ArticleActa pharmaceutica Sinica. B2022
Atractylenolide-I covalently binds to CYP11B2, selectively inhibits aldosterone synthesis, and improves hyperaldosteronism.
Article in Acta pharmaceutica Sinica. B, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 27 citations in OpenAlex.
- Renalase stimulates aldosterone production via PMCA4b/cAMP in NCI-H295R cells.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Effects and mechanism of carrier-free self-assembled nanoparticles of natural products in attenuating pulmonary edema.Journal of nanobiotechnology · 2026Article
- Curcumin ameliorates metabolic dysfunction-associated steatotic liver diseaseActa pharmaceutica Sinica. B · 2026Article
- From target specificity to metabolic efficiency: Design and optimization of etomidate analogues for potential improvement in postoperative outcomes.Acta pharmaceutica Sinica. B · 2026Article
- Atractylenolide I mitigates Alzheimer's disease pathology in ApoEActa biochimica et biophysica Sinica · 2026Article
- Anticancer Potential of Atractylenolides I-III: Efficacy, Mechanisms, Pharmacokinetics, and Safety.Molecules (Basel, Switzerland) · 2026Review
- Lab-on-a-chip: an advanced technology for the modernization of traditional Chinese medicine.Chinese medicine · 2024Review
- Tetrandrine inhibits aldosterone synthesis by covalently targeting CYP11A1 to attenuate hypertension.Frontiers in pharmacology · 2024Article
- Evaluating the role of aldosterone synthesis on adrenal cell fate.Frontiers in endocrinology · 2024Review
- Chemical Constitution, Pharmacological Effects and the Underlying Mechanism of Atractylenolides: A Review.Molecules (Basel, Switzerland) · 2023Review
- ATL I, Acts as a SIRT6 Activator to Alleviate Hepatic Steatosis in Mice via Suppression of NLRP3 Inflammasome Formation.Pharmaceuticals (Basel, Switzerland) · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
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Abstract
Hyperaldosteronism is a common disease that is closely related to endocrine hypertension and other cardiovascular diseases. Cytochrome P450 11B2 (CYP11B2), an important enzyme in aldosterone (ALD) synthesis, is a promising target for the treatment of hyperaldosteronism. However, selective inhibitors targeting CYP11B2 are still lacking due to the high similarity with CYP11B1. In this study, atractylenolide-I (AT-I) was found to significantly reduce the production of ALD but had no effect on cortisol synthesis, which is catalyzed by CYP11B1. Chemical biology studies revealed that due to the presence of Ala320, AT-I is selectively bound to the catalytic pocket of CYP11B2, and the C8/C9 double bond of AT-I can be epoxidized, which then undergoes nucleophilic addition with the sulfhydryl group of Cys450 in CYP11B2. The covalent binding of AT-I disrupts the interaction between heme and CYP11B2 and inactivates CYP11B2, leading to the suppression of ALD synthesis; AT-I shows a significant therapeutic effect for improving hyperaldosteronism.
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