Oridonin delays aging through AKT signaling pathway
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA784535 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17065578_1.fastq.gz | Fastqsanger.gz | |||
| SRR17065578_2.fastq.gz | Fastqsanger.gz | |||
| SRR17065579_1.fastq.gz | Fastqsanger.gz | |||
| SRR17065579_2.fastq.gz | Fastqsanger.gz | |||
| SRR17065580_1.fastq.gz | Fastqsanger.gz |
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Project description:Aging is the major risk factor for chronic diseases and disability in human. There is no effective anti-aging clinical treatment. In this study, oridonin was selected based on the drug screening strategy of Connectivity MAP (CMAP) upon transcriptomes of 102 traditional Chinese medicines (TCM) treated cell lines. Oridonin is an anti-inflammatory drug and diterpenoid isolated from Rabdosia rubescens. Oridonin exhibited a variety of pharmacological activities, including anti-tumor, antibacteria and anti-inflammation. Here, we found that oridonin inhibited cellular senescence in human diploid fibroblasts (2BS and WI-38), indicated by decreased senescence-associated β-galactosidase (SA-β-gal) staining. Compared with the elderly control group, the positive cell rate in the oridonin intervention group was 48.5%, and the cell shape was similar to young cells. Oridonin prolonged the lifespan of yeast by 14.6%~48.9%, and prolonged the average life span of naturally aged mice by 21.6%. It also increased the healthspan of aged mice. In addition, oridonin also improved doxorubicin-induced cellular senescence and mouse senescence. Compared with the model group, the percentage of SA-β-gal positive cells in the oridonin treatment group was reduced to 59.8%. It prolonged the average life span of mice by 53.8% as well as the healthspan. Mechanistically, we show that oridonin delayed aging through the AKT signaling pathways and reverses the genetic changes caused by doxorubicin-induced cell senescence. Therefore, oridonin may be an ideal candidate for the development of anti-aging drugs, and it also provides therapeutic potential in other diseases.
2022-03-18 | GSE189789 | GEO
Project description:Aging is a major risk factor for chronic diseases and disability in humans. Nowadays, no effective anti-aging treatment is available clinically. In this study, oridonin was selected based on the drug screening strategy similar to Connectivity MAP (CMAP) but upon transcriptomes of 102 traditional Chinese medicines treated cell lines. Oridonin is a diterpenoid isolated from Rabdosia rubescens. As reported, Oridonin exhibits a variety of pharmacological activities, including antitumor, antibacterial and anti-inflammatory activities. Here, we found that oridonin inhibited cellular senescence in human diploid fibroblasts (2BS and WI-38), manifested by decreased senescence-associated β-galactosidase (SA-β-gal) staining. Compared with the elderly control group, the positive cell rate in the oridonin intervention group was reduced to 48.5%. Notably, oridonin prolonged the lifespan of yeast by 48.9%, and extended the average life span of naturally aged mice by 21.6%. Our mice behavior experiments exhibited that oridonin significantly improved the health status of naturally aged mice. In addition, oridonin also delayed doxorubicin-induced cellular senescence and mouse senescence. Compared with the model group, the percentage of SA-β-gal positive cells in the oridonin treatment group was reduced to 59.8%. It extended the average lifespan of mice by 53.8% and improved healthspan. Mechanistically, we showed that oridonin delayed aging through the AKT signaling pathway and reversed the genetic changes caused by doxorubicin-induced cell senescence. Therefore, oridonin is a potential candidate for the development of anti-aging drugs.
| S-EPMC9157590 | biostudies-literature
Project description:We applied Tet2⁺/⁻ bone marrow transplantation (BMT) mouse model to investigate the contribution of clonal hematopoiesis to cardiac aging. A transcriptome-guided small-molecule screening strategy was employed to identify potential therapeutic compounds. Target validation involved molecular docking, enzymatic inhibition, and surface plasmon resonance assays. Genetic and pharmacological perturbation experiments were conducted to examine pathway involvement. Tet2⁺/⁻-BMT mice exhibited age-progressive myocardial fibrosis, inflammation, senescence, and functional decline. Oridonin reversed CHIP- and aging-associated transcriptional signatures and attenuated cardiac remodeling. Mechanistically, oridonin inhibited KDM5C histone demethylase. Downregulation of the pro-senescent factor S100A8 and suppression of SASP-associated inflammation were observed.
2025-06-08 | GSE299167 | GEO
Project description:Epigallocatechin gallate delays age-related cataract development via the RASSF2/AKT pathway
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Project description:We applied Tet2⁺/⁻ bone marrow transplantation (BMT) mouse model to investigate the contribution of clonal hematopoiesis to cardiac aging. A transcriptome-guided small-molecule screening strategy was employed to identify potential therapeutic compounds. Target validation involved molecular docking, enzymatic inhibition, and surface plasmon resonance assays. Epigenetic regulation was assessed using chromatin immunoprecipitation sequencing (ChIP-seq) and transcriptomic profiling. Genetic and pharmacological perturbation experiments were conducted to examine pathway involvement.Genetic manipulation confirmed the KDM5C–SIRT2–SASP regulatory axis mediates oridonin’s effects.TET2-driven clonal hematopoiesis promotes cardiac aging via inflammatory and epigenetic pathways. These finding point that oridonin, as a novel epigenetic modulator, attenuates myocardial dysfunction by inhibiting the KDM5C–SIRT2–SASP axis, supporting its potential as a targeted therapeutic candidate for CHIP-associated cardiac aging.
