Biosynthesis and Multifaceted Characterization of Breynia nivosa-Derived Silver Nanoparticles: An Eco-Friendly Approach for Biomedical Applications.

This study presents an environmentally friendly synthesis of stable silver nanoparticles (Ag-NPs) using the methanolic extract of Breynia nivosa. Initial phytochemical analysis of the extract revealed the presence of alkaloids, flavonoids, glycosides, saponins, and tannins. Further characterization through high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analyses identified a diverse array of bioactive compounds, including hydroquinone, stearic acid, neophytadiene, 9,12-octadecadienoic acid (Z,Z), methyl ester, and others. The addition of B. nivosa methanolic extract to an AgNO3 solution resulted in a color change, confirming the green synthesis of Ag-NPs through the reduction of AgNO3, as made evident by ultraviolet-visible (UV-vis) spectroscopy. X-ray diffraction (XRD) analysis provided valuable insights into the crystal structure, and scanning electron microscopy (SEM) analysis visualized the predominantly spherical shape of the Ag-NPs. However, the zeta (ζ)-potential and dynamic light scattering (DLS) analyses confirmed the stability and nanoscale dimensions of the synthesized Ag-NPs. Meanwhile, Fourier transform infrared (FT-IR) spectra exhibited peaks indicative of various functional groups, including carboxylic acids, phenols, alkanes, and isocyanates. These functional groups played a crucial role in both the reduction and capping processes of the Ag-NPs. The study further explored the antioxidant activity, cytotoxicity, acetylcholinesterase inhibition, and α-amylase inhibition activities of the Ag-NPs of the B. nivosa extract, demonstrating their potential for biomedical and therapeutic applications. In conclusion, this environmentally sustainable synthesis of Ag-NPs from the B. nivosa extract, enriched with bioactive secondary metabolites detected through HPLC and GC-MS analysis, holds promise for diverse applications in the burgeoning field of green nanotechnology.

Host-guest coupling to potentially increase the bio-accessibility of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea by nanocarrier graphyne for brain tumor therapy, a comprehensive quantum mechanics study.

This study aimed to explore the potential of Host-Guest coupling with Nanocarrier graphyne (GPH) to enhance the bioavailability of the drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (LUM) for brain tumor therapy. The electronic, geometric, and excited-state properties of GPH, LUM, and the graphyne@1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea-complex (GPH@LUM-complex) were studied using DFT B3LYP/6-31G** level of theory. The results showed that the GPH@LUM-complex was stable with negative adsorption energy (-0.20 eV), and there was good interaction between GPH and LUM in the solvent phase. The weak interaction forces between the two indicated an easy release of the drug at the target site. The Frontier Molecular Orbitals (FMO), Charge Density Analysis (CDA), and Natural Bond Orbital (NBO) analysis supported LUM to GPH charge transfer during complex formation, and the Reduced Density Gradient (RDG) isosurfaces identified steric effects and non-bonded interactions. UV-visible examination showed the potential of the GPH@LUM-complex as a drug carrier with a blue shift of 23 nm wavelength in the electronic spectra. The PET process analysis revealed a fluorescence-quenching process, facilitating systematic drug delivery. The study concluded that GPH had potential as a carrier for delivering LUM, and different 2D nanomaterials could be explored for drug delivery applications. The theoretical study's findings may motivate researchers to investigate the practical applications of GPH@LUM-complex in oncology.

Development and in-vitro evaluation of chitosan and glyceryl monostearate based matrix lipid polymer hybrid nanoparticles (LPHNPs) for oral delivery of itraconazole.

