Anti-Influenza Virus Activities of Flavonoids from the Medicinal Plant Elsholtzia rugulosa

Abstract

Elsholtzia rugulosa (Lamiaceae), a common Chinese herb, is widely used in the treatment of cold and fever. In order to elucidate the action mechanism and the active principles from the plant against anti-influenza virus, the influenza virus neuraminidase (NA) activity assay and in vitro antiviral activity assay were established, and the isolation of the active principles was guided by NA activity. Finally, 5 active constituents were obtained, namely apigenin (1), luteolin (2), apiin (3), galuteolin (4) and luteolin 3′-glucuronyl acid methyl ester (5), respectively. They all belong to the flavonoids. The in vitro antiviral assay using a cytopathic effect (CPE) reduction method showed that they all possessed anti-influenza virus activity. Among them, apigenin and luteolin exhibited the highest activities against influenza virus (H3N2) with IC₅₀ values of 1.43 μg/mL and 2.06 μg/mL, respectively. The structure-activity relationship (SAR) of these flavonoids with different chemical structures and their anti-influenza virus activities was addressed in this study.

Abbreviations

CC₅₀:median cytotoxic concentration

CPE:cytopathic effect

DMEM:Dulbecco's minimum essential medium

FBS:fetal bovine serum

MDCK:Madin-Darby canine kidney

MES:2-N-morpholino-ethanesulfonic acid

MNCC:maximal non-cytotoxic concentration

MUNANA:2′-(4-methylumbelliferyl)-α-D-acetylneuraminic acid

Na:neuraminidase

SI:selective index

TCID₅₀:50 % tissue culture infective dose

Key words

Elsholtzia rugulosa - Lamiaceae - flavonoids - influenza virus - neuraminidase (NA)

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