Methanolic Extract of Aerva javanica Leaves Prevents LPS-Induced Depressive Like Behavior in Experimental Mice.

Aim: Depression is a chronic recurrent neuropsychiatric disorder associated with inflammation. This study explored the pharmacological activities of Aerva javanica leaves crude extract (Aj.Cr) on lipopolysaccharide (LPS)-induced depressive-like behavior in experimental mice. Methods: Aj.Cr was evaluated for its phenolic and flavonoid contents, bioactive potential, amino acid profiling and enzyme inhibition assays using different analytical techniques followed by in-silico molecular docking was performed. In addition, three ligands identified in HPLC analysis and standard galantamine were docked to acetyl cholinesterase (AchE) enzyme to assess the ligand interaction along with their binding affinities. In in-vivo analysis, mice were given normal saline (10 mL/kg), imipramine (10 mg/kg) and Aj.Cr (100, 300, and 500 mg/kg) orally for 14-consecutive days. On the 14th day, respective treatment was given 30-minutes before intra-peritoneal administration of (0.83 mg/kg) LPS. Open field, forced swim and tail suspension tests were performed 24-hours after LPS injection, followed by a sucrose preference test 48-hours later. Serum corticosterone levels, as well as levels of nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-alpha (TNF-), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and catecholamines were determined in brain tissues. Results: In-vitro results revealed that crude extract of Aj.Cr possesses anti-depressant agents with solid antioxidant potential. In-vivo analysis showed that LPS significantly increased depressive-like behavior followed by alteration in serum and tissue biomarkers as compared to normal control (p < 0.001). While imipramine and Aj.Cr (100, 300, and 500 mg/kg) treated groups significantly (p<0.05) improved the depressive-like behavior and biomarkers when compared to the LPS group. Conclusion: The mitigation of LPS-induced depressive-like behavior by Aj.Cr may be linked to the modulation of oxidative stress, neuro-inflammation and catecholamines due to the presence of potent bioactive compounds exerting anti-depressant effects.

Gisekia pharnaceoides Restores Colonic Mucosal Homeostasis by Regulating Antioxidant Enzyme System and Cytokines Signaling in Ulcerative Colitis Mice Model.

BACKGROUND: Gisekia pharnaceoides Linn. (Aizoaceae), traditionally known as baluka saag or sareli is commonly found in the deep Cholistan region of Pakistan. It is used by the native community for the mitigation of a range of diseases, including inflammatory disorders and gastric ulcers. OBJECTIVE: This study is designed to evaluate the defensive impact of G. pharnaceoides in acetic acid-induced ulcerative colitis in mice and to discover the mechanism for anti-inflammatory action. METHODS: The ethanolic crude extract of G. pharnaceoides (Gp.Cr) was prepared and evaluated for phytochemical substances by preliminary screening and HPLC analysis. Anti-inflammatory activity of Gp.Cr (300 and 500 mg/kg) was examined by administration of 200 µl of 7.5% acetic acid intra- rectally to induce ulcerative colitis and colonic mucosal injury, while mucosal homeostasis was evaluated by disease activity index, colonic ulcer score, and hematological parameters. The anti-inflammatory potential was quantified by assessing antioxidant enzymes (SOD, CAT, GPX-1), lipid peroxides, nitric oxide, and cytokines (IL-1ß, IL-6, TNF-α) immunoassays and further analyzed by histological analysis of colon tissues. RESULTS: Phytochemical screening of Gp.Cr revealed the presence of alkaloids, phenols, flavonoids, steroids, tannins, and saponins, while HPLC analysis confirmed the presence of quercetin, gallic acid, coumaric and sinapic acid. In acetic acid-induced ulcerative colitis model, Gp.Cr (300 and 500 mg/kg) along with sulphasalazine (500 mg/kg) decreased disease activity index, ulcer scores, and hematological parameters. Gp.Cr showed a significant anti-inflammatory potential by increasing antioxidant enzymes and decreasing lipid peroxides, nitric oxide, and cytokines levels. Histopathological examination showed a significant decline in ulceration and tissue disruption. CONCLUSION: Hence, the findings confirmed the effectiveness of G. pharnaceoides crude extract in the treatment of ulcerative colitis and might be a promising remedy to manage inflammatory disorders.

Immunomodulatory activity of mefenamic acid in mice models of cell-mediated and humoral immunity.

OBJECTIVES: Previously, different nonsteroidal anti-inflammatory drugs (NSAIDs) have been evaluated for their potential immunomodulatory activities. Mefenamic acid is a well-known NSAID and is used in the treatment of musculoskeletal disorders, inflammation, fever, and pain. To the best of our knowledge, promising data regarding the immunomodulatory activity of mefenamic acid is scarce. Current study investigates the immunomodulatory activity of mefenamic acid in different models of cell-mediated and humoral immunity. MATERIALS AND METHODS: Immunomodulatory effects on cell-mediated immunity were evaluated using dinitrochlorobenzene-induced delayed type hypersensitivity (DTH) and cyclophosphamide-induce myelosuppression assays. While effects on humoral immunity were evaluated using hemagglutination assay and mice lethality test. RESULTS: Hematological analysis showed that mefenamic acid significantly reduced white blood cell count, red blood cell (RBC) count, hemoglobin content, lymphocytes levels, and neutrophils levels in healthy mice as compared with control, suggesting the immunosuppressive activity of mefenamic acid. Treatment with mefenamic acid also significantly reduced all the hematological parameters in cyclophosphamide-induced neutropenic mice, as compared with positive control group. We found that treatment with mefenamic acid significantly suppressed DTH after 24 h, 48 h, and 72 h, as compared with positive control group. Mefenamic acid treated groups showed a significant reduction in antibody titer against sheep RBCs as compared to control group, similar to the effect of cyclophosphamide. We also found increased mice lethality rate in mefenamic acid treated groups, as compared with positive control group. CONCLUSIONS: The results provided basic information of immunosuppression of mefenamic acid on both cell-mediated and humoral immunity.