Phenolic Compounds from Morus nigra Regulate Viability and Apoptosis of Pancreatic β-Cells Possibly via SERCA Activity.
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ABSTRACT:
SUBMITTER: Heger V
PROVIDER: S-EPMC7236539 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Bioactivity of mulberry has been widely described, but mostly related to its fruits, while studies with leaves are scarce. Herein, in this study leaves of two mulberry species (Morus alba L. and Morus nigra L.) were characterized, compared, and evaluated in terms of their phenolic composition and antioxidant activity. Aiming to valorize mulberry leaves extracts which can be included in modern diet four different extracts (infusions, decoctions, tinctures and hydromethanolic) were examined. The chemical characterization was done by quantifying total phenolics (TPC), flavonoids (TFC) and phenolic acids (TPAC) content, L( +)ascorbic acid (ASA) and individual phenolic compounds in the extracts by HPLC technique. Moreover, DPPH and FRAP assays were used to assess the antioxidant activity of white and black mulberry leaves. Findings of these studies revealed that black mulberry leaves were richer in TFC and TPAC, while white mulberry leaves contained higher levels of individual phenolic compounds in water extracts. Gallic acid was found in the highest concentrations in two mulberry leave extracts. Correlation analysis showed strong relationships between antioxidant activity and TPC and TFC. This fact suggests the crucial role of phenolic compounds as antioxidant agents in white and black mulberry leaves. The results obtained in this study demonstrate that leaves of both white and black mulberry can be used as a valuable source of phenolic compounds with bioactive potential, which can be applied in the food sector, as foods and as promising source of natural ingredients.
| S-EPMC8629867 | biostudies-literature
Project description:PurposeRecent studies suggest that SIRT1-activating compounds (STAC) are a promising class of anticancer drugs, although their mechanism of action remains elusive. The main goal of this study is to determine the role of STACs as a potential therapy for pancreatic cancer. In addition, we also explored the mechanism by which these compounds affect pancreatic cancer.Experimental designUsing in vitro (cell culture experiments) and in vivo (xenograft experiments) approaches, we studied the role of SIRT1 agonists (STAC) in human pancreatic cancer cell viability and growth.ResultsWe show that SIRT1 is highly expressed in pancreatic cancer cells and that the STACs SRT1720, SRT1460, and SRT3025 inhibited cell growth and survival of pancreatic cancer cells. STACs enhanced the sensitivity of pancreatic cells to gemcitabine and paclitaxel, indicating that these drugs could be used in combination with other chemotherapy drugs. We also show that STACs were very effective in inhibiting tumor xenograft growth. In mechanistic studies, we observed that STACs activated a SIRT1 lysosomal-dependent cell death. Furthermore, the effect of STACs on cell viability was also dependent on the expression of the endogenous SIRT1 inhibitor DBC1.ConclusionsTaken together, our results reveal an essential role for SIRT1 and lysosomes in the death pathway regulated by STACs in pancreatic cancer cells. Clin Cancer Res; 22(10); 2496-507. ©2015 AACR.
| S-EPMC4867252 | biostudies-literature
Project description:Our recent studies have demonstrated multiple health-promoting benefits from black walnut kernels. These biological functions of black walnuts are likely associated with their bioactive constituents. Characterization of phenolic compounds found in black walnut could point out underexplored bioactive activities of black walnut extracts and promote the development of novel applications of black walnut and its by-products. In the present study, we assessed bioactivity profiles of phenolic compounds identified in the kernels of black walnuts using a high-throughput screening (HTS) approach. Black walnut phenolic compounds were evaluated in terms of their total antioxidant capacity, antioxidant response element (ARE) induction, and anticancer activities. The anticancer activities were identified by evaluating the effects of the phenolic compounds on the growth of the tumorigenic alveolar epithelial cells (A549) and non-tumorigenic lung fibroblast cells (MRC-5). Out of 16 phenolic compounds tested, several compounds (penta-O-galloyl-?-d-glucose, epicatechin gallate, quercetin, (-)-epicatechin, rutin, quercetin 3-?-d-glucoside, gallic acid, (+)-catechin, ferulic acid, syringic acid) exerted antioxidant activities that were significantly higher compared to Trolox, which was used as a control. Two phenolic compounds, penta-O-galloyl-?-d-glucose and quercetin 3-?-d-glucoside, exhibited antiproliferative activities against both the tumorigenic alveolar epithelial cells (A549) and non-tumorigenic lung fibroblast cells (MRC-5). The antioxidant activity of black walnut is likely driven not only by penta-O-galloyl-?-d-glucose but also by a combination of multiple phenolic compounds. Our findings suggested that black walnut extracts possibly possess anticancer activities and supported that penta-O-galloyl-?-d-glucose could be a potential bioactive agent for the cosmetic and pharmaceutical industries.
