Potential synergistic effects of quercetin with other phytoconstituents of Costus pictus (insulin plant) extract in the control of hyperglycemia and prevention of NSAID-induced gastroenteropathy in diabetic rats.

There is a need of multifactorial management to treat T2DM. Till date, no clinically simulated animal model and therapy for NSAID-induced gastroenteropathic damage (NSAID-iGD) in T2DM patients. T2DM was developed using high-fat diet plus multiple low doses of streptozotocin (30 mg/kg, IP). Rats treated with ethanolic extract of Insulin plant (EIP; 125, 250 and 500 mg/kg, PO; b.i.d.)/Quercetin (QCT; 50 mg/kg)/vehicle for total 10 days. Diclofenac sodium (DCF; 7.5 mg/kg, PO, b.i.d.) administered for final five days of EIP/vehicle administration. Rats fasted after last dose on the 9th day; water was provided ad libitum. 12 h after the last dose on 10th day, GI tracts assessed for haemorrhagic damage, XO activity, LPO, intestinal permeability, luminal pH alterations along with haematological, biochemical and histological parameters. The evidence suggested that DCF administration caused significant gastroenteropathic damage. In presence of T2DM, NSAID-iGD significantly exacerbated. Whereas, QCT/EIP treatment significantly attenuated T2DM dependent exacerbation of NSAID-iGD, and also efficiently managed T2DM in a dose-dependent manner. Low amount of QCT in EIP(190.96 ±â€¯7.5 ng/mg) than its effective dose(50 mg/kg) indicates that EIP's other phytoconstituents (e.g. Kaempferol, Ascorbic acid, Lupeol, Diosgenin, ß-sitosterol, Stigmasterol, ß-amyrin, etc.) giving synergistic actions. Costus pictus/QCT has potential to be promising candidate to treat patient with T2DM and NSAID-gastroenteropathy in T2DM.

In vitro - In vivo metabolism and pharmacokinetics of picroside I and II using LC-ESI-MS method.

Picroside I and II, iridoid glycosides, are the major active markers of roots and rhizomes of Picrorhiza kurroa (family: Scrophulariaceae). The rhizomes of P. kurroa have been traditionally used to treat worms, constipation, low fever, scorpion sting, asthma and ailments affecting the liver. Various Ayurvedic and herbal preparations are available in the market which contains P. kurroa e.g. Arogyavadhini vati, Tiktadi kwath, Picrolax capsules and suspension. These preparations are used without any significant pharmacokinetics data. Previously, we have reported that oral bioavailability of picroside I and II is low. Most of the iridoid glycosides are primarily metabolized by intestinal microbial flora. So, it is necessary to determine the metabolic profile of picroside I and II and check the correlation with lower bioavailability. Therefore, this study was designed to check metabolic (in vitro and in vivo) profile along with pharmacokinetic profile of picroside I and II. For this, a sensitive and selective LC-ESI-MS method was developed and validated for simultaneous determination of picroside I and II in rat plasma. Chromatographic separations were performed on C18 column. The mobile phase consisted of acetonitrile: 10 mM ammonium acetate buffer [90:10 v/v], pH 3.5. In-vitro Metabolic study was performed on rat liver microsomes and primary hepatocytes. In-vivo pharmacokinetic and metabolic profile of picroside I and II was generated after oral administration of Kutkin (mixture of picroside I and II) to Sprague-Dawley rats. Various pharmacokinetic parameters viz. Cmax, Tmax, AUC(0-t) were determined. In metabolic study, eight metabolites of picroside I and six metabolites of picroside II were identified in vitro, out of which four metabolites for each picroside I and picroside II were identified in vivo.

Comparative pharmacokinetic profiles of picrosides I and II from kutkin, Picrorhiza kurroa extract and its formulation in rats.

Picrosides I and II are the active chemical constituents, present in the roots and rhizomes of Picrorhiza kurroa Royle (family: Scrophulariaceae). The plant is ethnomedically claimed for the treatment of liver and upper respiratory tract infection, fever, dyspepsia and scorpion sting. This study attempts to determine the in vivo pharmacokinetic profile of picrosides I and II in rats after oral administration of three different preparations namely, kutkin (a mixture of picrosides I and II), P. kurroa extract and Picrolax® capsule (marketed formulation). A simple, precise, specific and sensitive method was developed for simultaneous quantification of picrosides I and II in rat plasma and was applied for the pharmacokinetic study. Pharmacokinetic parameters were calculated from the observed plasma concentration of picrosides I and II. The results showed a significant difference (p≤0.05) in oral bioavailability of picrosides I and II from different preparations. Both the compounds were found to be more bioavailable from P. kurroa extract followed by Picrolax® capsule and kutkin. Moreover, we also developed a novel method for isolation of kutkin from roots of P. kurroa with a high yield of 2.4% w/w. The information gained from this study provides a meaningful basis for clinical application and mechanistic study of such phytochemicals.