Neferine, a bisbenzylisoquinoline alkaloid, offers protection against cobalt chloride-mediated hypoxia-induced oxidative stress in muscle cells

Background: Neferine, a bisbenzylisoquinoline alkaloid, isolated from Nelumbo nucifera has a wide range of biological activities. Cobalt chloride (CoCl2) was known to mimic hypoxic condition. In the present study, we assessed the cytoprotective effect of neferine against CoCl2-induced oxidative stress in muscle cells. Methods: Rhabdomyosarcoma cells were exposed to different concentrations of CoCl2, and the IC50 value was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Lactate dehydrogenase and NO assays were performed in order to determine the cytotoxic effect of CoCl2. Reactive oxygen species generation and cellular antioxidant status were determined for evaluating oxidative stress. For analyzing the effect of neferine on CoCl2-induced apoptosis, propidium iodide staining was performed. Results: The results of the present study indicate that CoCl2 induces cell death in a dose-dependent manner. Neferine pretreatment at 700 nM concentration offers better cytoprotection in the cells exposed to CoCl2. Lactate dehydrogenase and NO release in the culture medium were restored after neferine pretreatment. CoCl2 triggers time-dependent reactive oxygen species generation in muscle cells. Further, results of propidium iodide staining, mitochondrial membrane potential, and intracellular calcium accumulation confirm that neferine offers protection against CoCl2-induced hypoxic injury. Depleted activities of antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase due to CoCl2 exposure were also reinstated in the group that received neferine pretreatment. Conclusion: Our study suggests that neferine from N. nucifera offers protection to muscle cells by counteracting the oxidative stress induced by CoCl2

Modulatory effect of Tinospora cordifolia extract on Cd-induced oxidative stress in Wistar rats

Background: Cadmium (Cd), a nonessential heavy metal, is a major environmental and public health concern. Oxidative stress plays an important role in Cd-induced kidney dysfunction. Tinospora cordifolia, a medicinal plant rich in phytochemicals, possesses antioxidant activity. The objective of the present study was to assess the protective effect of Tinospora cordifolia-stem methanolic extract (TCE) on Cd-induced nephrotoxicity in Wistar rats. Methods: Male Wistar rats were administered ∼5 mg/kg body weight Cd orally and 100 mg/kg body weight TCE for 28 days. At the end of Cd and TCE treatment, biochemical assays were performed in serum and tissue homogenate. Results: Cd-induced oxidative stress in the kidney resulted in increased levels of lipid peroxidation and protein carbonyl content with a significant decrease in cellular antioxidants, such as reduced GSH, SOD, CAT, GPX, and GST. Cd-induced nephrotoxicity was further confirmed by marked changes in the histology of the kidney and increased levels of kidney markers. Additionally, Cd-treated rats showed alterations in membrane-bound ATPase activity and decreased levels of tissue glycoproteins. Cotreatment with TCE considerably reduced the biochemical alterations in serum and renal tissue induced by Cd, and also restored ATPase activity and glycoproteins to near normal levels. Conclusion: Our results suggested that TCE with its antioxidant effect offered cytoprotection against Cd-induced toxicity in kidneys by restoring the altered cellular antioxidants and renal markers. TCE treatment for 28 days reversed ATPase activity and tissue glycoprotein levels. These results revealed the protective effect of TCE on Cd-induced toxicity in kidneys and oxidative stress

Reversal of doxorubicin resistance in lung cancer cells by neferine is explained by nuclear factor erythroid-derived 2-like 2 mediated lung resistance protein down regulation

