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Viral outbreaks had been a threat for the human race for a long time. Several epidemics and pandemics have been reported in the past with serious consequences on human health and subsequent social and economic aspects. According to WHO, viral infections continue to be a major health concern globally. Novel coronavirus, SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) causes the most recent infectious pandemic disease, COVID-19 (Coronavirus disease-19). As of now, there were 249 million infections of COVID-19 worldwide with a high mortality of more than 5 million deaths reported; and the number of new additional cases is drastically increasing. Development of therapies to treat the infected cases and prophylactic agents including vaccines that are effective towards different variants are crucial to curtail the COVID-19 pandemic. Owing to the fact that there is a high mortality and morbidity rate along with the risk of virus causing further epidemic outbursts, development of additional effective therapeutic and preventive strategies are highly warranted. Prevention, early detection and treatment will reduce the spread of COVID-19 pandemic. The present review highlights the novel mutations and therapeutic updates associated with coronaviruses along with the clinical manifestations—diagnosis, clinical management and, prophylactic and therapeutic strategies of COVID-19 infection. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the therapeutic efficacy and underlying molecular mechanisms of Bauhiniastatin-1 (BSTN1) to alleviate adiposity in diet-induced obese rodent model and in 3T3-L1 cells. Methods: BSTN1 was purified and confirmed through HPLC. In-vitro experiments such as MTT assay, Oil Red-O (ORO) stain, cellular lipid content, glycerol release and RT-PCR analysis were performed in 3T3-L1 cells in the presence and absence of BSTN1. In animal experiments, rats were divided into Group-I: normal pellet diet-fed, Group-II: HFD-fed, Groups-III, IV and V: HFD-fed BSTN1 (1.25, 2.5, and 5 mg/kg.b.wt./day/rat)-treated and Group-VI: HFD-fed Orlistat-treated. The rats were fed either normal diet or high fat diet (HFD) for 18 weeks and water ad-libitum. BSTN1 was orally administered from 13th week onwards to the selected HFD-fed groups. Body composition parameters, biochemical assays, histopathology examination and western blot analysis were performed to identify the predicted targets related to obesity. Molecular docking studies threw light on the binding interactions of BSTN1 against PPAR-γ, FAS and AMPK. Results: BSTN1 at 20 μM significantly (p < 0.001) inhibited adipocyte differentiation and lipid accumulation in 3T3-L1 cells. A conspicuous down-regulation in the mRNA expression levels of PPAR-γ, FAS and SREBP1 was observed but AMPK expression remained unchanged in BSTN1 treated 3T3-L1 cells. A substantial decrease in body weight gain, fat percent, total body fat, serum and liver lipid profile (except high-density lipoprotein), glucose, insulin and insulin resistance in BSTN1 treated rats was noticed in a dose dependent manner. In BSTN1 (5 mg/kg.b.wt.)-treated groups significantly (p < 0.01) elevated plasma adiponectin level but reduced leptin level as well as fall in serum AST and ALT were noticed. Further, the disturbed structural integrity and architecture of adipose and hepatic tissues due to high fat diet feeding were considerably recovered with BSTN1 treatment. Down-regulation in the protein expression level of PPAR-γ and activation of AMPK through phosphorylation was observed in BSTN1 treated rats than the untreated. Molecular docking studies revealed strong binding interactions of BSTN1 against PPAR-γ and AMPK and thus supported the experimental results. Conclusion: Taken together, the results suggest that BSTN1 could be a promising pharmacological molecule in the treatment of obesity and dyslipidemia. [ABSTRACT FROM AUTHOR]

