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

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

  • Phytomedicine. 2023 Oct:119:154977. doi: 10.1016/j.phymed.2023.154977.
Xi Chen 1,  Jia-Bin Yang 1,  Hui-Hui Cao 1,  Xiao-Chuan Fang 1,  Shan-Hong Liu 1,  Li-Fang Zou 1,  Jian-Hai Yu 2,  Jian-Ping Zuo 3,  Wei Zhao 2,  Zi-Bin Lu 4,  Jun-Shan Liu 5,  Lin-Zhong Yu 6
Affiliations

Affiliations

  • 1 Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China.
  • 2 Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, PR China.
  • 3 Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China.
  • 4 Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China. Electronic address: [email protected].
  • 5 Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, China, 510280, PR China. Electronic address: [email protected].
  • 6 Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China. Electronic address: [email protected].
PMID: 37506573 DOI: 10.1016/j.phymed.2023.154977
Abstract

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.

Keywords

Caveolin1; Dengue virus serotype 2; Envelope protein; Heat shock protein 70; Liang-Ge-San.

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