Aim: Development of multi drug resistance and dose limiting cardiotoxicity are hindering the use of Doxorubicin (Dox) in clinical settings. Augmented dox efflux induced by lung resistance protein (LRP) over expression has been related to multi drug resistance phenotype in various cancers. An alkaloid from lotus, Neferine (Nef) shows both anticancer and cardioprotective effects. Here, we have investigated the interconnection between nuclear factor erythroid-derived 2-like 2 (NRF2) and LRP in Dox resistance and how Nef can overcome Dox resistance in lung cancer cells by altering this signaling.Methods: Anti-proliferative and apoptotic-inducing effects of Nef and Dox combination in Parental and Dox resistant lung cancer cells were determined in monolayers and 3D spheroids. Intracellular Dox was analyzed using flow cytometry, siRNA knockdown and western blot analysis were used to elucidate NRF2-LRP crosstalk mechanism.Results: We observed that the Dox resistant lung cancer cells expressed higher levels of LRP, reduced glutathione (GSH) and NRF2. Combination of Dox and Nef induced apoptosis, leads to reactive oxygen species (ROS) generation, GSH depletion and reduction in LRP levels contributing to higher intracellular and intranuclear Dox accumulation. The use of N-acetylcysteine and knockdown studies confirmed an important role of ROS and NRF2 in LRP down regulation. Presence of NRF2 binding sites in LRP is support of direct interaction between LRP and NRF2.Conclusion: Nef sensitizes lung cancer cells to Dox by increasing intracellular and/or intra nuclear Dox accumulation via LRP down regulation. This is mediated by redox regulating NRF2. This decoded crosstalk mechanism reinforces the role of NRF2 and LRP in Dox resistance and as an important anticancer target

Neuroprotective Role of Phytochemicals

Neurodegenerative diseases are normally distinguished as disorders with loss of neurons. Various compounds are being tested to treat neurodegenerative diseases (NDs) but they possess solitary symptomatic advantages with numerous side effects. Accumulative studies have been conducted to validate the benefit of phytochemicals to treat neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD). In this present review we explored the potential efficacy of phytochemicals such as epigallocatechin-3-galate, berberin, curcumin, resveratrol, quercetin and limonoids against the most common NDs, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). The beneficial potentials of these phytochemicals have been demonstrated by evidence-based but more extensive investigation needs to be conducted for reducing the progression of AD and PD

Decapeptide from Potato Hydrolysate Induces Myogenic Differentiation and Ameliorates High Glucose-Associated Modulations in Protein Synthesis and Mitochondrial Biogenesis in C2C12 Cells

Sarcopenia is characterized as an age-related loss of muscle mass that results in negative health consequences such as decreased strength, insulin resistance, slowed metabolism, increased body fat mass, and a substantially diminished quality of life. Additionally, conditions such as high blood sugar are known to further exacerbate muscle degeneration. Skeletal muscle development and regeneration following injury or disease are based on myoblast differentiation. Bioactive peptides are biologically active peptides found in foods that could have pharmacological functions. The aim of this paper was to investigate the effect of decapeptide DI-10 from the potato alcalase hydrolysate on myoblast differentiation, muscle protein synthesis, and mitochondrial biogenesis in vitro. The treatment of C2C12 myoblasts with DI-10 (10 µg/mL) did not induce cell death. DI-10 treatment in C2C12 myoblast cells accelerates the phosphorylation of promyogenic kinases such as ERK, Akt and mTOR proteins in a dose-dependent manner. DI-10 improves myotubes differentiation and upregulates the expression of myosin heavy chain (MyHC) protein in myoblast cells under differentiation medium with high glucose. DI-10 effectively increased the phosphorylation of promyogenic kinases Akt, mTOR, and mitochondrial-related transcription factors AMPK and PGC1α expression under hyperglycemic conditions. Further, decapeptide DI-10 decreased the expression of Murf1 and MAFbx proteins, which are involved in protein degradation and muscle atrophy. Our reports support that decapeptide DI-10 could be potentially used as a therapeutic candidate for preventing muscle degeneration in sarcopenia

Extraction and Characterization of Fucoidan Derived from <i>Sargassum ilicifolium</i> and Its Biomedical Potential with In Silico Molecular Docking

