2. Academic Validation
  3. Dehydrotumulosic acid: a potential glucocorticoid receptor agonist with anti-coxsackievirus activity

Dehydrotumulosic acid: a potential glucocorticoid receptor agonist with anti-coxsackievirus activity

  • Phytomedicine. 2025 Oct:146:157107. doi: 10.1016/j.phymed.2025.157107.
Jieyu Li 1,  Yuanyuan Huang 1,  Qiting Luo 2,  Xinyi Luo 2,  Jiapeng Xu 2,  Wei Ye 2,  Xinrui Zhou 2,  Jiayi Diao 2,  Zhe Ren 3,  Ge Liu 2,  Yun Zou 4,  Yifei Wang 5,  Qinchang Zhu 6,  Zhiping Wang 7
Affiliations

Affiliations

  • 1 School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China; College of Pharmacy, Shenzhen Technology University, Shenzhen, 518118, PR China.
  • 2 College of Pharmacy, Shenzhen Technology University, Shenzhen, 518118, PR China.
  • 3 Institute of Biomedicine, College of Life Science and Technology, Guangdong Province Key Laboratory of Bioengineering Medicine, Key Laboratory of Innovative Technology Research on Natural Products and Cosmetics Raw Materials, Jinan University, Guangzhou, 510632, PR China.
  • 4 National Medical Products Administration Institute of Executive Development, Beijing, 100073, PR China. Electronic address: zouyun@nmpaied.org.cn.
  • 5 School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China; Institute of Biomedicine, College of Life Science and Technology, Guangdong Province Key Laboratory of Bioengineering Medicine, Key Laboratory of Innovative Technology Research on Natural Products and Cosmetics Raw Materials, Jinan University, Guangzhou, 510632, PR China. Electronic address: twangyf@jnu.edu.cn.
  • 6 College of Pharmacy, Shenzhen Technology University, Shenzhen, 518118, PR China. Electronic address: zhuqinchang@sztu.edu.cn.
  • 7 School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China. Electronic address: wzping-jshb@gdpu.edu.cn.
PMID: 40737846 DOI: 10.1016/j.phymed.2025.157107
Abstract

Background: Coxsackievirus infections cause a range of diseases, from hand-foot-and-mouth disease to severe conditions such as myocarditis and meningoencephalitis. High mutation rates and serotype diversity complicate clinical management, as no approved vaccines or therapies exist. Triterpenoids, natural compounds with Antiviral and immunomodulatory effects, offer potential as novel treatments.

Purpose: This study evaluated the Antiviral potential of dehydrotumulosic acid (DA), a triterpenoid derived from Poria cocos, against coxsackievirus B3 (CVB3) and Other serotypes, while exploring its mechanism of action.

Methods: The Antiviral activity of DA was tested in vitro across multiple coxsackievirus serotypes using cytopathic effect inhibition, qRT-PCR(quantitative Reverse Transcription Polymerase Chain Reaction), Western blotting, and plaque assays to measure viral replication, mRNA, and protein levels. Transcriptomic profiling and cellular thermal shift assays provided mechanistic insights.

Results: DA exhibited strong Antiviral effects against coxsackievirus B1 (CVB1), coxsackievirus B2 (CVB2), CVB3, coxsackievirus A16 (CVA16), and coxsackievirus A (CVA6), reducing viral replication, mRNA, and protein synthesis in a dose-dependent manner without cytotoxicity. Mechanistically, DA binds and activates the Glucocorticoid Receptor (GR), suppressing MAPK (Mitogen-Activated Protein Kinase) /ERK(Extracellular Signal-Regulated Kinase) signaling and proinflammatory cytokine production. Compared to dexamethasone, a known GR agonist, the effects of DA were more sustained, highlighting its dual Antiviral and anti-inflammatory benefits.

Conclusion: DA emerges as a promising host-targeted Antiviral agent for coxsackievirus infections, addressing the critical unmet need for effective therapies. Its innovative dual action-combining potent Antiviral activity with anti-inflammatory effects via GR activation-distinguishes it from existing approaches, offering a promising candidate for further development.

Keywords

Coxsackievirus; Dehydrotumulosic acid; Glucocorticoid receptor; MAPK signaling; Poria cocos.

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