Increased contractile responses to 5-hydroxytryptamine and Angiotensin II in high fat diet fed rat thoracic aorta

BACKGROUND: Feeding normal rats with high dietary levels of saturated fat leads to pathological conditions, which are quite similar to syndrome X in humans. These conditions such as hypertriglyceridemia, hypercholesterolemia, obesity, and hyperglycemia might induce hypertension through various mechanisms. Metabolic syndrome and the resulting NIDDM represent a major clinical challenge because implementation of treatment strategies is difficult. Vascular abnormalities probably contribute to the etiology of many diabetic complications including nephropathy, neuropathy, retinopathy, and cardiomyopathy. It has been shown that in Streptozotocin induced diabetic animals there is an increase in maximal responses to 5-Hydroxytryptamine and Angiotensin II. The purpose of this study was to evaluate High fat diet fed rats for the development of hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia and hyperglycemia and to assess their vascular responses to 5-Hydroxytryptamine and Angiotensin II. METHODS: Male Sprague Dawley rats were used for this study and were divided into two equal groups. One of the groups was fed with normal pellet diet and they served as the control group, whereas the other group was on a high fat diet for 4 weeks. Body weight, plasma triglycerides, plasma cholesterol, and plasma glucose were measured every week. Intraperitoneal glucose tolerance test was performed after 4 weeks of feeding. At the end of fourth week of high fat diet feeding, thoracic aortae were removed, and cut into helical strips for vascular reactivity studies. Dose-response curves of 5-Hydroxytryptamine and Angiotensin II were obtained. RESULTS: There was no significant difference in pD(2), with 5-Hydroxytryptamine and Angiotensin II in both groups but E(max )was increased. CONCLUSIONS: These results suggest that hypertension in high fat diet rats is associated with increased in vitro vascular reactivity to 5-HT and Ang II

Increased contractile responses to 5-hydroxytryptamine and Angiotensin II in high fat diet fed rat thoracic aorta

Abstract Background Feeding normal rats with high dietary levels of saturated fat leads to pathological conditions, which are quite similar to syndrome X in humans. These conditions such as hypertriglyceridemia, hypercholesterolemia, obesity, and hyperglycemia might induce hypertension through various mechanisms. Metabolic syndrome and the resulting NIDDM represent a major clinical challenge because implementation of treatment strategies is difficult. Vascular abnormalities probably contribute to the etiology of many diabetic complications including nephropathy, neuropathy, retinopathy, and cardiomyopathy. It has been shown that in Streptozotocin induced diabetic animals there is an increase in maximal responses to 5-Hydroxytryptamine and Angiotensin II. The purpose of this study was to evaluate High fat diet fed rats for the development of hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia and hyperglycemia and to assess their vascular responses to 5-Hydroxytryptamine and Angiotensin II. Methods Male Sprague Dawley rats were used for this study and were divided into two equal groups. One of the groups was fed with normal pellet diet and they served as the control group, whereas the other group was on a high fat diet for 4 weeks. Body weight, plasma triglycerides, plasma cholesterol, and plasma glucose were measured every week. Intraperitoneal glucose tolerance test was performed after 4 weeks of feeding. At the end of fourth week of high fat diet feeding, thoracic aortae were removed, and cut into helical strips for vascular reactivity studies. Dose-response curves of 5-Hydroxytryptamine and Angiotensin II were obtained. Results There was no significant difference in pD2, with 5-Hydroxytryptamine and Angiotensin II in both groups but Emax was increased. Conclusions These results suggest that hypertension in high fat diet rats is associated with increased in vitro vascular reactivity to 5-HT and Ang II.</p

Virtual Screening Enabled Selection of Antiviral Agents Against Covid-19 Disease Targeting Coronavirus Endoribonuclease NendoU: Plausible Mechanistic Interventions in the Treatment of New Virus Strain

SARS-CoV-2 is the seventh coronavirus that is reported to cause infection in Homo sapiens. Considering its pandemic nature, development of newer and effective therapeutic strategies, drug repurposing in combination with target validation approaches has led to the identification of new antiviral molecules. In current work, we performed virtual screening and molecular docking of 8548 ligands on target protein coronavirus endoribonuclease NendoU (6VWW). The molecules selected includes FDA approved drugs along with investigational or experimental drugs recommended for anticancer, antiviral, antimicrobial, and antiprotozoal properties. The thorough selection and their rationality with Covid-19 led us to propose that FDA approved drug DB00876 (Eprosartan), Investigational drugs DB15063 (Inarigivir soproxil), DB12307 (Foretinib) and DB01813 an experimental drug may be repurposed for treatment of Covid-19 disease.</p

