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Liang-Ge-San inhibits dengue virus serotype 2 infection by reducing caveolin1-induced cytoplasmic heat shock protein 70 translocation into the plasma membrane

文献类型：期刊论文

作者Chen, Xi1,2; Yang, Jia-bin1,2; Cao, Hui-hui1,2; Fang, Xiao-chuan1,2; Liu, Shan-hong1,2; Zou, Li-fang1,2; Yu, Jian-hai3; Zuo, Jian-ping4; Zhao, Wei3; Lu, Zi-bin1,2
刊名PHYTOMEDICINE
出版日期2023-10-01
卷号119页码:14
ISSN号0944-7113
关键词Liang-Ge-San Dengue virus serotype 2 Heat shock protein 70 Caveolin1 Envelope protein
DOI10.1016/j.phymed.2023.154977
通讯作者Lu, Zi-bin(huang624@smu.edu.cn) ; Liu, Jun-shan(liujunshan@smu.edu.cn) ; Yu, Lin-zhong(yulzh@smu.edu.cn)
英文摘要Background: Dengue virus (DENV) is a major public health threat. However, there are no specific therapeutic drugs for DENV. Many Chinese heat-cleaning formulas, such as Liang-Ge-San (LGS), have been frequently used in the virus-induced diseases. The antiviral effect of LGS has not been reported yet. Purpose: In this study, the effect of LGS on the inhibition of dengue virus serotype 2 (DENV-2) was investigated and the relevant mechanism was explored. Methods: High-performance liquid chromatography was applied to analyze the chemical characterization of LGS. The in vitro antiviral activities of LGS against DENV-2 were evaluated by time-of-drug-addition assay. The binding of heat shock protein 70 (Hsp70) and envelope (E) protein or caveolin1 (Cav1) were analyzed by immunofluorescence and immunoprecipitation assays. Then the role of Cav1 in the anti-DENV-2 effects of LGS was further examined. DENV-2 infected Institute of Cancer Research suckling mice (n = 10) and AG129 mice (n = 8) were used to examine the protective effects of LGS. Results: It was found that geniposide, liquiritin, forsythenside A, forsythin, baicalin, baicalein, rhein, and emodin maybe the characteristic components of LGS. LGS inhibited the early stage of DENV-2 infection, decreased the expression levels of viral E and non-structural protein 1 (NS1) proteins. LGS also reduced E protein and Hsp70 binding and attenuated the translocation of Hsp70 from cytoplasm to the cell membrane. Moreover, LGS decreased the binding of Hsp70 to Cav1. Further study showed that the overexpression of Cav1 reversed LGS-mediated E protein and Hsp70 inhibition in the plasma membrane. In the in vivo study, LGS was highly effective in prolonging the survival time, reducing viral loads. Conclusion: This work demonstrates for the first time that LGS exerts anti-DENV-2 activity in vitro and in vivo. LGS decreases DENV-2-stimulated cytoplasmic Hsp70 translocation into the plasma membrane by Cav1 inhibition, thereby inhibiting the early stage of virus infection. These findings indicate that LGS may be a candidate for the treatment of DENV.
WOS关键词HSP70 ; REPLICATION ; FEVER
资助项目National Natural Science Foundation of China[81730110]
WOS研究方向Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
语种英语
出版者ELSEVIER GMBH
WOS记录号WOS:001050675000001
源URL[http://119.78.100.183/handle/2S10ELR8/307004]  
专题新药研究国家重点实验室
通讯作者Lu, Zi-bin; Liu, Jun-shan; Yu, Lin-zhong
作者单位1.Southern Med Univ, Sch Tradit Chinese Med, Level Res Lab State Adm Tradit Chinese Med 3, Guangzhou 510515, Peoples R China
2.Southern Med Univ, Sch Tradit Chinese Med, Guangdong Prov Key Lab Chinese Med Pharmaceut, Guangzhou 510515, Peoples R China
3.Southern Med Univ, Sch Publ Hlth, Guangdong Prov Key Lab Trop Dis Res, Guangzhou 510515, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Southern Med Univ, Zhujiang Hosp, Dept Pharm, Guangzhou 510280, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Xi,Yang, Jia-bin,Cao, Hui-hui,et al. Liang-Ge-San inhibits dengue virus serotype 2 infection by reducing caveolin1-induced cytoplasmic heat shock protein 70 translocation into the plasma membrane[J]. PHYTOMEDICINE,2023,119:14.
APA Chen, Xi.,Yang, Jia-bin.,Cao, Hui-hui.,Fang, Xiao-chuan.,Liu, Shan-hong.,...&Yu, Lin-zhong.(2023).Liang-Ge-San inhibits dengue virus serotype 2 infection by reducing caveolin1-induced cytoplasmic heat shock protein 70 translocation into the plasma membrane.PHYTOMEDICINE,119,14.
MLA Chen, Xi,et al."Liang-Ge-San inhibits dengue virus serotype 2 infection by reducing caveolin1-induced cytoplasmic heat shock protein 70 translocation into the plasma membrane".PHYTOMEDICINE 119(2023):14.

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来源：上海药物研究所

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