Abstract

The drug under study is a herbomineral drug containing tortoise shell ash and ground seeds of Piper nigrum used in the treatment of cancer. Salaha-A was found to contain essential minerals that could have medicinal importance to human. Calcium was found to be the major element in the tortoise shell ash and piperine is the pioneer alkaloid found in Piper nigrum. This work evaluates the effects of Salaha-A at different doses on blood parameters and spleen tissues of rats which result in significant increase in erythrocytes, lymphocytes and granulocytes. P-glycoprotein (P-gp) over expression is found in many types and many stages of cancer cells which impaired the delivery of anticancer drug to target site of action thereby leading to ineffective treatment. Hence, an inhibition of P-gp function is an attractive strategy toward multidrug resistance. It was further postulated that the conjugation of piperine and calcium can inhibit the function of P-gp, thus, molecular docking studies were carried out to predict 3D structure of P-gp and piperine-Ca conjugate. The in silico analysis shows higher binding affinity of piperine-Ca conjugate to P-gp model (-9.54 kcal/mol) in comparison with piperine alone (-8.77 kcal/mol). Piperine-Ca conjugate has shown good pharmacokinetic properties and therefore may be co-administered with anticancer drugs as efflux modulator after undergoing further in-vitro and in-vivo studies.

Key words:  P-glycoprotein, herbomineral, calcium, Piper nigrum, piperine, pharmacokinetic.