| S-EPMC7583942 | biostudies-literature
Project description:Smac mimetic compounds (SMCs) are experimental small molecules that induce tumour necrosis factor alpha (TNF?)-dependent cancer cell death by targeting the inhibitor of apoptosis proteins. However, many cancer cell lines are resistant to SMC-mediated apoptosis despite the presence of TNF?. To add insight into the mechanism of SMC-resistance, we used functional siRNA-based kinomic and focused chemical screens and identified suppressor of morphogenesis in genitalia-1 (SMG1) and NF-?B-inducing kinase (NIK) as novel protective factors. Both SMG1 and NIK prevent SMC-mediated apoptosis likely by maintaining FLICE inhibitory protein (c-FLIP) levels to suppress caspase-8 activation. In SMC-resistant cells, the accumulation of NIK upon SMC treatment enhanced the activity of both the classical and alternative nuclear factor-?B pathways, and increased c-FLIP mRNA levels. In parallel, persistent SMG1 expression in SMC-resistant cells repressed SMC-mediated TNF?-induced JNK activation and c-FLIP levels were sustained. Importantly, SMC-resistance is overcome by depleting NIK and SMG1, which appear to facilitate the downregulation of c-FLIP in response to SMC and TNF? treatment, leading to caspase-8-dependent apoptosis. Collectively, these data show that SMG1 and NIK function as critical repressors of SMC-mediated apoptosis by potentially converging on the regulation of c-FLIP metabolism.
| S-EPMC3122057 | biostudies-literature
Project description:Phenolic compounds of Morus alba leaves are bioactive compounds with beneficial properties for human health. Therefore, in this study, an optimization of ultrasonic assisted extraction by Box-Behnken design was used for the first time to optimize factors such as the percentage of ethanol, ratio solvent/sample (v/w) and extraction time to reach the highest phenolic compound amounts (evaluated by HPLC-MS) while also evaluating in vitro antioxidant activity using DPPH, ABTS and FRAP assays. The optimal extraction conditions were 40% ethanol, 1/400 (w/v) and 35 min. Applying these optimal conditions, which were identified and quantified by HPLC-MS, resulted in the extraction of 21 phenolic compounds. According to these results, the main phenolic compounds in Morus alba leaves are the phenolic glycoside and phenolic acid named protocatechuic acid-glucoside and caffeoylquinic. In addition, Morus alba leaf extract contains flavonols such quercetin-3-O-6-acetylglucoside and rutin, which represent more than 7% of its total phenolic content.
| S-EPMC8834592 | biostudies-literature
Project description:Mulberry leaves are a well-known traditional Chinese medicine herb, and it has been observed since ancient times that leaves collected after frost have superior medicinal properties. Therefore, understanding the changes in critical metabolic components of mulberry leaves, specifically Morus nigra L., is essential. In this study, we conducted widely targeted metabolic profiling analyses on two types of mulberry leaves, including Morus nigra L. and Morus alba L., harvested at different times. In total, we detected over 100 compounds. After frost, 51 and 58 significantly different metabolites were identified in the leaves of Morus nigra L. and Morus alba L., respectively. Further analysis revealed a significant difference in the effect of defrosting on the accumulation of metabolites in the two mulberries. Specifically, in Morus nigra L., the content of 1-deoxynojirimycin (1-DNJ) in leaves decreased after frost, while flavonoids peaked after the second frost. In Morus alba L., the content of DNJ increased after frost, reaching its peak one day after the second frost, whereas flavonoids primarily peaked one week before frost. In addition, an analysis of the influence of picking time on metabolite accumulation in two types of mulberry leaves demonstrated that leaves collected in the morning contained higher levels of DNJ alkaloids and flavonoids. These findings provide scientific guidance for determining the optimal harvesting time for mulberry leaves.
| S-EPMC10305211 | biostudies-literature
Project description:Vitiligo, an acquired disorder characterized by depigmented skin patches, results from loss of epidermal melanocytes. Etiology of vitiligo is not clearly understood but environmental, biochemical, genetic, and immune factors play a role in its pathogenesis. There is evidence that melanocyte death is perpetuated by an autoimmune response that causes lesions to spread. 4-tertiary butyl phenol (4TBP) and monobenzyl ether of hydroquinone (MBEH) are phenolic compounds that are known as environmental causes of vitiligo. We used microarray to detail the global gene expression that occurs following exposure of melanocytes to 4-TBP or MBEH to identified distinct classes of up-regulated genes that may contribute to melanocyte loss in vitiligo. We show that human melanocytes exposed to 4-TBP and MBEH show increased production of some inflammatory cytokines. Interleukin-6 (IL6) and IL8, in particular, are expressed at the periphery of vitiligo lesions and may contribute to recruitment of immune components to the areas, perpetuating melanocyte loss. Cultured human epidermal melanocytes were treated with 4TBP or MBEH for 3, 6, or 24 hours and gene expression were compared with untreated cells.