Omicron, a new SARS-CoV-2 variant: assessing the impact on severity and vaccines efficacy

The reply letter has been put forth in response to the comment made by Karthyayani Priya Satish entitled “India and the COVID-19 Vaccine.” The comment was made in context to our published work “Exploring the covid-19 vaccine candidates against SARS-CoV-2 and its variants: where do we stand and where do we go?” The reply letter is concerned with the newer variant of SARS-CoV-2, i.e., Omicron and its impact on severity and vaccine efficacy. Though the variant is mild, as per the reports, the cases are rising at an unprecedented rate that may create havoc on humankind considering shortages of RT-PCR testing and prevailing unequal vaccine distribution and vaccine hesitancy

Exploring the COVID-19 vaccine candidates against SARS-CoV-2 and its variants: where do we stand and where do we go?

As of September 2021, 117 COVID-19 vaccines are in clinical development, and 194 are in preclinical development as per the World Health Organization (WHO) published draft landscape. Among the 117 vaccines undergoing clinical trials, the major platforms include protein subunit; RNA; inactivated virus; viral vector, among others. So far, USFDA recognized to approve the Pfizer-BioNTech (Comirnaty) COVID-19 vaccine for its full use in individuals of 16 years of age and older. Though the approved vaccines are being manufactured at a tremendous pace, the wealthiest countries have about 28% of total vaccines despite possessing only 10.8% of the total world population, suggesting an inequity of vaccine distribution. The review comprehensively summarizes the history of vaccines, mainly focusing on vaccines for SARS-CoV-2. The review also connects relevant topics, including measurement of vaccines efficacy against SARS-CoV-2 and its variants, associated challenges, and limitations, as hurdles in global vaccination are also kept forth

New PPARγ ligands based on 2-hydroxy-1,4-naphthoquinone: Computer-aided design, synthesis, and receptor-binding studies

FlexX-based molecular docking study was employed to identify 2-hydroxy-1,4-naphthoquinone as a new ‘acidic head group’ for the design of a novel series of PPARγ ligands. To provide the proof of concept, designed molecules were synthesized and evaluated in a standard radioligand-binding assay. Out of eight molecules, four were found to bind to the murine PPARγ with IC50 ranging from 0.2 to 56.2 μM as compared to standard pioglitazone, with IC50 of 0.7 μM

New PPARγ ligands based on barbituric acid: virtual screening, synthesis and receptor binding studies

A new series of PPARγ ligands based on barbituric acid (BA) has been designed employing virtual screening and molecular docking approach. To validate the computational approach, designed molecules were synthesized and evaluated in in vitro radioligand binding studies. Out of the total 14 molecules, 6 were found to bind to the murine PPARγ with IC<SUB>50</SUB> ranging from 0.1 to 2.5 μM as compared to reference standard, pioglitazone (IC<SUB>50</SUB> = 0.7 μM)

A potential therapeutic strategy for diabetes and its complications in the form of co-encapsulated antioxidant nanoparticles (NanoCAPs) of ellagic acid and coenzyme Q10: Preparation and evaluation in streptozotocin induced diabetic rats

Diabetes is a metabolic disorder and is associated with serious complications caused by oxidative stress. The existing therapies only delay or reduce the severity of these complications but cannot completely prevent or reverse them. Antioxidant therapy is one promising alternative strategy to assuage these complications. However, the poor biopharmaceutical properties of many antioxidants limit their use as first line therapies. Here we propose a new therapeutic strategy to treat diabetes using biodegradable nano-co-encapsulated antioxidant particles (NanoCAPs) of ellagic acid (EA) and coenzyme Q(10) (CoQ(10)). The combination of EA and CoQ(10) showed beneficial effects in ameliorating lipid peroxidation, dyslipidemia and in preventing organ damage in streptozotocin induced diabetic rats. Significantly lower dose of EA and CoQ(10) in NanoCAPs showed equal and sometimes more prominent results in comparison to simple suspension suggesting improved efficacy Additionally, a statistically significant increase was observed in plasma insulin levels with nanoparticulate formulation of EA and CoQ(10) combination in comparison to simple suspension of EA, CoQ(10) alone or in combination as well as CoQ(10) nanoparticles. Collectively, this data indicates the potential use of NanoCAPs of EA and CoQ(10) in diabetes and reducing the associated complications