1. Academic Validation
  2. Glaucocalyxin a protect liver function via inhibiting platelet over-activation during sepsis

Glaucocalyxin a protect liver function via inhibiting platelet over-activation during sepsis

  • Phytomedicine. 2022 Jun;100:154089. doi: 10.1016/j.phymed.2022.154089.
Jiang Jiang 1 Dengping Liu 2 Yuanyuan Wang 3 Wei Li 4 Zhihui Hong 1 Jianzhong An 2 Shigang Qiao 5 Zhanli Xie 6
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, The Second Affiliated Hospital of Soochow University, Suzhou, China.
  • 2 Institute of Clinical Medicine Research, Suzhou Science & Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
  • 3 Department of Intensive Care Unit, Suzhou Science & Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
  • 4 Cyrus Tang Hematology Center, Soochow University, Suzhou, China.
  • 5 Institute of Clinical Medicine Research, Suzhou Science & Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, China; Faculty of Anesthesiology, Suzhou Science & Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
  • 6 Institute of Clinical Medicine Research, Suzhou Science & Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, China. Electronic address: [email protected].
Abstract

Background: Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) is a perennial herb, and is traditionally used as folk medicine for treating inflammatory diseases and Cancer. Gaucocalyxin A (GLA) is an ent‑kaurane diterpenoid that is isolated from the aerial parts of R. japonica (Burm. f.) var. glaucocalyx (Maxim.). In a recent study, we found that GLA protects against acute liver dysfunction induced by Escherichia coli, which is likely related to its anti-inflammatory effects. However, the mechanism by which GLA protects liver injury during sepsis is unknown.

Aim: To evaluate the anti-inflammatory function of GLA and its regulatory effect on platelet function.

Method: An in vivo model of sepsis was established by inoculating mice with E. coli. Live function and platelet activation were evaluated through standard assays. The levels of pro-inflammatory factors were measured through ELISA and qRT-PCR.

Results: GLA alleviated liver dysfunction in the mouse model of sepsis. GLA-treated mice displayed lower complement activation and liver dysfunction after E. coli Infection. GLA alleviated the decrease in peripheral platelet counts by inhibiting their clearance by Kupffer cells in liver. Furthermore, GLA inhibited platelet activation through the RIP1/RIP3/Akt pathway and downregulated C3aR expression on the platelets, thereby inhibiting liver injury and dysfunction due to excessive complement activation.

Conclusion: GLA can inhibit platelet activation by reducing surface expression of C3aR, which protect the liver from injury induced by excessive complement activation. GLA is a novel therapeutic agent for controlling sepsis-related liver dysfunction.

Keywords

Complement activation; Gaucocalyxin A; Liver function; Platelet; Sepsis.

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