Ameliorations in dyslipidemia and atherosclerotic plaque by the inhibition of HMG-CoA reductase and antioxidant potential of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd in rabbits.

The assigned work was aimed to examine the capability of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd to inhibit HMG-CoA reductase and regression of the atherosclerotic plaque. The chemical fingerprinting of the test extract was assessed by LC-MS/MS. Consequently, the analyses of in-vitro, in-vivo, and in-silico were executed by using the standard protocols. The in-vitro assessment of the test extract revealed 74.1% inhibition of HMG-CoA reductase. In-vivo assessments of the test extract indicated that treated hypercholesterolemic rabbits exhibited a significant (P≤0.001) amelioration in the biomarker indices of the dyslipidaemia i.e., atherogenic index, Castelli risk index(I&II), atherogenic coefficient along with lipid profile. Subsequently, significant reductions were observed in the atherosclerotic plaque and antioxidant levels. The in-silico study of molecular docking shown interactions capabilities of the leading phytoconstituents of the test extract i.e., eicosanoic acid, linoleic acid, and flavan-3-ol with target protein of HMG-CoA reductase. The values of RSMF and potential energy of top docked complexes were show significant interactions. Accordingly, the free energy of solvation, interaction angle, radius of gyration and SASA were shown significant stabilities of top docked complex. The cumulative data of results indicate phytoconstituents of an aqueous seed extract of Acacia senegal have capabilities to inhibit the HMG-CoA reductase and improve the levels of antioxidants.

An open-label, randomized, 10 weeks prospective study on the efficacy of vitamin D (daily low dose and weekly high dose) in vitamin D deficient patients.

BACKGROUND: Vitamin D is an important vitamin required to maintain normal skeletal as well as nonskeletal functions. The daily supplementation of vitamin D not only have poor adherence to the regimen but also of doubtful efficacy in deficient patients. OBJECTIVES: The aim of this study was to compare the effect of oral high-dose vitamin D regimens (60,000 IU weekly) and daily low-dose vitamin D regimen of 1000 IU in mitigating symptoms and increase in serum levels of vitamin D in patients with hypovitaminosis D. MATERIALS AND METHODS: A total of 90 patients aged 18-60 years with vitamin D deficiency (serum levels < 30 ng/mL) were enrolled. A total of 38 subjects received 60,000 IU of vitamin D weekly with 500 mg/day calcium and 40 subjects received a dose of 1000 IU of vitamin D daily with 500 mg/day calcium for 10 weeks. Baseline and follow-up total serum vitamin D levels and improvement in symptoms were measured within and between groups. RESULTS: For high-dose vitamin D (60,000 IU weekly), the increase in mean serum vitamin D levels from baseline was 28.33 ng/mL over 10 weeks' treatment period; whereas for the low-dose group (1000 IU daily) the mean increment in serum vitamin D was 6.79 ng/mL for the same period. The mean difference in increase in serum vitamin D between two groups was highly significant (P < 0.001). In both the groups, decrease in myalgia as evaluated on visual analog scale was observed after 10 weeks. CONCLUSIONS: High-dose vitamin D (60,000 IU weekly) regimen rapidly normalized 25(OH) D levels and ensure symptomatic relief earlier than daily dosing of 1000 IU vitamin D for same duration.

Endocannabinoid System: A Multi-Facet Therapeutic Target.

Cannabis sativa is also popularly known as marijuana. It has been cultivated and used by man for recreational and medicinal purposes since many centuries. Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries. The research of drugs acting on endocannabinoid system has seen many ups and downs in the recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve "protective role" in many medical conditions. Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson's disease, Huntington's disease, Alzheimer's disease and Tourette's syndrome could possibly be treated by drugs modulating endocannabinoid system. Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008. Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists. One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that act selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted. Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids. In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as "protective" and "disease inducing substance", time-dependent changes in the expression of cannabinoid receptors.