Berberine Improves Inflammatory Responses of Diabetes Mellitus in Zucker Diabetic Fatty Rats and Insulin‐Resistant HepG2 Cells through the PPM1B Pathway
Open accessAbstract
Berberine (BBR), a natural compound extracted from a Chinese herb, has been shown to effectively attenuate insulin resistance (IR) and inflammation in the clinic. However, its ameliorative mechanism against IR is not well defined. This study is aimed at investigating the effect of BBR and protein phosphatase, Mg 2+ /Mn 2+ ‐dependent 1B (PPM1B) on IR. Biochemical measurements and liver histopathology were detected using the biochemical analyzer and HE staining in ZDF rats, respectively. Microarray analysis of liver tissues was performed, and differentially expressed gene (DEG) levels were examined by quantitative real‐time PCR (qPCR) and Western blot. Additionally, the effect of BBR was also explored in HepG2‐IR cells. The glucose oxidase method and the fluorescent glucose analog were used to detect glucose consumption and uptake, respectively. The PKA inhibitor H89, ELISA, qPCR, Western blot, and immunofluorescence staining were employed to estimate the expression levels of related signaling pathways. To evaluate the roles of PPM1B, HepG2‐IR cells were stably infected with lentivirus targeting PPM1B. The administration of BBR drastically decreased the body weight, urine volume, blood glucose, blood urea nitrogen (BUN), CHOL, hepatic index levels, and pathologic changes and improved ALB levels in ZDF rats with PPM1B upregulation. Furthermore, BBR effectively improves glucose consumption, uptake, and inflammation in HepG2‐IR cells. The knockdown of PPM1B expression aggravated the inflammatory response and glycometabolism disorder in HepG2‐IR cells. Mechanistically, a reversal in the expression of cAMP, PKA, PPM1B, PPAR γ , LRP1, GLUT4, NF‐ κ B p65, JNK, pIKK β Ser181, IKK β , IRS‐1 Ser307, IRS‐1, IRS‐2 Ser731, IRS‐2, PI3K p85, and AKT Ser473 contributes to ameliorate IR in HepG2‐IR cells with BBR treatment. Altogether, these results suggest that BBR might regulate IR progression through the regulation of the cAMP, PKA, PPM1B, PPAR γ , LRP1, GLUT4, NF‐ κ B p65, JNK, pIKK β Ser181, IKK β , IRS‐1 Ser307, IRS‐1, IRS‐2 Ser731, IRS‐2, PI3K p85, and AKT Ser473 expression in the liver.
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Berberine improves obesity and hyperlipidemia by reducing TG, TC, and LDL and increasing HDL in several metabolic disorders.
“Whether used alone or combined with other therapies, meta-analyses [16, 72] suggested that berberine improve obesity and hyperlipidemia by reducing TG, TC, and LDL and increasing HDL in the setting of several metabolic disorders along with improving glucose metabolism.”
From The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials (2021) · cites this paper as [72]
Berberine improves glucose metabolism in several metabolic disorders.
“Whether used alone or combined with other therapies, meta-analyses [16, 72] suggested that berberine improve obesity and hyperlipidemia by reducing TG, TC, and LDL and increasing HDL in the setting of several metabolic disorders along with improving glucose metabolism.”
From The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials (2021) · cites this paper as [72]
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- Authors
- Wu, Y. S., Li, Z. M., Chen, Y. T., Dai, S. J., Zhou, X. J., Yang, Y. X., Lou, J. S., Ji, L. T., Bao, Y. T., Xuan, L., Lin, L. N., & Li, C. Y.
- Affiliations
- Zhejiang Chinese Medical University (CN)
- Hangzhou Normal University (CN)
- Venue
- Journal of Immunology Research
- Publisher
- Wiley
- Published
- 2020-01
- Volume
- 2020
- Issue
- 1
- Pages
- 2141508-2141508
- ISSN
- 2314-7156 (ISSN-L)
- 2314-8861
- PMC
- PMC7450322
- OpenAlex
- W3054928484
- Cited by
- 25
- References
- 39
- Citations by year
- 2025: 2 · 2024: 8 · 2023: 5 · 2022: 3 · 2021: 7
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Immunology Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81673839, 81373507)
- Topics
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- berberine, insulin resistance, PPM1B, protein phosphatase 2A, diabetes mellitus, liver inflammation, cAMP/PKA signaling, PPARγ, LRP1, GLUT4, NF-κB, JNK, IKKβ, IRS-1, insulin receptor substrate 2, PI3K/Akt signaling, glucose uptake, hepatic steatosis
- MeSH terms
- Protein Phosphatase 2C, Cyclic AMP, Animals, Anti-Inflammatory Agents, Berberine, Cell Survival, Diabetes Mellitus, Experimental, Disease Models, Animal, Energy Metabolism, Glucose, Humans, Insulin, Insulin Resistance, Liver, Signal Transduction, Biomarkers, NF-kappa B, Mice, Knockout, Computational Biology, Gene Silencing, Gene Expression Profiling, Rats, Hep G2 Cells
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