Sakuranetin ameliorates streptozotocin-induced diabetes in rodents by inhibiting caspase-3 activity, modulating hematological parameters, and suppressing inflammatory cytokines: a molecular docking and dynamics study.

Diabetes affects people of all ages, regardless of gender and background. To date, there is no evidence for the effect of sakuranetin against the streptozotocin (STZ)-induced diabetes paradigm. The research was directed to evaluate the antidiabetic activity of sakuranetin in the STZ model invoking the diabetes-induced disease paradigm. STZ (I.P. 60 mg/kg) is directed to induce type 2 diabetes in experimental rats. Recent research pursued to regulate the anti-diabetic ability of sakuranetin at both 10 and 20 mg/kg in STZ-induced rats. Furthermore, molecular docking research was implemented to evaluate sakuranetin requisite attraction to inflammatory indicators. Various anti-diabetic [(glucose, hemoglobin A1c (HbA1c), and insulin)], lipid profile [triglycerides (TG), total cholesterol (TC), and high-density lipoproteins (HDL)], hematological parameters [Hemoglobin (HGB), packed cell volume (PCV), red blood cells (RBC), mean corpuscular volume (MCV), platelet (PLT), and white blood cells (WBC), pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)], antioxidant level [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH)], lipid oxidation, and caspase-3 were evaluated. Furthermore, molecular docking and dynamics were performed for TNF-α (2AZ5), IL-6 (1ALU), IL-1ß (6Y8M), Caspase-3 (1NME) and serum insulin (4IBM) target ligands. Sakuranetin treatment at both doses restored the biochemical parameters i.e. blood glucose, insulin, HbA1c, lipid profile, hematological parameters, pro-inflammatory markers, antioxidant levels, lipid oxidation, and caspase-3 in the context of diabetic rats. It also showed favorable binding affinity on inflammatory markers. Sakuranetin binds to proteins 2AZ5, 1ALU, 6Y8M, 1NME, and 4IBM at -7.489, -6.381, -6.742, -7.202, and -8.166 Kcal/mol, respectively. All of the findings from the molecular dynamics simulations points toward a considerable change in the conformational dynamics of protein upon binding with sakuranetin. The potential use of sakuranetin as an alternative diabetes medication will aid future research as a potent anti-diabetic agent.Communicated by Ramaswamy H. Sarma.

Experimental evidence of the neurotoxic effect of monosodium glutamate in adult female Sprague Dawley rats: The potential protective role of Zingiber officinale Rosc. rhizomes.

Strategies to prevent the health abnormalities associated with the extensive use of MSG (monosodium glutamate) as a flavoring booster are badly needed. The current study was conducted to investigate oxidative stress, inflammation, and abnormal lipid profile as the main risk factors of neurotoxicity in MSG-exposed female albino rats. Besides, the effect of concurrent consumption of Zingiber officinale rhizomes powder was studied at low doses. Twenty rats (total) were split into 4 separate groups. The 1st group was a negative control group (without any treatment), while the others received 6 mg MSG/kg. The 2nd group was left untreated, whereas the 3rd and 4th groups were given a regular laboratory diet that included ginger rhizome powder supplements (GRP, 0.5 & 1%, respectively) for six weeks. In brain tissue homogenates, exposure to MSG caused a significant depletion of gamma-aminobutyric acid (GABA) and total protein levels, while triglycerides and cholesterol contents were significantly elevated. Moreover, a noteworthy upsurge in oxidative load and inflammation markers was also noticed associated with a marked reduction of antioxidant levels, which histopathological staining verified further. The rat diet formulated with GRP, with a dose-dependent effect, resulted in increased GABA and total protein contents and attenuated inflammation, oxidative stress, abnormal lipid profile, and marked histological changes in cerebral cortical neurons of MSG-administered animals. Therefore, this study reveals that GRP shields rats against the neurotoxicity that MSG causes. The anti-inflammatory as well as antioxidant, and lipid-normalizing properties of rhizomes of ginger may be accountable for their observed neuroprotective action.

CDC2-like (CLK) protein kinase inhibition as a novel targeted therapeutic strategy in prostate cancer.

Dysregulation of alternative splicing is a feature of cancer, both in aetiology and progression. It occurs because of mutations in splice sites or sites that regulate splicing, or because of the altered expression and activity of splice factors and of splice factor kinases that regulate splice factor activity. Recently the CDC2-like kinases (CLKs) have attracted attention due to their increasing involvement in cancer. We measured the effect of the CLK inhibitor, the benzothiazole TG003, on two prostate cancer cell lines. TG003 reduced cell proliferation and increased apoptosis in PC3 and DU145 cells. Conversely, the overexpression of CLK1 in PC3 cells prevented TG003 from reducing cell proliferation. TG003 slowed scratch closure and reduced cell migration and invasion in a transwell assay. TG003 decisively inhibited the growth of a PC3 cell line xenograft in nude mice. We performed a transcriptomic analysis of cells treated with TG003. We report widespread and consistent changes in alternative splicing of cancer-associated genes including CENPE, ESCO2, CKAP2, MELK, ASPH and CD164 in both HeLa and PC3 cells. Together these findings suggest that targeting CLKs will provide novel therapeutic opportunities in prostate cancer.