2. Academic Validation
  3. Microbial transformation and inhibitory effect assessment of uvaol derivates against LPS and HMGB1 induced NO production in RAW264.7 macrophages

Microbial transformation and inhibitory effect assessment of uvaol derivates against LPS and HMGB1 induced NO production in RAW264.7 macrophages

  • Bioorg Med Chem Lett. 2022 Feb 15;58:128523. doi: 10.1016/j.bmcl.2021.128523.
Xuewa Jiang 1,  Pingping Shen 1,  Jing Zhou 1,  Haixia Ge 2,  Richa Raj 1,  Weiwei Wang 3,  Boyang Yu 4,  Jian Zhang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
  • 2 School of Life Sciences, Huzhou University, Huzhou 313000, PR China.
  • 3 Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.
  • 4 Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu, China.
  • 5 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu, China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu, China; ZhenPing Expert Workstation for Zhang Jian, Zhenping, Ankang, Shaanxi, 725699, PR China. Electronic address: [email protected].
PMID: 34973341 DOI: 10.1016/j.bmcl.2021.128523
Abstract

For the discovery of new pentacyclic Triterpenes as a potential anti-inflammatory agent, microbial transformation of uvaol by Penicilium griseofulvum CICC 40293 and Streptomyces griseus ATCC 13273 was investigated. Stereoselective hydroxylation and epoxidation reactions were observed in the biotransformation. Moreover, six new metabolites were isolated and structurally elucidated by HR-ESI-MS and NMR spectrum. All the compounds were evaluated upon the inhibitory effects of nitric oxide (NO) release in RAW 264.7 cells induced by lipopolysaccharide (LPS) and high-mobility group box 1 (HMGB1). Among them, compound 3 (13, 28-epoxy-3β, 7β, 21β-trihydroxy-urs-11-ene) with the unique epoxy structure and compound 5 (3β, 21β, 24, 28-tetrahydroxy-urs-12-en-30-oic acid), exhibited a considerable inhibitory effect on both models while compound 2 (urs-12-ene-3β, 7β, 21β, 28-tetraol) showed a significant bias in the LPS-induced inflammatory response with IC50 value of 2.22 μM. Therefore, this study could provide some insights on the discovery of the pentacyclic triterpene leads for the treatment of either DAMPs or PAMPs triggered inflammation.

Keywords

Anti-inflammatory agents; Biotransformation; HMGB1; Pentacyclic triterpene; Uvaol.

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