Pharmacology

Adipocyte Transdifferentiation and its Molecular Targets

2014-01-01T00:00:00Z

Adipocyte Transdifferentiation and its Molecular Targets Rajan, Sujith; Gupta, Abhishek; Beg, Muheeb; Shankar, Kripa; Srivastava, Ankita; Varshney, Salil; Kumar, Durgesh; Gaikwad, A N According to World Health Organization obesity is defined as an excessive accumulation of fat, which increases risk of other metabolic disorders such as insulin resistance, dyslipidemia, hypertension, cardiovascular diseases, etc. There are two types of adipose tissue, white and brown adipose tissue (BAT) and later have recently gathered interest of the scientific community. Discovery of BAT has opened avenues for new therapeutic strategy for the treatment of obesity and related metabolic syndrome. BAT utilizes accumulated fatty acids for energy expenditure; hence it is seen as one of the possible alternates to the current treatment. Moreover, browning of white adipocyte on exposure to cold, as well with some of the pharmacological agents present exciting outcomes and indicate the feasibility of transdifferentiation. A better understanding of molecular pathways and differentiation factors, those play key role in transdifferentiation are of extreme importance in designing novel strategies for the treatment of obesity and associated metabolic disorders

Epigenetic regulation of G Protein Coupled Receptor signaling and its implications in psychiatric disorders

2016-01-01T00:00:00Z

Epigenetic regulation of G Protein Coupled Receptor signaling and its implications in psychiatric disorders Dogra, Shalini; Sona, Chandan; Kumar, Ajeet; Yadav, P N G protein-coupled receptors (GPCRs) act as a relay center through which extracellular signals, in the form of neurotransmitters or therapeutics, are converted into an intracellular response, which ultimately shapes the overall response at the tissue and behavioral level. Remarkably in similar ways, epigenetic mechanisms also modulate the expression pattern of a large number of genes in response to the dynamic environment inside and outside of the body, and consequently overall response. Emerging evidences from the pharmacogenomics and preclinical studies clearly suggest that these two distinct mechanisms criss-cross each other in several neurological disorders. At one hand such cross-talks between two distinct mechanisms make more challenging to understand the disease etiology, while on the other hand if dealt appropriately, such situations might provide an opportunity to find novel druggable target and strategy for the treatment of complex diseases. In this review article, we have summarized and highlighted the main findings that tie epigenetic mechanisms to GPCR mediated signaling in the pathophysiology of central nervous system (CNS) disorders, including depression, addiction and pain.

Curcuma oil reduces endothelial cell mediated inflammation in post myocardial ischemia /reperfusion in rats

2014-01-01T00:00:00Z

Curcuma oil reduces endothelial cell mediated inflammation in post myocardial ischemia /reperfusion in rats Manhas, A; khanna, V; Prakash, P; Goyal, D; Malasoni, Richa; Naqvi, Arshi; Dwivedi, Anila; Dikshit, Madhu; Jagavelu, Kumaravelu Endothelial cells initiated inflammation persisting in post myocardial infarction needs to be controlled and moderated for avoiding fatal complications. Curcuma oil (C.oil, Herbal Medicament) a standardized hexane soluble fraction of Curcuma longa has possessed neuroprotective effect. However, its effect on MI/RP and endothelial cells remain incompletely defined. Here, using in vivo rat myocardial ischemia/reperfusion (MI/RP) injury model and in vitro cellular approaches using EA.hy926 endothelial cells, ELISA, RT-PCR and myograph, we provide evidence that with effective regimen and preconditioning of rats with C.oil (250 mg/kg, P.O.), before and after MI/RP surgery protects rats from MI/RP induced injury. C.oil treatment reduces left ventricular ischemic area and endothelial cell induced inflammation, specifically in the ischemic region (*p < 0.0001) and improved endothelial function by reducing the expression of pro-inflammatory genes and adhesion factors on endothelial cells both in vitro and in vivo. Furthermore, mechanistic studies have revealed that C.oil reduced the expression of adhesion factors like E-selectin (#p = 0.0016) and ICAM-1 ($p = 0.0069) in initiating endothelial cells induced inflammation. In line, to the RT-PCR expression data, C.oil reduced the adhesion of inflammatory cells to endothelial cells as assessed by the interaction of THP-1 monocytes with the endothelial cells using flow based adhesion and under inflammatory conditions. Conclusion: These studies provide evidence that salutary effect of C.oil on MI/RP could be achieved with pre and post treatment of rats, C.oil reduced MI/RP induced injury by reducing the endothelial cell mediated inflammation, specifically in the ischemic zone of MI/RP rat heart.

Withania somnifera shows protective effect in monocrotaline-induced pulmonary hypertension

2015-01-01T00:00:00Z

Withania somnifera shows protective effect in monocrotaline-induced pulmonary hypertension Kaur, Gurpreet; Singh, Neetu; Samuel, S S; Bora, H K; Sharma, Sharad; Pachauri, S D; Dwivedi, A K; Siddiqui, H H; Hanif, Kashif Context: Withania somnifera (Linn.) Dunal (Solanaceae), a clinically used herbal drug in Ayurveda, shows potent antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective effects. However, the efficacy of W. somnifera in pulmonary hypertension (PH), a cardiopulmonary disorder, remains unexplored. Objective: The present study investigates the effect of W. somnifera root powder on Monocrotaline (MCT)-induced PH in rats. Materials and methods: In preventive studies, W. somnifera root powder (50 and 100 mg/kg/day, p.o.) was administered from day 1 following single administration of MCT (60 mg/kg, s.c.) in Sprague Dawley (SD) rats. After 35 days, right ventricular pressure (RVP) was measured in anaesthetized rats. Various physical markers of right ventricular hypertrophy (RVH) were measured in isolated hearts. Markers of endothelial function, inflammation, and oxidative stress were estimated in lung homogenate. Vasoreactivity of pulmonary arteries was also studied. In therapeutic treatment, W. somnifera (50 and 100 mg/kg/day, p.o.) was administered from day 21 to 35 post-MCT administration. Results: Preventive treatment with 50 and 100 mg/kg W. somnifera significantly reduced the RVP (32.18 ± 1.273 mmHg and 29.98 ± 1.119 mmHg respectively, vs. 42.96 ± 1.789 mmHg of MCT) and all markers of RVH in MCT-challenged rats. There was improvement in inflammation, oxidative stress and endothelial dysfunction and attenuation of proliferative marker and apoptotic resistance in lungs. Therapeutic treatment with W. somnifera (100 mg/kg) also reduced RVP and RVH. Discussion: This study demonstrated that W. somnifera significantly protected against MCT-induced PH due to its antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective properties.