Ecdysteroids from the Korean Endemic Species Ajuga spectabilis with Activities against Glucocorticoid Receptors and 11β-Hydroxysteroid Dehydrogenase Type 1
Open accessAbstract
High Resolution Image Download MS PowerPoint Slide Two new ecdysteroids, spectasterone A ( 1 ) and spectasterone B ( 2 ), together with four known ecdysteroids, breviflorasterone ( 3 ), ajugalactone ( 4 ), 20-hydroxyecdysone ( 5 ), and polypodine B ( 6 ) were isolated from the Korean endemic plant Ajuga spectabilis using feature-based molecular networking analysis. The chemical structures of 1 and 2 were determined based on the interpretation of NMR and mass spectrometric data. Their absolute configurations were established using 3 J H, H coupling constants, NOESY interactions, Mosher’s method, and ECD and DP4+ calculations. To identify their biological target, a machine learning-based prediction system was applied, and the results indicated that ecdysteroids may have 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)-related activity, which was further supported by molecular docking results of ecdysteroids with 11β-HSD1. Following this result, all the isolated ecdysteroids were tested for their ability to affect the expression of 11β-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptors (GRs) in HaCaT cells irradiated with UVB. Compounds 2 – 5 exhibited inhibition of 11β-HSD1 expression and increases in GR activity.
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20E reverted UVB-increased expression of 11β-hydroxysteroid dehydrogenase type 1 and restored the level of GC receptor in HaCaT cells.
“Seemingly in contradiction with the above report, 20E reverted UVB-increased expression of 11β-hydroxysteroid dehydrogenase type 1 (an enzyme converting cortisol to inactive cortisone, therefore preventing induction of GC receptor expression) and restored the level of GC receptor in HaCaT cells [35].”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [35]
The Biological Evaluation section reports that ecdysteroids 2–5 lowered UVB-induced 11β-HSD1 expression and restored GR expression in HaCaT cells; the Abstract identifies compound 5 as 20-hydroxyecdysone (20E). However, the citing sentence’s parenthetical describes the enzyme’s conversion in the opposite direction from the paper’s Introduction, which says 11β-HSD1 converts inactive glucocorticoids to active ones. Page numbers are not provided in our copy. (LLM, conf=0.88)
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“…in contradiction with the above report, 20E reverted UVB-increased expression of 11 β -hydroxysteroid dehydrogenase type 1 (an enzyme converting cortisol to inactive cortisone, therefore preventing induction of GC receptor expression) and restored the level of GC receptor in HaCaT cells [35].”
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“Similar to our result, in a study, Parr et al. also showed that a reduction in serum corticosterone levels accompanies the anabolic activity of 20E [9], which might also be explained by the inhibition of 11-β -hydroxysteroid dehydrogenase 1 enzyme expression reported for 20E [55].”
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- Authors
- Park, I., Park, K., Lee, H.-S., Hong, S.-M., Sriramulu, D. K., Hwang, H., Song, S., Baek, J. G., Kim, D. H., Kim, S. Y., Kwon, J., & Kwon, H. C.
- Affiliations
- Korea Institute of Science and Technology (KR)
- Gachon University (KR)
- Corresponding author
- Kwon, Jaeyoung
- Kwon, Hak Cheol
- ORCID
- Venue
- ACS Omega
- Publisher
- American Chemical Society (ACS)
- Published
- 2023-07-13
- Volume
- 8
- Issue
- 29
- Pages
- 26191-26200
- ISSN
- 2470-1343 (ISSN-L)
- PMC
- PMC10373211
- OpenAlex
- W4384205692
- Cited by
- 11
- References
- 25
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 1
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- ACS Omega (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Korea Institute of Science and Technology (2E32641)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phytochemical Studies and Bioactivities
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry and Biological Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioactive natural compounds
- Keywords
- ecdysteroids, 11β-hydroxysteroid dehydrogenase type 1, glucocorticoid receptor, UVB-induced skin damage, HaCaT keratinocytes, structure elucidation, absolute configuration, molecular networking, molecular docking, Korean endemic plants
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