Indian Council of Medical Research-National Institute of Traditional Medicine, Belagavi 590010, India.
KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research (KAHER), Belagavi 590010, India.
Toxins (Basel). 2022 Sep 20;14(10):649. doi: 10.3390/toxins14100649.
Careya arborea, Punica granatum, Psidium guajava, Holarrhena antidysenterica, Aegle marmelos, and Piper longum 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 Vibrio cholerae. Cholera toxin (CT) and non-membrane damaging cytotoxin (NMDCY) in cell free culture filtrate (CFCF) of V. cholerae were quantified using GM1 ELISA and cell-based assays, respectively. Hydro-alcoholic extracts of these plants and lyophilized juice of P. granatum 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 P. longum. C. arborea, P. granatum, H. antidysenterica and A. marmelos showed >50% binding inhibition of CT to GM1 receptor. C. arborea, P. granatum, and P. guajava 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.
枇把叶、石榴、番石榴、三桠苦、余甘子和荜茇是印度常用于治疗腹泻疾病的传统药物。本研究调查了这些植物对霍乱弧菌分泌的毒素引起的细胞毒性和肠毒性的抑制活性。使用 GM1 ELISA 和基于细胞的测定法分别定量测定霍乱毒素 (CT) 和非膜损伤细胞毒素 (NMDCY) 在霍乱弧菌无细胞培养滤液 (CFCF) 中的含量。测试了这些植物的水醇提取物和石榴冻干汁对 CT 诱导 CHO 细胞系中环腺苷酸 (cAMP) 水平升高、CT 与神经节苷脂 GM1 受体结合以及 NMDCY 诱导的细胞毒性的抑制作用。除荜茇外,所有提取物均能显著降低 CFCF 处理的 CHO 细胞系中 cAMP 水平。三桠苦、石榴、余甘子对 CT 与 GM1 受体的结合抑制率>50%。三桠苦、石榴和番石榴能有效降低 NMDCY 引起的 CHO 细胞系的细胞毒性和形态改变。此外,在结扎回肠模型中,这三种植物对 CFCF 诱导的肠毒性的疗效在成年小鼠中得到了验证,表现在结扎回肠组织中液体蓄积量、cAMP 水平和肠黏膜组织病理学变化的减少。因此,这些植物可以进一步验证其在临床上用于治疗霍乱的功效。