The inhibitory effect of iridoid glycoside extracted from Fructus Gardeniae on intracellular acidification and extracellular Ca 2+ influx induced by influenza A virus

Abstract

Influenza is a serious public health problem that causes severe illnesses and deaths for higher risk populations. Iridoid glycoside is one of the main active components from Fructus Gardeniae with antivirus and anti-inflammatory characteristics. The present study was designed to investigate the inhibitory effect of iridoid glycoside extracted from Fructus Gardeniae (IGE) on influenza and explore the potential mechanism of the action. In vitro, IGE exhibited highest activity against influenza virus A/FM1/47 induced visible cytopathic effect (CPE), with half maximal inhibitory concentration and therapeutic index values of 3.15 mg/mL and 11.37, respectively, and the replication of influenza virus A/FM1/47 was inhibited markedly by IGE at the concentrations of 25, 12.5 and 6.25 mg/mL. In vivo, treatment of mice with IGE decreased pulmonary index, viral titers and M2 protein expression in a dose-dependent manner. IGE increased the declining pHi induced by influenza virus significantly at the concentrations of 25 and 12.5 mg/mL 0.5 or 1 h post-infection, respectively. IGE treatment inhibited elevation of [Ca²⁺]i significantly at the concentrations of 25 and 12.5 mg/mL 0.5, 1 or 24 h post-infection, respectively. In addition, IGE reduced the rate of early-apoptotic cells at the concentrations of 25, 12.5 and 6.25 mg/mL, but showed no apparent effect on the rate of late-apoptotic cells. Our study demonstrates that IGE possesses antiviral activity against influenza A virus, and the antiviral action might be related to the inhibition of intracellular acidification and Ca²⁺ influx during fusion and uncoating of influenza replication cycle.