Unveiling the Cardioprotective Power: Liquid Chromatography-Mass Spectrometry (LC-MS)-Analyzed Neolamarckia cadamba (Roxb.) Bosser Leaf Ethanolic Extract against Myocardial Infarction in Rats and In Silico Support Analysis.

Neolamarckia cadamba (Roxb.) Bosser, a member of the Rubiaceae family, is a botanical species with recognized therapeutic properties. It is commonly used in traditional medicine to treat cardiac ailments and other disorders. However, the precise active constituents and the potential mechanisms by which they manage cardiovascular disorders remain unclear. Therefore, this study aimed to ascertain the bioactive components and investigate their underlying mechanisms of action. N. cadamba is used to treat cardiovascular disorders using the integrated metabolomic methodology. An HPLC-QTOF-MS/MS analysis determined the potential chemicals in the N. cadamba leaf ethanol extract (NCEE). A thorough investigation of the NCEE samples used in this study led to the identification of 32 phytoconstituents. Of the 32 compounds, 19 obeyed Lipinski's rule of five (RO5). A molecular docking study directed towards HMG-CoA reductase used 19 molecules. The reference drug atorvastatin indicated a binding energy of -3.9 kcal/mol, while the other substances, Cinchonain Ib and Dukunolide B, revealed binding energies of -5.7 and -5.3 kcal/mol, respectively. Both phytocompounds showed no toxicity and exhibited favorable pharmacokinetic properties. In vivo study results concluded that treatment with NCEE significantly reduced the cardiac myocardial infarction (MI) marker CK-MB and atherogenic risk indices, such as the atherogenic index plasma (AIP), cardiac risk ratio (CRR), and atherogenic coefficient (AC) in isoproterenol-induced MI rats. In MI rats, NCEE therapy significantly improved the antioxidant system of the heart tissue, as evidenced by the increased levels of GSH and SOD, lower levels of the oxidative stress marker MDA, and significantly decreased HMG-CoA activity. Additionally, electrocardiogram (ECG) signals from rats treated with NCEE resembled those treated with traditional atorvastatin to treat myocardial infarction. This study used H&E staining to show that administering NCEE before treatment reduced cardiac myocyte degeneration in rats with myocardial infarction, increased the presence of intact nuclei, and increased myocardial fiber strength. The potential cardioprotective effect observed in myocardial infarction (MI) rats treated with NCEE can be extrapolated from computational data to be caused by Cinchonain Ib.

Agaricus Subrufescens ameliorates ovarian dysfunction and regulates altered biochemical parameters in rats with Letrozole induced polycystic ovarian syndrome.

