[Mechanism of Baidi Jielv Anshen Formula regulating abnormal polarization of amygdala microglia in mice with anxiety disorder based on CB2R mediated TLR4 signaling pathway].

Authors

Yang Liu, Hai-Peng Guo, Ting-Ting Wang, Man-Shu Zou, Hong-Qing Zhao, Lin Tang, Hai-Xia He, Ting-Ting Ren, Yu-Hong Wang, Yuan-Shan Han

Published in

Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. Volume 51. Issue 10. Pages 2855-2866.

Abstract

Based on cannabinoid receptor 2(CB2R) mediated Toll-like receptor 4(TLR4) signaling pathway, this study aimed to explore the mechanism of regulating the abnormal polarization of amygdala microglia in mice with anxiety disorder by Baidi Jielv Anshen Formula. The anxiety-like mouse model was established by chronic restraint stress(CRS) 21 d and randomly divided into 6 groups of a blank group, a model group, a high-dose Baidi Jielv Anshen Formula group(10.92 g·kg~(-1)), a medium-dose Baidi Jielv Anshen Formula group(5.46 g·kg~(-1)), a low-dose Baidi Jielv Anshen Formula group(2.73 g·kg~(-1)), and a positive drug diazepam group(2 mg·kg~(-1)). The mice in each group were given intragastric administration on the 8th day of modeling. After 14 days of continuous administration, anxiety-like behavior was evaluated by open field test, elevated plus maze test, and light-dark box test. The number of proto-oncogene c-fos positive cells was detected by immunofluorescence(IF), and glutamic acid(Glu) and gamma-aminobutyric acid(GABA) were detected by enzyme-linked immunosorbent assay(ELISA). Endocannabinoid system-related proteins in amygdala were detected by Western blot. Ionized calcium binding adaptor molecule 1(Iba-1), a marker protein of microglia in amygdala, was detected by IF, nitric oxide synthase(iNOS) and arginase 1(Arg-1) were detected by IF and Western blot, and the morphology and polarization of microglia were evaluated. Proinflammatory cytokines and anti-inflammatory cytokines were detected by Western blot to evaluate the amygdala inflammation. The protein associated TLR4 signaling pathway was detected by Western blot to evaluate the activation of the TLR4 pathway. The results showed that both Baidi Jielv Anshen Formula and diazepam could significantly improve the anxiety-like behavior of CRS-induced mice, and could increase the center distance and center time in open field test to varying degrees, improve OE% and OT% in the elevated plus maze test, and increase the time spent and distance traveled in the light compartment in the light-dark box test. At the same time, the level of c-fos in amygdala can be significantly reduced and the over-activation of amygdala neurons can be alleviated by Baidi Jielv Anshen Formula. The CB2R feedback protein increase induced by CRS was significantly inhibited by Baidi Jielv Anshen Formula. It also significantly reduced the excessive activation of microglia in amygdala, restored the balance of M1/M2 polarization, and inhibited the production of inflammatory cytokines. The expression of TLR4 pathway-related proteins can be down-regulated. Therefore, Baidi Jielv Anshen Formula may inhibit the TLR4 signaling pathway by activating CB2R, restore the polarization balance of microglia, inhibit neuroinflammation, improve the over-activation of amygdala, and play an anti-anxiety role.

PMID:
42392744
Bibliographic data and abstract were imported from PubMed on 03 Jul 2026.

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