Role of nutraceutical against exposure to pesticide residues: power of bioactive compounds.

Pesticides play a crucial role in modern agriculture, aiding in the protection of crops from pests and diseases. However, their indiscriminate use has raised concerns about their potential adverse effects on human health and the environment. Pesticide residues in food and water supplies are a serious health hazards to the general public since long-term exposure can cause cancer, endocrine disruption, and neurotoxicity, among other health problems. In response to these concerns, researchers and health professionals have been exploring alternative approaches to mitigate the toxic effects of pesticide residues. Bioactive substances called nutraceuticals that come from whole foods including fruits, vegetables, herbs, and spices have drawn interest because of their ability to mitigate the negative effects of pesticide residues. These substances, which include minerals, vitamins, antioxidants, and polyphenols, have a variety of biological actions that may assist in the body's detoxification and healing of harm from pesticide exposure. In this context, this review aims to explore the potential of nutraceutical interventions as a promising strategy to mitigate the toxic effects of pesticide residues.

The Ethnopharmacological Properties of Green-Engineered Metallic Nanoparticles against Metabolic Disorders.

Metabolic syndrome is a multifaceted pathophysiologic condition that is largely caused by an imbalance between caloric intake and energy expenditure. The pathogenesis of metabolic syndrome is determined by an individual's genetic/epigenetics and acquired factors. Natural compounds, notably plant extracts, have antioxidant, anti-inflammatory, and insulin-sensitizing properties and are considered to be a viable option for metabolic disorder treatment due to their low risk of side effects. However, the limited solubility, low bioavailability, and instability of these botanicals hinder their performance. These specific limitations have prompted the need for an efficient system that reduces drug degradation and loss, eliminates unwanted side effects, and boosts drug bioavailability, as well as the percentage of the drug deposited in the target areas. The quest for an enhanced (effective) drug delivery system has led to the formation of green-engineered nanoparticles, which has increased the bioavailability, biodistribution, solubility, and stability of plant-based products. The unification of plant extracts and metallic nanoparticles has helped in the development of new therapeutics against metabolic disorders such as obesity, diabetes mellitus, neurodegenerative disorders, non-alcoholic fatty liver, and cancer. The present review outlines the pathophysiology of metabolic diseases and their cures with plant-based nanomedicine.

Protection Against Drug-Induced Liver Injuries Through Nutraceuticals via Amelioration of Nrf-2 Signaling.

Hepatotoxicity caused by the overdose of various medications is a leading cause of drug-induced liver injury. Overdose of drugs causes hepatocellular necrosis. Nutraceuticals are reported to prevent drug-induced liver failure. The present article aims to review the protection provided by various medicinal plants against hepatotoxic drugs. Ayurveda is considered a conventional restorative arrangement in India. It is consistently used for ages and is still used today to cure drug-induced hepatotoxicity by focusing on antioxidant stress response pathways such as the nuclear factor erythroid-2 (Nrf-2) antioxidant response element signaling pathway. Nrf-2 is a key transcription factor that entangles Kelch-like ECH-associating protein 1, a protein found in the cell cytoplasm. Some antioxidant enzymes, such as gamma glycine cysteine ligase (γ-GCL) and heme oxygenase-1 (HO-1), are expressed in Nrf-2 targeted genes. Their expression, in turn, decreases the stimulation of hepatic macrophages and induces the messenger RNA (mRNA) articulation of proinflammatory factors including tumor necrosis factor α. This review will cover various medicinal plants from a mechanistic view and how they stimulate and interact with Nrf-2, the master regulator of the antioxidant response to counterbalance oxidative stress. Interestingly, therapeutic plants have become popular in the medical sector due to safer yet effective supplementation for the prevention and treatment of new human diseases. The contemporary study is expected to collect information on a variety of therapeutic traditional herbs that have been studied in the context of drug-induced liver toxicity, as nutraceuticals are the most effective treatments for oxidative stress-induced hepatotoxicity. They are less genotoxic, have a lower cost, and are readily available. Together, nutraceuticals exert protective effects against drug-induced hepatotoxicity through the inhibition of oxidative stress, inflammation, and apoptosis. Its mechanism(s) are considered to be associated with the γ-GCL/HO-1 and Nrf-2 signaling pathways.KEY TEACHING POINTSThe liver is the most significant vital organ that carries out metabolic activities of the body such as the synthesis of glycogen, the formation of triglycerides and cholesterol, as well as the formation of bile.Acute liver failure is caused by the consumption of certain drugs; drug-induced liver injury is the major condition.The chemopreventive activity of nutraceuticals may be related to oxidative stress reduction and attenuation of biosynthetic processes involved in hepatic injury via amelioration of the nuclear factor erythroid-2 (Nrf-2) signaling pathway.Nrf-2 is a key transcription factor that is found in the cell cytoplasm resulting in the expression of various genes such as gamma glycine cysteine ligase and heme oxygenase-1.Nutraceutical-rich phytochemicals possess high antioxidant activity, which helps in the prevention of hepatic injury.

