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Aim: The study was designed to develop and analyze curcumin nanoparticles. Methods: Curcumin nanoparticles were formulated and evaluated. Their efficacy in protecting against brain damage was investigated in a rat model of ischemic stroke, considering motor function, muscle strength and antioxidant enzyme activity. Results: Curcumin nanoparticles displayed a zeta potential of -55 ± 13.5 mV and an average particle size of 51.40 ± 21.70 nm. In ischemic stroke rat models, curcumin nanoparticle treatment significantly improved motor functions, and muscle strength and increased the activities of antioxidant enzymes like glutathione peroxidase, glutathione, glutathione S-transferase, superoxide dismutase and catalase, reducing oxidative stress and inflammation. Conclusion: Curcumin nanoparticles showed significant neuroprotective effects in ischemic stroke models.

Tridax procumbens (TP) is a traditional Indian therapeutic plant and was evaluated for its blood glucose lowering abilities, as well as for its ability to curb diabetic neuropathy (DN). Administrating 45 mg/kg body weight of streptozotocin (STZ) intraperitoneally for four weeks, DN was induced in Wistar rats. After the rats' tails were clipped, the blood glucose levels were measured. Body weight and urine volume were also assessed. Oxidative stress makers such as superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), catalase (CAT), inflammatory cytokines for instance tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were estimated. Further, protein kinase C (PKC-β) and vascular endothelial growth factor (VEGF) were also estimated as angiogenic markers. Behavioral parameters were also evaluated by using cold allodynia using acetone test, hot allodynia using Eddy's hot plate, grip strength test using Rota rod, and hyperalgesia test using Tail flick technique. The statistical assessment of findings was done employing one-way (ANOVA) analysis of variance, and subsequently Turkey as post hoc with GraphPad Prism software package. The ingestion of TP for 1 month in DN rats stemmed in a substantial decline in blood glucose concentrations matched to nontreated rats with DN. There had been a considerable improvement in DN as evident from the finding from biochemical markers. The serum level of antioxidant defense enzymes was significantly increased, while the activities of TBARS had been substantially reduced in the TP treated rats with DN. TP averted DN-triggered surge levels of TNF-α and IL-6 in the serum. Further, PKC-β and VEGF concentrations had been also reduced by the treatment TP. The findings of this research demonstrated that the restorative impact of TP on DN rats might be linked to the anti-inflammatory and antioxidative antiangiogenic retorts. [ABSTRACT FROM AUTHOR]

Methylmercury (MeHg) is a neurotoxin that induces neurotoxicity and cell death in neurons. MeHg increases oligodendrocyte death, glial cell activation, and motor neuron demyelination in the motor cortex and spinal cord. As a result, MeHg plays an important role in developing neurocomplications similar to amyotrophic lateral sclerosis (ALS). Recent research has implicated c-JNK and p38MAPK overactivation in the pathogenesis of ALS. Apigenin (APG) is a flavonoid having anti-inflammatory, antioxidant, and c-JNK/p38MAPK inhibitory activities. The purpose of this study is to determine whether APG possesses neuroprotective effects in MeHg-induced neurotoxicity in adult rats associated with ALS-like neuropathological alterations. In the current study, the neurotoxin MeHg causes an ALS-like phenotype in Wistar rats after 21 days of oral administration at a dose of 5 mg/kg. Prolonged administration of APG (40 and 80 mg/kg) improved neurobehavioral parameters such as learning memory, cognition, motor coordination, and grip strength. This is mainly associated with the downregulation of c-JNK and p38MAPK signaling as well as the restoration of myelin basic protein within the brain. Furthermore, APG inhibited neuronal apoptotic markers (Bax, Bcl-2, and caspase-3), restored neurotransmitter imbalance, decreased inflammatory markers (TNF- and IL-1), and alleviated oxidative damage. As a result, the current study shows that APG has neuroprotective potential as a c-JNK and p38MAPK signaling inhibitor against MeHg-induced neurotoxicity in adult rats. Based on these promising findings, we suggested that APG could be a potential new therapeutic approach over other conventional therapeutic approaches for MeHg-induced neurotoxicity in neurobehavioral, molecular, and neurochemical abnormalities. Graphical Abstract [ABSTRACT FROM AUTHOR]

