Impact of time-restricted feeding on kidney injury in male rats with experimental metabolic syndrome.

Disruptions to circadian rhythm may be implicated in the pathogenesis of metabolic syndrome (Met-S). For example, eating during an extended period of the day may negatively impact the circadian rhythms governing metabolic control, contributing, therefore, to Met-S and associated end-organ damage. Accordingly, time-restricted eating (TRE)/feeding (TRF) is gaining popularity as a dietary intervention for the treatment and prevention of Met-S. To date, no studies have specifically examined the impact of TRE/TRF on the renal consequences of Met-S. The proposed study seeks to use a model of experimental Met-S-associated kidney disease to address this knowledge gap, disambiguating therein the effects of calorie restriction from the timing of food intake. Spontaneously hypertensive rats will consume a high-fat diet (HFD) for 8 weeks and then be allocated by stratified randomisation according to albuminuria to one of three groups. Rats will have free 24-h access to HFD (Group A), access to HFD during the scheduled hours of darkness (Group B) or access to HFD provided in the form of two rations, one provided during the light phase and one provided during the dark phase, equivalent overall in quantity to that consumed by rats in Group B (Group C). The primary outcome measure will be a change in albuminuria. Changes in food intake, body weight, blood pressure, glucose tolerance, fasting plasma insulin, urinary excretion of C-peptide and renal injury biomarkers, liver and kidney histopathology and inflammation, and fibrosis-related renal gene expression will be assessed as secondary outcomes.

Targeting the Platelet-Activating Factor Receptor (PAF-R): Antithrombotic and Anti-Atherosclerotic Nutrients.

Platelet-activating factor (PAF) is a lipid mediator that interacts with its receptor (PAF-R) to carry out cell signalling. However, under certain conditions the binding of PAF to PAF-R leads to the activation of pro-inflammatory and prothrombotic pathways that have been implicated in the onset and development of atherosclerotic cardiovascular diseases (CVD) and inflammatory diseases. Over the past four decades, research has focused on the identification and development of PAF-R antagonists that target these inflammatory diseases. Research has also shown that dietary factors such as polar lipids, polyphenols, and other nutrient constituents may affect PAF metabolism and PAF-R function through various mechanisms. In this review we focus on the inhibition of PAF-R and how this may contribute to reducing cardiovascular disease risk. We conclude that further development of PAF-R inhibitors and human studies are required to investigate how modulation of the PAF-R may prevent the development of atherosclerotic cardiovascular disease and may lead to the development of novel therapeutics.

Nuciferine from Nelumbo nucifera Gaertn. attenuates isoproterenol-induced myocardial infarction in Wistar rats.

The study explored the cardioprotective role of the methanolic leaf extract of Nelumbo nucifera and nuciferine against isoproterenol-induced myocardial infarction (MI) in Wistar rats. Pretreatment with leaf extract and nuciferine (200 and 20 mg/kg body weight, respectively) against MI induced by isoproterenol (85 mg/kg body weight) significantly decreased heart weight; levels of cardiac markers such as lactate dehydrogenase and creatine kinase-MB were similar to those in controls. The treatment significantly increased the content of endogenous antioxidants and decreased lipid peroxidation in all treated groups. Treated groups showed a significant reduction in heartbeats per minute as compared with the MI-induced positive control. The MI-induced group showed pathological implications such as tachycardia, left atrial enlargement, and anterolateral ST-elevated MI, which were absent in treated groups. Histology confirmed that the leaf extract and nuciferine prevented structural abnormality and inflammation in heart and liver tissues of treated groups. On in silico analysis, nuciferine showed stronger binding interaction with both ß1 and ß2 adrenergic receptors than isoproterenol. Hence, the leaf extract of N. nucifera and nuciferine could be used as plant-based cardioprotective agents.

Nuciferine Attenuates Doxorubicin-Induced Cardiotoxicity: An In Vitro and In Vivo Study.

