ArticleActa pharmacologica Sinica2023
Ginseng-derived panaxadiol ameliorates STZ-induced type 1 diabetes through inhibiting RORγ/IL-17A axis.
Article in Acta pharmacologica Sinica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Effects of Korean Red ginseng on the regulation of inflammation, cell death, and fibrosis in a mouse model of rheumatoid arthritis featuring spike protein overexpression.Journal of ginseng research · 2026Article
- Panaxadiol promotes angiogenesis against chronic cerebral hypoperfusion injury through the VEGF-A/p38 MAPK/Src signaling pathway.Journal of ginseng research · 2026Article
- Network pharmacology andWorld journal of gastroenterology · 2025Article
- Panaxadiol Attenuates Neuronal Oxidative Stress and Apoptosis in Cerebral Ischemia/Reperfusion Injury via Regulation of the JAK3/STAT3/HIF-1α Signaling Pathway.CNS neuroscience & therapeutics · 2025Article
- Integrating network pharmacology and experimental validation to reveal the anti-growth mechanism of panaxadiol against glioblastoma via calcium signaling.Frontiers in molecular biosciences · 2025Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
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Abstract
Retinoic-acid-receptor-related orphan receptor γ (RORγ) is a major transcription factor for proinflammatory IL-17A production. Here, we revealed that the RORγ deficiency protects mice from STZ-induced Type 1 diabetes (T1D) through inhibiting IL-17A production, leading to improved pancreatic islet β cell function, thereby uncovering a potential novel therapeutic target for treating T1D. We further identified a novel RORγ inverse agonist, ginseng-derived panaxadiol, which selectively inhibits RORγ transcriptional activity with a distinct cofactor recruitment profile from known RORγ ligands. Structural and functional studies of receptor-ligand interactions reveal the molecular basis for a unique binding mode for panaxadiol in the RORγ ligand-binding pocket. Despite its inverse agonist activity, panaxadiol induced the C-terminal AF-2 helix of RORγ to adopt a canonical active conformation. Interestingly, panaxadiol ameliorates mice from STZ-induced T1D through inhibiting IL-17A production in a RORγ-dependent manner. This study demonstrates a novel regulatory function of RORγ with linkage of the IL-17A pathway in pancreatic β cells, and provides a valuable molecule for further investigating RORγ functions in treating T1D.
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