Dataset Information

Cucurbitacin B Exerts Antiaging Effects in Yeast by Regulating Autophagy and Oxidative Stress.

ABSTRACT: The budding yeast Saccharomyces cerevisiae has been used as a model organism for the basic mechanism of aging, which provides useful assay systems for measuring both replicative and chronological lifespans. In the course of our screening program for substances that extend replicative lifespan, cucurbitacin B (CuB) was found as a hit compound from a compound library, which contains cerebrosides, phenols, sesquiterpenoid, triterpenoids, and sterols isolated from natural products by our research group. Importantly, it prolonged not only the replicative lifespan but also the chronological lifespan in yeast. CuB increased ATG32 gene expression, suggesting that CuB induces autophagy. Indeed, the GFP signal generated from the cleavage of GFP-Atg8, which is a signature of autophagy, was increased upon CuB treatment. On the other hand, CuB failed to increase the chronological lifespans when either ATG2 or ATG32, essential autophagy genes, was deleted, indicating that the lifespan extension by CuB depends on autophagy induction. Furthermore, CuB significantly increased superoxide dismutase (Sod) activity and the survival rate of yeast under oxidative stress, while it decreased the amount of reactive oxygen species (ROS) and malondialdehyde (MDA) production, indicating that CuB has activity to antagonize oxidative stress. Additionally, CuB did not affect replicative lifespans of sod1, sod2, uth1, and skn7 mutants with the K6001 background, indicating that aging-related genes including SOD1, SOD2, UTH1, and SKN7 participate in the antiaging effect of CuB. These results suggest that CuB exerts antiaging activity by regulating autophagy, ROS, antioxidative ability, and aging-related genes. Finally, we discuss the possible intracellular targets of CuB based on the phenotypic comparison between the CuB and global gene deletion databases.

SUBMITTER: Lin Y

PROVIDER: S-EPMC6589324 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cucurbitacin B Exerts Antiaging Effects in Yeast by Regulating Autophagy and Oxidative Stress.

Lin Yanfei Y Kotakeyama Yuki Y Li Jing J Pan Yanjun Y Matsuura Akira A Ohya Yoshikazu Y Yoshida Minoru M Xiang Lan L Qi Jianhua J

Oxidative medicine and cellular longevity 20190602

The budding yeast <i>Saccharomyces cerevisiae</i> has been used as a model organism for the basic mechanism of aging, which provides useful assay systems for measuring both replicative and chronological lifespans. In the course of our screening program for substances that extend replicative lifespan, cucurbitacin B (CuB) was found as a hit compound from a compound library, which contains cerebrosides, phenols, sesquiterpenoid, triterpenoids, and sterols isolated from natural products by our rese ...[more]

PMID: 31281576

Similar Datasets

Project description:Background: Anoectochilus roxburghii (Orchidaceae) is a traditional Chinese medicinal herb with anti-inflammatory, antilipemic, liver protective, immunomodulatory, and other pharmacological activities. Kinsenoside (KD), which shows protective effects against a variety types of liver damage, is an active ingredient extracted from A. roxburghii. However, the liver protective effects and potential mechanisms of KD in alcoholic liver disease (ALD) remain unclear. This study aimed to investigate the liver protective activity and potential mechanisms of KD in ALD. Methods: AML12 normal mouse hepatocyte cells were used to detect the protective effect of KD against ethanol-induced cell damage. An alcoholic liver injury model was induced by feeding male C57BL/6J mice with an ethanol-containing liquid diet, in combination with intraperitoneal administration of 5% carbon tetrachloride (CCl4) in olive oil. Mice were divided into control, model, silymarin (positive control), and two KD groups, treated with different doses. After treatment, hematoxylin-eosin and Masson's trichrome staining of liver tissues was performed, and serum alanine aminotransferase (ALT) and aspartate transaminase (AST) levels were determined to assess the protective effect of KD against alcoholic liver injury. Moreover, proteomics techniques were used to explore the potential mechanism of KD action, and ELISA assay, immunohistochemistry, TUNEL assay, and western blotting were used to verify the mechanism. Results: The results showed that KD concentration-dependently reduced ethanol-induced lipid accumulation in AML12 cells. In ALD mice model, the histological examination of liver tissues, combined with the determination of ALT and AST serum levels, demonstrated a protective effect of KD in the alcoholic liver injury mice. In addition, KD treatment markedly enhanced the antioxidant capacity and reduced the endoplasmic reticulum (ER) stress, inflammation, and apoptosis compared with those in the model group. Furthermore, KD increased the phosphorylation level of AMP-activated protein kinase (AMPK), inhibited the mechanistic target of rapamycin, promoted the phosphorylation of ULK1 (Ser555), increased the level of the autophagy marker LC3A/B, and restored ethanol-suppressed autophagic flux, thus activating AMPK-dependent autophagy. Conclusion: This study indicates that KD alleviates alcoholic liver injury by reducing oxidative stress and ER stress, while activating AMPK-dependent autophagy. All results suggested that KD may be a potential therapeutic agent for ALD.