Background/Aims: Diabetes mellitus is a pandemic metabolic disorder that is affecting a majority of populations in recent years. There is a requirement for new drugs that are safer and cheaper due to the side effects associated with the available medications. Methods: We investigated the anti-diabetic activity of leaves of Anisomeles malabarica following bioactivity guided fractionation. The different solvent (hexane, ethyl acetate, methanol and water) extracts of A. malabarica leaves were used in acute treatment studies to evaluate and identify the active fraction. The ethyl acetate extract was subjected to further fractionation using silica gel column chromatography and the compounds were identified by LC-SRM/MS and GC-MS. Additional chronic treatment studies were carried out using this active fraction (AMAF) for 30 days in experimental diabetic rats. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), plasma insulin levels and glucose tolerance were measured along with insulin resistance/sensitivity indicators (HOMA-IR, HOMA-ß and QUICKI) to assess the beneficial effects of A. malabarica in the management of diabetes mellitus. Results: Among the different solvent extracts tested, ethyl acetate extract showed maximum (66%) anti-hyperglycemic activity. The hexane and ethyl acetate (1:1) fraction that has maximum anti-diabetic activity was identified as active fraction of A. malabarica (AMAF). The FBG, HbA1c, plasma insulin levels and insulin sensitivity/resistance indicators such as glucose tolerance, HOMA-IR, HOMA-ß and QUICKI were significantly improved to near normal in diabetic rats treated with AMAF. Further, we identified key flavonoids and fatty acids as the anti-diabetic active principles from the AMAF of A. malabarica leaves. Conclusion: The results of our study suggest that Anisomeles malabarica has potential anti-diabetic activity in STZ induced diabetic rats. [ABSTRACT FROM AUTHOR]

Background: This study was aimed to evaluate the protective effects of a novel anti-hyperglycemic 'Mcy protein' isolated from the fruits of Momordica cymbalaria in streptozotocin induced- diabetes rat model. Materials and Methods: Wild type and Streptozotocin induced diabetic male wistar albino rats were either treated with single intraperitoneal injection of 2.5 mg Mcy protein/kg body weight or acetate buffer daily for 30 days. Fasting blood glucose and, serum and tissue lipid levels were measured along with biochemical analysis for hepatic and renal function tests. Results: Mcy protein significantly reduced the fasting blood glucose and, serum as well as tissue lipid levels (p<0.05), besides normalizing the levels of liver and kidney function markers in the treated diabetic rats when compared to the diabetic controls. Our studies also showed the pancreatic islet regeneration in Mcy treated rats. Conclusion: Mcy protein can alleviate hyperlipidemia and help manage diabetes by stimulating insulin secretion without evident toxic effects on liver and kidney. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim of the study: A new antihyperglycemic protein was identified in the aqueous extract of fruits of Momordica cymbalaria by bioassay-guided fractionation. The study was aimed at isolation and characterization of this protein. Materials and methods: The active principle was purified to homogeneity by ammonium sulphate precipitation, gel filtration column chromatography on Sephadex G-50 followed by reverse phase HPLC. Its N-terminal amino acid sequence was identified and compared in the protein data bank. Optimum dose and route of administration of the active principle was determined in STZ induced diabetic rats. Results: A 17kDa protein with an isoelectric point of 5.0 was identified as the active principle of antidiabetic action present in the aqueous extract of fruits of MC. It is named as M.Cy protein and found to be a novel protein by comparing its N-terminal amino acid sequence with those in the protein data bank. It did not produce any hypoglycemia in either normal or diabetic rats. Conclusions: The results suggest that ‘M.Cy protein’, present in the fruits of Momordica cymbalaria is an effective antihyperglycemic active principle in STZ induced diabetic rats at a dose of 2.5mg/kgb.w. [Copyright &y& Elsevier]

