Berberine alleviates oxidized low‐density lipoprotein‐induced macrophage activation by downregulating galectin‐3 via the NF‐κB and AMPK signaling pathways
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Macrophage activation plays a central role in neoatherosclerosis and in‐stent restenosis after percutaneous coronary intervention (PCI). Galectin‐3, mainly expressed on macrophages, is an important regulator of inflammation. This study aimed to investigate the effects of berberine (BBR) on oxidized low‐density lipoprotein (ox‐LDL)‐induced macrophage activation and galectin‐3 expression and their underlying mechanisms. THP‐1‐derived macrophages were pretreated with BBR prior to stimulation with ox‐LDL. Galectin‐3 expression was measured by real‐time PCR, Western blotting, and confocal microscopy. Macrophage activation was assessed by lipid accumulation, expression of inflammatory cytokines, and CD11b and CD86. Plasma galectin‐3 levels were measured in patients undergoing PCI at baseline and after BBR treatment for 3 months. BBR suppressed ox‐LDL‐induced upregulation of galectin‐3 and macrophage activation. Overexpression of galectin‐3 intervened the inhibitory effect of BBR on macrophage activation. BBR activated phospho‐AMPK and inhibited phospho‐NF‐κB p65 nuclear translocation. AMPK inhibition and NF‐κB activation abolished the inhibitory effects of BBR on galectin‐3 expression and macrophage activation. Combination of BBR and rosuvastatin exerted greater effects than BBR or rosuvastatin alone. However, BBR treatment did not further reduce plasma galectin‐3 after PCI in patients receiving standard therapy. In conclusion, BBR alleviates ox‐LDL‐induced macrophage activation by downregulating galectin‐3 via the NF‐κB and AMPK signaling pathways.
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Berberine targets NF-κB to improve insulin resistance and inflammation.
“For patients with T2DM, the main function of berberine is as a SIRT1 or AMPK agonist to mimic energy restriction [75–77] and to target on NF-κB [78] to improve insulin resistance and inflammation as well as to alleviate the activation of ox-LDL-induced macrophages [79].”
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 [78]
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References 44 · Cited by 80
- Authors
- Pei, C., Zhang, Y., Wang, P., Zhang, B., Fang, L., Liu, B., & Meng, S.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Haematopoiesis and Leukocyte Biology Laboratory Baker Heart and Diabetes Research Institute Melbourne Victoria Australia
- Corresponding author
- Meng, Shu
- Venue
- Phytotherapy Research
- Publisher
- Wiley
- Published
- 2018-11-06
- Volume
- 33
- Issue
- 2
- Pages
- 294-308
- ISSN
- 0951-418X (ISSN-L)
- 1099-1573
- PMC
- PMC6587449
- OpenAlex
- W2899951482
- Cited by
- 80
- References
- 44
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 16 · 2023: 13 · 2022: 14 · 2021: 6 · 2020: 8 · 2019: 7
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Phytotherapy Research (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81270207)
- Science and Technology Commission of Shanghai Municipality (16401972000)
- Topics
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- berberine, oxidized LDL, macrophage activation, galectin-3, NF-κB signaling, AMPK signaling, in-stent restenosis, percutaneous coronary intervention, rosuvastatin, atherosclerosis, inflammation, THP-1 macrophages
- MeSH terms
- Aged, Aged, 80 and over, Berberine, Cells, Cultured, Female, Gene Expression Regulation, Humans, Inflammation, Lipoproteins, LDL, Macrophage Activation, Macrophages, Male, Middle Aged, Signal Transduction, Down-Regulation, NF-kappa B, Galectin 3, Transcription Factor RelA, AMP-Activated Protein Kinases, Percutaneous Coronary Intervention
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