Gan-Lu-Siao-Du-yin, a prescription of traditional Chinese medicine, inhibited enterovirus 71 replication, translation, and virus-induced cell apoptosis

Ya Ju Hsieh; Ming Hong Yen; Ya Wen Chiang; Chia Feng Yeh; Lien Chai Chiang; Den En Shieh; IJeng Yeh; Jung San Chang

doi:10.1016/j.jep.2016.03.034

Gan-Lu-Siao-Du-yin, a prescription of traditional Chinese medicine, inhibited enterovirus 71 replication, translation, and virus-induced cell apoptosis

J Ethnopharmacol. 2016 Jun 5:185:132-9. doi: 10.1016/j.jep.2016.03.034. Epub 2016 Mar 16.

Authors

Ya Ju Hsieh¹, Ming Hong Yen², Ya Wen Chiang³, Chia Feng Yeh³, Lien Chai Chiang⁴, Den En Shieh⁵, IJeng Yeh⁶, Jung San Chang⁷

Affiliations

¹ Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
² School of Pharmacy and Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Taiwan.
³ Department of Renal Care, College of Medicine, Kaohsiung Medical University, Taiwan.
⁴ Department of Microbiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan.
⁵ Department of Food Science and Technology, Tajen University of Technology, Ping-Tung, Taiwan.
⁶ Division of Internal Medicine, Department of Emergency Medicine, Kaohsiung Medical University Hospital, Taiwan.
⁷ Department of Renal Care, College of Medicine, Kaohsiung Medical University, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan. Electronic address: cjs@kmu.edu.tw.

PMID: 26993050
DOI: 10.1016/j.jep.2016.03.034

Abstract

Ethnopharmacological relevance: Gan-Lu-Siao-Du-yin (GLSDY) is a prescription of traditional Chinese medicine. GLSDY contains 11 ingredients and is commonly used for endemic diseases. Enterovirus 71 (EV71) is an endemic disease that can cause meningoencephalitis with mortality and neurologic sequelae without any effective management. It is unknown whether GLSDY is effective against EV71 infection.

Aim of the study: To test the hypothesis that GLSDY can protect cell from EV71-induced injury.

Materials and methods: Effects of a hot water extract of GLSDY on EV71 were tested in human foreskin fibroblast cells (CCFS-1/KMC) and human rhabdomyosarcoma cells (RD cells) by plaque reduction assay and flow cytometry respectively. Inhibition of viral replication was further examined by reverse quantitative RT-PCR (qRT-PCR). Its effect on viral protein translation and virus-induced apoptosis were examined by western blot.

Results: GLSDY was dose-dependently effective against EV71 infection (p<0.0001) in both CCFS-1/KMC cells and RD cells. GLSDY was highly effective when supplemented after viral inoculation (P<0.0001) with an IC50 of 8.7μg/mL. GLSDY inhibited viral RNA replication (P<0.0001), formation of viral structural proteins (VP0, VP1, VP2 and VP3) and non-structural proteins (protease 2B and 3AB). Furthermore, 300μg/mL GLSDY is effective to inhibit virus-induced apoptosis possibly through direct inhibition of caspase-8 and indirectly by inhibition of Bax.

Conclusions: GLSDY is cheap and readily available to manage EV71 infection by inhibiting viral replication, viral protein formations, and EV71-induced apoptosis.

Keywords: Antiviral; Baicalein (PubChem CID: 5281605); Baicalin (PubChem CID: 64982); Chlorogenic acid (PubChem CID: 1794427); Forsythin (PubChem CID: 12314162); Management; TCM; Treatment; Wogonin (PubChem CID: 5281703); Wogonoside (PubChem CID: 29927693).

MeSH terms

Apoptosis / drug effects*
Cell Line, Tumor
Drugs, Chinese Herbal / pharmacology*
Enterovirus A, Human / drug effects*
Fibroblasts / virology*
Humans
Rhabdomyosarcoma / virology*
Tissue Array Analysis
Virus Replication / drug effects*

Substances

Drugs, Chinese Herbal
gan-lu-siao-du-yin