Baicalin prevents LPS-induced activation of TLR4/NF-κB p65 pathway and inflammation in mice via inhibiting the expression of CD14

Ya-jun Fu1, Bo Xu1, Shao-wei Huang1, Xia Luo1, Xiang-liang Deng1,2,3, Shuang Luo1, Chang Liu1, Qing Wang1, Jin-yan Chen4, Lian Zhou1
1 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
2 School of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China
3 The Second Affiliated Hospital of Guangdong Pharmaceutical University, Yunfu 527300, China
4 School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
Correspondence to: Xiang-liang Deng:, Lian Zhou:,
DOI: 10.1038/s41401-020-0411-9
Received: 12 October 2019
Accepted: 27 March 2020
Advance online: 26 May 2020


Previous studies have shown that baicalin, an active ingredient of the Chinese traditional medicine Huangqin, attenuates LPS- induced inflammation by inhibiting the activation of TLR4/NF-κBp65 pathway, but how it affects this pathway is unknown. It has been shown that CD14 binds directly to LPS and plays an important role in sensitizing the cells to minute quantities of LPS via chaperoning LPS molecules to the TLR4/MD-2 signaling complex. In the present study we investigated the role of CD14 in the anti- inflammatory effects of baicalin in vitro and in vivo. Exposure to LPS (1 μg/mL) induced inflammatory responses in RAW264.7 cells, evidenced by marked increases in the expression of MHC II molecules and the secretion of NO and IL-6, and by activation of MyD88/NF-κB p65 signaling pathway, as well as the expression of CD14 and TLR4. These changes were dose-dependently attenuated by pretreatment baicalin (12.5–50 μM), but not by baicalin post-treatment. In RAW264.7 cells without LPS stimulation, baicalin dose-dependently inhibit the protein and mRNA expression of CD14, but not TLR4. In RAW264.7 cells with CD14 knockdown, baicalin pretreatment did not prevent inflammatory responses and activation of MyD88/NF-κB p65 pathway induced by high concentrations (1000 μg/mL) of LPS. Furthermore, baicalin pretreatment also inhibited the expression of CD14 and activation of MyD88/NF-κB p65 pathway in LPS-induced hepatocyte-derived HepG2 cells and intestinal epithelial-derived HT-29 cells. In mice with intraperitoneal injection of LPS and in DSS-induced UC mice, oral administration of baicalin exerted protective effects by inhibition of CD14 expression and inflammation. Taken together, we demonstrate that baicalin pretreatment prevents LPS-induced inflammation in RAW264.7 cells in CD14-dependent manner. This study supports the therapeutic use of baicalin in preventing the progression of LPS-induced inflammatory diseases.
Keywords: inflammatory diseases; baicalin; CD14; TLR4; NF-κB p65; RAW264.7 cells

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