Evidences of in vivo cytotoxic and apoptotic potential of anthelmintic phytochemical kaempferol derivative isolated from Lysimachia ramosa (Wall. ex Duby) in Wistar rats

Abstract

Background Lysimachia ramosa (Wall. ex Duby) is a traditionally used medicinal plant in Meghalaya, a northeastern state of India. The people use the leaves of the plant to cure gastrointestinal worm infection. Kaempferol derivative, isolated from the leaves of the plant L. ramosa, was found to be the active anthelmintic compound in previous studies. The phytochemical present in the leaves causes alterations in the ultrastructure of the tegument of cestode, its glycogen content and tegumental enzymes. However, it has been found in the review of the literature that phytoproduct should be consumed in a limited dose during longtime treatment period to avoid any potential ill effects on the health of the consumers as many plant-based products are found to be toxic beyond a safe dose limit. Thereby, it becomes necessary to check the potential toxic effects of the active compound taking an animal model. Hence, the present study had been carried out to evaluate the toxicity of the active component on Wistar rats to find out the safe dose of the test compound for oral consumption through observations, if any, on chromosomal abnormalities, ultrastructural changes in bone marrow cells and apoptosis in liver and kidney. Results The result shows kaempferol derivative causes a significant rise in chromosomal abnormalities (2.83 ± 0.19%, 3.83 ± 0.11%) and a significant decline in mitotic indices (3.17 ± 0.02%, 3.10 ± 0.01%) upon treatment with 500 mg and 1000 mg/kg b.w. dosages. At this level, the number of micronucleated erythrocytes increases significantly in the animals (2.33 ± 0.33%, 3.15 ± 0.24%). Intercellular integrity and eosinophil in the bone marrow are observed to be deformed and damaged on treatment with 1000 mg compound/kg b.w. of animals. Apoptotic indices are seen to be increased significantly (3.12 ± 0.18%, 6.17 ± 0.17%) and (2.43 ± 0.13%, 4.17 ± 0.17%) for the liver and kidney, respectively, in the animals of higher-dose treatment groups. Conclusions The compound, kaempferol derivative in the present study, has been found to have cytotoxic and pro-apoptotic effects on the test animals beyond a certain dose, if consumed for longer period of time. Therefore, it can be concluded that kaempferol derivative extracted from Lysimachia ramosa should be tested for future trials on animals/humans at dose below 250 mg/kg body weight.