2025-06-08 | GSE299168 | GEO
Project description:Oridonin is a nature diterpenoid mainly isolated from Chinese herb Rabdosia rubescens and other Isodon species. Nowadays, most of studies focused on the pharmacological effects of oridonin, the metabolism of which remains unclear. In order to investigate the effect of oridonin on metabolism-related genes, we used the second-generation transcriptome sequencing(RNA-seq) to determine the expression changes of each gene in HepG2 cells treated with oridonin.
2021-04-09 | GSE112908 | GEO
Project description:Oridonin, as a natural terpenoids isolated from traditional Chinese medicinal herb Rabdosia rubescens, exhibits anticancer activity against multiple cancers with the IC50 ranging from 10 ¦ÌM to 100 ¦ÌM. We observed that SLC7A11 inhibitor Imidazole ketone erastin (1 ¦ÌM) potently increase the anti-proliferative activity of oridonin at low concentrations. Preliminary investigation demonstrated that combination of Imidazole ketone erastin (1 ¦ÌM) and oridonin induced apoptosis and ferroptosis only in a fraction of cells. To explore the synergistic anti-tumor mechanism of combination of oridonin and Imidazole ketone erastin, second-generation transcriptome sequencing(RNA-seq) was utilized to determine the transcriptome change in Hela cells affected by oridonin and Imidazole ketone erastin. PCA analysis showed that the group of oridonin or Imidazole ketone erastin alone located near the control group, while the group of combination gathered far away from the control group, indirectly indicating that combination of oridonin and Imidazole ketone erastin had synergistic biology function.
2023-12-31 | GSE193751 | GEO
Project description:Analysis of WT-Ctl v.s. WT-Ori and R878H-Ctl v.s. R878H-Ori hematopoietic stem cell (lineage-, c-kit+ Sca-1+ CD150+, CD34-). The four population of hematopoietic stem cell (HSC) were purified from the bone marrow of WT and R878H recipent mice treated with vehicle or oridonin. Results provide insight into the role of oridonin in R878H HSC.
2021-05-13 | GSE174362 | GEO
Project description:Increased expression of FOXM1 delays natural and progeroid aging phenotypes
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Project description:The mTOR (mammalian Target of Rapamycin) pathway is constitutively activated in Diffuse Large B-Cell Lymphoma (DLBCL). mTOR inhibition has been shown to have clinical activity in patients with DLBCL, although overall response rates remain low. We therefore evaluated differences in the transcriptome between DLBCL cell lines with differential sensitivity to the mTOR inhibitor Rapamycin, to (A) identify gene-expression patterns(GEP) capable of identifying sensitivity to Rapamycin, (B) understand the underlying mechanisms of resistance to Rapamycin in DLBCL and (C) identify bioactive molecules likely to synergize with mTOR inhibitors. Using Affymetrix HuGene ST 1.0 microarrays, we were able to identify a gene expression signature capable of accurately predicting sensitivity and resistance to Rapamycin in DLBCL cell lines. Pathway analysis identified the serine/threonine kinase Akt as central to the differentially-expressed gene network. Connectivity mapping of our datasets identified compounds targeting the AKT pathway with a high likelihood of reversing the GEP associated with resistance to Rapamycin. Specifically, we evaluated the HIV protease inhibitor (PI) Nelfinavir, which is known to have anti-cancer and Akt-inhibitory properties, as well as the small molecule Akt inhibitor MK-2206, for their potential to synergize with to Rapamycin in DLBCL. Nelfinavir and MK-2206 caused profound inhibition of cell viability in combination with Rapamycin in DLBCL cell lines. Low nanomolar concentrations of Rapamycin inhibited phosphorylation of Akt and also downstream targets of activated mTOR when used in combination with these Akt inhibitors. These findings have the potential to significantly improve patient selection for mTOR inhibitor therapy, and to improve rates and depths of response. More broadly, they support the use of global RNA expression and connectivity mapping to improve patient selection and identify synergistic drug combinations for cancer therapy. DLBCL cell lines were tested for Rapamycin sensitivity and classified as "sensitive" or "resistant." Genome-wide analysis of all cell lines were performed using the Affymetrix HuGene ST 1.0 Array Platform. Genes with differential expression between sensitive and resistant cell lines were analyzed using Statistical Analysis of Microarrays (SAM) software, and a signature of genes determnined. This signature was found to accurately predict sensitivity or resistance of other DLBCL cell lines, and to identify the protein kinase Akt as central to resistance.
2012-04-29 | E-GEOD-27255 | biostudies-arrayexpress