Itraconazole (ICZ) is a broad spectrum antifungal drug, but used as second or third line therapy due to its low and erratic oral bioavailability. This work was carried out to prepare and characterize matrix type lipid-polymer hybrid nanoparticles (LPHNPs) for dissolution enhancement of ICZ. LPHNPs were prepared using solvent diffusion/emulsification technique. Matrix LPHNPs were composed of chitosan (polymer), glyceryl monostearate (lipid) and poloxamer 188 (stabilizer). LPHNPs loaded with ICZ (LPHNPs-1, LPHNPs-2, LPHNPs-3 and LPHNPs-4) were developed using varying concentration of chitosan whereas LPHNPs (LPHNPs-5, LPHNPs-6, LPHNPs-7 and LPHNPs-8) were prepared using varying concentrations of poloxamer 188. LPHNPs loaded with ICZ were further evaluated for entrapment efficiency, particle size, polydispersity index (PDI), zeta potential and dissolution profiles at biorelevant pH conditions. The particle size (LPHNPs-1 to LPHNPs-4) was found to be in range of 421-588 nm with PDI values 0.34-0.41. The particles size of LPHNPs-5 to LPHNPs-8 was found to be in range of 489-725 nm with PDI 0.34-0.74. The entrapment efficiency of LPHNPs-1 to LPHNPs-4 was found to be in range of 85.21%-91.34%. The entrapment efficiency of LPHNPs-5 to LPHNPs-8 was found to be in range 78.32%-90.44%. . The scanning electron microscopy of optimized formulations LPHNPs-1 and LPHNPs-5 indicated formation of oval shaped nanoparticles. DSC thermogram of ICZ loaded LPHNPs also depicted the conversion of crystalline form of ICZ into amorphous form demonstrating the internalization and dissolution enhancement of drug in the hybrid matrix. The cumulative drug dissolved at acidic pH 1.2 was found to be 23.3% and 19.8% for LPHNPs-1 and LPHNPs-5 respectively. Similarly at basic pH values 7.4, cumulative amount of drug dissolved was 90.2% and 83.4% for LPHNPs-1 and LPHNPs-5 respectively. Drug dissolution kinetics exhibited fickian diffusion best described by Korse-meyer Peppas model. The results suggested that chitosan and glyceryl monostearate based matrix LPHNPs could be used as promising approach for dissolution enhancement of ICZ which could further increase its bioavailability.

Neurotoxic effects of environmental contaminants-measurements, mechanistic insight, and environmental relevance.

Pollution is a significant and growing concern for any population regardless of age because these environmental contaminants exhibit different neurodegenerative effects on persons of different ages. These environmental contaminants are the products of human welfare projects like industry, automobile exhaust, clinical and research laboratory extrudes, and agricultural chemicals. These contaminants are found in various forms in environmental matrices like nanoparticles, particulate matter, lipophilic vaporized toxicants, and ultrafine particulate matter. Because of their small size, they can easily cross blood-brain barriers or use different cellular mechanisms for assistance. Other than this, these contaminants cause an innate immune response in different cells of the central nervous system and cause neurotoxicity. Considering the above critiques and current needs, this review summarizes different protective strategies based on bioactive compounds present in plants. Various bioactive compounds from medicinal plants with neuroprotective capacities are discussed with relevant examples. Many in vitro studies on clinical trials have shown promising outcomes using plant-based bioactive compounds against neurological disorders.

Biochemical Investigation of Inhibitory Activities of Plant-Derived Bioactive Compounds Against Carbohydrate and Glucagon-Like Peptide-1 Metabolizing Enzymes.

The aim of current study was to investigate the inhibitory activities of resveratrol and taxifolin against α-amylase, α-glucosidase, and DPP-IV enzymes via in vitro analysis which was further validated by in silico studies. The analysis of molecular docking was also done to determine the binding capabilities of resveratrol and taxifolin with α-amylase, α-glucosidase, and DPP-IV enzymes. Resveratrol and taxifolin having IC50 values, 47.93 ± 5.21 µ M and 45.86 ± 3.78 µ M , respectively, showed weaker effect than acarbose (4.6 ± 1.26 µ M ) on α-amylase but showed significant effect to inhibit α-glucosidase (32.23 ± .556 µ M and 31.26 ± .556 µ M , respectively). IC50 value of resveratrol and taxifolin (5.638 ± .0016 µ M and 6.691 ± .004 µ M ) in comparison to diprotin A (IC50: 7.21 ± .021 µ M ) showed that they have significant inhibitory effect on DPP-IV enzyme. Our results illustrated that resveratrol and taxifolin have potential to prevent the metabolism of carbohydrates via inhibition of α-amylase and α-glucosidase, and prolongs metabolic function of incretin by inhibiting the enzymatic activity of DPP-IV. The results of molecular docking have also revealed that resveratrol and taxifolin have significant affinity to bind with α-amylase, α-glucosidase, and DPP-IV in comparison with standard drugs such as acarbose, miglitol, and diprotin.