Chemotherapeutic drugs are a known factor that impairs the system of life due to their severe side effects. A more worrying fact is that the patients administered with doxorubicin fall under the risk of cardiotoxicity. The evolution of exploring plant-derived compounds is a possible way to combat health issues in therapeutic applications. Hence, this study focuses on the protective effect of plant-based compound nuciferine (NFN) against doxorubicin-induced cardiotoxicity in both in vitro and in vivo models. In this investigation, nuciferine significantly reduces DOX-mediated cardiotoxicity by mitigating reactive oxygen species, thereby preventing DNA fragmentation, regulating apoptosis genes and reducing the caspase 3/7 levels in vitro. Besides, nuciferine has shown significant protection against DOX-induced cardiac impairment and the upregulation of cardiogenic markers in vivo. The DOX-induced oxidative stress can be mitigated via enhancing the endogenous antioxidants, thereby controlling ROS-mediated apoptosis. In virtue of these potential features, nuciferine can be a budding candidate to address therapeutic needs.

Lotusine, an alkaloid from Nelumbo nucifera (Gaertn.), attenuates doxorubicin-induced toxicity in embryonically derived H9c2 cells.

Cardiotoxicity is the major challenge in chemotherapy with doxorubicin (DOX) or adriamycin. Doxorubicin manifests oxidative stress via an uncontrolled progression of reactive oxygen species in cardiomyocytes; thereby, dysregulation and dysfunction of myocardium thus lead to apoptosis. Several attempts have been made to overcome this side effect in patients with antioxidant-rich supplements to control the free radicals. Plant-based or plant-derived compounds pay more attention to cure such complications in patients for supporting the treatment, revitalizing or regulating the normal metabolism. Hence, our study focused on pretreatment of embryonically derived rat cardiomyocytes (H9c2) with phytocompound lotusine to prevent DOX-mediated oxidative stress. From the experiment, the DOX-exposed cells have shown morphological abnormalities such as reduced cell size, shrinkage, blebbing, and chromatin condensation, whereas no such deformities were observed in lotusine-pretreated cells even after the exposure to DOX. Increased endogenous antioxidants with reduced lipid peroxidation were observed in lotusine-pretreated cells, whereas the antioxidants were reduced along with increased lipid peroxidation in doxorubicin-exposed cells. A decreased reactive oxygen species generation was evidenced with the 2',7'-dichlorofluorescein diacetate (DCF-DA) staining method. In qPCR analysis, the lotusine-pretreated cells have mitigated doxorubicin-mediated apoptosis by downregulating the pro-apoptotic gene Bax and apoptotic executor caspase-3. It was further confirmed with the luminometric assay, which resulted in lesser luminescence in lotusine-pretreated cells, whereas higher luminescence was recorded in doxorubicin-alone-treated cells. In conclusion, the present study revealed that the lotusine pretreatment has exhibited potential cardioprotective activity against DOX-induced oxidative stress by increasing the intracellular antioxidant defense.

Protective effect of Nelumbo nucifera (Gaertn.) against H2O2-induced oxidative stress on H9c2 cardiomyocytes.

Ischemic heart disease (IHD), a severe condition of myocardium facing impediment in the supply of basic needs for cellular metabolism is caused by atherosclerosis. Though statin drugs could control the use of surgery on IHD patients, the complete rehabilitation or prophylaxis can be achieved through herbal-based medicines viz. either in the form of crude extract or pure phytocompounds. In the present study, pretreatment with leaf extract of Nelumbo nucifera Gaertn. was investigated for cardioprotective activity-in vitro by mitigating H2O2-induced oxidative stress. Analysis such as estimation of antioxidants, lipid peroxidation, and DNA fragmentation assay revealed significant protective effect of plant extract on cardiomyocytes. Reactive oxygen species detection was done by using 2',7'-dichlorofluorescein diacetate, apoptosis detection with Acridine Orange/Ethidium Bromide and nuclear damage detection by diamidino-2-phenylindole which confirmed the protective effect of N. nucifera extract. In addition, gene expression studies of apoptotic regulatory genes (Bcl2 and Cas-9) resulted in significant protection of nucifera extract pretreated and maintained cells. To conclude, in vitro cardioprotective activity of N. nucifera against H2O2 induced oxidative stress was achieved at the concentration of 50 µg/ml. Therefore, major phytocompounds present in extract could be beneficial in managing cardiac complications in the future.

