ReferenceID 5000
Oxyresveratrol Inhibits TNF-α-Stimulated Cell Proliferation in Human Immortalized Keratinocytes (HaCaT) by Suppressing AKT Activation
Pharmaceutics
Psoriasis is a complex inflammatory disease characterized by hyperproliferative keratinocyte caused by active PI3K/AKT signaling. TNF-alpha concentrated in the psoriatic lesions stimulates AKT activation. We previously d
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Record Fields
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- Reference Id
- 5000
- Evidence Id
- 21590
- Core Evidence Id
- 21590
- Source Reference Id
- 3254
- Herb2 Reference Id
- HBREF004051
- Subject Paper Key
- HBIN021880_35056961
- Pubmed Id
- 35056961
- Doi
- 10.3390/pharmaceutics14010063
- Paper Title
- Oxyresveratrol Inhibits TNF-α-Stimulated Cell Proliferation in Human Immortalized Keratinocytes (HaCaT) by Suppressing AKT Activation
- Paper Abstract
- Psoriasis is a complex inflammatory disease characterized by hyperproliferative keratinocyte caused by active PI3K/AKT signaling. TNF-alpha concentrated in the psoriatic lesions stimulates AKT activation. We previously discovered that oxyresveratrol inhibited inflammation via suppressing AKT phosphorylation, therefore oxyresveratrol may possess a conserved property to block AKT activation and proliferation in keratinocyte in response to TNF-alpha. Our current study proved that oxyresveratrol exhibited potent anti-proliferative effects against TNF-alpha. These effects are explained by the findings that oxyresveratrol could potentially inhibit TNF-alpha-stimulated AKT and GSK3-beta activation in a dose-dependent manner, and its inhibitory pattern was comparable to that of a specific PI3K inhibitor. Results from immunofluorescence supported that oxyresveratrol effectively inhibited AKT and GSK3-beta activation in individual cells upon TNF-alpha stimulation. Furthermore, functional assay confirmed that oxyresveratrol repressed the expansion of the HaCaT colony over 3 days, and this was caused by the ability of oxyresveratrol to induce cell cycle arrest at S and G2/M phases and the reduction in the expression of a proliferative marker (Ki-67) and a survival marker (MCL-1). Given the importance of TNF-alpha and the PI3K/AKT pathway in the psoriatic phenotype, we anticipate that oxyresveratrol, which targets the TNF-alpha-stimulated PI3K/AKT pathway, would represent a promising psoriasis therapy in the near future.
- Journal
- Pharmaceutics
- Publish Year
- 2021
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Psoriasis; Inflammatory Disease; Psoriatic
- Paper Title Cn
- Paper Title En
- Oxyresveratrol Inhibits TNF-α-Stimulated Cell Proliferation in Human Immortalized Keratinocytes (HaCaT) by Suppressing AKT Activation
- Bilingual Status
- semi_complete