Biochemical Investigation of Therapeutic Potential of Resveratrol Against Arsenic Intoxication.

Arsenic has been reported to cause damaging effects on different body organs. This study was designed to evaluate the protective effect of resveratrol (RSV) against arsenic trioxide (ATO)-induced intoxication in experimental animals. Twenty-four Wistar rats were allocated in 4 groups: group 1: control group, received normal diet; group 2: received ATO (3 mg/kg); group 3: received RSV (8 mg/kg) 30 minutes before administration of ATO; and group 4: received ascorbic acid (25 mg/kg) 30 minutes before administration of ATO. Treatments were given to experimental rats daily for consecutive 8 days. At the end of experimental period, bioaccumulation of arsenic in liver and kidney was assessed by hydride generation-atomic absorption spectrophotometer to investigate the association of arsenic accumulation with histological aberrations. Following parameters were also investigated: serum biochemical profile (alanine aminotransferase, aspartate transaminase, alkaline phosphatase, blood urea nitrogen, and creatinine) for evaluation of liver and kidney functions and lipid peroxidation and oxidative stress (malondialdehyde, glutathione, superoxide dismutase, catalase, and glutathione peroxidase) in tissue homogenates of liver and kidney for estimation of oxidative status. The findings of this study indicate that RSV remarkably ameliorated the hepatic and renal toxicity in arsenic-exposed rat model due to its strong antioxidant potential.

Exposure of Environmental Contaminants and Development of Neurological Disorders.

In this era of technology, neurological disorders are the most prevalent disorders in growing population. Alzheimer's and Parkinson's diseases are the most common neurological disorders which are manifested by any abnormality in the structure and functions of neurons present in brain and spinal cord. Exposure to environmental pollution is a serious issue which is associated with high morbidity and mortality rate in the worldwide. Air pollutants are the major contributors to induce the inflammation in lungs and brain which ultimately impairs the normal functioning of CNS. Air pollution persuades CNS pathology by inducing the oxidative stress, activation of microglial cells, neuroinflammation and alteration in permeability of blood brain barrier. Similarly, exposure of heavy metals also exhibits the major and long-lasting effects on brain and causes cognitive dysfunction. Likewise, pesticides have also major influence on the etiology of neurological disorders. Pesticides such as paraquat and rotenone are involved in the pathogenesis of Parkinson's disease. Treatment strategy for environmental pollutants-induced neurological disorders is a challenging task because conventional therapeutics are effective but do not have optimum therapeutic efficacy against such type of disorders. This article addresses how the environmental pollutants are involved in the pathogenesis of neurological disorders and treatment strategies to reduce the occurrence of neurological disorders.

Prevalence of contamination of aflatoxin M1 in milk: a retrospective analysis of studies conducted in Pakistan.

Aflatoxins, produced by multiple fungal species, are present in several kinds of food items and animal feed. Several studies conducted in Pakistan have reported the presence of aflatoxin M1 (AFM1) in milk. Hence, owing to the public health concern and absence of general statistics regarding the prevalence of AFM1 contamination, current study was aimed to investigate the prevalence of AFM1 in milk in Pakistan. For this study, various databases were searched from 2007 to 2020. A random effect model was applied for analytical purpose and heterogeneity of selected studies was investigated with an I2 index. Comprehensive meta-analysis (version 3) was used for analysis of data. According to the results, prevalence of AFM1 in milk was 84.4% (95% CI 75.0-90.7%). Regarding the heterogeneity based on meta-regression, it has been observed that there was a significant difference between the effect of year of study and sample size with prevalence of AFM1 in animal milk. These results suggest that AFM1 contamination in animal milk is high in Pakistan. Hence, continuous monitoring of AFM1 in animal milk requires utmost attention from the respective food and drug regulatory authorities of Pakistan so that the strict actions and preventive measures should be taken to prevent the prevalence of exposure of AFM1 in animal milk.