Project description:BackgroundA disintegrin and metalloproteinase 17 (ADAM17) is a transmembrane protein that is widely expressed in various tissues; it mediates the shedding of many membrane-bound molecules, involving cell-cell and cell-matrix interactions. We investigated the role of ADAM17 within mouse cardiac fibroblasts (mCFs) in heart fibrosis.MethodsmCFs were isolated from the hearts of neonatal mice. Effects of ADAM17 on the differentiation of mCFs towards myofibroblasts and their fibrotic behaviors following induction with TGF-β1 were examined. The expression levels of fibrotic proteins, such as collagen I and α-SMA, were assessed by qRT-PCR analysis and western blotting. Cell proliferation and migration were measured using the CCK-8 and wound healing assay. To identify the target gene for ADAM17, the protein levels of the components of endoplasmic reticulum (ER) stress and the PINK1/Parkin pathway were assessed following ADAM17 silencing. The effects of ADAM17 silencing or treatment with thapsigargin, a key stimulator of acute ER stress, on mCFs proliferation, migration, and collagen secretion were also examined. In vivo, we used a mouse model of cardiac fibrosis established by left anterior descending artery ligation; the mice were administered oral gavage with a selective ADAM17 inhibitor (TMI-005) for 4 weeks after the operation.ResultsWe found that the ADAM17 expression levels were higher in fibrosis heart tissues and TGF-β1-treated mCFs. The ADAM17-specific siRNAs decreased TGF-β1-induced increase in the collagen secretion, proliferation, and migration of mCFs. Knockdown of ADAM17 reduces the activation of mCFs by inhibiting the ATF6 branch of ER stress and further activating mitophagy. Moreover, decreased ADAM17 expression also ameliorated cardiac fibrosis and improved heart function.ConclusionsThis study highlights that mCF ADAM17 expression plays a key role in cardiac fibrosis by regulating ER stress and mitophagy, thereby limiting fibrosis and improving heart function. Therefore, ADAM17 downregulation, within the physiological range, could exert protective effects against cardiac fibrosis.

Project description:Phenolic compounds present in common beans (Phaseolus vulgaris L.) have been reported to possess antimicrobial, anti-inflammatory and ultraviolet radiation (UVR) protective properties. UVR from sunlight, which consists of UV-B and UV-A radiations, induces reactive oxygen species (ROS) and free radical formation, consequently activating proteinases and enzymes such as elastase and tyrosinase, leading to premature skin aging. The objective of this work was to extract, characterize and evaluate the antioxidant and antiaging potential of polyphenols from a black bean endemic variety. The polyphenolic extract was obtained from black beans by supercritical fluid extraction (SFE) using CO2 with a mixture of water-ethanol as a cosolvent and conventional leaching with a mixture of water-ethanol as solvent. The polyphenolic extracts were purified and characterized, and antioxidant potential, tyrosinase and elastase inhibitory potentials were measured. The extract obtained using the SFE method using CO2 and H2O-Ethanol (50:50 v/v) as a cosolvent showed the highest total phenolic compounds yield, with 66.60 ± 7.41 mg GAE/g coat (p > 0.05) and 7.30 ± 0.64 mg C3GE/g coat (p < 0.05) of anthocyanins compared to conventional leaching. Nineteen tentative phenolic compounds were identified in leaching crude extract using ESI-QTOF. Quercetin-3-D-galactoside was identified in crude and purified extracts. The purified SFC extract showed IC50 0.05 ± 0.002 and IC50 0.21 ± 0.008 mg/mL for DPPH and ABTS, respectively. The lowest IC50 value of tyrosinase inhibition was 0.143 ± 0.02 mg/mL and 0.005 ± 0.003 mg/mL of elastase inhibition for leaching purified extract. Phenolic compounds presented theoretical free energy values ranging from -5.3 to -7.8 kcal/mol for tyrosinase and -2.5 to -6.8 kcal/mol for elastase in molecular docking (in silico) studies. The results suggest that the purified extracts obtained by SFE or conventional leaching extraction could act as antioxidant and antiaging ingredients for cosmeceutical applications.

Dataset Information

Cucurbitacin B Exerts Antiaging Effects in Yeast by Regulating Autophagy and Oxidative Stress.

Publications

Cucurbitacin B Exerts Antiaging Effects in Yeast by Regulating Autophagy and Oxidative Stress.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets