Hibiscetin attenuates lipopolysaccharide-evoked memory impairment by inhibiting BDNF/caspase-3/NF-κB pathway in rodents.

This study explores the neuroprotective potential of hibiscetin concerning memory deficits induced by lipopolysaccharide (LPS) injection in rats. The aim of this study is to evaluate the effect of hibiscetin against LPS-injected memory deficits in rats. The behavioral paradigms were conducted to access LPS-induced memory deficits. Various biochemical parameters such as acetyl-cholinesterase activity, choline-acetyltransferase, antioxidant (superoxide dismutase, glutathione transferase, catalase), oxidative stress (malonaldehyde), and nitric oxide levels were examined. Furthermore, neuroinflammatory parameters such as tumor necrosis factor-α, interleukin-1ß (IL-1ß), IL-6, and nuclear factor-kappa B expression and brain-derived neurotrophic factor as well as apoptosis marker i.e., caspase-3 were evaluated. The results demonstrated that the hibiscetin-treated group exhibited significant recovery in LPS-induced memory deficits in rats by using behavioral paradigms, biochemical parameters, antioxidant levels, oxidative stress, neuroinflammatory markers, and apoptosis markers. Recent research suggested that hibiscetin may serve as a promising neuroprotective agent in experimental animals and could offer an alternative in LPS-injected memory deficits in rodent models.

Development of Statistically Optimized Piperine-Loaded Polymeric Nanoparticles for Breast Cancer: In Vitro Evaluation and Cell Culture Studies.

Piperine (PPN) is a natural alkaloid derived from black pepper (Piper nigrum L.) and has garnered substantial attention for its potential in breast cancer therapy due to its diverse pharmacological properties. However, its highly lipophilic characteristics and poor dissolution in biological fluids limit its clinical application. Therefore, to overcome this limitation, we formulate and evaluate PPN-encapsulated polycaprolactone (PCL) nanoparticles (PPN-PCL-NPs). The nanoparticles were prepared by a single-step nanoprecipitation method and further optimized by a formulation design approach. The influence of selected independent variables PCL (X1), poloxamer 188 (P-188; X2), and stirring speed (SS; X3) were investigated on the particle size (PS), polydispersity index (PDI), and % encapsulation efficiency (EE). The selected optimized nanoparticles were further assessed for stability, in vitro release, and in vitro antibreast cancer activity in the MCF-7 cancer cell line. The PS, PDI, zeta potential, and % EE of the optimized PPN-PCL-NPs were observed to be 107.61 ± 5.28 nm, 0.136 ± 0.011, -20.42 ± 1.82 mV, and 79.53 ± 5.22%, respectively. The developed PPN-PCL-NPs were stable under different temperature conditions with insignificant changes in their pharmaceutical attributes. The optimized PPN-PCL-NPs showed a burst release for the first 6 h and later showed sustained release for 48 h. The PPN-PCL-NPs exhibit exceptional cytotoxic effects in MCF-7 breast tumor cells in comparison with the native PPN. Thus, the formulation of PPN-loaded PCL-NPs can be a promising approach for better therapeutic efficacy against breast cancer.

Synthesis, Characterization, and Biological Properties of Iron Oxide Nanoparticles Synthesized from Apis mellifera Honey.

Green approaches for nanoparticle synthesis have emerged as biocompatible, economical, and environment-friendly alternatives to counteract the menace of microbial drug resistance. Recently, the utilization of honey as a green source to synthesize Fe2O3-NPs has been introduced, but its antibacterial activity against one of the opportunistic MDR pathogens, Klebsiella pneumoniae, has not been explored. Therefore, this study employed Apis mellifera honey as a reducing and capping agent for the synthesis of iron oxide nanoparticles (Fe2O3-NPs). Subsequent to the characterization of nanoparticles, their antibacterial, antioxidant, and anti-inflammatory properties were appraised. In UV-Vis spectroscopic analysis, the absorption band ascribed to the SPR peak was observed at 350 nm. XRD analysis confirmed the crystalline nature of Fe2O3-NPs, and the crystal size was deduced to be 36.2 nm. Elemental analysis by EDX validated the presence of iron coupled with oxygen in the nanoparticle composition. In ICP-MS, the highest concentration was of iron (87.15 ppm), followed by sodium (1.49 ppm) and other trace elements (<1 ppm). VSM analysis revealed weak magnetic properties of Fe2O3-NPs. Morphological properties of Fe2O3-NPs revealed by SEM demonstrated that their average size range was 100-150 nm with a non-uniform spherical shape. The antibacterial activity of Fe2O3-NPs was ascertained against 30 clinical isolates of Klebsiella pneumoniae, with the largest inhibition zone recorded being 10 mm. The MIC value for Fe2O3-NPs was 30 µg/mL. However, when mingled with three selected antibiotics, Fe2O3-NPs did not affect any antibacterial activity. Momentous antioxidant (IC50 = 22 µg/mL) and anti-inflammatory (IC50 = 70 µg/mL) activities of Fe2O3-NPs were discerned in comparison with the standard at various concentrations. Consequently, honey-mediated Fe2O3-NP synthesis may serve as a substitute for orthodox antimicrobial drugs and may be explored for prospective biomedical applications.

Profiling the Hsp70 Chaperone Network in Heat-Induced Proteotoxic Stress Models of Human Neurons.

Heat stroke is among the most hazardous hyperthermia-related illnesses and an emerging threat to humans from climate change. Acute brain injury and long-lasting brain damage are the hallmarks of this condition. Hyperthermic neurological manifestations are remarkable for their damage correlation with stress amplitude and long-term persistence. Hyperthermia-induced protein unfolding, and nonspecific aggregation accumulation have neurotoxic effects and contribute to the pathogenesis of brain damage in heat stroke. Therefore, we generated heat-induced, dose-responsive extreme and mild proteotoxic stress models in medulloblastoma [Daoy] and neuroblastoma [SH-SY5Y] and differentiated SH-SY5Y neuronal cells. We show that heat-induced protein aggregation is associated with reduced cell proliferation and viability. Higher protein aggregation in differentiated neurons than in neuroblastoma precursors suggests a differential neuronal vulnerability to heat. We characterized the neuronal heat shock response through RT-PCR array analysis of eighty-four genes involved in protein folding and protein quality control (PQC). We identify seventeen significantly expressed genes, five of which are Hsp70 chaperones, and four of their known complementing function proteins. Protein expression analysis determined the individual differential contribution of the five Hsp70 chaperones to the proteotoxic stress response and the significance of only two members under mild conditions. The co-expression analysis reveals significantly high co-expression between the Hsp70 chaperones and their interacting partners. The findings of this study lend support to the hypothesis that hyperthermia-induced proteotoxicity may underlie the brain injury of heat stroke. Additionally, this study presents a comprehensive map of the Hsp70 network in these models with potential clinical and translational implications.

Protective Effect of Fustin against Huntington's Disease in 3-Nitropropionic Treated Rats via Downregulation of Oxidative Stress and Alteration in Neurotransmitters and Brain-Derived Neurotrophic Factor Activity.

Researchers have revealed that Rhus verniciflua heartwood, which contains fustin as an important component, possesses antioxidant-mediated, anti-mutagenic, and anti-rheumatoid arthritis characteristics. Additionally, out of the numerous plant-derived secondary metabolites, there are various research papers concentrating on flavonoids for potential advantages in neurological illnesses. The current study aims to assess the neuroprotective potential of fustin in rodents over 3-nitropropionic acid (3-NPA)-induced Huntington's disease (HD)-like consequences. The efficacy of fustin 50 and 100 mg/kg was studied with multiple-dose administrations of 3-NPA, which experimentally induced HD-like symptoms in rats for 22 days. At the end of the study, several behavioral tests were performed including a beam walk, rotarod, and grip strength tests. Similarly, some biochemical parameters were assessed to support oxidative stress (reduced glutathione-GSH, superoxide dismutase-SOD, catalase-CAT, and malondialdehyde-MDA), alteration in neurotransmitters (gamma-aminobutyric acid-GABA-and glutamate), alteration in brain-derived neurotrophic factor activity, and nitrite levels. Additionally, pro-inflammatory parameters were carried out to evaluate the neuroinflammatory responses associated with streptozotocin such as TNF-α, IL-1ß, and COX in the perfused brain. The fustin-treated group exhibited a significant restoration of memory function via modulation in behavioral activities. Moreover, 3-NPA altered biochemical, neurotransmitters, brain protein levels, and neuroinflammatory measures, which fustin efficiently restored. This is the first report demonstrating the efficacy of novel phytoconstituent fustin as a potential future candidate for the treatment of HD via offering neuroprotection by subsiding the oxidative and enzymatic activity in the 3-NPA experimental animal paradigm.

