic Medicinal Materials, Guizhou Provincial Department of Education, Guizhou Medical University
  3. 3Key Laboratory of Quality Control and Evaluation of Traditional Chinese and Ethnic Medicines, Administration for Market Regulation of Guizhou Province
  4. 4Guiyang Longmaster Information Technology Co, Ltd.
  5. 5College of Computer Science and Technology, Guizhou University
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Abstract

Introduction: Sophora flavescens is traditionally used in TCM and Miao/Mongolian/Yi ethnomedicines for hepatobiliary disorders, yet its bioactive flavonoid constituents and mechanisms remain incompletely understood. This study investigated the anti-hepatic fibrosis efficacy, mechanism, and target of the ethyl acetate fraction (EAF) from S. flavescens and its key lavandulyl flavonoid kurarinol A (KA).

Methods: A CCl4-induced mouse hepatic fibrosis model was established to evaluate liver injury and fibrosis by H&E/Masson staining and detection of serum ALT/AST and hepatic α-SMA/fibronectin/Hyp. A TGF-β1-activated LX-2 cell model was established, with cell viability, migration, and apoptosis evaluated by MTS, wound-healing, and Annexin V-FITC/PI assays. Transcriptomics, KEGG analysis, molecular docking, Molecular dynamics (MD) simulation, CETSA, and MyD88 knockdown/overexpression assays were applied to explore the underlying mechanism.

Results: In vivo , EAF (50 and 100 mg/kg) alleviated CCl4-induced liver injury and fibrosis and decreased the levels of fibrotic serum biomarkers. In vitro , KA significantly inhibited LX-2 cell activation with an IC50 of 12.65 μM (n = 3), suppressing cell proliferation and migration while inducing apoptosis. KA’s anti-fibrotic activity was validated only in vitro , and its contribution to the in vivo efficacy of the EAF remains inferred rather than directly proven. Mechanistically, KA downregulated key signaling molecules of the TLR4/NF- κ B pathway, thereby blocking pathway activation. Molecular docking, MD simulations and CETSA supported a direct interaction between KA and MyD88. MyD88 knockdown and overexpression assays further supported that MyD88 serves as a candidate molecular target mediating KA’s anti-fibrotic activity.

Conclusion: The EAF exerts anti-fibrotic effects in vivo, and KA exhibits consistent anti-fibrotic activity in vitro . These findings support MyD88 as a potential molecular target mediating KA’s in vitro anti-fibrotic activity via TLR4/NF- κ B signaling. These findings not only validate the traditional use of S. flavescens in hepatobiliary disorders, but also offer a promising MyD88-targeting candidate warranting lead optimization for anti-fibrotic drug development.

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Cite

BibTeXRIS
BibTeX
@article{chen2026kurarinol,
  title = {{Kurarinol A from Sophora flavescens suppresses hepatic stellate cell activation via the TLR4/MyD88/NF-κB pathway}},
  author = {Xing-Jun Chen and Qian Wang and Mu-Zhen Wang and Xu Zhang and Shang-Gao Liao and Zhu Zeng and Xiao-Peng Li and Lihui Wang and Bo Tu and Yan Lin},
  journal = {Frontiers in Pharmacology},
  year = {2026},
  month = oct,
  doi = {10.3389/fphar.2026.1948257},
  url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1948257/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Kurarinol A from Sophora flavescens suppresses hepatic stellate cell activation via the TLR4/MyD88/NF-κB pathway
AU  - Xing-Jun Chen
AU  - Qian Wang
AU  - Mu-Zhen Wang
AU  - Xu Zhang
AU  - Shang-Gao Liao
AU  - Zhu Zeng
AU  - Xiao-Peng Li
AU  - Lihui Wang
AU  - Bo Tu
AU  - Yan Lin
PY  - 2026
DA  - 2026/10/22
JO  - Frontiers in Pharmacology
DO  - 10.3389/fphar.2026.1948257
UR  - https://www.frontiersin.org/articles/10.3389/fphar.2026.1948257/full
AB  - Introduction: Sophora flavescens is traditionally used in TCM and Miao/Mongolian/Yi ethnomedicines for hepatobiliary disorders, yet its bioactive flavonoid constituents and mechanisms remain incompletely understood. This study investigated the anti-hepatic fibrosis efficacy, mechanism, and target of the ethyl acetate fraction (EAF) from S. flavescens and its key lavandulyl flavonoid kurarinol A (KA).  Methods: A CCl4-induced mouse hepatic fibrosis model was established to evaluate liver injury and fibrosis by H&E/Masson staining and detection of serum ALT/AST and hepatic α-SMA/fibronectin/Hyp. A TGF-β1-activated LX-2 cell model was established, with cell viability, migration, and apoptosis evaluated by MTS, wound-healing, and Annexin V-FITC/PI assays. Transcriptomics, KEGG analysis, molecular docking, Molecular dynamics (MD) simulation, CETSA, and MyD88 knockdown/overexpression assays were applied to explore the underlying mechanism.  Results: In vivo , EAF (50 and 100 mg/kg) alleviated CCl4-induced liver injury and fibrosis and decreased the levels of fibrotic serum biomarkers. In vitro , KA significantly inhibited LX-2 cell activation with an IC50 of 12.65 μM (n = 3), suppressing cell proliferation and migration while inducing apoptosis. KA’s anti-fibrotic activity was validated only in vitro , and its contribution to the in vivo efficacy of the EAF remains inferred rather than directly proven. Mechanistically, KA downregulated key signaling molecules of the TLR4/NF- κ B pathway, thereby blocking pathway activation. Molecular docking, MD simulations and CETSA supported a direct interaction between KA and MyD88. MyD88 knockdown and overexpression assays further supported that MyD88 serves as a candidate molecular target mediating KA’s anti-fibrotic activity.  Conclusion: The EAF exerts anti-fibrotic effects in vivo, and KA exhibits consistent anti-fibrotic activity in vitro . These findings support MyD88 as a potential molecular target mediating KA’s in vitro anti-fibrotic activity via TLR4/NF- κ B signaling. These findings not only validate the traditional use of S. flavescens in hepatobiliary disorders, but also offer a promising MyD88-targeting candidate warranting lead optimization for anti-fibrotic drug development.
SN  - 1663-9812
ER  -