Toxicity and Selective Biochemical Assessment of Quercetin, Gallic Acid, and Curcumin in Zebrafish.

In recent years, numerous research outcomes were established on various naturally occurring compounds that have been shown to have beneficial antioxidant and other biological activities. Antioxidant defence mechanism plays a vital role in combating various diseases mainly due to oxidative stress. However, various models have been utilized to identify their bioactivities using these compounds (quercetin, gallic acid and curcumin). Their toxicity level also has to be explored to determine the threshold levels on the usage of these compounds. In this study, we investigated the lethal concentration of these compounds and abnormalities, biochemical and morphological changes in zebrafish embryo (Danio rerio). Toxicity level was evaluated by calculating the LD50 on the embryonic stages at 24, 48 and 72 h. Antioxidant parameters such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and biological assays such as lipid peroxidation, protein estimation were performed. Microscopic evaluations were also observed to find out morphological abnormalities. However, these naturally derived compounds are reported to have their protective and curative role in many health complications. From the above assays, we are studying the effect of the drugs in both biochemical and molecular way in the zebrafish model organism.

Evaluation of Octyl-ß-D-Glucopyranoside (OGP) for Cytotoxic, Hemolytic, Thrombolytic, and Antibacterial Activity.

The current study indicates that octyl-ß-D-glucopyranoside (OGP) as a detergent which has the ability to make the lipid layer stiff. OGP was subjected for toxicity studies and in vitro cytotoxicty assays on cancerous HeLa and non-cancerous myoblasts H9c2 cell lines. Test against aquatic organisms were carried out in Artemia salina and LC50 values were calculated. Hemolytic activity tested for blood bio-compalibity showed hemolysis rate of 10-16%, followed by thrombolytic activity to burst the clots in blood. Also, the samples showed good lysis when compared to the standard streptokinase. Furthermore, α-amylase activity has been carried out to check the inhibition of α-amylase by the OGP. Finally, antibacterial activity has been tested against four different pathogens and their MIC values have been calculated.

Photocatalytic degradation of synthetic food dye, sunset yellow FCF (FD&C yellow no. 6) by Ailanthus excelsa Roxb. possessing antioxidant and cytotoxic activity.

The purpose of our work is to identify the bioactive compounds of bark and leaves extract from Ailanthus excelsa Roxb. and to explore its effectiveness against synthetic food dye. The presence of primary and secondary metabolites was confirmed by carrying out phytochemicals analysis. With the prior knowledge accessible on the indispensable secondary metabolites holding antioxidant and cytotoxicity activity, the quantitative screening of total phenolic and flavonoid content in methanolic and aqueous extract of bark and leaves from Ailanthus excelsa were done. Comparatively, a higher value of flavonoid (161±0.3µg/mg) and phenolic acid content (152.4±0.14µg/mg) was found in bark extract. By FTIR analysis, the characteristic peak was obtained at 1581.63 and 1598.99cm-1 confirmed the presence of functional groups associated to flavonoids and other phenolic groups respectively. In bark extract, 81% of DPPH inhibition was observed when compared to ascorbic acid (standard) 92% of free radical scavenging activity. Bark extract from Ailanthus excelsa exhibited 71% cytotoxicity against HeLa cell line (cervical cancer). In examining the toxicity level of crude extracts with red blood cells (RBC), the bark extract was showed a very less (2.8%) haemolytic activity. They also showed maximum zone of inhibition in antibacterial activity i.e. 13±0.5mm against Escherichia coli culture. At a concentration of 10mg/mL of crude extract from A. excelsa, 55% degradation of sunset yellow dye was observed. It concludes that, the compounds present in the A. excelsa, especially the bark extract showed better photocatalytic, haemolytic, antioxidant, cytotoxicity and antibacterial activity when compared to leaves extract.