2. Academic Validation
  3. Novel 18β-glycyrrhetinic acid derivatives as a Two-in-One agent with potent antimicrobial and anti-inflammatory activity

Novel 18β-glycyrrhetinic acid derivatives as a Two-in-One agent with potent antimicrobial and anti-inflammatory activity

  • Bioorg Chem. 2022 May;122:105714. doi: 10.1016/j.bioorg.2022.105714.
Borong Tu 1,  Jinfeng Liang 1,  Yi Ou 1,  Xinyue Zhang 1,  Wende Zheng 1,  Rihui Wu 1,  Lishe Gan 1,  Dongli Li 1,  Yujing Lu 2,  Jiaqiang Wu 1,  Weiqian David Hong 3,  Kun Zhang 4,  Panpan Wu 5,  Jingwei Jin 6,  Wing-Leung Wong 7
Affiliations

Affiliations

  • 1 School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, PR China.
  • 2 School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, PR China. Electronic address: luyj@gdut.edu.cn.
  • 3 School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, PR China; Department of chemistry, University of Liverpool, Liverpool L69 7ZD, United Kingdom. Electronic address: davidhwq@liverpool.ac.uk.
  • 4 School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, PR China. Electronic address: kzhang@gdut.edu.cn.
  • 5 School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, PR China. Electronic address: wyuchemwpp@126.com.
  • 6 School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, PR China. Electronic address: wyuchemjjw@126.com.
  • 7 School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, PR China. Electronic address: wleungwong@outlook.com.
PMID: 35276603 DOI: 10.1016/j.bioorg.2022.105714
Abstract

18β-glycyrrhetinic acid (GA) is a well-known natural compound of oleanane-type triterpene and is found possessing antimicrobial and anti-inflammatory properties. Nonetheless, its relatively low bioactivity restricts its potential in pharmaceutical applications. To maximize the potential use of this natural herbal compound as antimicrobial and anti-inflammatory agents, the rational modification of GA to enhance its pharmacological activity with low toxicity and to understand the mechanism of action is critically essential. We reported herein the design and synthesis of a series of new GA derivatives. The antimicrobial activities of these new compounds were evaluated by inhibition zone test and minimum inhibitory concentration (MIC) assay. In addition, the anti-inflammatory activity was evaluated by LPS induced BV2 cells inflammation model and 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced ear inflammation mice model. It was found that the derivatives functionalized with a di-substituted phenyl group at the 2-position of GA generally displayed high antimicrobial activity against Gram-positive bacteria (MIC down to 2.5 μM) and potent anti-inflammatory effects (inhibition of NO production up to 55%, comparable to dexamethasone). The in vitro and in vivo results also showed that GA-O-02 and GA-O-06 exert their anti-inflammatory activities through downregulation of NO, pro-inflammatory cytokines and chemokines (IL-1β, IL-6, IL-12, TNF-α, MCP-1 and MIP-1α) and upregulation of anti-inflammatory cytokines (IL-10). The anti-inflammatory mechanism may involve the inhibition of NF-κB, MAPKs and PI3K/Akt related inflammatory signaling pathways and activation of Nrf2/HO-1 signaling pathway. The results demonstrated that GA-O-02 and GA-O-06 possess great application potential as potent antimicrobial and anti-inflammatory agents.

Keywords

18β-Glycyrrhetinic acid; Anti-inflammatory; Antimicrobial; Mechanism; Oleanane derivatives.

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