Appraisal of the Antioxidant Activity, Polyphenolic Content, and Characterization of Selected Himalayan Herbs: Anti-Proliferative Potential in HepG2 Cells.

Natural antioxidants derived from plants have played a vital role in preventing a wide range of human chronic conditions and provide novel bioactive leads for investigators in pharmacotherapy discovery. This work was designed to examine the ethnopharmacological role of Urtica dioica (UD), Capsella bursa-pastoris (CBP), and Inula racemosa (IR). The total phenolic and flavonoid contents (TPC and TFC) were illustrated through colorimetric assays, while the antioxidant activity was investigated through DPPH and ABTS assays. The evaluation of phytochemicals by FT-IR of UD and CBP revealed high contents of aliphatic amines, while IR showed a major peak for ketones. The antioxidant activity, TPC and TFC were highest in the ethanol extract of UD, followed by CBP, and IR showed the lowest activity. All of the extracts revealed significant antioxidant capacities along a dosage gradient. Through a HPLC analysis at a wavelength of 280 nm, UD leaves demonstrated an intense peak of quercetin, and the peak for rutin was less intense. CBP (whole plant), instead, demonstrated a major yield of rutin, and a peak for quercetin was not observed in CBP. IR (rhizomes) showed both quercetin and rutin. All of the extracts were significantly cytotoxic to HepG2 cells after 48 h with the trend IR > UD > CBP. The outcomes of this study may be effective in the selection of specific plants as realistic sources of the bioactive components that might be useful in the nutraceutical progression and other biomedical efficacies.

Geospatial epidemiology of hypertension and its risk factors in India: Findings from National Family Health Survey (2015-2016).

Background: The fourth round of National Family Health Survey (2015-2016) measured blood pressure for the first time and provided a unique opportunity of exploring trends in hypertension prevalence across states and districts for the first time. Aim: This study will be the first in India to estimate the geospatial variation of hypertension among those in the 15-49 years age group in India. Materials and Methods: Out of a total of 616,346 selected occupied households, 601,509 were successfully interviewed, giving a response rate of 98%. We adjusted the proportion of hypertension obtained by using national sample weights. We built a multivariable logistic regression model to assess the determinants of hypertension. Results: The overall weighted prevalence of hypertension was 11.7%, and the prevalence was 11.1% in females and 11.0% in males. Urban areas had a higher prevalence (13.0%) compared to rural areas (11.0%). Those with no education (14.4%) and those who reported smoking (16.5%) had hypertension. Consumption of alcohol, fruits, and eggs was also found to be significantly related to hypertension. Conclusion: Hypertension epidemic is spreading alarmingly in India across rural and urban populations. Disturbingly, the hypertension prevalence is now becoming more concentrated among the poor. This phenomenon has serious implications for the country's social and economic well-being. Urgent preventive measures need to be taken at a multidisciplinary level.

Therapeutic Antiaging Strategies.

Aging constitutes progressive physiological changes in an organism. These changes alter the normal biological functions, such as the ability to manage metabolic stress, and eventually lead to cellular senescence. The process itself is characterized by nine hallmarks: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These hallmarks are risk factors for pathologies, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Emerging evidence has been focused on examining the genetic pathways and biological processes in organisms surrounding these nine hallmarks. From here, the therapeutic approaches can be addressed in hopes of slowing the progression of aging. In this review, data have been collected on the hallmarks and their relative contributions to aging and supplemented with in vitro and in vivo antiaging research experiments. It is the intention of this article to highlight the most important antiaging strategies that researchers have proposed, including preventive measures, systemic therapeutic agents, and invasive procedures, that will promote healthy aging and increase human life expectancy with decreased side effects.

