In this project, in vitro absorption enhancement activity of P-gp substrates Fexofenadine (Fx) and Ciprofloxacin (Cp) were evaluated in everted rat gut sac model and Caco-2 cell lines. Verapamil was used as P-gp inhibitor. Piper betel, Trachyspermum ammi, Plumbago zeylanica, Trikatu, Moringaoleifera, Murraya koenigii, Ferulafoitida Zingiber officinale, Cheilocostus speciosus, Capsicum frutescens Operculina turpethum Holarrhena antidysenterica Mesuaferrea, Tinospora cordifolia, and Picrorhiza kurroa, were selected and extracted with 99% alcohol and fresh juices of Citrus limon, Punica granatum seeds were also studied. In-vitro studies depicted that Fexofenadine and Ciprofloxacin absorption was increased greater than 20% in the presence of Operculinaturpethum, Capsicum frutescens, Holarrhena Antidysenterica, Tinospora cordifolia, Trikatu, Trachyspermum ammi, Plumbago zeylanica. The flux of the ciprofloxacin transport was in the range of 9-23 mcg/min and Papp 2.6 × 10-5 cm/sec to 4.1 × 10-5 cm/sec whereas Fexofenadine flux was in the range of 2-7.7 mcg/min and Papp 4.16 × 10–6 cm/sec to 1.62 × 10-5 cm/sec. In vitro antimicrobial activity of ciprofloxacin on selected microbes in presence of extracts also depicted synergistic activity. Histological studies revealed that there is no significant variation observed in the isolated sac in presence of the extracts. CaCo2 cell lines studies showed that, formulation enhanced the absorption of fexofenadine greater than 50%. Tablets were prepared and evaluated using the plant extracts which yielded >20% absorption enhancement of the substrates. In conclusion, tablet formulation containing the alcoholic extracts of Trachyspermum ammi, Plumbago zylanicum, Capsicum frutescens, Operculina turpethum, Holarrhena Antidysenterica, Tinospora cordifolia and Trikatu can act as an absorption enhancer for fexofenadine and ciprofloxacin. The mechanism of action of these herbs could be due to P-gp inhibition. Further clinical studies are needed to prove its efficacy in humans.
In silico and In vitro Perspective to Elucidate the Anticancer Effect of Natural Compound Hesperetin in Inhibiting Mammalian Target of Rapamycin Pathway