Harnessing Lipid Polymer Hybrid Nanoparticles for Enhanced Oral Bioavailability of Thymoquinone: In Vitro and In Vivo Assessments.

The clinical application of phytochemicals such as thymoquinone (THQ) is restricted due to their limited aqueous solubility and oral bioavailability. Developing mucoadhesive nanocarriers to deliver these natural compounds might provide new hope to enhance their oral bioavailability. Herein, this investigation aimed to develop THQ-loaded lipid-polymer hybrid nanoparticles (THQ-LPHNPs) based on natural polymer chitosan. THQ-LPHNPs were fabricated by the nanoprecipitation technique and optimized by the 3-factor 3-level Box−Behnken design. The optimized LPHNPs represented excellent properties for ideal THQ delivery for oral administration. The optimized THQ-LPHNPs revealed the particles size (PS), polydispersity index (PDI), entrapment efficiency (%EE), and zeta potential (ZP) of <200 nm, <0.25, >85%, and >25 mV, respectively. THQ-LPHNPs represented excellent stability in the gastrointestinal milieu and storage stability in different environmental conditions. THQ-LPHNPs represented almost similar release profiles in both gastric as well as intestinal media with the initial fast release for 4 h and after that a sustained release up to 48 h. Further, the optimized THQ-LPHNPs represent excellent mucin binding efficiency (>70%). Cytotoxicity study revealed much better anti-breast cancer activity of THQ-LPHNPs compared with free THQ against MDA-MB-231 and MCF-7 breast cancer cells. Moreover, ex vivo experiments revealed more than three times higher permeation from the intestine after THQ-LPHNPs administration compared to the conventional THQ suspension. Furthermore, the THQ-LPHNPs showed 4.74-fold enhanced bioavailability after oral administration in comparison with the conventional THQ suspension. Therefore, from the above outcomes, mucoadhesive LPHNPs might be suitable nano-scale carriers for enhanced oral bioavailability and therapeutic efficacy of highly lipophilic phytochemicals such as THQ.

Rosinidin Protects against Cisplatin-Induced Nephrotoxicity via Subsiding Proinflammatory and Oxidative Stress Biomarkers in Rats.

BACKGROUND: Rosinidin is a flavonoid anthocyanin pigmentation found in shrub flowers such as Catharanthus roseus and Primula rosea. The molecular docking studies predicted that rosinidin has adequate structural competency, making it a viable medicinal candidate for the treatment of a wide range of disorders. The current study intends to assess rosinidin nephroprotective efficacy against nephrotoxicity induced by cisplatin in rats. MATERIALS AND METHODS: Oral acute toxicity tests of rosinidin were conducted to assess potential toxicity in animals, and it was shown to be safe. The nephroprotective effect of rosinidin 10, and 20 mg/kg were tested in rats for 25 days with concurrent administration of cisplatin. Several biochemical parameters were measured to support enzymatic and non-enzymatic oxidative stress such as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH). Likewise, changes in several non-protein-nitrogenous components and blood chemistry parameters were made to support the theory linked with the pathogenesis of chemical-induced nephrotoxicity. RESULTS: Cisplatin caused significant changes in biochemical, enzymatic, and blood chemistry, which rosinidin efficiently controlled. CONCLUSIONS: The present investigation linked rosinidin with nephroprotective efficacy in experimental models.