OBJECTIVE: The objective of this study is to investigate the effects of an ethanolic extract derived from Agaricus subrufescens on rat models exhibiting Polycystic Ovarian Syndrome (PCOS) induced by Letrozole. METHODS: A total of thirty female Wistar rats were divided into five groups, each consisting of six rats. The negative control group was administered a volume of 1 mL of a 0.5% solution of carboxy methylcellulose (CMC). Letrozole (1 mg/kg) was administered to additional groups for a duration of 21 days in order to induce polycystic ovary syndrome (PCOS). Animals designated as positive controls were euthanized on the 22nd day. Both the test group and the standard group were subjected to treatment from the 22nd day to the 36th day. The experimental group was administered ethanolic extract of Agaricus subrufescens at doses of 200 mg/kg and 400 mg/kg p.o, while the control group received clomiphene citrate at a dose of 1 mg/kg. The study observed various physiological markers in individuals with polycystic ovarian disease, including estimated blood glucose levels, total cholesterol levels, triglyceride levels, and hormonal fluctuations such as increased testosterone and estrogen levels, as well as decreased progesterone levels. The presence of menstrual irregularities was confirmed through the examination of vaginal smears and histopathological changes in the ovaries. RESULTS: The consumption of Agaricus subrufescens was found to have a significant impact on various physiological parameters, including blood glucose levels, testosterone levels, anovulation, and menstrual irregularity. All therapeutic interventions significantly normalized the levels of serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT). The rats with polycystic ovary syndrome (PCOS) that were induced by Letrozole exhibited increased levels of urea and creatinine. The findings of this study indicate that the administration of Agaricus subrufescens therapy has a protective effect on renal function, as evidenced by a reduction in serum levels of urea and creatinine. In rats with polycystic ovary syndrome (PCOS) induced by Letrozole, the inhibition of hepatic synthesis, promotion of ovarian follicle immaturity, and elevation of androgen secretions result in an increase in the weight of the liver and ovaries. The weight of endocrine organs exhibited a decrease across all treatment groups. The histopathological examination of PCOS specimens revealed an increased presence of cysts and theca lutein cells. The group of rats with polycystic ovary syndrome (PCOS) that did not receive treatment exhibited a higher number of cysts compared to the groups that received treatment. CONCLUSION: This study demonstrated that the administration of Letrozole orally resulted in the development of polycystic ovarian disease. The results indicated heightened levels of blood glucose, total cholesterol, and triglycerides, as well as alterations in hormone levels such as increased testosterone and estrogen, and decreased progesterone. These hormonal changes were accompanied by menstrual irregularities, which were confirmed through the examination of vaginal smears and histopathological analysis of the ovaries in the control group with polycystic ovarian disease. The treatment groups that received Agaricus subrufescens exhibited a decrease in blood glucose, total cholesterol, and testosterone levels.

Synthesis and Hypoglycemic and Anti-inflammatory Activity Screening of Novel Substituted 5-[Morpholino(Phenyl)Methyl]-Thiazolidine-2,4-Diones and Their Molecular Docking Studies.

OBJECTIVES: The aim was the synthesis of novel substituted 5-[morpholino(phenyl)methyl]-thiazolidine-2,4-diones and screening for their in vivo hypoglycemic activity and in vitro anti-inflammatory activity, as well as molecular docking studies to find out active potential lead molecules. MATERIALS AND METHODS: Substituted aromatic aldehydes, thiazolidine-2,4-dione, and morpholine on Mannich reaction gave the title compounds. They were characterized by physical and spectral methods. In vivo hypoglycemic activity was examined in alloxan induced Wistar albino rats by tail tipping method. In vitro anti-inflammatory activity was tested by human red blood cell (HRBC) membrane stabilization and protein denaturation. Using AutoDock, molecular docking studies were carried out to find out the best fit ligands. RESULTS: Series of substituted 5-[morpholino(phenyl)methyl]-thiazolidine-2,4-diones were synthesized and chemically they were confirmed by spectral techniques. Acute toxic studies of in vivo hypoglycemic activity results revealed that compounds 4c, 4h, and 4n exhibited good activity at 35 mg/kg body weight. Chronic toxic study results indicated that compounds 4h and 4n exhibited good activity at 70 mg/kg body weight. Anti-inflammatory activity results indicated the highest inhibition was shown by compounds 4k and 4f at 500 µg/mL in HRBC membrane stabilization. In protein denaturation, the highest inhibition was shown by compound 4k at 500 µg/mL. In molecular docking studies, compounds 4h and 4n exhibited higher binding affinity at PPARγ receptor protein and compound 4k exhibited higher binding affinity at COX-1 and COX-2 actives sites. CONCLUSION: Microwave irradiation produced high yield in short reaction times. The presence of electron releasing groups at the para position of the phenyl ring may give the ability to produce hypoglycemic activity and the presence of electron withdrawing groups at the para position of the phenyl ring causes anti-inflammatory activity. The results showed that some compounds exhibited good hypoglycemic and anti-inflammatory activities. Compounds 4h and 4n exhibited higher binding affinity at PPARγ receptor protein and compound 4k exhibited higher binding affinity at COX isoenzymes' active sites in molecular docking studies.