Synthesis, characterization, in-silico, and pharmacological evaluation of new 2-amino-6­trifluoromethoxy benzothiazole derivatives.

Alzheimer's disease (AD), a relentless neurodegenerative disorder, is still waiting for safer profile drugs, risk factors affecting AD's pathogenesis include aß accumulation, tau protein hyperphosphorylation, and neuroinflammation. This research aimed to synthesize 2-amino-6­trifluoromethoxy benzothiazole schiff bases. Synthesis was straightforward, combining the riluzole skeleton with compounds containing the azomethine group. Schiff bases synthesized were characterized spectroscopically using proton NMR (1H NMR), and FTIR. In-vivo biological evaluation against scopolamine-induced neuronal damage revealed that these newly synthesized schiff bases were effective in protecting neurons against neuroinflammatory mediators. In-vitro results revealed that these compounds had remarkable potential in improving the anti-oxidant levels. It downregulated glutathione (GSH), glutathione S-transferase (GST), catalase levels, and upregulated lipid peroxidation (LPO) levels. Immunohistochemical studies revealed that groups treated with the newly synthesized schiff bases had reduced expression of inflammatory mediators such as cyclooxygenase 2 (COX-2), JNK, tumor necrosis factor (TNF-α), nuclear factor kappa B (NF-kB) in contrast to the disease group. Moreover, molecular docking studies on these compounds also showed that they possessed a better binding affinity for above mentioned inflammatory mediators. The results of these studies showed that 2-amino-6-trifluoromethoxy benzothiazole schiff bases are remarkably effective against oxidative stress-mediated neuroinflammation.

New pyrazolone derivatives, synthesis, characterization, and neuroprotective effect against PTZ- induced neuroinflammation in mice.

Objectives: The study was aimed at synthesis of the new derivatives of the pyrazolone nucleus, and their spectroscopic and pharmacological analysis and evaluation. Materials and Methods: Three series of compounds, with 2-picolinic acid (I a-d), 3-picolinic acid (II a-d), and 4-picolinic acid (III a-d) were synthesized and characterized by FT-IR, 1HNMR, 13C NMR, elemental, and melting points. The new compounds were then evaluated for their anti-oxidant, anti-inflammatory, and anti-epileptic potential. The hind paw edema model was used to screen anti-inflammatory potential, while the anticonvulsant effect was evaluated by employing the acute model of anti-epileptic activity. The in vivo anti-oxidant potential was determined through glutathione (GSH), glutathione-S-transferase (GST), catalase, and lipid peroxidase enzyme (LPO) assays. The expression of key biomarkers involved in inflammation and neuroprotection, including tumor necrotic factors alpha (TNF-α) and phosphorylated nuclear factor kappa B (NF-κB), was detected through enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Results: The tested compounds showed anti-oxidant potential. The selected compounds exhibited good anti-inflammatory potential. The PTZ-induced elevation of these inflammatory mediators and oxidative stress were ameliorated significantly by the selected compound Ic. Results of molecular analysis (ELISA and Western blot analysis) for potent compound Ic showed a prominent inhibitory effect against neuroinflammatory mediators, including TNF-α and NF-κB. Conclusion: It is concluded that the derivative Ic ameliorated PTZ-induced seizures, oxidative stress, and inflammatory cascades by regulating the NF-κB/ TNF-α/ROS pathway.

Phytochemical investigation and pharmacological evaluation of methanolic flower extract of Saussurea heteromalla.

Saussurea heteromalla is the one of specie of Saussurea plant belonging to family Asteraceae. The Saussurea heteromalla found extensively in Pakistan. The literature review highlights numerous biological aspects of Saussurea heteromalla. This research therefore aims to assess its potential anti-inflammatory, antioxidant, anti-cancer. Carrageenan induced rat paw edema model was used for the evaluation of anti-inflammatory activity. DPPH method was used to evaluate anti-oxidant activity. The MTT (3- [4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide) test was used to assess the viability of the cells for the assessment of the cytotoxic effect of the extract. Methanolic Saussurea heteromalla flowers extract analysis carried by GC-MS, result 19 different peaks. The methanolic extract of Saussurea heteromalla at 400mg/kg dose have equal anti-inflammatory action when compare with standard that is diclofenac sodium. Anti-oxidant activity of methanolic extract is also very good. IC50 value of methanol extract was 25µg/ml. 18.72% cell survive out of 100 when methanolic flower extract of Saussurea heteromalla was given at the dose of 400mg, which shows the cytotoxic effect. This activity shows that plant Saussurea heteromalla methanolic flowers extract have anti-inflammatory, anti-oxidant, cytotoxic effect. The isolation and characterization-based investigations proclaiming the biologically leading active molecule are worthy for further study in this regard.

Frequency, Prevalence, Interaction, and Gender Differences of Six Psychosocial Factors in Patients Presenting to a Psychiatric Emergency Service.

INTRODUCTION: The psychiatric emergency service (PES) has become an increasingly utilized patient care approach over the past 50 years. Psychosocial factors play an important role in PES utilization and disposition of patients in this environment. PES utilization in our region has increased 450% in the past 18 years, while the population has changed <1%. Our objective was to determine the frequency and relationship between six psychosocial factors in our patients, in comparison to the general population. METHODS: We completed a retrospective chart review of 160 patients selected at random who utilized the PES during 2009-2010. We looked for historical presence of a broken family, abuse or neglect, substance abuse, legal problems, violence, or incomplete education. We also looked at the relationship of these factors to race and gender. RESULTS: 75% had three or more of the factors measured. In our population, substance abuse and broken family were most prevalent. Females had significantly more abuse or neglect as compared to males, while male subjects had significantly more substance abuse and legal issues than females. The presence of a broken family was strongly associated with abuse or neglect, while violence was associated with incomplete education and legal issues. The prevalence of these factors in our patients was higher than the general population. CONCLUSION: The average patient presenting to the PES has multiple major psychosocial problems at higher frequencies than the general population. Understanding the relationship between multiple psychosocial factors and increasing PES utilization can direct us towards addressing the problems causing the increase in PES presentation. A planned future prospective study will examine the incidence of these psychosocial factors in patients presenting to the PES as compared to the general population.

Phytochemical and GCMS approaches to identify active constituents in Erythrina suberosa bark extract and evaluation of its therapeutic potency.

Humans rely on plants as a necessitous source of their food, energy, cosmetics and medicines, as medicinal plants are rich source of new therapeutically active compounds from decades. Current study was designed to separate and identify active constituents of Erythrina suberosa bark extract using phytochemical screening and gas chromatography and mass spectroscopy, respectively and evaluated their therapeutic activities. E. suberosa bark extract contained saponins, glycosides, alkaloids, tannins, terpenoids, phenols and 44 active compounds identified by phytochemical and gas chromatography and mass spectroscopic analysis. Therapeutic potentials of E. suberosa bark extract was evaluated by such as cytotoxicity, anti-inflammatory and antioxidant assay. Surprisingly, bark extract shows the concentration dependent cytotoxicity against human fibroblast malignant melanoma-144 cell lines and remarkably inhibited (15.18(plusmn;1.13%, at 400mg/ml) growth of cancer cells after 24 hours treatment. In addition, the E. suberosa bark extract also exhibited anti-inflammatory effect at higher doses (400mg/kg) and moderate antioxidant activity is also noticed through (2, 2-diphenyl-1-picrylhydrazyl radical) assay. These findings indicate that E. suberosa bark extract exhibited prominent anticancer and anti-inflammatory activities and might be serve as a potent therapeutic agent in future.