In Vitro and In Vivo Inhibitory Activities of Selected Traditional Medicinal Plants against Toxin-Induced Cyto- and Entero- Toxicities in Cholera.
Rajitha CharlaPriyanka P PatilArati A BhatkandeNisha R KhodeVenkanna BalaganurHarsha V HegdeDarasaguppe R HarishSubarna RoyPublished in: Toxins (2022)
<i>Careya arborea</i>, <i>Punica granatum</i>, <i>Psidium guajava</i>, <i>Holarrhena antidysenterica</i>, <i>Aegle marmelos</i>, and <i>Piper longum</i> are commonly used traditional medicines against diarrhoeal diseases in India. This study investigated the inhibitory activity of these plants against cytotoxicity and enterotoxicity induced by toxins secreted by <i>Vibrio cholerae.</i> Cholera toxin (CT) and non-membrane damaging cytotoxin (NMDCY) in cell free culture filtrate (CFCF) of <i>V. cholerae</i> were quantified using GM1 ELISA and cell-based assays, respectively. Hydro-alcoholic extracts of these plants and lyophilized juice of <i>P. granatum</i> were tested against CT-induced elevation of cAMP levels in CHO cell line, binding of CT to ganglioside GM1 receptor and NMDCY-induced cytotoxicity. Significant reduction of cAMP levels in CFCF treated CHO cell line was observed for all extracts except <i>P. longum. C. arborea, P. granatum, H. antidysenterica</i> and <i>A. marmelos</i> showed &gt;50% binding inhibition of CT to GM1 receptor. <i>C. arborea, P. granatum,</i> and <i>P. guajava</i> effectively decreased cytotoxicity and morphological alterations caused by NMDCY in CHO cell line. Further, the efficacy of these three plants against CFCF-induced enterotoxicity was seen in adult mice ligated-ileal loop model as evidenced by decrease in volume of fluid accumulation, cAMP levels in ligated-ileal tissues, and histopathological changes in intestinal mucosa. Therefore, these plants can be further validated for their clinical use against cholera.