Protective Effect of Fustin Against Ethanol-Activated Gastric Ulcer via Downregulation of Biochemical Parameters in Rats.

The fustin plant-derived bioflavonoid obtained from a common plant known as lacquer tree from family Anacardiaceae, formally known as Rhus verniciflua Stokes, is known to exert a variety of therapeutic properties. The current investigation proved the anti-ulcerative property of fustin on ethanol-induced gastric ulcers in an experimental animal model. The fustin 50 and 100 mg/kg was studied in an experimental rat model by performing an 8 day protocol. The ulcer index, pH, total acidic content, and biochemical parameters such as glutathione (GSH), superoxide dismutase (SOD), catalase activity (CAT), malondialdehyde (MDA), interleukin-1ß, prostaglandin E-2, tumor necrosis factor-α (TNF-α), myeloperoxidase, and nitric oxide (NO) in serum were measured. The gastric parameter such as ulcer index, pH, and acidic content was maintained in the fustin groups compared to the ethanol control group. Clinical presentation of gastric ulcers includes a significant increase in serum levels, GSH, SOD, and CAT and decreased MDA, TNF-α, interleukin-1ß, and prostaglandin E-2 parameters in contrast to normal groups. The treatment regimen with fustin has significantly restored all serum parameters in test groups. The current study helps to develop reasonable phytochemical options for the innervations of chemical-induced gastric ulcers.

Antiamnesic Potential of Malvidin on Aluminum Chloride Activated by the Free Radical Scavenging Property.

Objectives: Malvidin, a dietary anthocyanin can be a potent drug for the treatment of neuronal toxicity. The investigation was aimed to study the antioxidant role of malvidin against aluminum chloride (AlCl3)-induced neurotoxicity in rats. Methods: To evaluate the neuroprotective role of malvidin, the rats were divided into four different groups: group I received saline, group II received AlCl3, and groups III and IV were administered with 100 and 200 mg/kg malvidin after AlCl3 for 60 days. During the evaluation period, all the groups were subjected to a behavioral test. On the 61st day of the study, rat brains were removed and used for a neurochemical assay. Results: From the present study, malvidin ameliorated the effects of AlCl3 on behavioral parameters. Biochemical investigation revealed that oral treatment of malvidin shows neuroprotective effects through regulation of antioxidant levels and neuroinflammation in the AlCl3-exposed rats. Conclusion: The results indicate that malvidin possesses antioxidant activity via acetylcholinesterase inhibition and regulation of oxidative stress in neuronal cells. Hence, malvidin could be a potential drug in correcting Alzheimer's disease.

Vitamin D attenuates COVID-19 complications via modulation of proinflammatory cytokines, antiviral proteins, and autophagy.

INTRODUCTION: Global emergence of coronavirus disease-19 (COVID-19) has clearly shown variable severity, mortality, and frequency between and within populations worldwide. These striking differences have made many biological variables attractive for future investigations. One of these variables, vitamin D, has been implicated in COVID-19 with rapidly growing scientific evidence. AREAS COVERED: The review intended to systematically explore the sources, and immunomodulatory role of vitamin D in COVID-19. Search engines and data sources including Google Scholar, PubMed, NCBI, Scopus, and Web of Science were used for data collection. The search terms used were Vitamin D, COVID-19, immune system, and antiviral mechanism. Overall, 232 sources of information were collected and 188 were included in this review. EXPERT OPINION: Interaction of vitamin D and vitamin D receptor (VDR) triggers the cellular events to modulate the immune system by regulation of many genes. Vitamin D operates as a double-edged sword against COVID-19. First, in macrophages, it promotes the production of antimicrobial and antiviral proteins like ß-defensin 2 and cathelicidin, and these proteins inhibit the replication of viral particles and promote the clearance of virus from the cells by autophagy. Second, it suppresses cytokine storm and inflammatory processes in COVID-19.

