Berberine Down-Regulated Myostatin Expression and Facilitated Metabolism via Smad Pathway in Insulin Resistant Mice
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OBJECTIVE: To explore the effect of berberine (BBR) on skeletal muscle mass and metabolism and the possible mechanism. METHODS: Eight-week-old male C57BL/6 mice were fed with a high-fat diet (HFD) for 8 weeks to establish the insulin resistance obesity model. Then, mice were randomly divided into two groups (normal chow diet (NCD) and HFD), while NCD and HFD were further classified into two groups respectively, which were NCD+CS (Carmellose Sodium), NCD+BBR, HFD+CS and HFD+BBR. After the BBR intervention, insulin tolerance test (ITT) and glucose tolerance test (GTT) were carried out. Metabolic parameters and inflammatory biomarkers were detected. Various parts of adipose tissue and gastrocnemius were separated and measured. The gastrocnemius muscle was selected for tissue staining. The mRNA expression of myostatin (Mstn) was tested by quantitative real-time PCR (RT-PCR). Western blotting was performed to detect the expression of Mstn, phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), small ribonucleoprotein particle protein 2 (Smd2), small ribonucleoprotein particle protein 3 (Smd3), and small ribonucleoprotein particle protein 4 (Smd4). RESULTS: <0.001) were decreased significantly, while muscle mass was increased in the HFD group after being treated with BBR. Meanwhile, the glucose and lipid metabolic disorders as well as inflammation status were improved. RT-PCR and Western blotting analysis showed that, after being fed with HFD the expression of Mstn mRNA and Mstn were significantly increased, and decreased after being treated with BBR. Western blotting analysis also showed that, compared with the NCD group, the expressions of Smad2, Smad3, and Smad4 were all increased in the HFD group, but after being treated with BBR, the expressions of Smad3 and Smad4 were decreased. CONCLUSION: Our study revealed that BBR could improve metabolic disorders and inflammation status, decrease Mstn expression, and increase skeletal muscle mass, which was associated with the Smad pathway.
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A comprehensive meta-analysis of randomized clinical trials found that berberine significantly improves lipid profiles, reduces triglycerides, total cholesterol, and LDLs, increases HDLs, and lowers insulin resistance and fasting glucose in patients with metabolic disorders.
“Notably, a comprehensive meta-analysis of randomized clinical trials found that berberine significantly improves lipid profiles, reduces triglycerides, total cholesterol, and low-density lipoproteins (LDLs), increases high-density lipoproteins (HDLs), and lowers insulin resistance and fasting glucose in patients with metabolic disorders”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [108]
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Experimental — accuracy not yet measuredExperimental studies demonstrate that berberine enhances skeletal muscle AMPK phosphorylation, SIRT1 activation, and PGC-1α expression.
“Experimental studies further demonstrate that berberine enhances skeletal muscle AMPK phosphorylation, SIRT1 activation, and PGC-1α expression, which are key drivers of mitochondrial function and energy metabolism”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [108]
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“Experimental studies further demonstrate that berberine enhances skeletal muscle AMPK phosphorylation, SIRT1 activation, and PGC-1 α expression, which are key drivers of mitochondrial function and energy metabolism [108].”
- Authors
- Chen, L., Su, X., & Hu, Y.
- Affiliations
- Fudan University (CN)
- Corresponding author
- Hu, Yu
- ORCID
- Venue
- Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
- Publisher
- Informa UK Limited
- Published
- 2020-11
- Volume
- Volume 13
- Pages
- 4561-4569
- ISSN
- 1178-7007 (ISSN-L)
- PMC
- PMC7695611
- OpenAlex
- W3106606729
- Cited by
- 10
- References
- 30
- Citations by year
- 2025: 2 · 2024: 1 · 2022: 6 · 2021: 1
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Diabetes Metabolic Syndrome and Obesity (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- Fudan University
- Topics
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- berberine, myostatin, Smad signaling, insulin resistance, skeletal muscle mass, high-fat diet, obesity, glucose metabolism, lipid metabolism, inflammation, Smad3, SMAD4, Smad2, PI3K/Akt signaling, gastrocnemius
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