Daio-Orengedokudo works as a cell-proliferating compound in endothelial cells
Ki-Ho Cho1, Woo-Sang Jung, Sung-Uk Park
1College of Oriental Medicine, Kyung Hee University, Seoul, Korea.
Abstract:
Daio-Orengedokuto is a combination drug that has inhibitory effects on HMG-CoA reductase and pancreatic lipase. Here we investigated whether Daio-Orengedokuto has effects on vascular endothelial cells. To determine its effects on blood vessels, we examined roles of Daio-Orengedokuto in cell migration, cell apoptosis and cell cycle progression over bovine aortic endothelial cells (BAECs). Interestingly, Daio-Orengedokuto was shown to work as an anti-apoptotic agent, a cell cycle progressive agent and a cell-migration inducing agent in BAECs, whereas it was known to act as a tumor suppressor in cancer cells (unpublished data). The inducing effect of Daio-Orengedokuto on cell-cycle progression and cell migration in endothelium suggests that Daio-Orengedokuto may be referred to as a drug, inducing angiogenesis, healing wounds, and (or) remodeling vascular tissue. Then we further investigated which signaling molecules were activated by Daio-Orengedokuto and found that extracellular signal-regulated kinase (ERK) phosphorylation and IkappaB degradation were stimulated by the Daio-Orengedokuto treatment in BAECs. More interestingly, pretreatment with PD compound, an ERK inhibitor, blocked the anti-apoptosis induced by Daio-Orengedokuto. In conclusion, Daio-Orengedokuto plays a role in endothelial cell proliferation via activation of MAP kinase.
Insights
Daio-Orengedokuto promotes vascular endothelial cell proliferation by inhibiting apoptosis and enhancing migration. This traditional Japanese medicine activates extracellular signal-regulated kinase (ERK) signaling, suggesting potential therapeutic applications in wound healing and vascular remodeling.
Area of Science:
- Pharmacology
- Cell Biology
- Vascular Biology
Background:
- Daio-Orengedokuto is a multi-component herbal medicine with known inhibitory effects on HMG-CoA reductase and pancreatic lipase.
- Its effects on vascular endothelial cells, particularly in the context of proliferation and survival, were previously unexplored.
Purpose of the Study:
- To investigate the impact of Daio-Orengedokuto on vascular endothelial cells.
- To determine its effects on endothelial cell migration, apoptosis, and cell cycle progression.
Main Methods:
- Bovine aortic endothelial cells (BAECs) were treated with Daio-Orengedokuto.
- Assays were performed to evaluate cell migration, apoptosis, and cell cycle progression.
- Western blotting was used to assess the activation of signaling pathways, including extracellular signal-regulated kinase (ERK) and IkappaB.
Main Results:
- Daio-Orengedokuto demonstrated anti-apoptotic, cell cycle-promoting, and cell migration-inducing effects in BAECs.
- Treatment stimulated extracellular signal-regulated kinase (ERK) phosphorylation and IkappaB degradation.
- Inhibition of ERK with PD compound blocked the anti-apoptotic effects of Daio-Orengedokuto.
Conclusions:
- Daio-Orengedokuto promotes endothelial cell proliferation through the activation of the mitogen-activated protein kinase (MAPK) pathway, specifically via ERK signaling.
- These findings suggest Daio-Orengedokuto's potential role in promoting angiogenesis, wound healing, and vascular tissue remodeling.
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