Therapeutic Interventions of Novel SGLT2 Inhibitors Against Metabolic Disorders: Transforming the Association into Perspectives.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are an emerging group of therapeutic agents that show their tremendous glucose lowering activity without producing hypoglycemia, which is one of the major drawbacks of existing antidiabetic therapy. Comprehensive literature was searched in English using electronic databases including PubMed, ScienceDirect, Medline, Scopus and Embase. SGLT2 inhibitors reduce blood glucose levels by producing glucosuria via insulin-independent pathway. The major mechanism by which SGLT2 inhibitors are involved in glucose homeostasis is to prevent the reabsorption of glucose in the proximal convoluted tubule and increase glucose excretion in the urine. Deterioration of ß-cells, impairment of functions and development of insulin resistance do not affect the efficacy of SGLT2 inhibitors. SGLT2 inhibitors significantly reduce HbA1c, ameliorate glycemic control and control body weight. SGLT2 inhibitors can block Na+/H+ exchanger (NHE) 1 and play a significant role in treatment of heart failure especially in diabetic patients. They have also positive effects on different metabolic syndromes which cumulatively ameliorate the risk factors for cardiovascular diseases in diabetic patients. SGLT2 inhibitors can improve kidney function by reducing inflammation and improving renal microvasculature up to its original state. The increase in triglyceride level has a strong relationship with coronary artery disease in diabetic patients when combined with other indicators of metabolic disorders while SGLT2 inhibitors cause a significant reduction in plasma triglyceride level in diabetic patients. We have comprehensively summarized the features, mechanism of action of SGLT2 inhibitors and their impact on various metabolic syndrome traits, including diabetic condition, renal dysfunctioning, arterial stiffness, hypertension, lipid profile and cardiovascular diseases. The aim of this review to examine the safety, efficacy and therapeutic properties of SGLT2 inhibitors in renal and diabetic patients.

Pathophysiology of atherosclerosis: Association of risk factors and treatment strategies using plant-based bioactive compounds.

Under physiological conditions, endothelial cells act as protective barrier which prevents direct contact of blood with circulating factors via production of tissue plasminogen activator. Risk factors of metabolic disorders are responsible to induce endothelial dysfunction and may consequently lead to prognosis of atherosclerosis. This article summarizes the process of atherosclerosis which involves number of sequences including formation and interaction of AGE-RAGE, activation of polyol pathway, protein kinase C, and hexosamine-mediated pathway. All these mechanisms can lead to the development of oxidative stress which may further aggravate condition. Different pharmacological interventions are being used to treat atherosclerosis, however, these might be associated with mild to severe side effects. Therefore, plant-based bioactive compounds having potential to combat and prevent atherosclerosis in diabetic patients are attaining recent focus. By understanding process of development and mechanisms involved in atherosclerotic plaque formation, these bioactive compounds can be better option for future therapeutic interventions for atherosclerosis treatment. PRACTICAL APPLICATIONS: Atherosclerosis is one of major underlying disorders of cardiovascular diseases which occur through multiple mechanisms and is associated with metabolic disorders. Conventional therapeutic interventions are not only used to treat atherosclerosis, but are also commonly associated with mild to severe side effects. Therefore, nowadays, bioactive compounds having potential to combat and prevent atherosclerosis in diabetic patients are preferred. By understanding mechanisms involved in atherosclerotic plaque formation, bioactive compounds can be better understood for treatment of atherosclerosis. In this manuscript, we have focused on treatment strategies of atherosclerosis using bioactive compounds notably alkaloids and flavonoids having diverse pharmacological and therapeutic potentials with special focus on the mechanism of action of these bioactive compounds suitable for treatment of atherosclerosis. This manuscript will provide the scientific insights of bioactive compounds to researchers who are working in the area of drug discovery and development to control pathogenesis and development of atherosclerosis and its associated cardiometabolic disorders.