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BMC Complementary Medicine and Therapies

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Open Access 01-12-2019 | Metformin | Research article

Inhibitory effects of berberine on proinflammatory M1 macrophage polarization through interfering with the interaction between TLR4 and MyD88

Authors: Jing Gong, Jingbin Li, Hui Dong, Guang Chen, Xin Qin, Meilin Hu, Fen Yuan, Ke Fang, Dingkun Wang, Shujun Jiang, Yan Zhao, Wenya Huang, Zhaoyi Huang, Fuer Lu

Published in: BMC Complementary Medicine and Therapies | Issue 1/2019

Abstract

Backgrounds

Inflammation is recognized as the key pathological mechanism of type 2 diabetes. The hypoglyceamic effects of berberine (BBR) are related to the inhibition of the inflammatory response, but the mechanism is not completely clear.

Methods

The inflammatory polarization of Raw264.7 cells and primary peritoneal macrophages were induced by LPS, and then effects and underlying mechanisms of BBR were explored. An inflammatory model was established by LPS treatment at different concentrations for different treatment time. An ELISA assay was used to detect the secretions of TNF-α. RT-PCR was applied to detect M1 inflammatory factors. The F4/80⁺ ratio and CD11c⁺ ratio of primary peritoneal macrophages were determined by flow cytometry. The expressions of p-AMPK and TLR4 were detected by Western blot. The cytoplasmic and nuclear distributions of NFκB p65 were observed by confocal microscopy. The binding of TLR4 to MyD88 was tested by CoIP, and the affinity of BBR for TLR4 was assessed by molecular docking.

Results

Upon exposure to LPS, the secretion of TNF-α and transcription of inflammatory factors in macrophages increased, cell morphology changed and protrusions appeared gradually, the proportion of F4/80⁺CD11c⁺ M1 macrophages increased, and the nuclear distribution of NFκB p65 increased. BBR pretreatment partially inhibited the changes mentioned above. However, the expression of TLR4 and p-AMPK did not change significantly after LPS intervention for 3 h. Meanwhile, CoIP showed that the interaction between TLR4 and MyD88 increased, and BBR inhibited the binding. Molecular docking suggested that BBR might interact with TLR4.

Conclusions

Inflammatory changes were induced in macrophages after LPS stimulation for 3 h, and BBR pretreatment inhibited inflammatory polarization. BBR might interact with TLR4 and disturb TLR4/MyD88/NFκB signalling pathway, and it might be the mechanism by which BBR attenuated inflammation in the early phase.

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Title: Inhibitory effects of berberine on proinflammatory M1 macrophage polarization through interfering with the interaction between TLR4 and MyD88
Authors: Jing Gong
Jingbin Li
Hui Dong
Guang Chen
Xin Qin
Meilin Hu
Fen Yuan
Ke Fang
Dingkun Wang
Shujun Jiang
Yan Zhao
Wenya Huang
Zhaoyi Huang
Fuer Lu
Publication date: 01-12-2019
Publisher: BioMed Central
Keyword: Metformin
Published in: BMC Complementary Medicine and Therapies / Issue 1/2019
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-019-2710-6

ACC 2024 Congress

Springer Medicine

Inhibitory effects of berberine on proinflammatory M1 macrophage polarization through interfering with the interaction between TLR4 and MyD88

Abstract

Backgrounds

Methods

Results

Conclusions

ACC 2024 Congress

Springer Medicine

Abstract

Backgrounds

Methods

Results

Conclusions

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