Antidiabetic Activity and In Silico Molecular Docking of Polyphenols from Ammannia baccifera L. subsp. Aegyptiaca (Willd.) Koehne Waste: Structure Elucidation of Undescribed Acylated Flavonol Diglucoside.

Chemical investigation of the aerial parts of Ammania aegyptiaca ethanol extract (AEEE) showed high concentrations of polyphenol and flavonoid content, with notable antioxidant activity. Undescribed acylated diglucoside flavonol myricetin 3-O-ß-4C1-(6″-O-galloyl glucopyranoside) 7-O-ß-4C1-glucopyranoside (MGGG) was isolated from the aerial parts of AEEE, along with four known polyphenols that had not been characterized previously from AEEE. The inhibitory effects of MGGG, AEEE, and all compounds against α-amylase, pancreatic lipase and ß-glucosidase were assessed. In addition, molecular docking was used to determine the inhibition of digestive enzymes, and this confirmed that the MGGG interacted strongly with the active site residues of these enzymes, with the highest binding free energy against α-amylase (-8.99 kcal/mol), as compared to the commercial drug acarbose (-5.04 kcal/mol), thus justifying its use in the potential management of diabetes. In streptozotocin (STZ)-induced diabetic rats, AEEE significantly decreased high serum glucose, α-amylase activity and serum liver and kidney function markers, as well as increasing insulin blood level. Moreover, AEEE improved the lipid profile of diabetic animals, increased superoxide dismutase (SOD) activity, and inhibited lipid peroxidation. Histopathological studies proved the decrease in pancreas damage and supported the biochemical findings. These results provide evidence that AEEE and MGGG possess potent antidiabetic activity, which warrants additional investigation.

Phenolics from Physalis peruviana fruits ameliorate streptozotocin-induced diabetes and diabetic nephropathy in rats via induction of autophagy and apoptosis regression.

The objective of our study was to evaluate the effect of Physalis peruviana L. fruits in the management of diabetes and diabetic nephropathy in relation to its metabolic profile. In-vitro α-amylase, ß-glucosidase, and lipase inhibition activities were assessed for the ethanolic extract (EtOH) and its subfractions. Ethyl acetate (EtOAc) fraction showed the highest α-amylase, ß-glucosidase, and lipase inhibition effect. In vivo antihyperglycemic testing of EtOAc in streptozotocin (STZ)-induced diabetic rats showed that it decreased the blood glucose level, prevented the reduction in body weight, improved serum indicators of kidney injury (urea, uric acid, creatinine), and function (albumin and total protein). EtOAc increased autophagic parameters (LC3B, AMPK) and depressed mTOR contents. Histopathology revealed that EtOAc ameliorated the pathological features and decreased the glycogen content induced by STZ. The immunohistochemical analysis showed that EtOAc reduced P53 expression as compared to the STZ-diabetic group. UPLC-ESI-MS/MS metabolite profiling of EtOAc allowed the identification of several phenolic compounds. Among the isolated compounds, gallic acid, its methylated dimer and the glycosides of quercetin had promising α-amylase and ß-glucosidase inhibition activity. The results suggest that the phenolic-rich fraction has a protective effects against diabetic nephropathy presumably via enhancing autophagy (AMPK/mTOR pathway) and prevention of apoptosis (P53 suppression).

Novel antiproliferative agents bearing morpholinopyrimidine scaffold as PI3K inhibitors and apoptosis inducers; design, synthesis and molecular docking.

Two series of novel morpholinopyrimidine derivatives were synthesized and screened for their in-vitro cytotoxic activity against 60 tumor cell line by the National Cancer Institute, USA. The in-vitro cytotoxic IC50 values for the most active compounds 6e, 6g, and 6l against the most sensitive cell line leukemia SR were estimated (IC50 = 0.76, 13.59, and 4.37 uM, respectively). To investigate their PI3K enzyme inhibition activity, the assay was done on Class IA (α, ß, & δ) isoforms. The IC50 values were very promising: compound [6e = 11.73 (α), 6.09 (ß), 11.18 (δ)], compound [6g = 8.43 (α), 15.84 (ß), 30.62 (δ)], and compound [6l = 13.98 (α), 7.22 (ß), 10.94 (δ)], compared to the reference compound LY294002 = 6.28 (α), 4.51 (ß), 4.60 (δ) uM, respectively. Moreover, cell cycle analysis and annexin V-FITC staining were done on Leukemia SR, there was arrest at G2/M phase and apoptosis was induced. Finally, docking study was performed to analyze the interactive mode of these derivatives in PI3Kα ATP-binding site. These outcomes proved that compounds 6e, 6g, and 6l are potential leads for further optimization as antileukemic agents.

Molecular networking aided metabolomic profiling of beet leaves using three extraction solvents and in relation to its anti-obesity effects.

In the present study, the efficiency of three different solvents (H2O, acidified H2O, and 70% Methanol) for metabolites extraction from the leaves of sugar beet (Beta vulgaris subsp. vulgaris var. rubra) was investigated along with their inhibitory activity on pancreatic α-amylase and lipase for obesity management. The metabolic profile of the three extracts was analyzed by ultra-performance liquid chromatography (UPLC) coupled with electrospray ionization high-resolution mass spectrometric (ESI-HRMS-MS). Mass spectrometry-based molecular networking was employed to aid in metabolites annotation and for the visual investigation of the known metabolites and their analogues. The study led to the tentative identification of 45 metabolites including amino acids, purine derivatives, phenolic acids, flavonoids, fatty acids, and an alkaloid, articulating 24 compounds as a first time report from beet leaves along with 2 new putatively identified compounds: a flavone feruloyl conjugate (39) and a malonylated acacetin diglycoside (40). The three extracting systems exhibited comparable efficiency for pulling out the secondary metabolites from the beet leaves. The in vitro study supported this finding and demonstrated that the three extracts inhibited the activity of both pancreatic α-amylase and lipase enzymes with no significant difference observed regarding the percentage of the inhibition of the enzymes. Conclusively, the extraction protocol has a minimal effect on the anti-obesity properties of beet leaves.

A Novel Biochemical Study of Anti-Ageing Potential of Eucalyptus Camaldulensis Bark Waste Standardized Extract and Silver Nanoparticles.

Eucalyptus camaldulensis Dehnh belongs to family Myrtaceae. They are massive in Egypt. Although reputed for high phenolic content, barks are considered waste. Ageing is a natural phenomenon caused by apoptosis and senescence resulting in wrinkles. The phytochemical analysis of the 70% ethanolic Eucalyptus camaldulensis bark extract (EBE) and evaluation of its anti-ageing potential and as silver nanoparticles (AgNPs) were conducted in this study. Ultra performance liquid chromatography / electrospray ionization mass spectrometry of EBE fingerprint revealed twenty compounds, where Rutin was major. EBE was standardized to contain 1.26 % Rutin. AgNPs synthesized by green synthesis, were characterized by transmission electron microscope and zeta potential measurement. Both EBE and AgNPs were subjected to MTT assay in HFB4 cells and cell cycle arrest. Flow cytometry was used to assess apoptosis and p16 INK4a. Genetic expression of p53 and p21 and telomerase level were determined. Anti-wrinkle enzyme assays were done. AgNps were spherical, 468.7 nm in size and with Poly dispersity index of 0.817 ± 0.129. EBE and AgNPs with IC50 0.156 mg/mL ± 0.05 and 2.315 ± 0.07 µg/mL expressed significant difference in % of cells (DNA content) at G2/M, apoptotic cells numbers, p53 and p21expression and p16INK4a vs aged cells (P < 0.0001). Both expressed significant increase in telomerase (P < 0.0001). They exhibited elastase, collagenase and tyrosinase inhibition (75 ± 4.3 and 75.9 ± 6.8 % at 300 µg/mL, 58 ± 4.8 and 63 ± 2.3, at 500 µg/mL, 51 ± 4.8 and 65 ± 5.87, at 500 µg/mL, respectively. Although it is considered waste, EBE and Ag NPs are anti-ageing candidates as they inhibit apoptosis, senescence and prevent wrinkles formation.

Decreased Serum Level of Gamma-amino Butyric Acid in Egyptian Infertile Females with Polycystic Ovary Syndrome is Correlated with Dyslipidemia, Total Testosterone and 25(OH) Vitamin D Levels.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders around the world. Increasing evidence suggests that neurotransmitter Gamma-aminobutyric acid (GABA) is involved in the pathogenesis of PCOS through its central role in the hypothalamus. However, the peripheral role of GABA in PCOS has not been sufficiently investigated in spite of its existence in peripheral organs. First, the aim of this study is to, investigate serum GABA level in Egyptian PCOS patients. Second, to explore the correlation between serum GABA level with Body Mass Index (BMI), dyslipidemia, totaltestosterone and 25 (OH) vitamin D. METHODS: Eighty PCOS patients and eighty age-matched healthy females were included in this study. All parameters were assessed colourimetrically or with ELISA. RESULTS: PCOS patients exhibited significantly decreased serum GABA level compared to controls (p < 0.001). There was a significant positive correlation between serum GABA and 25(OH) vitamin D levels (r = 0.26, p = 0.018), and a significant negative correlation with total testosterone (r = - 0.3, p = 0.02), total cholesterol (TC) (r = - 0.31, p = 0.01) and LDL-Cholesterol (LDL-C) (r = - 0.23, p = 0.045), respectively. CONCLUSIONS: The findings of this study suggest that disrupted GABA level in the peripheral circulation is an additional contributing factor to PCOS manifestations. GABA deficiency was correlated with 25 (OH) vitamin D deficiency, dyslipidemia, and total testosterone. Further investigations for GABA adjustment might provide a promising means for better management of PCOS symptoms.

Centaurea pumilio L. extract and nanoparticles: A candidate for healthy skin.

Centaurea pumilio was the subject of phytochemical and biological studies, and its extract was used in the green synthesis of silver nanoparticles (AgNPs). Liquid chromatography/electrospray ionization mass spectrometry allowed the tentative identification of twenty-nine phytoconstituents of C. pumilio methanolic extract (CME), while column chromatography led to the identification of eight phenolic compounds. The neutral red uptake method showed the safety of CME and AgNPs on skin cells (HaCaT cell lines), while their high antioxidant potentials were demonstrated based on their oxygen radical absorbance capacity, and these results were confirmed in vivo. Additionally, CME and AgNPs had promising abilities to retard the ageing process and combat dark spots by potently inhibiting collagenase, elastase and tyrosinase, in addition to antimicrobial activity against skin infection-causing strains, especially Staphylococcus aureus, which was further confirmed by the significant phagocytic activity of neutrophils via engulfment. This study presents C. pumilio as a candidate for healthy skin.