Fufang Luohanguo Qingfei granules reduces influenza virus susceptibility via MAVS-dependent type I interferon antiviral signaling.

Autor: Lu YH; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, College of Pharmacy, Guangxi Medical University, Nanning, 530021, China; Guangxi Key Laboratory of Pharmaceutical Precision Detection and Screening, Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Education Department, China., Wang M; Hainan General Hospital, Department of Pharmacy, Haikou, 570311, China., Lin JQ; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, College of Pharmacy, Guangxi Medical University, Nanning, 530021, China., Wang MY; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, College of Pharmacy, Guangxi Medical University, Nanning, 530021, China., Zhou LY; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, College of Pharmacy, Guangxi Medical University, Nanning, 530021, China., He SH; Guangxi Institute for Food and Drug Control, Nanning, 530021, China., Yi YT; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, College of Pharmacy, Guangxi Medical University, Nanning, 530021, China., Wei X; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, College of Pharmacy, Guangxi Medical University, Nanning, 530021, China., Huang QJ; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, College of Pharmacy, Guangxi Medical University, Nanning, 530021, China; Guangxi Key Laboratory of Pharmaceutical Precision Detection and Screening, Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Education Department, China., Su ZH; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, College of Pharmacy, Guangxi Medical University, Nanning, 530021, China., Yang J; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, College of Pharmacy, Guangxi Medical University, Nanning, 530021, China., Guo HW; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, College of Pharmacy, Guangxi Medical University, Nanning, 530021, China. Electronic address: hongweiguo@gxmu.edu.cn., He RR; Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, College of Pharmacy, Jinan University, Guangzhou, 612505, China. Electronic address: rongronghe@jnu.edu.cn., Luo Z; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, College of Pharmacy, Guangxi Medical University, Nanning, 530021, China; Guangxi Key Laboratory of Pharmaceutical Precision Detection and Screening, Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Education Department, China. Electronic address: luozhuo@gxmu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2024 Apr 24; Vol. 324, pp. 117780. Date of Electronic Publication: 2024 Jan 24.
DOI: 10.1016/j.jep.2024.117780
Abstrakt: Ethnopharmacological Relevance: Fufang Luohanguo Qingfei granules (LQG) is a Chinese patent medicine, clinically used to treat flu-like symptoms including cough with yellow phlegm, impeded phlegm, dry throat and tongue. However, the protective activity of LQG against influenza infection is indeterminate.
Aim of the Study: This study is to investigate the therapeutic effect of LQG on influenza infection and elucidate its underlying mechanism.
Materials and Methods: In vivo: A viral susceptible mouse model induced by restraint stress was established to investigate LQG's beneficial effects on influenza susceptibility. MAVS knockout (Mavs -/- ) mice were used to verify the potential mechanism of LQG. In vitro: Corticosteroid (CORT)-treated A549 cells were employed to identify the active ingredients in LQG. Mice morbidity and mortality were monitored daily for 21 days. Histopathologic changes and inflammatory cytokines in lung tissues were examined by H&E staining and ELISA. RNA-seq was used to explore the signaling pathway influenced by LQG and further confirmed by qPCR. Immunoblotting and immunohistochemistry (IHC) were used to determine the protein levels. CO-IP and DARTS were applied to detect protein-protein interaction and compound-protein interaction, respectively.
Results: LQG effectively attenuated the susceptibility of restrained mice to H1N1 infection. LQG significantly boosted the production of IFN-β transduced by mitochondrial antiviral-signaling protein (MAVS), while MAVS deficiency abrogated its protective effects on restrained mice infected with H1N1. Moreover, in vitro studies further revealed that mogroside Ⅱ B, amygdalin, and luteolin are potentially active components of LQG.
Conclusion: These results suggested that LQG inhibited the mitofusin 2 (Mfn2)-mediated ubiquitination of MAVS by impeding the E3 ligase synoviolin 1 (SYVN1) recruitment, thereby enhancing IFN-β antiviral response. Overall, our work elaborates a potential regimen for influenza treatment through reduction of stress-induced susceptibility.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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