Resistance of solid tumors to treatment is significantly attributed to pharmacokinetic reasons at both cellular and multi-cellular levels. Anticancer agent must be bio-available at the site of action in a cytotoxic concentration to exert its proposed activity. P-glycoprotein (P-gp) is a member of the ATP-dependent membrane transport proteins; it is known to pump substrates out of cells in ATP-dependent mechanism. The over-expression of P-gp in tumor cells reduces the intracellular drug concentrations, which decreases the cytotoxicity of a broad spectrum of antitumor drugs. Accordingly, P-gp inhibitors/blockers are potential enhancer for the cellular bioavailability of several clinically important anticancer drugs such as, anthracyclines, taxanes, vinca alkaloids, and podophyllotoxins. Besides several chemically synthesized P-gp inhibitors/blockers, some naturally occurring compounds and plant extracts were reported for their modulation of multidrug resistance; however, this review will focus only on major classes of naturally occurring inhibitors viz., flavonoids, coumarins, terpenoids, alkaloids and saponins.

Securigera securidaca (L.) Degen & Döefl., Fabaceae, has been widely used in the Iranian, Indian and Egyptian folk medicine as antidiabetic and anti-hyperlipidemic remedy. Phenolic profiling of the ethanolic extract (90%) of the flowers of S. securidaca was performed via HPLC-DAD-MS/MS analysis in the positive and negative ion modes. The total polyphenols and flavonoids in the flowers were determined colorimetrically, and the quantification of their components was carried out using HPLC-UV. Total phenolics and flavonoids estimated as gallic acid and rutin equivalents were 82.39±2.79mg/g and 48.82±1.95mg/g of the dried powdered flowers, respectively. HPLC-DAD-MS/MS analysis of the extract allowed the identification of 39 flavonoids and eight phenolic acids. Quantitative analysis of some flavonoids and phenolics (mg/100g powdered flowers) revealed the presence of isoquercetrin (3340±2.1), hesperidin (32.09±2.28), naringin (197.3±30.16), luteolin (10.247±0.594), chlorogenic acid (84.22±2.08), catechin (3.94±0.57) and protocatechuic acid (34.4±0.15), in the extract. Moreover, the acute toxicity, hypoglycemic and hypolipidemic effects of the extract were investigated using alloxan induced diabetes in rats in a dose of 100, 200, and 400mg/kgbwt. The ethanolic extract was safe up to a dose of 2000mg/kg. All tested doses of the flower extract showed marked decrease in blood glucose level by 31.78%, 66.41% and 63.8% at 100, 200 and 400mg/kgbwt, respectively, at p<0.05. Regarding the anti-hyperlipidemic effect, a dose of 400mg/kg of the flower extract showed the highest reduction in serum triacylglycerides and total cholesterol levels (68.46% and 51.50%, respectively at p<0.05). The current study proved the folk use of the flowers of S. securidaca as anti-diabetic and anti-hyperlipidemic agent which could be attributed to its high phenolic content