Antitumor and Anthelmintic Potentials of Pleurolobus gangeticus (L.) J. St. - Hil. ex H. Ohashi & K. Ohashi and Tragia involucrata Linn.

Abstract

Search for therapeutically potent natural products goes on and plants are the precious storehouse of bioactive molecules that have the potential to be developed into new drugs. The broad objective of the current study was to test and scientifically validate the pharmacological potentials of two herbs viz. Pleurolobus gangeticus and Tragia involucrata. Initial in vitro assays to evaluate the anticancer potentials of solvent extracts of these plants were conducted in lymphoma cell lines such as DLA and YAC-1. Lowest IC 50 values were obtained for ethanol extracts, among other extracts, of both plants in inhibiting cell proliferation. Further, a higher mitotic index was observed in extract treated PBMC cells, when compared to untreated controls or reference drug colchicine. The GC-MS and LC-MS analysis of the ethanol extracts revealed the presence of several pharmacologically important compounds, and in order to ascertain the possibility of these molecules to interact with the mitotic spindle fibers, in silico methods were used. It was revealed that several of these molecules are having high affinity binding with the colchicine binding site of the αβ tubulin. This indicates that extract components could be binding to or interfering the microtubule assembly in the division initiated cells thereby arresting its cell cycle eventually leading to apoptosis. Flow cytometry analysis revealed a dose dependent increase in the early apoptotic cells by the treatment of these extracts. Considering the promising results in the in silico and in vitro systems, antitumor studies that followed the toxicity studies were performed in mice model. Ethanol extract treated animals showed a significant decrease in tumour burden compared to the vehicle controls and histopathological examinations of the tumour tissues showed clear evidence for apoptosis. In our next efforts the anthelmintic potential of the extracts were evaluated using in vitro nematode and trematode models. The nematicidal effects were evaluated by egg hatch and larval paralysis assays using the eggs and larvae of Haemonchus contortus. A dose dependent egg hatch inhibition and larval paralysis was observed by the treatment of ethanol extracts of both plants. The trendwas similar in the trematocidal assay using the parasite Fischoederius cobboldi. The histological sections of flukes treated with the ethanol extracts showed disrupted muscle layers, in comparison to intact tissues in vehicle controls. Masson's trichrome staining that particularly stains the collagen fibers and muscles also confirmed the disruption of the collagen and muscle fibers by the extract treatment. In conclusion, the biological activity elicited by the extracts may be attributed this individual or synergistic activity of the phytocompounds present in the extracts and further studies are therefore highly desirable in this regard.