Parkinson’s disease (PD) is a gradual deterioration of dopaminergic neurons, leading to motor impairments. Social isolation (SI), a recognized stressor, has recently gained attention as a potential influencing factor in the progress of neurodegenerative illnesses. We aimed to investigate the intricate relationship between SI and PD progression, both independently and in the presence of manganese chloride (MnCl₂), while evaluating the punicalagin (PUN) therapeutic effects, a natural compound established for its cytoprotective, anti-inflammatory, and anti-apoptotic activities. In this five-week experiment, seven groups of male albino rats were organized: G1 (normal control), G2 (SI), G3 (MnCl₂), G4 (SI + MnCl₂), G5 (SI + PUN), G6 (MnCl₂ + PUN), and G7 (SI + PUN + MnCl₂). The results revealed significant changes in behavior, biochemistry, and histopathology in rats exposed to SI and/or MnCl₂, with the most pronounced effects detected in the SI rats concurrently exposed to MnCl₂. These effects were associated with augmented oxidative stress biomarkers and reduced antioxidant activity of the Nrf2/HO-1 pathway. Additionally, inflammatory pathways (HMGB1/RAGE/TLR4/NF-ᴋB/NLRP3/Caspase-1 and JAK-2/STAT-3) were upregulated, while dysregulation of signaling pathways (PI3K/AKT/GSK-3β/CREB), sustained endoplasmic reticulum stress by activation PERK/CHOP/Bcl-2, and impaired autophagy (AMPK/SIRT-1/Beclin-1 axis) were observed. Apoptosis induction and a decrease in monoamine levels were also noted. Remarkably, treatment with PUN effectively alleviated behaviour, histopathological changes, and biochemical alterations induced by SI and/or MnCl₂. These findings emphasize the role of SI in PD progress and propose PUN as a potential therapeutic intervention to mitigate PD. PUN’s mechanisms of action involve modulation of pathways such as HMGB1/RAGE/TLR4/NF-ᴋB/NLRP3/Caspase-1, JAK-2/STAT-3, PI3K/AKT/GSK-3β/CREB, AMPK/SIRT-1, Nrf2/HO-1, and PERK/CHOP/Bcl-2.

Mefenamic acid functions as a nonsteroidal anti-inflammatory drug (NSAID) of the fenamate class, which treats pain and inflammation by inhibiting cyclooxygenase (COX-1 and COX-2) enzymes to decrease prostaglandin production. Mefenamic acid has strong therapeutic properties that help to treat arthritis and dysmenorrhea. The rapid dissolution of orodispersible tablets (ODTs) makes them an effective treatment option for patients with dysphagia. This study developed and evaluated mefenamic acid ODTs through direct compression while adding super-disintegrants, including croscarmellose sodium, crospovidone, and sodium starch glycolate, to improve drug release and disintegration speed. Pre-formulation analysis through FTIR spectroscopy showed that the drug and excipients maintained compatibility without detectable interactions. Product quality assessment included tests for hardness and weight variation, friability and disintegration time, dissolution studies, and stability testing. The performance of the formulation was evaluated through supplementary tests that measured the moisture uptake, wetting time, and water absorption ratio. The zero-order model provided the most accurate explanation of drug release kinetics among the model-dependent approaches, which included the zero-order, first-order, Higuchi, and Hixson-Crowell models. The combination of 7% croscarmellose sodium in formulation F1 produced the best results by enabling quick dissolution while maintaining the optimal disintegration time and improving drug absorption and patient compliance. Stability tests showed that the formulation structure remained consistent during the entire testing period, thus proving its durability. The direct compression method was effective for manufacturing stable mefenamic acid ODTs according to this research. This research demonstrates how super-disintegrants boost formulation performance, establishing ODTs as a promising drug delivery system for better therapeutic results and patient medication compliance.

The liver is the second largest organ in the body, playing a crucial role in maintaining homeostasis and regulating metabolism. However, the prevalence of liver diseases has been rising steadily due to an increase in both infectious and non-infectious factors. Medicinal plants offer a remarkable opportunity to enhance our healthcare system by addressing various diseases through their ability to control oxidative stress and support metabolic processes. This revision improves readability while retaining the original meaning. In the present study, purified methanol extracts of Martynia annua and Polygonum viviparum at different concentrations were used to explore the antioxidant and hepatoprotective potential against abiotic stress on liver cells. Firstly total flavonoids and total phenolic contents of both plants were measured and then their antioxidant activities were determined through DPPH radical scavenging activity and FRAP assay. Moreover, bioactive compounds and in vitro hepatoprotective potential among these plants were determined through LC-MS and Liver Slice Culture assay respectively. In P. viviparum high amounts of TPC and TFC were observed with maximum antioxidant potential in terms of DPPH inhibition at 84% and high ferric-reducing ability at 240 mg/mL. The presence of different phytoconstituents like Myricetin, Gallic acid, Ferulic acid, Chlorogenic acid, Sweroside, Morroniside, Echonoside, Swertiamarin and Protocatechuic acid were confirmed in M. annua and P. viviparum in LC-MS study. The maximum hepatoprotective potential in terms of minimum cytotoxicity 6% and 9% were observed in M. annua and P. viviparum respectively. It was revealed that both plants have stunning hepatoprotective properties to prevent liver from toxicants and their related complications due to high antioxidant potential and active metabolites.

Remarkably, treatment with PUN effectively alleviated behaviour, histopathological changes, and biochemical alterations induced by SI and/or MnCl2. These findings emphasize the role of SI in PD progress and propose PUN as a potential therapeutic intervention to mitigate PD. PUN's mechanisms of action involve modulation of pathways such as HMGB1/RAGE/TLR4/NF-ᴋB/NLRP3/Caspase-1, JAK-2/STAT-3, PI3K/AKT/GSK-3β/CREB, AMPK/SIRT-1, Nrf2/HO-1, and PERK/CHOP/Bcl-2.