Objective: To investigate the therapeutic efficacy of andrographolide, a plant derived compound, against chikungunya virus(CHIKV) infection. Methods: Using flow cytometry and immunoblotting assay, in vitro viral prote...Objective: To investigate the therapeutic efficacy of andrographolide, a plant derived compound, against chikungunya virus(CHIKV) infection. Methods: Using flow cytometry and immunoblotting assay, in vitro viral protein expression was studied in THP-1 cells line. In Balb/c mouse neonates, viral RNA copy number was determined by real time PCR. Results:The results showed reduced CHIKV protein expression on andrographolide treatment in CHIKV-infected human peripheral blood mononuclear cells, Vero cells and THP-I cell line.In vivo, andrographolide treatment to CHIKV-infected neonates reduced viral RNA copy number. Further. andrographolide also increased cytotoxic T lymphocytes both in vitro and in vivo. Andrographolide also activated host innate immune pathways, viz., protein kinase R.phosphorylated eukaryotic initiation factor 2 α, retinoic acid inducible gene-Ⅰ and interferon regulatory factor 3/7, thereby increasing IFN-a secretion. CHIKV-induced nuclear factor κlight chain enhancer of activated B cells and tumor necrosis factor-a was also reduced on andrographolide treatment. Conclusion: Andrographolide inhibits CHIKV by suppressing viral protein expression and up-regulating host innate immunity and hence could be an effective therapeutic agent against CHIKV infection.展开更多
基金Defence Research & Development Organmzation (DRDO)is gratefully acknowledged for the financial support in the form NBC subproject
文摘Objective: To investigate the therapeutic efficacy of andrographolide, a plant derived compound, against chikungunya virus(CHIKV) infection. Methods: Using flow cytometry and immunoblotting assay, in vitro viral protein expression was studied in THP-1 cells line. In Balb/c mouse neonates, viral RNA copy number was determined by real time PCR. Results:The results showed reduced CHIKV protein expression on andrographolide treatment in CHIKV-infected human peripheral blood mononuclear cells, Vero cells and THP-I cell line.In vivo, andrographolide treatment to CHIKV-infected neonates reduced viral RNA copy number. Further. andrographolide also increased cytotoxic T lymphocytes both in vitro and in vivo. Andrographolide also activated host innate immune pathways, viz., protein kinase R.phosphorylated eukaryotic initiation factor 2 α, retinoic acid inducible gene-Ⅰ and interferon regulatory factor 3/7, thereby increasing IFN-a secretion. CHIKV-induced nuclear factor κlight chain enhancer of activated B cells and tumor necrosis factor-a was also reduced on andrographolide treatment. Conclusion: Andrographolide inhibits CHIKV by suppressing viral protein expression and up-regulating host innate immunity and hence could be an effective therapeutic agent against CHIKV infection.