EFFECT OF HYDROALCOHOLIC EXTRACT OF ACHYRANTHES ASPERA ON HALOPERIDOLINDUCED PARKINSON'S DISEASE IN WISTAR RATS

  Objective: Prolonged usage of neuroleptics in psychotic disorders such as schizophrenia provokes extrapyramidal symptoms that are also seen in Parkinson's disease. An attempt has been made to study the neuroprotective role of Achyranthes aspera hydroalcoholic (HA) extract on haloperidol-induced Parkinson's symptoms in Wistar rats.Methods: The present study deals with the antiparkinson effect of HA extract of A. aspera on haloperidol (2 mg/kg intraperitoneal administration)- induced catatonia in Wistar rats. The motor coordination in case of haloperidol-treated animals was studied by performing rotarod test and hang test. Dopamine and 3,4-dihydroxyphenylacetic acid were estimated using an electrochemical detector and high-performance liquid chromatography. The antioxidant status was also assessed to know the neurotoxicity of haloperidol by estimating the levels of lipid peroxidation, superoxide dismutase, glutathione (GSH) peroxidase, and reduced GSH by performing individual assays.Results: All these assessments were done on 24 Wistar rats which were divided into four groups (n=6). HA was administered at 200 and 400 mg/kg doses, 30 minutes before haloperidol treatment for 20 days. HA significantly (*p<0.05, **p<0.01) improved the antioxidant status.Conclusion: The results shown that HA shows a protective role in haloperidol catalepsy and also possess antioxidant property

Nanogels as novel drug nanocarriers for CNS drug delivery

Nanogels are highly recognized as adaptable drug delivery systems that significantly contribute to improving various therapies and diagnostic examinations for different human diseases. These three-dimensional, hydrophilic cross-linked polymers have the ability to absorb large amounts of water or biological fluids. Due to the growing demand for enhancing current therapies, nanogels have emerged as the next-generation drug delivery system. They effectively address the limitations of conventional drug therapy, such as poor stability, large particle size, and low drug loading efficiency. Nanogels find extensive use in the controlled delivery of therapeutic agents, reducing adverse drug effects and enabling lower therapeutic doses while maintaining enhanced efficacy and patient compliance. They are considered an innovative drug delivery system that highlights the shortcomings of traditional methods. This article covers several topics, including the involvement of nanogels in the nanomedicine sector, their advantages and limitations, ideal properties like biocompatibility, biodegradability, drug loading capacity, particle size, permeability, non-immunological response, and colloidal stability. Additionally, it provides information on nanogel classification, synthesis, drug release mechanisms, and various biological applications. The article also discusses barriers associated with brain targeting and the progress of nanogels as nanocarriers for delivering therapeutic agents to the central nervous system

Neuroprotective potential of Marsilea quadrifolia Linn against monosodium glutamate-induced excitotoxicity in rats

Background: Excitotoxicity is a condition in which neurons are damaged/injured by the over-activation of glutamate receptors. Excitotoxins play a crucial part in the progression of several neurological diseases. Marsilea quadrifolia Linn (M. quadrifolia) is a very popular aquatic medicinal plant that has been utilised for a variety of therapeutic benefits since ancient times. Its chemical composition is diverse and includes phenolic compounds, tannins, saponins, flavonoids, steroids, terpenoids, alkaloids, carbohydrates and several others that possess antioxidant properties.Objective: The objective of the present study was to investigate the neuroprotective potential of M. quadrifolia against monosodium glutamate (MSG)-induced excitotoxicity in rats.Methods: A high-performance thin-layer chromatography (HPTLC) analysis of chloroform extract of M. quadrifolia (CEMQ) was conducted to identify the major constituents. Further, the in silico docking analysis was carried out on selected ligands. To confirm CEMQ’s neuroprotective effects, the locomotor activity, non-spatial memory, and learning were assessed.Results and discussion: The present study confirmed that CMEQ contains quercetin and its derivatives in large. The in-silico findings indicated that quercetin has a better binding affinity (−7.9 kcal/mol) towards the protein target 5EWJ. Animals treated with MSG had 1) a greater reduction in the locomotor score and impairment in memory and learning 2) a greater increase in the blood levels of calcium and sodium and 3) neuronal disorganization, along with cerebral edema and neuronal degeneration in the brain tissues as compared to normal control animals. The changes were however, significantly improved in animals which received standard drug memantine (20 mg/kg) and CEMQ (200 and 400 mg/kg) as compared to the negative control. It is plausible that the changes seen with CEMQ may be attributed to the N-methyl-D-aspartate (NMDA) antagonistic properties.Conclusion: Overall, this study indicated that M. quadrifolia ameliorated MSG-induced neurotoxicity. Future investigations are required to explore the neuroprotective mechanism of M. quadrifolia and its active constituents, which will provide exciting insights in the therapeutic management of neurological disorders

In silico study of traditional Chinese medicinal compounds targeting alzheimer's disease amyloid beta-peptide (1–42)

The objective of this study is to recognize the potential traditional Chinese medicinal compound by virtual screening and docking analysis for the amyloid-beta disaggregation mechanism on Alzheimer's disease management. The selected target PDB ID: 1IYT was retrieved from protein data bank database. By uploading an optimized target structure in iScreen virtual screening tool, traditional Chinese medicinal compounds were shortlisted based on scoring functions. The resulted three common compounds were subjected to druglikeness, ADMET prediction and Autodock Vina analysis using Molinspiration, pkCSM and PyRx tool respectively. By considering all the results obtained in filter analysis, the ligand sanggenol A was shortlisted. The energy minimized ligand sanggenol A structure was docked against the optimized amyloid-beta peptide solution structure using Autodock 4.2.6 software. The binding energies for ten conformations of docked sanggenol A - beta amyloid complex is reported. Among ten conformations, three topmost conformations having better binding energies are interpreted with hydrophobic, hydrophilic, pi-pi and pi-cation interactions. Based on these scientific evidences, in silico study approach concludes that sanggenol A as a promising lead candidate which can be carried out for the further preclinical and clinical studies to prove for the management of Alzheimer's disease

Impact of nanocarrier aggregation on EPR-mediated tumor targeting

The aim of this study was to investigate the influence of excipients on retaining the particle size of methotrexate (MTX) loaded chitosan nanocarriers (CsNP) during lyophilization, which relates to the ability to enlarge the particle size and target specific areas. The nanocarriers were prepared using the ionic gelation technique with tripolyphosphate as a crosslinker. Three lyophilized formulations were used: nanosuspension without Lyoprotectant (NF), with mannitol (NFM), and with sucrose (NFS). The lyophilized powder intended for injection (PI) was examined to assess changes in particle size, product integrity, and comparative biodistribution studies to evaluate targeting ability. After lyophilization, NFS was excluded from in-vivo studies due to the product melt-back phenomenon. The particle size of the NF lyophile significantly increased from 176 nm to 261 nm. In contrast, NFM restricted the nanocarrier size to 194 nm and exhibited excellent cake properties. FTIR, XRD, and SEM analysis revealed the transformation of mannitol into a stable β, δ polymorphic form. Biodistribution studies showed that the nanocarriers significantly increased MTX accumulation in tumor tissue (NF = 2.04 ± 0.27; NFM = 2.73 ± 0.19) compared to the marketed PI (1.45 ± 0.25 μg), but this effect was highly dependent on the particle size. Incorporating mannitol yielded positive results in restricting particle size and favoring successful tumor targeting. This study demonstrates the potential of chitosan nanocarriers as promising candidates for targeted tumor drug delivery and cancer treatment.</p