Novelkaraya gum micro-particles loaded Ganoderma lucidum polysaccharide regulate sex hormones, oxidative stress and inflammatory cytokine levels in cadmium induced testicular toxicity in experimental animals.

Presented research aimed to develop a spray drying process without the use of organic solvents for the preparation of novel Karaya gum polymer microparticles (MPs) of Ganoderma lucidum polysaccharide (GLP). The prepared microparticles were characterized and evaluated. Prepared novel karaya gum micro-particles loaded Ganoderma lucidum polysaccharide (GLP MPs) were observed an effect on cadmium (CAD) induced testicular toxicity. A total of 40 rats (male) was divided into 4 groups viz. 1. Control group, 2. GLP MPs (250 mg/kg, 60 days of b.w per day), 3. CAD (60 days of 30 mg/l/day), 4. GLP MPs + CAD. CAD was responsible for altering the sex hormones, oxidative stress and inflammatory cytokines. Furthermore, elevated levels of indicator of oxidative stress, malondialdehyde, and a reduced action of SOD, GSH, and CAT (antioxidant enzymes), were observed in the tissues of the testicles of CAD- treated group. Such harmful occurrences were followed by an up-regulation in proinflammatory cytokines (TNF-α, IL-1ß) levels, protein expression of Nrf2, and HO-1 expression was decreased. GLP MPs pre-treatment significantly abrogated these toxic effects which were confirmed histologically. This study concluded that pre-treatment with GLP MPs exerts a protective effect against CAD-induced male reproductive testicular toxicity.

The Potential Impact of Smog Spell on Humans' Health Amid COVID-19 Rages.

Rapid and unchecked industrialization and the combustion of fossil fuels have engendered a state of fear in urban settlements. Smog is a visible form of air pollution that arises due to the over-emissions of some primary pollutants like volatile organic compounds (VOCs), hydrocarbons, SO2, NO, and NO2 which further react in the atmosphere and give rise to toxic and carcinogenic secondary smog components. Smog reduces the visibility on roads and results in road accidents and cancellation of flights. Uptake of primary and secondary pollutants of smog is responsible for several deleterious diseases of which respiratory disorders, cardiovascular dysfunction, neurological disorders, and cancer are discussed here. Children and pregnant women are more prone to the hazards of smog. The worsening menace of smog on one hand and occurrence of pandemic i.e., COVID-19 on the other may increase the mortality rate. But the implementation of lockdown during pandemics has favored the atmosphere in some ways, which will be highlighted in the article. On the whole, the focus of this article will be on the dubious relationship between smog and coronavirus.

Fustin Ameliorates Elevated Levels of Leptin, Adiponectin, Serum TNF-α, and Intracellular Oxidative Free Radicals in High-Fat Diet and Streptozotocin-Induced Diabetic Rats.

Fustin is a prominent ingredient of Rhus verniciflua Stokes (Anacardiaceae) and has a wide range of pharmacological and clinical effects. The present study attempted to evaluate the antidiabetic potential of fustin in streptozotocin- and high-fat diet-induced diabetes in rats. The efficacy of fustin 50 mg/kg and 100 mg/kg/day p.o. was studied in 60% of total calories from fat as a high-fat diet along with single-dose administration streptozotocin (50 mg/kg, i.p.) experimentally induced diabetes in rats for 42 days. The mean body weight; blood glucose; and biochemical parameters such as lipid profile, total protein (TP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), insulin, leptin levels, adiponectin levels, glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activity in serum were measured. The rats' weight was maintained in the fustin groups compared to the diabetic control group. Diabetes caused a significant increase in serum levels in blood glucose, lipid profile, MDA, TNF-α, ALT, and AST parameters and a decrease in serum insulin, adiponectin, leptin, GSH, SOD, and CAT compared to healthy rats. The treatment regimen with fustin (50 and 100 mg/kg) significantly restored all serum parameters in test groups. The present study found clinical evidence for the first time regarding the significant antidiabetic property of fustin, which could be a worthwhile candidate for the treatment of diabetes.