2012-12-01 | E-GEOD-31641 | biostudies-arrayexpress
Project description:Vitiligo, an acquired disorder characterized by depigmented skin patches, results from loss of epidermal melanocytes. Etiology of vitiligo is not clearly understood but environmental, biochemical, genetic, and immune factors play a role in its pathogenesis. There is evidence that melanocyte death is perpetuated by an autoimmune response that causes lesions to spread. 4-tertiary butyl phenol (4TBP) and monobenzyl ether of hydroquinone (MBEH) are phenolic compounds that are known as environmental causes of vitiligo. We used microarray to detail the global gene expression that occurs following exposure of melanocytes to 4-TBP or MBEH to identified distinct classes of up-regulated genes that may contribute to melanocyte loss in vitiligo. We show that human melanocytes exposed to 4-TBP and MBEH show increased production of some inflammatory cytokines. Interleukin-6 (IL6) and IL8, in particular, are expressed at the periphery of vitiligo lesions and may contribute to recruitment of immune components to the areas, perpetuating melanocyte loss.
2012-12-01 | GSE31641 | GEO
Project description:The aim of this work was to evaluate the antioxidant potential of teas prepared from twenty-four commercially available berries and flowers of Sambucus nigra L. in relation to their phenolic profile, as reflected by the most representative phenolic acids (caffeic, chlorogenic, p-coumaric, ferulic, gallic and syringic acids); flavonols (quercetin, kaempferol, myricetin and rutin); and total phenolic (TPC), phenolic acid (TAC) and flavonoid (TFC) contents. The infusions prepared from elderflowers contained more abundant phenolic compounds than the elderberry infusions. The TPC of these infusions ranged from 19.81 to 23.90 mg of gallic acid equivalents/g dry weight of sample (GAE/g DW) for elderberries and from 15.23 to 35.57 mg GAE/g DW for elderflowers, whereas the TFC ranged from 2.60 to 4.49 mg of rutin equivalents/g dry weight of sample (RUTE/g DW) in elderberry infusions and from 5.27 to 13.19 mg RUTE/g DW in elderflower infusions. Among the phenolic compounds quantified in this study, quercetin (2.07-9.48 mg/g DW) and myricetin (1.17-9.62 mg/g DW) had the highest concentrations in the teas prepared from berries and flowers, respectively. Moreover, the antioxidant potential of elder infusions assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and ferric reducing antioxidant power (FRAP) assays revealed that the teas prepared from flowers had higher mean DPPH and FRAP activities than the teas prepared from berries. Therefore, elder beverages could be important dietary sources of natural antioxidants that contribute to the prevention of diseases caused by oxidative stress.
| S-EPMC5325840 | biostudies-literature
Project description:Black mulberry (Morus nigra L.) fruits are known due to their delicious, sweet and slightly acid flavor and high anthocyanin content. In the present study, the diversity of phytochemical, sensory, and antioxidant characteristics of the fruits of 20 black mulberry genotypes, from the Artvin region of Turkey, were evaluated. As important phytochemical assessments in fruits, we chromatographically (HPLC/DAD) determined glucose (7.22 to 11.10 g/100 g fresh weight (fw)) and fructose content (6.32 and 9.94 g/100 g fw), as well as predominant organic acid in black mulberry genotypes fruits-malic acid (6.02-11.44 g/100 g fw), followed by citric acid. Titrative determination was used for ascorbic acid, finding contents of 17.41-28.33 mg/100 g fw. There was found a great diversity of sensory (taste, juiciness, and aroma) characteristics, indicating a richness of the fruit germplasm. Antioxidant parameters, such as total phenolic (TP) and anthocyanin (TA) content, were assessed spectrometrically; antioxidant activity (AA) was assessed by DPPH and FRAP assays; individual flavonoids and phenolic acids were determined chromatographically (HPLC/DAD). Antioxidant characteristics of the fruits, defined by TP and TA content, ranged from 1951 to 2733 μg GAE/g fw and 508-712 μg C3GE/g fw, respectively. The most abundant compounds of flavonoids and phenolic acids groups were determined to be rutin (47.10-97.20 mg/100 g fw) and chlorogenic acid (51.3-90.8 mg/100 g fw). AA results, measured by the DPPH method as EC50 value, ranged between 16.10 and 25.45 μg/mL; a FRAP assay revealed values of AA between 9.80 and 13.22 μmol TE/g fw. Significant differences in phytochemical and antioxidant qualities were observed among the analyzed M. nigra genotypes. Regarding the best values of phytochemical and antioxidant characteristics, three genotypes of M. nigra were selected to be recommended for fruit production. The results thus highlight the potential for the exploitation of local black mulberry genotypes through crop selection and breeding program.
| S-EPMC9311561 | biostudies-literature