ABSTRACT
Hericium erinaceum is an edible and medicinal mushroom widely used in Korea, Japan, and China. On the search for biologically active compounds supporting the medicinal usage, the MeOH extract of the fruiting bodies of H. erinaceum was investigated for its chemical constituents. Six compounds were isolated and identified as hericenone D (1), (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3ß-ol (2), erinacerin B (3), hericenone E (4), hericenone F (5) and isohericerin (6) by comparing their spectroscopic data with previously reported values. The inhibitory effects on adriamycin-induced cellular senescence in human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs) of the isolates (1-6) were studied. Among the isolated compounds, ergosterol peroxide (2) reduced senescence associated ß-galactosidase (SA-ß-gal) activity increased in HUVECs treated with adriamycin. According to experimental data obtained, the active compound may inspire the development of a new pharmacologically useful substance to be used in the treatment and prevention of age-related diseases.
Subject(s)
Agaricales/chemistry , Cellular Senescence/drug effects , Human Umbilical Vein Endothelial Cells/cytology , Human Umbilical Vein Endothelial Cells/drug effects , Benzopyrans/chemistry , Benzopyrans/isolation & purification , Benzopyrans/pharmacology , Dose-Response Relationship, Drug , Doxorubicin/antagonists & inhibitors , Doxorubicin/pharmacology , Ergosterol/analogs & derivatives , Ergosterol/chemistry , Ergosterol/isolation & purification , Ergosterol/pharmacology , Fibroblasts/drug effects , Fibroblasts/enzymology , Heterocyclic Compounds, 2-Ring/chemistry , Heterocyclic Compounds, 2-Ring/isolation & purification , Heterocyclic Compounds, 2-Ring/pharmacology , Human Umbilical Vein Endothelial Cells/enzymology , Humans , Indoles/chemistry , Indoles/isolation & purification , Indoles/pharmacology , Molecular Structure , Palmitates/chemistry , Palmitates/isolation & purification , Palmitates/pharmacology , Phenols/chemistry , Phenols/isolation & purification , Phenols/pharmacology , Skin/cytology , Skin/drug effects , Structure-Activity Relationship , Terpenes/chemistry , Terpenes/isolation & purification , Terpenes/pharmacology , beta-Galactosidase/antagonists & inhibitors , beta-Galactosidase/metabolismABSTRACT
Cellular senescence contributes to tissue and organismal aging, tumor suppression and progress, tissue repair and regeneration, and age-related diseases. Thus, aging intervention might be beneficial for treatment and prevention of diverse age-related diseases. In the present study, we investigated whether four compounds purified from Inula japonica exert inhibitory activity against cellular senescence induced by adriamycin in human umbilical vein endothelial cells (HUVECs). Among them, compound 4 (quercetagetin 3,4'-dimethyl ether) showed inhibitory activity against cellular senescence, which was confirmed by senescence-associated ß-galactosidase (SA-ß-gal) activity, p53 and p21 protein levels, and intracellular ROS levels. Compound 4 also reduced SA-ß-gal activity in HUVECs under replicative senescence. These results suggest that compound 4 represses cellular senescence in HUVECs and might be useful for the development of dietary supplements or cosmetics that alleviate tissue aging or age-related diseases.
Subject(s)
Cellular Senescence/drug effects , Chromones/pharmacology , Ethers/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Inula/chemistry , Chromones/isolation & purification , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Doxorubicin/toxicity , Ethers/isolation & purification , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Reactive Oxygen Species/metabolism , Tumor Suppressor Protein p53/metabolism , beta-Galactosidase/metabolismABSTRACT
Cellular senescence influences tumor suppression and progress, tissue repair and regeneration, tissue and organismal aging, and age-related diseases. Aging intervention might be an advantageous target for prevention and treatment of diverse age-related diseases. In this study, we investigated whether (-)-loliolide purified from the crude extract of Polygonum aviculare exerted inhibitory activity against cellular senescence in human dermal fibroblasts (HDFs). (-)-Loliolide diminished senescence-associated ß-galactosidase activity (SA-ß-gal), the level of p21 protein, and the level of reactive oxygen species in senescent cells induced by adriamycin treatment. (-)-Loliolide also attenuated SA-ß-gal activity in HDFs under replicative senescence. These findings imply that (-)-loliolide rescues cellular senescence in HDFs and might be useful for the development of dietary supplements or cosmetics that ameliorate tissue aging or age-associated diseases.
Subject(s)
Benzofurans/pharmacology , Cellular Senescence/drug effects , Dermis/drug effects , Fibroblasts/drug effects , Plant Extracts/pharmacology , Polygonum , Benzofurans/chemistry , Benzofurans/isolation & purification , Cellular Senescence/physiology , Dermis/cytology , Dermis/physiology , Dose-Response Relationship, Drug , Fibroblasts/physiology , Humans , Plant Extracts/chemistry , Plant Extracts/isolation & purificationABSTRACT
Cellular senescence is known to contribute to tissue aging, a variety of age-related diseases, tissue regeneration, and cancer. Therefore, aging intervention might be useful for prevention of aging as well as age-related disease. In this study, we investigated compounds from Polygonum aviculare to determine if they inhibited cellular senescence in human primary cells, human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs). Ten compounds from P. aviculare were purified and their inhibitory effects on adriamycin-induced cellular senescence were measured by observing senescence-associated ß-galactosidase (SA-ß-gal) activity and reactive oxygen species. Among them, compound 9 (quercetin-3-O-ß-D-glucuronide) showed inhibitory effects against cellular senescence in HDFs and HUVECs treated with adriamycin. Additionally, compound 9 rescued replicative senescence in HDFs and HUVECs. These data imply that compound 9 represses cellular senescence in human primary cells and might be useful for the development of dietary supplements or cosmetics that ameliorate tissue aging or aging-associated diseases.
