ArticleEBioMedicine2019
Identification of a natural inhibitor of methionine adenosyltransferase 2A regulating one-carbon metabolism in keratinocytes.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Loss of MFE-2 impairs microglial lipid homeostasis and drives neuroinflammation in Alzheimer's pathogenesis.Nature aging · 2025Article
- Article
- SAM/SAH Mediates Parental Folate Deficiency-Induced Neural Cell Apoptosis in Neonatal Rat Offspring: The Expression of Bcl-2, Bax, and Caspase-3.International journal of molecular sciences · 2023Article
- Targeting the transcription factor HES1 by L-menthol restores protein phosphatase 6 in keratinocytes in models of psoriasis.Nature communications · 2022Article
- Current Knowledge in Skin Metabolomics: Updates from Literature Review.International journal of molecular sciences · 2022Review
- Psoriasis Vulgaris of Blood Heat Syndrome in Plasma Based on Widely Targeted Techniques.Journal of healthcare engineering · 2022Article
- Boswellic acids/Boswellia serrata extract as a potential COVID-19 therapeutic agent in the elderly.Inflammopharmacology · 2021Review
- A Review of Small-Molecule Inhibitors of One-Carbon Enzymes: SHMT2 and MTHFD2 in the Spotlight.ACS pharmacology & translational science · 2021Review
- SZB120 Exhibits Immunomodulatory Effects by Targeting eIF2α to Suppress Th17 Cell Differentiation.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer.Journal for immunotherapy of cancer · 2021Article
- Research progress and perspective in metabolism and metabolomics of psoriasis.Chinese medical journal · 2020Article
- Methionine metabolism in health and cancer: a nexus of diet and precision medicine.Nature reviews. Cancer · 2019Review
- An Update on Pharmacological Potential of Boswellic Acids against Chronic Diseases.International journal of molecular sciences · 2019Review
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPsoriasis is a common chronic inflammatory skin disease which lacks effective strategies for the treatment. Natural compounds with biological activities are good tools to identify new targets with therapeutic potentials. Acetyl-11-keto-β-boswellic acid (AKBA) is the most bioactive ingredient of boswellic acids, a group of compounds with anti-inflammatory and anti-cancer properties. Target identification of AKBA and metabolomics analysis of psoriasis helped to elucidate the molecular mechanism underlying its effect, and provide new target(s) to treat the disease.
methodsTo explore the targets and molecular mechanism of AKBA, we performed affinity purification, metabolomics analysis of HaCaT cells treated with AKBA, and epidermis of imiquimod (IMQ) induced mouse model of psoriasis and psoriasis patients.
findingsAKBA directly interacts with methionine adenosyltransferase 2A (MAT2A), inhibited its enzyme activity, decreased level of S-adenosylmethionine (SAM) and SAM/SAH ratio, and reprogrammed one‑carbon metabolism in HaCaT cells. Untargeted metabolomics of epidermis showed one‑carbon metabolism was activated in psoriasis patients. Topical use of AKBA improved inflammatory phenotype of IMQ induced psoriasis-like mouse model. Molecular docking and site-directed mutagenesis revealed AKBA bound to an allosteric site at the interface of MAT2A dimer.
interpretationOur study extends the molecular mechanism of AKBA by revealing a new interacting protein MAT2A. And this leads us to find out the dysregulated one‑carbon metabolism in psoriasis, which indicates the therapeutic potential of AKBA in psoriasis. FUND: The National Natural Science Foundation, the National Program on Key Basic Research Project, the Shanghai Municipal Commission, the Leading Academic Discipline Project of the Shanghai Municipal Education Commission.
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