2. Academic Validation
  3. Lithospermic acid targeting heat shock protein 90 attenuates LPS-induced inflammatory response via NF-кB signalling pathway in BV2 microglial cells

Lithospermic acid targeting heat shock protein 90 attenuates LPS-induced inflammatory response via NF-кB signalling pathway in BV2 microglial cells

  • Immunol Res. 2025 Feb 19;73(1):54. doi: 10.1007/s12026-025-09600-1.
Jie Guo # 1,  Chen-Guang Li # 2,  Feng-Yi Mai # 3,  Jing-Rong Liang 2,  Ze-Hao Chen 2,  Jiao Luo 1,  Ming-Chao Zhou 1,  Yu-Long Wang 4,  Wen-Tao Yang 5
Affiliations

Affiliations

  • 1 Department of Rehabilitation Medicine, Shenzhen Second People's Hospital, Shenzhen, 518035, China.
  • 2 Pain Department, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), Shenzhen, 518052, China.
  • 3 Department of Human Cell Biology and Genetics, Southern University of Science and Technology School of Medicine, Shenzhen, 518055, China.
  • 4 Department of Rehabilitation Medicine, Shenzhen Second People's Hospital, Shenzhen, 518035, China. ylwang688@163.com.
  • 5 Pain Department, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), Shenzhen, 518052, China. yangwentao3000@126.com.
  • # Contributed equally.
PMID: 39969702 DOI: 10.1007/s12026-025-09600-1
Abstract

Microglia function as a vital constituent in the maintenance of brain homeostasis. Aberrant microglial activation, however, may contribute to neurodegenerative diseases. Lithospermic acid (LA) is a plant-derived polycyclic phenolic carboxylic acid isolated from Salvia miltiorrhiza. The present study investigated the potential effects of lithospermic acid on LPS-induced neuroinflammation in BV2 microglial cells and determined the mechanism of action of this compound. Cells were pre-treated with lithospermic acid for 1 h and incubated with LPS for 24 h. qPCR, immunofluorescence, and immunoblot assays were used to determine the expression of iNOS, COX2, NF-κB p65, and HSP90 expression. ELISA was employed to measure the production of pro-inflammatory cytokines. Lithospermic acid dramatically reduced LPS-stimulated cell migration and decreased NF-κB p65 nuclear translocation. Furthermore, lithospermic acid also markedly decreased the production of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α in a dose-dependent manner. Additionally, lithospermic acid inhibited NO and PGE2 production in response to LPS, and it also inhibited the expression of iNOS and COX2 in a dose-dependent manner. Molecular docking and experimental verification have demonstrated that lithospermic acid inhibits the activity and expression of HSP90. Small interfering RNA knockdown of HSP90 expression, which abrogated LPS-induced inflammation. These findings suggest that the lithospermic acid targeting HSP90 attenuates LPS-induced inflammatory response via the NF-κB signalling pathway in BV2 microglial cells. Collectively, lithospermic acid may offer therapeutic benefits for neurodegenerative disorders associated with microglial activation and could serve as a potential inhibitor/agent for the treatment of neuroinflammation.

Keywords

Anti-inflammatory effects; BV2 microglial cells; Lithospermic acid; NF-кB signalling pathway.

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