Fucoidan, a polymer derived from seaweed, poses a broad range of biological applications, and its potential medicinal benefits have been widely studied over the past decade. In this study, fucoidan was extracted from marine macroalga Sargassum ilicifolium and its bioactive potential for in silico molecular docking was investigated. Additionally, the computational in silico docking studies were applied on the fucoidan against anticancer and antioxidant target proteins by using Glide ligand docking, Schrodinger software. The FT-IR analysis revealed that fucoidan mainly consisted of the fucose residues (59.1%) and a few monosaccharides, such as uronic acid (11.7%) and sulphate (18.3%). The in vitro tests revealed that fucoidan possessed various antioxidative properties and anticoagulant activities. Fucoidans played an inhibitory role in the colony formation of HepG2 cells. The NADPH oxidase (−7.169 Kcal/mol) and cellular tumor antigen p53 protein (−6.205 Kcal/mol) exhibited the highest antioxidant and anticancer proteins, respectively. Overall, the present study results provide a theoretical foundation for broadening the application of fucoidan from S. ilicifolium as a pharmaceutical ingredient

Tinospora cordifolia extract attenuates cadmium-induced biochemical and histological alterations in the heart of male Wistar rats

[[abstract]]Persistence of cadmium (Cd) in the environment causes serious ecological problems. Tinospora cordifolia is a medicinal herb used in Ayurveda for treating various metabolic disorders and toxic conditions. The present study investigates the protective effect of T. cordifolia stem methanolic extract (TCME) on a heavy metal, Cd-induced cardiotoxicity in male Wistar rats. Male albino Wistar rats were divided into four groups (n = 6). The animals after treatment for 28 days with Cd and TCME were analysed for biochemical and histological changes in the serum and heart tissues. Cd induced lipid peroxidation and protein carbonylation was significantly reduced by TCME. TCME also reduced the histological alterations induced by Cd treatment in the heart tissues with diminished loss of myocardial fibers. Administration of TCME effectively prevented the altered levels of serum marker enzymes (creatine kinase and lactate dehydrogenase), antioxidants, such as superoxide dismutase, catalase, glutathione, glutathione peroxidase and glutathione-S-transferase, and glycoproteins contents such as hexose, hexoseamine, fucose, and sialic acid by Cd intoxication. TCME also offered protection against the change in levels of Na+K+ATPase, Mg2+ATPase and Ca2+ATPase activities against Cd toxicity. The study suggests TCME as a potent cardioprotective agent against Cd induced toxicity. Keywords CadmiumTinospora cordifoliaOxidative stressHeartAntioxidant enzyme

VH-4-A Bioactive Peptide from Soybean and Exercise Training Constrict Hypertension in Rats through Activating Cell Survival and AMPKα1, Sirt1, PGC1α, and FoX3α

Hypertension is a chronic disease related to age, which affects tens of millions of people around the world. It is an important risk factor that causes myocardial infarction, heart failure, stroke, and kidney damage. Bioactive peptide VHVV (VH-4) from soybean has shown several biological activities. Physical exercise is a cornerstone of non-pharmacologic treatment for hypertension and has established itself as an effective and complementary strategy for managing hypertension. The present study evaluates the efficacy of VH-4 supplement and swimming exercise training in preventing hypertension in spontaneously hypertensive rats (SHR). SHR animals were treated with VH-4 (25 mg/kg by intraperitoneal administration) and swimming exercise (1 h daily) for eight weeks, and the hemodynamic parameters, histology, and cell survival pathway protein expression were examined. In SHR rats, increased heart weight, blood pressure, and histological aberrations were observed. Cell survival protein p-PI3K and p-AKT and antiapoptosis proteins Bcl2 and Bcl-XL expression decreased in SHR animals. SIRT1 and FOXO3 were decreased in hypertensive rats. Both bioactive peptide VH-4 treatment and swimming exercise training in hypertensive rats increased the cell survival proteins p-PI3K and p-AKT and AMPKα1, Sirt1, PGC1α, and FoX3α proteins. Soy peptide VH-4, along with exercise, acts synergistically and prevents hypertension by activating cell survival and AMPKα1, Sirt1, PGC1α, and FoX3α proteins