Abstract
Traditional Triphala (three fruits), consisting of Phyllanthus emblica, Terminalia chebula, and Terminalia bellirica, presents a broad range of biological activities. However, its ability to inhibit dengue virus (DENV) infection has not been reported yet. Herein, the authors investigated the efficiency of three different Triphala formulations and its individual extract constituents to inhibit DENV infection. Treatment with T. bellirica extract or Triphala formulated with a high ratio of T. bellirica extract showed remarkable efficiency in significantly lowering DENV infection in Vero cells. Their effects were further studied in Huh7 cells, to address its potential ability in human cells. Treatment with 100 μg/mL of T. bellirica extract or Triphala resulted in an approximate 3000-fold or 1000-fold lowering of virus production, respectively. Furthermore, the treatment diminished IL-6 and CXCL-10 expressions, which are the hallmark of the cytokine storm phenomenon in DENV infection. The HPLC profiling demonstrated gallic acid as a major compound, the treatment by which showed its ability to effectively inhibit DENV infection after virus entry. Molecular docking demonstrated that gallic acid was able to interact with DENV NS5 protein, which could be one of Triphala’s antiviral mechanism. This study offers Triphala formulation and its ingredient, T. bellirica extract, as a natural based pharmaceutical to be used in DENV infection treatment.
Highlights
Natural products serve as valuable sources of bioactive substances which have been used in medical purpose since ancient times
The Triphala formulation is a combination of Phyllanthus emblica, Terminalia chebula, and Terminalia bellirica, the biological properties of which are well documented in relation to the treatment of cancer, immunomodulation and antioxidants, as are its antimicrobial properties [1]
P. emblica, T. chebula, and T. bellirica which are the constituents of Triphala was evaluated for the antiviral activity against dengue virus (DENV)-2 infection, which is the most virulent serotype in Vero cells
Summary
Natural products serve as valuable sources of bioactive substances which have been used in medical purpose since ancient times. The natural substances and their metabolites provided either therapeutic potential or a great degree of safety to be applied in modern drug discovery and pharmaceuticals. Triphala (three fruits) is one of the most well-known herbal formulation in ayurvedic medicine and its therapeutic potential has been reported for a wide range of diseases. In addition to the diverse uses of Triphala, the antiviral activity of T. chebula has been reported to inhibit hepatitis B viral infection [2]. Treatment with T. chebula extract was capable of inhibiting hepatitis B virus multiplication by lowering viral DNA and surface antigen (HBsAg) levels in the extracellular medium of HepG2 2.2.15 cells [2].
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