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Berberine Attenuates Cardiac Hypertrophy Through Inhibition of mTOR Signaling Pathway
Xing Chen1,2, Xingzuan Jiang1, Chuanfang Cheng2
1Department of Geriatrics, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.
Insights
Berberine treatment ameliorates cardiac hypertrophy in rats and H9c2 cells by inhibiting the mammalian target of rapamycin (mTOR) signaling pathway, suggesting its potential as a therapeutic agent for cardiac conditions.
Area of Science:
- Cardiovascular Biology
- Pharmacology
- Molecular Medicine
Background:
- Cardiac hypertrophy is a significant risk factor for heart failure.
- Berberine has shown potential benefits for cardiac hypertrophy, but its mechanisms are not fully understood.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms underlying berberine's effects on cardiac hypertrophy.
- To evaluate berberine's efficacy in both in vivo and in vitro models of cardiac hypertrophy.
Main Methods:
- Cardiac hypertrophy was induced in rats via transverse aorta constriction (TAC) and in H9c2 cells using norepinephrine (NE).
- Berberine treatment was administered to assess its impact on cardiac function, histology, and protein/mRNA expression.
- Key signaling pathways, including mammalian target of rapamycin (mTOR), were analyzed using Western blot and qRT-PCR.
Main Results:
- Berberine treatment significantly ameliorated TAC-induced cardiac hypertrophy and fibrosis in rats.
- Berberine inhibited the activation of the mTOR signaling pathway (phospho-mTOR, phospho-4EBP1, phospho-p70 S6K) in both rat models and NE-treated H9c2 cells.
- A concentration of 10 μM berberine, but not 1 μM, effectively reduced NE-induced hypertrophy in H9c2 cells.
Conclusions:
- Berberine demonstrates cardioprotective effects against pressure-overloaded and norepinephrine-induced cardiac hypertrophy.
- The mechanism involves the inhibition of the mTOR signaling pathway.
- Berberine represents a potential therapeutic candidate for treating cardiac hypertrophy and failure.
Purpose:
Berberine was reported to exert beneficial effects on cardiac hypertrophy. However, its cellular and molecular mechanisms still remained unclear.
Methods:
Cardiac hypertrophy was induced in male Sprague-Dawley (SD) rats by transverse aorta constriction (TAC), with or without 6-week treatment of berberine. Echocardiography was performed to evaluate cardiac function. Rats were then sacrificed for histological assay, with detection for proteins and mRNA. H9c2 cells were pretreated with berberine of different concentrations (0, 1 μM, and 10 μM), followed by treatment with 2 μM norepinephrine (NE). Cells of different groups were measured for cell surface area, with mRNA detected by qRT-PCR and proteins by western blot.
Results:
Compared with the sham group, rats of the TAC group showed significantly increased cardiac hypertrophy and fibrosis, which could be ameliorated by treatment with berberine. Western blot showed that mammalian target of rapamycin (mTOR) signaling-related protein expressions, including phospho-mTOR, phospho-4EBP1, and phospho-p70 S6K (Thr389), but not phospho-p70 S6K (Ser371), were significantly increased in the TAC group, which were inhibited by berberine treatment. H9c2 cells were treated with NE to induce hypertrophy with increased cell surface area and mRNA expressions of anp and bnp. Berberine of 10 μM, but not 1 μM, significantly ameliorated NE-induced hypertrophy and inhibited protein expressions of mTOR signaling pathway similar to those in the rat model.
Conclusions:
Berberine can exert cardioprotective effects on both pressure-overloaded cardiac hypertrophy and failure in vivo and NE-induced hypertrophy in vitro. Our results suggest berberine could be a potential treatment for patients with cardiac hypertrophy and failure.
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