Adverse effects of textile dyes on antioxidant enzymes and cholinesterase activities in Drosophila melanogaster (Oregon R+).

The effluents from textile dyeing industry are causing water pollution and may transform into more toxic and carcinogenic chemical species by environmental conditions. Therefore systemic toxicity of textile dyes is major health concern. Hence, this study sought to examine the toxic effect of disperse textile dyes on important systemic enzymes in the larvae of wild type Drosophila melanogaster (Oregon R+). Drosophila larvae were fed with corn-sugar-yeast diets containing two disperse dyes, Disperse blue-124 and Disperse black-9 (1, 10 and 100 mg/mL) for 2 days (48 h) and subsequent the enzymatic estimations were carried out using larval homogenate. In silico molecular docking studies were also performed to analyze the binding interaction of these dyes with acetyl choline esterase enzyme. Disperse black 9 shows more strong binding by occupying a groove and forming one hydrogen bond with Tyr465 of acetyl choline esterase enzyme while Disperse blue-124 shows surface binding without forming any hydrogen bond. Drosophila larvae fed on these dyes exhibited a dose-dependent increase in acetyl choline esterase enzymatic activity (1.8 fold increase with Disperse black-9, 100 mg/mL) while 4.4-folds Disperse blue-124, 100 mg/mL). Both Disperse Blue and Disperse Black dyes altered the activities of antioxidant enzymes Catalase (CAT, increased more than 2.5 fold), Superoxide dismutase (SOD, increased more than two folds) and showed a dose-dependent increase in Xanthine oxidase and lipid peroxidation (LPO) levels (more than 3 folds). Therefore both the disperse dyes were found to dysregulate the activities of antioxidant enzymes which may be the underlying mechanism for their toxic effects.

Modulation of the Functional Components of Growth, Photosynthesis, and Anti-Oxidant Stress Markers in Cadmium Exposed Brassica juncea L.

Abstract: Heavy metals (including Cadmium) are being entered into the environment through various sources and cause toxicity to plants. Response of Brassica juncea L. var. RLC-1 was evaluated after exposing them to different concentration of cadmium (Cd) for seven days. Seeds of B. juncea were treated with different concentrations of Cd like 0.2-0.6 mM for 7 days, allowing them to grow in Petri-dishes, and seedlings were examined for different physiological responses. Following exposure to Cd, in the seedlings of B. juncea, growth parameters (root and shoot length), stress markers (lipid peroxidation and H2O2 content), secondary metabolites, photosynthetic pigments, and ion analysis, were estimated along with enzymatic and non-enzymatic antioxidants. We observed a significant reduction in root and shoot length after Cd treatment as compared to control seedlings. Malondialdehyde and H2O2 contents were increased accompanied by enhanced Cd uptake. Activities of antioxidative enzymes were also significantly altered following Cd exposure to the seedlings of B. juncea. Conclusively, we suggest that Cd exposure to the seedlings triggered an induction of several defense responses in B. juncea including major metabolites.

Biotinylation of lysine 16 in histone H4 contributes toward nucleosome condensation.

Holocarboxylase synthetase (HLCS) is part of a multiprotein gene repression complex and catalyzes the covalent binding of biotin to lysines (K) in histones H3 and H4, thereby creating rare gene repression marks such as K16-biotinylated histone H4 (H4K16bio). We tested the hypothesis that H4K16bio contributes toward nucleosome condensation and gene repression by HLCS. We used recombinant histone H4 in which K16 was mutated to a cysteine (H4K16C) for subsequent chemical biotinylation of the sulfhydryl group to create H4K16Cbio. Nucleosomes were assembled by using H4K16Cbio and the 'Widom 601' nucleosomal DNA position sequence; biotin-free histone H4 and H4K16C were used as controls. Nucleosomal compaction was analyzed using atomic force microscopy (AFM). The length of DNA per nucleosome was ∼30% greater in H4K16Cbio-containing histone octamers (61.14±10.92nm) compared with native H4 (46.89±12.6nm) and H4K16C (47.26±10.32nm), suggesting biotin-dependent chromatin condensation (P<0.001). Likewise, the number of DNA turns around histone core octamers was ∼17.2% greater in in H4K16Cbio-containing octamers (1.78±0.16) compared with native H4 (1.52±0.21) and H4K16C (1.52±0.17), judged by the rotation angle (P<0.001; N=150). We conclude that biotinylation of K16 in histone H4 contributes toward chromatin condensation.