Background: Organophosphorus insecticides are well known to induce hepatotoxicity. One among this is chlorpyrifos (CPF), which is an insecticide inducing various toxicities including in liver. Objective: This investigation focused on CPF-induced oxidative damage in rat hepatocytes primary culture and the protective effect of Cactus cladode aqueous extract. Materials and Methods: Hepatocytes were treated with CPF (50, 75, and 150 μM) and cactus aqueous extract. On treatment for 48 h, mortality within these cells was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide test, reactive oxygen species (ROS) levels were measured by H2DCFDA test. Furthermore, heat shock protein 70 (HSP70) and CYP1A1/2 levels were determined using western blot analysis. Annexin V and 4',6-diamidino-2-phenylindole analysis was run to determine the level of cell death and cytoprotection exerted by CPF and extracts, respectively. Results: The results showed that CPF increases the levels of H2O2 and HSP70 and induces CYP1A1/2 and mortality within these cells. In the other side of this study, the co-treatment of these cells with CPF and Cactus cladode aqueous extract showed a recovery of these parameters. It also has been found that the Cactus cladode aqueous extract has the potential to do cytoprotective effect by preventing necrosis induced by CPF. Conclusion: Taken together, these findings suggest that the toxicity exerted by CPF in hepatocytes are involved with the generation of ROS and the regulation of well-controlled programmed cell death, which could be well protected by the Cactus cladode extract pretreatment. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a complicated and incapacitating neurodegenerative malady that emanates following the dopaminergic (DArgic) nerve cell deprivation in the substantia nigra pars compacta (SN-PC). The etiopathogenesis of PD is still abstruse. Howbeit, PD is hypothesized to be precipitated by an amalgamation of genetic mutations and exposure to environmental toxins. The aggregation of α-synucelin within the Lewy bodies (LBs), escalated oxidative stress (OS), autophagy-lysosome system impairment, ubiquitin-proteasome system (UPS) impairment, mitochondrial abnormality, programmed cell death, and neuroinflammation are regarded as imperative events that actively participate in PD pathogenesis. The central nervous system (CNS) relies heavily on redox-active metals, particularly iron (Fe) and copper (Cu), in order to modulate pivotal operations, for instance, myelin generation, synthesis of neurotransmitters, synaptic signaling, and conveyance of oxygen (O2). The duo, namely, Fe and Cu, following their inordinate exposure, are viable of permeating across the blood–brain barrier (BBB) and moving inside the brain, thereby culminating in the escalated OS (through a reactive oxygen species (ROS)-reliant pathway), α-synuclein aggregation within the LBs, and lipid peroxidation, which consequently results in the destruction of DArgic nerve cells and facilitates PD emanation. This review delineates the metabolism of Fe and Cu in the CNS, their role and disrupted balance in PD. An in-depth investigation was carried out by utilizing the existing publications obtained from prestigious medical databases employing particular keywords mentioned in the current paper. Moreover, we also focus on decoding the role of metal complexes and chelators in PD treatment. Conclusively, metal chelators hold the aptitude to elicit the scavenging of mobile/fluctuating metal ions, which in turn culminates in the suppression of ROS generation, and thereby prelude the evolution of PD. [ABSTRACT FROM AUTHOR]

[Display omitted] • NR is neuroprotective, reduced infarction, improved motor and cognitive function. • NR ameliorated behavioral parameters, oxidative stress and neuroinflammatory markers. • Data indicate that NR has therapeutic potential against ischemic stroke in rat model. Resveratrol is a nutraceutical compound that has exciting pharmacological potential in different diseases, including stroke. Due to its low bioavailability, the efficacy of resveratrol is minimal. Hence, the present study is aimed to synthesize and characterize nanoparticles of resveratrol (NR) followed by evaluating the neuroprotective role and elucidate the mechanism of NR in a rat model of middle cerebral artery occlusion (MCAO). Male Wistar rats (280–300 g) were pretreated with various doses (125 µg, 250 µg, and NR 500 µg; once daily, i.p.) of NR or vehicle (nanostructured lipid carriers) for 10 days. MCAO was performed for 2 h followed by reperfusion of 22 h. After 24 h of MCAO, animals were tested for the neurological outcome and were sacrificed for the analysis of infarct volume, oxidative, inflammatory, and apoptotic markers. NR-treated rats showed a substantial reduction in infarction compared to saline controls in parallel with improved motor and cognitive function. Further, NR pretreatment ameliorated oxidative stress markers and attenuated activities of antioxidant enzymes and Na+ K+ ATPase. The enhanced activities of caspases −3 and −9 and cytokines: interleukin-1β, and −6, and tumor necrosis factor-ɑ) in the MCAO group were significantly protected with the treatment of 500 µg of NR. Taken together, these data indicate that inhibition by NR has therapeutic potential in the ischemic stroke model. Further investigations into the therapeutic efficacy and post-treatment protocols are needed to confirm whether NR treatment could be a promising candidate for a stroke. [ABSTRACT FROM AUTHOR]