We previously identified a set of transcription regulators, referred to as TIPs (tension-induced/inhibited proteins), with a role in myogenic versus adipogenic differentiation. Here we report that the TIP family comprises eight isoforms, all bearing a SANT (switching-defective protein 3, adaptor 2, nuclear receptor corepressor, and transcription factor IIIB) domain and some of them presenting S-adenosyl-L-methionine (SAM) and nuclear receptor box (NRB) motifs, all characteristic of histone-modifying enzymatic complexes. TIPs have SANT-dependent, p300-mediated histone acetyltransferase (HAT) activity. Ectopic TIP-6 (SANT+ SAM- NRB-) but not TIP-6ΔSANT induced de novo PPARγ2-mediated adipogenic gene expression in NIH 3T3 cells and promoted preadipocyte differentiation into fat cells. TIP-6 was also involved in mediating hormonally/biochemically induced adipogenic differentiation of 3T3-L1 cells. Furthermore, TIP-6 was identified in adipose tissue in vivo. TIP-6 bound directly and indirectly to p300 and histone H4 (H4). Deletion of the SANT domain did not abolish TIP-6 interaction with p300 and H4 but eliminated direct TIP-6 binding to p300. Chromatin immunoprecipitation assays showed the recruitment of TIP-6, TIP-6ΔSANT, and p300 to the PPARγ2 promoter, but H3/H4 acetylation occurred only when p300 was directly associated with TIP-6. These studies demonstrated the importance of TIPs in the recruitment of p300 to specific promoters and in the regulation of p300 HAT activity through the involvement of the SANT domain. Furthermore, we identified TIP-6 as a new member of the adipogenic cascade. [ABSTRACT FROM AUTHOR]

Green tea (Camellia sinensis) is a popular beverage consumed all over the world due to its health benefits. Many of these beneficial effects of green tea are attributed to polyphenols, particularly catechins. The present study focuses on underlying anti-platelet aggregation, anti-thrombotic, and anti-lipidemic molecular mechanisms of green tea in South Indian smokers. Materials and methods : We selected 120 South Indian male volunteers for this study to collect the blood and categorised them into four groups; control group individuals (Controls), smokers, healthy control individuals consuming green tea, and smokers consuming green tea. Smokers group subjects have been smoking an average 16–18 cigarettes per day for the last 7 years or more. The subjects (green tea consumed groups) consumed 100 mL of green tea each time, thrice a day for a one-year period. LC-MS analysis revealed the presence of multiple phytocompounds along with catechins in green tea extract. Increased plasma lipid peroxidation (LPO), protein carbonyls, cholesterol, triglycerides, and LDL-cholesterol with decreased HDL-cholesterol levels were observed in smokers compared to the control group and the consumption of green tea showed beneficial effect. Furthermore, docking studies revealed that natural compounds of green tea had high binding capacity with 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA) when compared to their positive controls, whereas (−) epigallocatechin-3-gallate (EGCG) and (−) epicatechin-gallate (ECG) had high binding capacity with sterol regulatory element-binding transcription factor 1 (SREBP1c). Further, our ex vivo studies showed that green tea extract (GTE) significantly inhibited platelet aggregation and increased thrombolytic activity in a dose dependent manner. In conclusion, in smokers, catechins synergistically lowered oxidative stress, platelet aggregation and modified the aberrant lipid profile. Furthermore, molecular docking studies supported green tea catechins' antihyperlipidemic efficacy through strong inhibitory activity on HMG-CoA reductase and SREBP1c. The mitigating effects of green tea on cardiovascular disease risk factors in smokers that have been reported can be attributed majorly to catechins or to their synergistic effects. [Display omitted] • Green tea is consumed as a beverage worldwide due to its beneficial effects. • Green tea consumption lowers oxidative stress and normalizes lipid profile in smokers. • Molecular docking studies revealed green tea catechins' inhibitory activity on HMG-CoA reductase and SREBP1c. • In vitro studies revealed that green tea possesses anti-platelet aggregation and anti-thrombotic functions. • The protective effects reported can be attributed majorly to catechins. [ABSTRACT FROM AUTHOR]

