Mechanism of Lian Hua Qing Wen capsules regulates the inflammatory response caused by M 1 macrophage based on cellular experiments and computer simulations.

Autor: Zong YH; University of Tibetan Medicine, Lhasa, PR China., Cao JF; College of Medicine, Southwest Jiaotong University, Chengdu, PR China., Zhao Y; Chengdu Medical College, Chengdu, PR China., Gao M; Chengdu Medical College, Chengdu, PR China., Chen WL; Chengdu Medical College, Chengdu, PR China., Wu M; Chengdu Medical College, Chengdu, PR China., Xu X; Chengdu Medical College, Chengdu, PR China., Xu ZY; Chengdu Medical College, Chengdu, PR China., Zhang XQ; University of Tibetan Medicine, Lhasa, PR China., Tang JZ; Chengdu Medical College, Chengdu, PR China., Liu Y; Chengdu Medical College, Chengdu, PR China., Hu XS; Chengdu Medical College, Chengdu, PR China., Wang SQ; Chengdu Medical College, Chengdu, PR China., Zhang X; Chengdu Medical College, Chengdu, PR China. Electronic address: 954073462@qq.com.
Jazyk: angličtina
Zdroj: Acta tropica [Acta Trop] 2024 Sep; Vol. 257, pp. 107320. Date of Electronic Publication: 2024 Jul 14.
DOI: 10.1016/j.actatropica.2024.107320
Abstrakt: Purpose: The polarization of macrophages with the resulting inflammatory response play a crucial part in tissue and organ damage due to inflammatory. Study has proved Lian Hua Qing Wen capsules (LHQW) can reduce activation of inflammatory response and damage of tissue derived from the inflammatory reactions. However, the mechanism of LHQW regulates the macrophage-induced inflammatory response is unclear. Therefore, we investigated the mechanism of LHQW regulated the inflammatory response of M 1 macrophages by cellular experiments and computer simulations.
Methods: This study has analysed the targets and mechanisms of macrophage regulating inflammatory response at gene and protein levels through bioinformatics. The monomeric components of LHQW were analyzed by High Performance Liquid Chromatography (HPLC). We established the in vitro cell model by M 1 macrophages (Induction of THP-1 cells into M 1 macrophages). RT-qPCR and immunofluorescence were used to detect changes in gene and protein levels of key targets after LHQW treatment. Computer simulations were utilized to verify the binding stability of monomeric components and protein targets.
Results: Macrophages had 140,690 gene targets, inflammatory response had 12,192 gene targets, intersection gene targets were 11,772. Key monomeric components (including: Pinocembrin, Fargesone-A, Nodakenin and Bowdichione) of LHQW were screened by HPLC. The results of cellular experiments indicated that LHQW could significantly reduce the mRNA expression of CCR5, CSF2, IFNG and TNF, thereby alleviating the inflammatory response caused by M1 macrophage. The computer simulations further validated the binding stability and conformation of key monomeric components and key protein targets, and IFNG/Nodakenin was able to form the most stable binding conformation for its action.
Conclusion: In this study, the mechanism of LHQW inhibits the polarization of macrophages and the resulting inflammatory response was investigated by computer simulations and cellular experiments. We found that LHQW may not only reduce cell damage and death by acting on TNF and CCR5, but also inhibit the immune recognition process and inflammatory response by regulating CSF2 and IFNG to prevent polarization of macrophages. Therefore, these results suggested that LHQW may act through multiple targets to inhibit the polarization of macrophages and the resulting inflammatory response.
Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed.
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Databáze: MEDLINE