Vitex Trifolia L. Inhibits Mast Cell-Mediated Allergic Inflammation by Targeting PI3K/AKT, p38, and NF-κB Signaling Cascades

Abstract

Ethnopharmacological relevance: Vitex trifolia L. (VT), a medicinal plant widespread in India and China, has widely been used as indigenous medicine by the native people to alleviate various inflammatory ailments.

Aim of the study: The study aimed to demonstrate the mast cell-mediated anti-inflammatory effect of VT and elucidate its mechanism of action.

Study design and methods: Bioactive extract (VTME) and fractions (VTM1, VTM5, and VTM6) yielded from bioassay-guided fractionation of leaves of VT were examined for potential regulatory effects on various inflammatory mediators and signaling pathway proteins using phorbol-12-myristate-13-acetate plus calcium Ionophore A23187 (PMACI)-stimulated human mast cell line (HMC-1). Flow cytometry, fluorescence-based assay, enzyme-linked immunosorbent assay (ELISA), and western blotting were employed when appropriate.

Results: Bioactive extract and fractions of VT dose-dependently inhibited the PMACI-induced release of β-hexosaminidase and change in cell shape associated with mast cell degranulation. Further, VTME, VTM1, VTM5 and VTM6 significantly inhibited the PMACI-stimulated levels of intracellular Ca 2+ in HMC-1 cells (p < 0.05). Furthermore, VTME, VTM1, and VTM6 attenuated the pro-inflammatory cytokine production (tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and granulocyte-monocyte colony-stimulating factor (GM-CSF)) by downregulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), p38 MAPK (mitogen-activated protein kinase), and nuclear factor (NF)-κB signaling pathways. However, VTM5 exhibited a distinct pattern of anti-inflammatory action by inhibiting the production of TNF-α, IL-6, and GM-CSF by targeting the PI3K/Akt and NF-κB signaling.

Conclusions: The results of the study provide a scientific basis for the employment of VT in TCM and Indian ayurvedic medicine, thereby suggesting VT as a potential therapeutic candidate for mast cell-derived allergic-inflammatory diseases.

Note:

Funding Information: This work was supported by SRM Institute of Science and Technology, Tamil Nadu, India.

Declaration of Interests: The authors declare no conflict of interest.

Keywords: Vitex trifolia L., Inflammation, cytokines, HMC-1, TCM