Adipocyte development and adipose tissue expansion have many implications for human diseases, including obesity. Obesity is a debilitating disorder and a risk factor for metabolic disorders including insulin resistance and diabetes mellitus, due in part to an overabundance of adipocytes and adipocyte dysfunction. In recent years, obesity has become a global pandemic with approximately one-third of US adults classified as obese. Adipose tissue has recently been identified as a major metabolic organ, classified into white adipose tissue (WAT) and brown adipose tissue (BAT). Other than lifestyle modifications and invasive surgeries, only a very limited number of drugs are available to treat obesity and overweight. P311 has been shown to play a key role in blood pressure regulation, vascular contractility and tissue remodeling. Here we present a role for P311 in adipogenesis using a 3T3-L1 cell culture model. P311 expression is initiated with the induction of adipogenesis and increased during adipogenesis. This increase correlates with an increase in the expression of the key adipogenic transcriptional factors PPARγ2 and C/EBPα. In addition, siRNA-mediated P311 knockdown inhibits adipogenic differentiation in 3T3-L1 cells. Finally, P311 binds to the PPARγ2 promoter, implicating P311 mediates adipogenesis partly through PPARγ activation. Image 1 • P311 plays a role in adipogenesis. • P311 has transcriptional regulatory/coregulatory function. • P311 is an intrinsically disordered protein. [ABSTRACT FROM AUTHOR]

[Display omitted] The latest global pandemic corona virus disease − 2019 (COVID-19) caused by the virus SARS-CoV-2 is still a matter of worrying concern both for the scientific communities and health care organizations. COVID-19 disease is proved to be a highly contagious disease transmitted through respiratory droplets and even close contact with affected individuals. COVID-19 disease is also understood to exhibit diverse symptoms of ranging severities i.e., from mild fatigue to death. Affected individuals' susceptibility to induce immunologic dysregulation phenomena termed 'cytokine storm' seems to be playing the damaging role of escalating the disease manifestation from mild to severe. Cytokine storm in patients with severe symptoms is understood to be characterized by enhanced serum levels of many cytokines including interleukin-1β, interleukin-6, IP-10/CXCL10, TNF, interferon-γ, MIP-1α, MIP-1β and VEGF. Since cytokine production in general is the most important antiviral defense response, understanding the COVID-19 associated cytokine storm in particular and differentiating it from the regular cytokine production response becomes crucial in developing an effective therapeutic strategy. This review focuses on the potential targeting of COVID-19 associated cytokine storm and its challenges. [ABSTRACT FROM AUTHOR]

Asparagus gonoclados Baker is a traditional folk remedy used for diabetes, diuretic, galactogogue, gastric ulcer activities etc. The present investigation was intended to evaluate the beneficial effect of the A.gonoclados (Lilliaceae) root tubers against diabetes mellitus. Different solvent extracts of root tubers of A. gonoclados were used to study the antihyperglycemic activity in streptozotocin (45 mg/kg.wt) induced diabetic rats. Oral glucose tolerance test was performed in diabetic and normal rats treated with A.gonoclados. Total phenolic content (TPC), total flavanoid content (TFC) and total steroidal saponins content (TSSC) were measured in different solvent extracts. Following bioassay guided fractionation method antihyperglycemic active fraction of A. gonoclados (AGAF) was isolated from the ethanol extract (AGEE) by silica gel column chromatography. We further tested relationship between insulin stimulation effect and the influence of active fraction on K+-ATP and Ca2+ channels opening in normal and diabetic rats. The characterization of AGAF was carried out by LC-ESI-MS/MS. Among the different solvent extracts, the ethanol extract (AGEE) at a dose of 500 mg/kg b.wt has produced maximum (67%) reduction in fasting blood glucose levels (FBG) in diabetic treated rats after 6 h of oral administration when compared to the standard drug glibenclamide (40%). AGEE also showed dose-dependent inhibitory effect on the activities of α-glucosidase (74.73%) and α-amylase (76.47%), which is comparable to the activity of standard drug acarbose (88.42%). AGEE was found to have the richest quantity of TPCs (138.4 ± 0.39 μg/mg gallic acid equivalents), TFCs (64.8 ± 0.54 μg/mg quercetin equivalents) and TSSCs (12.9 ± 0.11μg/mg sarasapogenin equivalents). We identified 8 potential antihyperglycemic compounds in AGAF by LC-ESI-MS/MS analysis. From our current study we confirm that A. gonoclados root tubers have potent antihyperglycemic activity and it can be a unique drug/formulation for the management of diabetes mellitus. Image 1 [ABSTRACT FROM AUTHOR]