Stability of Terminalia bellirica Extract and Its Combination Effect with Alpha-Mangostin in Inhibiting Dengue Virus Infection

Dengue virus (DENV) infection has been reported to be continuously increasing worldwide. Currently, there is no effective treatment specific to DENV infection, in addition, the efficiencies of the vaccines are not fully effective against all four circulating DENV serotypes. Therefore, the development of an anti-viral agent to combat DENV infection and lower the risk of disease progression is needed, especially in the endemic area. This study investigated the effect of Terminalia bellirica extract and its combination with alpha-mangostin (α-MG) in lowering the DENV serotype 2 infection in Vero cells and A549 lung adenocarcinoma cells. The phytochemical characterization of T. bellirica extract demonstrated that T. bellirica extract contained a total phenolic compound of 198.29 ± 15.95 mg gallic acid/g extract in which the gallic acid was the major bioactive compound, judged by HPLC. Treatment with 50 μg/mL of T. bellirica extract caused over 50% of DENV envelope protein reduction in Vero cells and showed no significant attenuation upon the six rounds of thermal stress exposures. At an equal concentration, the efficiency of T. bellirica extract in A549 cells was lower than that of Vero cells; however, combination with low-dose α-MG (0.5-2 μg/mL) showed to significantly improve the inhibitory activity of T. bellirica extract. This study demonstrated the great stability of T. bellirica extract to inhibit DENV infection and suggested a combination approach with α-MG offered protection against the DENV tissue tropism.