Effect of moringa seed extract in chlorpyrifos-induced cerebral and ocular toxicity in mice.

Chlorpyrifos (CPF) is one of the most commonly used organophosphosphate-based (OP) insecticides. Its wide use has led to higher morbidity and mortality, especially in developing countries. Moringa seed extracts (MSE) have shown neuroprotective activity, antioxidant, anti-inflammatory, and antibacterial features. The literature lacks data investigating the role of MSE against CPF-induced cerebral and ocular toxicity in mice. Therefore, we aim to investigate this concern. A total of 40 mature male Wistar Albino mice were randomly distributed to five groups. Initially, they underwent a one-week adaptation period, followed by a one-week treatment regimen. The groups included a control group that received saline, MSE 100 mg/kg, CPF 12 mg/kg, CPF-MSE 50 mg/kg, and CPF-MSE 100 mg/kg. After the treatment phase, analyses were conducted on serum, ocular, and cerebral tissues. MSE100 and CPF-MSE100 normalized the pro-inflammatory markers (interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α)) and AChE serum levels. CPF-MSE50 significantly enhanced these serum levels compared to CPF; however, it showed higher levels compared to the control. Moreover, the tissue analysis showed a significant decrease in oxidative stress (malondialdehyde (MDA) and nitric oxide (NO)) and an increase in antioxidant markers (glutathione (GSH), glutathione peroxidase (GSH-PX)), superoxide dismutase (SOD), and catalase (CAT) in the treated groups compared to CPF. Importantly, the significance of these effects was found to be dose-dependent, particularly evident in the CPF-MSE100 group. We conclude that MSE has a promising therapeutic effect in the cerebral and ocular tissues of CPF-intoxicated mice, providing a potential solution for OP public health issues.

Wheat ergot fungus-derived and modified drug for inhibition of intracranial aneurysm rupture due to dysfunction of TLR-4 receptor in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a form of dementia that strikes elderly people more frequently than it does younger people. The cognitive skills and memory of Alzheimer's sufferers continue to deteriorate over time. Recent studies have shown that patients with AD have greater amounts of inflammatory markers in their bodies, which suggests that inflammation occurs early on in the progression of the disease. There is a possibility that Aß oligomers and fibrils can be recognised by TLRs, in addition to the microglial receptors CD14, CD36, and CD47. When Aß binds to either CD36 or TLR4, it sets off a chain reaction of inflammatory chemokines and cytokines that ultimately results in neurodegeneration. Diabetes and Alzheimer's disease have both been recently related to TLR4. The activation of TLR4 has been connected to a variety of clinical difficulties that are associated with diabetes, in addition to the internal environment of the body and the microenvironment of the brain. TLR4 inhibitors have been shown in clinical investigations to not only lessen the likelihood of getting sick but also to increase the average longevity. RESULT: In this work we used molecular docking and molecular dynamics modelling to investigate the effectiveness of FDA-approved antidiabetic plant derived drugs in combating the TLR4 receptor. Molecular docking experiments were used to make a prediction regarding the most important interactions involving 2-Bromoergocryptine Mesylate. With a binding affinity of -8.26 kcal/mol, it stood out from the other candidates as the one with the greatest potential. To verify the interaction pattern that takes place between 2-Bromoergocryptine Mesylate and the TLR4 receptor, a molecular dynamic simulation was run at a time scale of 150 nanoseconds. Because of this, 2-Bromoergocryptine Mesylate was able to make substantial contact with the active site, which led to increased structural stability during the process of the complex's dynamic development. CONCLUSION: As a result of this, the results of our research may be relevant for future research into the efficacy of 2-bromoergocryptine mesylate as a potential lead treatment for TLR4 receptors in intracranial aneurysm rupture in AD.

Acrylamide-induced peripheral neuropathy: manifestations, mechanisms, and potential treatment modalities.

Acrylamide is a chemical monomer; its polymer compounds are used in the manufacture of plastic, papers, adhesive tapes, dyes, and food packaging. Lately, scientists found that cooking (mainly roasting, baking, and frying) yields acrylamide. In addition to fried/baked potatoes, coffee and bakery products still contain substantial amounts of acrylamide. Acrylamide has toxic effects on different body systems include genitourinary, reproductive, nervous system, along with being a carcinogenic substance. The neurotoxicity of acrylamide includes central and peripheral neuropathy. In humans, the clinical manifestations include sensory or motor peripheral neuropathy, drowsiness, or cerebellar ataxia. Likewise, it presents with skeletal muscle weakness, hindlimb dysfunction, ataxia, and weight loss in animals. The suggested mechanisms for acrylamide neurotoxicity include direct inhibition of neurotransmission, cellular changes, inhibition of key cellular enzymes, and bonding of kinesin-based fast axonal transport. Moreover, it is suggested that acrylamide's molecular effect on SNARE core kinetics is carried out through the adduction of NSF and/or SNARE proteins. Lately, scientists showed disruption of focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) cell signaling pathways in human differentiating neuroblastoma SH-SY5Y cells, exposed to acrylamide. Different treatment modalities have been revealed to shield against or hasten recovery from acrylamide-induced neuropathy in preclinical studies, including phytochemical, biological, and vitamin-based compounds. Still, additional studies are needed to elucidate the pathogenesis and to identify the best treatment modality.