Novel therapeutic intervention of coenzyme Q10 and its combination with pioglitazone on the mRNA expression level of adipocytokines in diabetic rats.

AIMS: Aim of the present study was to investigate the effect of co-administration coenzyme Q10 and pioglitazone on the mRNA expression of adipocytokines in white adipose tissues of chemically induced type 2 diabetes mellitus in rats. MAIN METHODS: Diabetes was induced by administration of streptozotocin (65 mg/kg, i.p.), followed by nicotinamide (110 mg/kg, i.p.) 15 min later. The diabetic rats were treated coenzyme Q10 (Q10, 10 mg/kg, p.o.) or pioglitazone (PIO, 20 mg/kg, p.o.) alone and their combination for four weeks. Biochemical parameters like FBS level, insulin and HbA1c along with tissue levels of MDA, SOD, CAT and GSH were estimated. The mRNA levels of ADIPOQ, RBP4, RETN, IL-6 and TNF-α in White Adipose Tissue (WAT) were measured. KEY FINDINGS: Treatment with Q10 + PIO showed a significant reduction in the levels of FBS, HbA1c and a significant increase in insulin levels as compared to normal control group. Additionally, there was a significant change in the levels of biomarkers of oxidative stress after treatment with Q10 + PIO as compared to streptozotocin-nicotinamide group. Treatment with Q10 + PIO also significantly altered the mRNA expression of ADIPOQ, RETN, IL-6 and TNF-α when compared to monotherapy. However, mRNA expression of RBP4 did not alter in Q10 + PIO treated animal as compared to Q10 or PIO alone. SIGNIFICANCE: It is concluded that co-administration of Q10 and PIO has been shown the better therapeutic effect on the mRNA expression of adipocytokines and oxidative stress parameters as compared to either Q10 or PIO.

Antimalarial Phytochemicals Identification from Euphorbia Hirta against Plasmepsin Protease: an In Silico Approach.

BACKGROUND: Aspartic protease found in plasmodium parasites such as plasmepsin I, II and IV plays an important role in the degradation of hemoglobin. The studies have shown that effective drug must be able to inhibit more than one type of plasmepsin to avoid further growth of parasites and to prevent resistance of drug. Therefore, plasmepsins are believed to be excellent drug target for malarial disease. Extract of the plant Euphorbia hirta has been proved to exert antimalarial activity. However, molecular mechanism of this activity was not described. AIM: The aim of present investigation is to identify antimalarial phytochemicals of Euphorbia hirta as plasmepsin protease inhibitors using an in silico approach. MATERIALS AND METHODS: Docking studies were performed on three different protein targets plasmepsin I, II, and IV using iGEMDOCK. ADME and bioactivity predictions were done using molinspiration online tool. Toxicity studies were performed using ProTox-II online tool. RESULTS: In the docking studies seven compounds showed significant inhibitory activity with low docking score as compared to standard drug artemisinin. Six compounds showed no violations as per Lipinski rule. Bioactivity prediction states that all the compounds may act through enzyme inhibition. The results of in silico studies suggest that out of the eleven selected phytochemicals isorhamnetin and pinocembrin have more drug likeliness properties and lesser in silico toxicity with more binding affinity than artemisinin on all receptors. CONCLUSION: These findings indicate that isorhamnetin and pinocembrin have promising potential for development of antimalarial drug as plasmepsin inhibitors.

Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: Design and in vivo study.

The objective of present work was to utilize potential of nanostructured lipid carriers (NLCs) for improvement in oral bioavailability of raloxifene hydrochloride (RLX). RLX loaded NLCs were prepared by solvent diffusion method using glyceryl monostearate and Capmul MCM C8 as solid lipid and liquid lipid, respectively. A full 3(2) factorial design was utilized to study the effect of two independent parameters namely solid lipid to liquid lipid ratio and concentration of stabilizer on the entrapment efficiency of prepared NLCs. The statistical evaluation confirmed pronounced improvement in entrapment efficiency when liquid lipid content in the formulation increased from 5% w/w to 15% w/w. Solid-state characterization studies (DSC and XRD) in optimized formulation NLC-8 revealed transformation of RLX from crystalline to amorphous form. Optimized formulation showed 32.50 ± 5.12 nm average particle size and -12.8 ± 3.2 mV zeta potential that impart good stability of NLCs dispersion. In vitro release study showed burst release for initial 8 h followed by sustained release up to 36 h. TEM study confirmed smooth surface discrete spherical nano sized particles. To draw final conclusion, in vivo pharmacokinetic study was carried out that showed 3.75-fold enhancements in bioavailability with optimized NLCs formulation than plain drug suspension. These results showed potential of NLCs for significant improvement in oral bioavailability of poorly soluble RLX.

Maxcal-C (a polyherbal formulation) prevents ovariectomy-induced osteoporosis in rats.

OBJECTIVES: The aim of the present study was to investigate the anti-osteoporotic activity of Maxcal-C in ovariectomy (OVX)-induced osteoporosis in rats. MATERIALS AND METHODS: Sham-operated control rats were designated as Group I; Group II animals served as OVX control; Group III OVX control rats treated with Calcium Sandoz (50 mg/kg, p.o.); Group IV and V OVX control rats treated with Maxcal-C (250 and 500 mg/kg, p.o.), respectively. All the aforementioned treatments were given for four weeks after the development of osteoporosis. At the end of the treatment, serum biochemical parameters such as serum calcium and alkaline phosphate were measured. After sacrificing the animals, femoral bone parameters with histology, body weight, and bone breaking strength of 5(th) lumbar vertebra were measured. RESULTS: The treatment with Maxcal-C showed a significant improvement in serum biochemical, femoral bone parameters, and bone breaking strength of 5(th) lumbar vertebra with histopathological changes. CONCLUSION: The finding of the present study indicates that Maxcal-C showed a potential anti-osteoporotic activity. These results support the traditional use of Maxcal-C in the treatment of osteoporosis.