Flavonoids comprise an exclusive class of biomolecules with extensive therapeutic features. Rutin is one of the flavonoids that has antioxidant, anticancer

Purpose Gliflozins (SGLT2 inhibitors) and statins are key treatments commonly used in patients with ischemic heart failure. Although both are well known for diminishing cardiovascular risk and heart failure–related mortality, the possible synergistic benefits of using them together have not been thoroughly investigated. This study aimed to correlate serum levels of Statins and SGLT2i in addition to estimate the ejection fraction and selected laboratory parameters to indicate the synergistic effect of their combination in ischemic heart disease patients. Methods In this prospective, randomized, controlled trial, 81participating patients with ischemic heart disease at department of cardiology, Fayoum University, were randomly enrolled into three groups: SGLT2i group (GPI) (n = 26) who took Dapagliflozin (10 mg) daily, Statin group (GPII) (n = 34) who administrated Atorvastatin (40 mg) or Rosuvastatin (40 mg) daily and Combination group (GPIII) (n = 21) who took both Statin and Dapagliflozin. They had been on treatment for three months before blood sampling. The trough plasma concentrations of the included patients were assessed by ultra-performance liquid chromatography (UPLC). Ejection fraction was assessed by echocardiography, laboratory tests were performed, and data were analyzed with SPSS v22 (p < 0.05). Results Group: III showed no adverse effects, maintained stable drug levels as the mean was 7.3 ng/ml and SD was 4.4 ng/ml (p-value 0.66), demonstrated improved ejection fraction, lipid profiles and additional metabolic benefits from SGLT2i. Conclusion Dapagliflozin–statin combination therapy appears potentially beneficial for heart disease patients without affecting drug levels, though larger studies are needed to confirm.

Background: Postmenopausal women are at high risk of Alzheimer’s disease (AD) incidence and progression. Irisin, an exercise-induced myokine, has neuroprotective and antiaging effects against AD, especially in menopausal women suffering from insulin resistance (IR). For the first time, the novel role of irisin induced by melatonin (MTN) or/and physical exercise (PHE) was investigated in the current ovariectomized (OVX)/AD rat model by modulating brain neuroinflammation and IR-related markers. Methods: Fifty female Wistar rats were divided into five groups, with one representing a sham group. AD was induced in the other four bilateral OVX rat groups by daily intraperitoneal injection of D-galactose/AlCl₃ (60 and 10 mg/kg, respectively) for 42 days. Group III–V: Animals were exposed to MTN (10 mg/kg/day; i.p.), PHE, and a combination of these, respectively, in the final 14 days of the experiment. Results: The OVX/AD rats showed significant deterioration in learning, memory, neurochemical, and histopathological examinations, while the MTN or/and PHE treatments significantly increased serum and brain irisin, improving memory in a Y-maze assessment. Thus, hippocampal histopathological alterations and IR-related markers decreased. In addition, suppressed hippocampal amyloid-beta protein expression and neuroinflammatory content of tumor necrosis factor-alpha (TNF-α), p38 mitogen-activated protein kinase (p38 MAPK), and NOD-like receptor protein-3 (NLRP3) were associated with an increase in peroxisome proliferator-activated receptor-gamma (PPAR-γ) protein expression and insulin-like growth factor-1 content in hippocampal tissues, collectively suppressing glial fibrillary acidic protein (GFAP) content, leading to an increase in brain-derived neurotrophic factor expression. Conclusions: Irisin induction may serve as a novel avenue in AD/menopause treatment and prevention via modulating the TNF-α/p38 MAPK/PPAR-γ/NLRP3/GFAP pathway.