Potential natural mTOR inhibitors screened by in silico approach and suppress hepatic stellate cells activation
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Updated: Feb 18, 2026
Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
Varadharajan Thiyagarajan1, Kuan-Wei Lee1, Max K Leong1,2
1a Department of Life Science and Institute of Biotechnology , National Dong Hwa University , Shoufeng, Hualien , 97401 , Taiwan.
Abstract:
The mammalian target of rapamycin (mTOR), an atypical serine/threonine kinase, plays a central role in the regulation of cell proliferation, growth, differentiation, migration, and survival. In this study, the 3-D structure of the mTOR (PDB ID: 2FAP) was used for the docking of 47 natural compounds and compared with pharmacophore model of 14 known mTOR inhibitors to identify the novel and specific natural inhibitor. The top four compounds, rutin, curcumin, antroquinonol, and benzyl cinnamate, have been selected based on their PLP score and further validated with hepatic stellate cells NHSC and THSC. Curcumin and antroquinonol significantly inhibited NHSC and THSC cells proliferation in a dose-dependent manner, whereas rutin and benzyl cinnamate showed less alteration of cell viability. Rutin inhibited the phosphorylation of mTOR (p-mTOR) and p-p70 S6 K in NHSC and THSC cells by Western blotting. Additionally, p-p70 S6 K protein was significantly decreased by incubation with benzyl cinnamate and curcumin in THSC cells. Taken together, this result suggests that rutin is a potential mTOR inhibitor in screen hits of molecular docking to hamper the activation of HSC and further applications in the treatment of liver fibrosis.
Insights
Rutin and other natural compounds were screened as potential inhibitors of mammalian target of rapamycin (mTOR). Rutin showed promise in inhibiting mTOR signaling pathways, suggesting its potential for treating liver fibrosis.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- The mammalian target of rapamycin (mTOR) is a key kinase regulating cell growth, proliferation, and survival.
- Dysregulation of mTOR signaling is implicated in various diseases, including liver fibrosis.
Purpose of the Study:
- To identify novel natural compounds that inhibit mTOR using molecular docking.
- To evaluate the efficacy of selected natural compounds in inhibiting hepatic stellate cell activation.
Main Methods:
- 3-D structure of mTOR (PDB ID: 2FAP) used for docking 47 natural compounds.
- Pharmacophore model of 14 known mTOR inhibitors used for comparison.
- In vitro validation using hepatic stellate cells (NHSC and THSC) and Western blotting.
Main Results:
- Rutin, curcumin, antroquinonol, and benzyl cinnamate were identified as top potential mTOR inhibitors.
- Curcumin and antroquinonol inhibited cell proliferation; rutin inhibited mTOR and p70 S6K phosphorylation.
- Rutin demonstrated potential to hamper hepatic stellate cell activation.
Conclusions:
- Rutin is a potential natural inhibitor of mTOR, identified through molecular docking and in vitro studies.
- Rutin's ability to inhibit mTOR signaling suggests its therapeutic potential for liver fibrosis treatment.
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