Genotoxicity and apoptosis in Drosophila melanogaster exposed to benzene, toluene and xylene: attenuation by quercetin and curcumin.

Monocyclic aromatic hydrocarbons (MAHs) such as benzene, toluene and xylene are being extensively used for various industrial and household purposes. Exposure to these hydrocarbons, occupationally or non-occupationally, is harmful to organisms including human. Several studies tested for toxicity of benzene, toluene and xylene, and interestingly, only a few studies looked into the attenuation. We used Drosophila model to test the genotoxic and apoptotic potential of these compounds and subsequently evaluated the efficiency of two phytochemicals, namely, quercetin and curcumin in attenuating test chemical induced toxicity. We exposed third instar larvae of wild type Drosophila melanogaster (Oregon R+) to 1.0-100.0 mM benzene, toluene or xylene, individually, for 12, 24 and 48 h and examined their apoptotic and genotoxic potential. We observed significantly (P<0.001) increased apoptotic markers and genotoxicity in a concentration- and time-dependent manner in organisms exposed to benzene, toluene or xylene. We also observed significantly (P<0.001) increased cytochrome P450 activity in larvae exposed to test chemicals and this was significantly reduced in the presence of 3',4'-dimethoxyflavone, a known Aryl hydrocarbon receptor (AhR) blocker. Interestingly, we observed a significant reduction in cytochrome P450 activity, GST levels, oxidative stress parameters, genotoxic and apoptotic endpoints when organisms were exposed simultaneously to test chemical along with quercetin or curcumin. The study further suggests the suitability of D. melanogaster as an alternate animal model for toxicological studies involving benzene, toluene and xylene and its potential in studying the protective role(s) of phytochemicals.

Potential risk of progressive multifocal leukoencephalopathy with natalizumab therapy: possible interventions.

Natalizumab (Tysabri) is an effective therapy for multiple sclerosis. Recently, 3 patients who were treated with natalizumab developed progressive multifocal leukoencephalopathy (PML), an opportunistic infection of the brain with the polyomavirus JC. The pathogenesis of natalizumab-associated PML may be different from that of PML not associated with the drug. We reviewed biologically feasible interventions for patients diagnosed as having PML or other infections while receiving natalizumab therapy. Existing interventions include antiviral treatment, immunomodulatory therapies, hematopoietic growth factors, plasma exchange, intravenous immunoglobulins, and leukapheresis and autotransfusion of leukocytes. In addition, we examined the feasibility of experimental therapies, including small interfering RNA, the in vivo use of antiserum, and recombinant natalizumab-blocking molecules. There is only circumstantial evidence that any of the proposed treatments will benefit patients with multiple sclerosis treated with natalizumab who may develop PML. In addition, the expected incidence of PML in this patient population will likely be too low to test any of the proposed interventions in a controlled manner. Because it is currently impossible to identify patients at risk, and thus to prevent PML as a consequence of natalizumab therapy, it is important that neurologists be aware of possible therapeutic interventions.

Inhibition of platelet aggregation by rat globin.

This study was undertaken to identify and characterize the anti-aggregatory protein factor present in rat polymorphonuclear leukocytes (PMNs) supernatant. Since the purified protein exhibited sequence homology to beta globin, globin was also isolated from rat blood by acid-acetone precipitation and was purified on Superdex-75 column in FPLC. Elution of rat globin on the gel filtration column yielded two peaks of approximately 60 and 30 kDa as observed in the PMNs supernatant. Purity of globin and eluted fractions was further evaluated by SDS-PAGE. Platelet aggregation induced by agonists viz. adenosine-5'-diphosphate (ADP; 2-5 microM), arachidonic acid (AA; 10 microM), A23187 (2.50 microg/ml) was inhibited by globin and the purified fractions. ADP-induced rise in intracellular calcium levels and expression of CD62 on the platelets were reduced by both globin and active fraction of PMNs supernatant. Results obtained suggest that globin or globin-related protein present in the PMNs supernatant inhibits platelet aggregation response.