Metformin: A Small Molecule with Multi-Targets and Diverse Therapeutic Applications

Metformin is one of the most prescribed agents in the treatment of type 2 diabetes. Its history goes back to the use of goat’s rue (Galega officinalis Linn., Fabaceae). G. officinalis is rich in galegine, a guanidine derivative with a blood glucose-lowering effect. Research based on the effects of guanidine rich on this traditional herbal medicine led to the development of metformin. Metformin continues to serve as a multi-target drug. Its benefits for treating/controlling several diseases were thoroughly discovered over time. These include health disorders such as cancers, obesity, periodontitis, cardiovascular, liver, skin, and renal disorders. Moreover, there is evidence to propose that metformin postpones the aging processes as well as modulates the microbiota to promote better health. So far, it is not fully understood, how metformin can accomplish such pleiotropic pharmacological and therapeutic effects. Metformin may decrease malignancy via suppressing the signal of insulin/IGF-1, avoiding the release of cytokines via NF-κB, and increasing the immune reaction to cancer cells. This chapter discusses the history of metformin discovery, chemistry, its role in diabetic patients, and proposed molecular mechanisms to shed more light on the diverse effects and its ability to target multiple signaling pathways

Special Issue—“Natural Products That Might Change Society”

This Special Issue of Molecules gathers eight research papers and two review articles covering the isolation, identification, and biological activity of selected natural products, with the aim of discovering potential candidates that could change society and improve human health [...

Naturally Occurring Chromone Glycosides: Sources, Bioactivities, and Spectroscopic Features

Chromone glycosides comprise an important group of secondary metabolites. They are widely distributed in plants and, to a lesser extent, in fungi and bacteria. Significant biological activities, including antiviral, anti-inflammatory, antitumor, antimicrobial, etc., have been discovered for chromone glycosides, suggesting their potential as drug leads. This review compiles 192 naturally occurring chromone glycosides along with their sources, classification, biological activities, and spectroscopic features. Detailed biosynthetic pathways and chemotaxonomic studies are also described. Extensive spectroscopic features for this class of compounds have been thoroughly discussed, and detailed 13C-NMR data of compounds 1–192, have been added, except for those that have no reported 13C-NMR data

Potential of Hibiscus sabdariffa L. and Hibiscus Acid to Reverse Skin Aging

Hibiscus sabdariffa L. (HS) has a long history of edible and medicinal uses. In this study, the biological activities of the extracts, chromatographic fractions, and hibiscus acid obtained from HS were evaluated for their potential bioactivities. Their ability to promote extracellular matrix synthesis in skin fibroblasts was evaluated by enzyme-linked immunosorbent assays. Their anti-inflammatory activity was evaluated in a nitric oxide (NO)–Griess inflammatory experiment. Furthermore, hibiscus acid was found to have a strong anti-oxidative stress effect through the establishment of an oxidative stress model induced by hydrogen peroxide. Several assays indicated that hibiscus acid treatment can effectively reduce extracellular adenosine triphosphate (ATP) secretion and carbonyl protein production, as well as maintain a high level of reduced/oxidized glutathione (GSH/GSSG) in skin cells, thus providing a possible mechanism by which hibiscus acid can counter antioxidative stress. The present study is the first to explore the reversing skin aging potential and the contributory component of HS

Bioactive compounds from Tipuana tipu growing in Egypt

Abstract: Six compounds were isolated from methanolic extracts of the leaf and the bark of Tipuana tipu growing in Egypt. The isolated compounds were identified as 1-Nonadecanol (1), β-sitosterol (2), Alpinumisoflavone (3), β-sitosterol glucoside (4), Protocatechualdehyde (5) and Protocatechuic acid (6), based on different spectroscopic data (UV, IR, NMR and MS). This is the first report for the isolation of compounds 1 & 3-6 from Tipuana tipu. Compound 1 is isolated for the first time from family Fabaceae. Compounds 2 and 3 showed a promising anticancer activity, while compound 5 displayed a remarkable in vivo anti-inflammatory activity compared to indomethacin. [Amen YM, Marzouk AM, Zaghloul MG, Afifi MS. Bioactive compounds from Tipuana tipu growing in Egypt. J Am Sci 2013;9(10

Anti-Phototoxicity Effect of Phenolic Compounds from Acetone Extract of <i>Entada phaseoloides</i> Leaves via Activation of COX-2 and iNOS in Human Epidermal Keratinocytes

