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.
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- Doctoral Theses [37]