Subject(s)
Antioxidants/pharmacology , Cellular Senescence/drug effects , Drug Discovery , Endothelium, Vascular/drug effects , Quercetin/analogs & derivatives , Skin Aging/drug effects , Skin/drug effects , Antioxidants/chemistry , Antioxidants/isolation & purification , Cell Survival/drug effects , Cells, Cultured , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Ethnopharmacology , Glucuronides/chemistry , Glucuronides/isolation & purification , Glucuronides/pharmacology , Human Umbilical Vein Endothelial Cells/cytology , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Medicine, Korean Traditional , Molecular Structure , Osmolar Concentration , Plant Components, Aerial/chemistry , Polygonum/chemistry , Quercetin/chemistry , Quercetin/isolation & purification , Quercetin/pharmacology , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Skin/cytology , Skin/metabolism , beta-Galactosidase/antagonists & inhibitors , beta-Galactosidase/metabolismABSTRACT
Cellular senescence contributes to tissue and organismal aging, tumor suppression and progress, tissue repair and regeneration, and age-related diseases. Thus, aging intervention might be a promising target for treatment and prevention of diverse age-related diseases. In the present study, we investigated whether juglanin purified from the crude extract of Polygonum aviculare exerted inhibitory activity against cellular senescence in human dermal fibroblasts (HDFs). Juglanin decreased senescence-associated ß-galactosidase activity (SA-ß-gal) and the level of reactive oxygen species in senescent cells induced by adriamycin treatment. Juglanin also repressed SA-ß-gal activity in HDFs under replicative senescence. These results suggest that juglanin represses cellular senescence in HDFs and might be useful for the development of dietary supplements or cosmetics that alleviate tissue aging or age-related diseases.
Subject(s)
Cellular Senescence/drug effects , Glycosides/pharmacology , Kaempferols/pharmacology , Cells, Cultured , Dermis/cytology , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/metabolism , Glycosides/chemistry , Glycosides/isolation & purification , Humans , Kaempferols/chemistry , Kaempferols/isolation & purification , Polygonum/chemistry , Reactive Oxygen Species/metabolism , beta-Galactosidase/metabolismABSTRACT
Inflammation is an underlying basis for the molecular alterations that link aging and age-related pathological processes. In a previous study, we found that secretory phospholipase A(2) (sPLA(2)) induced cellular senescence in human dermal fibroblasts (HDFs). To further investigate the association of inflammation with cellular senescence, the effects of PGE(2) on cellular senescence in HDFs were investigated, since PGE(2) is the most abundant prostanoid. PGE(2) treatment induces cellular senescence, as determined by a decrease in cell proliferation and an increase in senescence-associated ß-galactosidase staining. Notably, PGE(2) treatment increased the IGFBP5 protein level. While treatment with PGE(2) antagonists repressed PGE(2)-induced cellular senescence, increasing intracellular cAMP accelerated cellular senescence. Down-regulation of IGFBP5 inhibited PGE(2)-induced cellular senescence. Taken together, these results suggest that PGE(2) may play an important role in controlling cellular senescence of HDFs through the regulation of IGFBP5 and therefore may contribute to inflammatory disorders associated with aging.
Subject(s)
Cellular Senescence/physiology , Dinoprostone/physiology , Insulin-Like Growth Factor Binding Protein 5/physiology , Skin/cytology , Base Sequence , Blotting, Western , Cells, Cultured , DNA Primers , Fibroblasts/cytology , Humans , Promoter Regions, Genetic , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Since cellular senescence involves organismal aging as well as diverse diseases, aging intervention might contribute to inhibit the aging process as well as aging-associated diseases. We tried to search for effective compounds from the root bark of ULMUS DAVIDIANA that are able to inhibit cellular senescence in human fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs). Twenty-two compounds from the root bark of U. DAVIDIANA were isolated and screened for their inhibitory effects on adriamycin-induced cellular senescence by measuring senescence-associated ß-galatosidase (SA- ß-gal) activity. Among twenty-two compounds isolated, epifriedelanol (3), ssioriside (15), and catechin-7-O- ß-D-glucopyranoside (22) had inhibitory effects on adriamycin-induced cellular senescence in HDFs. Friedelin (2), epifriedelanol (3), and catechin-7-O- ß-apiofuranoside (18) were active in HUVECs. In particular, epifriedelanol (3) suppressed adriamycin-induced cellular senescence as well as replicative senescence in HDFs and HUVECs. These results suggest that epifriedelanol (3) reduces cellular senescence in human primary cells and might be used to develop dietary supplements or cosmetics that modulate tissue aging or aging-associated diseases.