The extract from Entada phaseoloides was employed as active ingredients of natural origin into cosmetic products, while the components analysis was barely reported. Using LC-DAD-MS/qTOF analysis, eleven compounds (1–11) were proposed or identified from acetone extract of E. phaseoloides leaves (AE). Among them, six phenolic compounds, protocatechuic acid (2), 4-hydroxybenzoic acid (3), luteolin-7-O-β-d-glucoside (5), cirsimaritin (6), dihydrokaempferol (9), and apigenin (10), were isolated by various chromatographic techniques. Protocatechuic acid (2), epicatechin (4), and kaempferol (11) at a concentration 100 μM increased the HaCaT cells viability of the UVB-irradiated cell without any cytotoxicity effect and reduced the expression of COX-2 and iNOS inflammation gene. Moreover, compounds 2 and 4 could have potent effects on cell migration during wound closure. These results suggest that compounds 2, 4, and 11 from AE have anti-photoaging properties and could be employed in pharmaceutical and cosmeceutical products

New Butyroside D from Argan Press Cake Possess Anti-Melanogenesis Effect via MITF Downregulation in B16F10 and HEM Cells

Hyperpigmentation is a skin condition where patches of skin become darker in color due to excess melanin production upon UV exposure leading to melasma, which are lentigines or post inflammatory hyperpigmentation that psychologically affecting a great number of people. The present study investigates the anti-melanogenic effect of Butyroside D and the underling mechanism. After the confirmation of the non-cytotoxic effect of Butyroside D on B16F10 cells, we proceeded with analyzing the impact of the treatment at low and high concentration (i.e., 0.2 &mu;M and 2 &mu;M) using gene profiling analysis and examined the differentiation in gene expression. Our results identify cyclic adenosine monophosphate (cAMP), Wnt/&beta;-catenin and Mitogen-Activated Protein Kinase (MAPK) signaling pathways to be downregulated upon treatment with Butyroside D. These pathways were targeted to further validate the effect of Butyroside D on membrane receptors melanocortin 1 receptor (MC1R) and receptor tyrosine kinase (c-Kit), related microphthalmia-associated transcription factor (MITF) and consequently tyrosinase (TYR), and tyrosine-related protein-1 (TYRP-1) that were all shown to be downregulated and, therefore, leading to the repression of melanin biosynthesis. Finally, the anti-melanogenic effect of Butyroside D was confirmed on human epidermal melanocytes (HEM) cells by inhibiting the activation of cAMP pathway generally mediated through &alpha;-melanocyte-stimulating hormone (&alpha;-MSH) and MC1R. Overall, this study suggests the potential applicability of this purified compound for the prevention of hyperpigmentation conditions

Grape-Leaf Extract Attenuates Alcohol-Induced Liver Injury via Interference with NF-κB Signaling Pathway

Grape (Vitis vinifera) leaf extracts (GLEs) are known to be rich in phenolic compounds that exert potent antioxidant effects. Given the vulnerability of the liver to oxidative damage, antioxidants have been proposed as therapeutic agents and coadjuvant drugs to ameliorate liver pathologies. The current study was designed to characterize secondary metabolites and investigate the hepatoprotective effects of GLE and its underlying mechanisms. The secondary metabolites were profiled using HPLC&ndash;PDA&ndash;ESI-MS, and forty-five compounds were tentatively identified. In experimental in vivo design, liver injury was induced by oral administration of high doses of ethanol (EtOH) for 12 days to male Sprague Dawley rats that were split into five different groups. Blood samples and livers were then collected, and used for various biochemical, immunohistochemical, and histopathological analyses. Results showed that GLE-attenuated liver injury and promoted marked hepatic antioxidant effects, in addition to suppressing the increased heat-shock protein-70 expression. Moreover, GLE suppressed EtOH-induced expression of nuclear factor-&kappa;B (NF-&kappa;B) p65 subunit and proinflammatory cytokine tumor necrosis factor-&alpha;. Caspase-3 and survivin were enhanced by EtOH intake and suppressed by GLE intake. Finally, EtOH-induced histopathological changes in liver sections were markedly normalized by GLE. In conclusion, our results suggested that GLE interferes with NF-&kappa;B signaling and induces antioxidant effects, which both play a role in attenuating apoptosis and associated liver injury in a model of EtOH-induced liver damage in rats