2. Academic Validation
  3. Salvianolic acid B improves the microcirculation in a mouse model of sepsis through a mechanism involving the platelet receptor CD226

Salvianolic acid B improves the microcirculation in a mouse model of sepsis through a mechanism involving the platelet receptor CD226

  • Br J Pharmacol. 2024 Oct 23. doi: 10.1111/bph.17371.
Xuemei Li 1 2,  Shanshou Liu 3,  Jiangang Xie 3,  Lin Liu 3,  Chujun Duan 1 4,  Lu Yang 1,  Yuling Wang 1,  Yilin Wu 1,  Niqi Shan 1,  Yun Zhang 1,  Yuan Zhang 1,  Ran Zhuang 1
Affiliations

Affiliations

  • 1 Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China.
  • 2 College of Life Sciences, Northwest University, Xi'an, Shaanxi, China.
  • 3 Department of Emergency, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
  • 4 Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi, China.
PMID: 39443080 DOI: 10.1111/bph.17371
Abstract

Background and purpose: Salvianolic acid B (SalB) demonstrates diverse clinical applications, particularly in cardiovascular and cerebral protection. This study primarily investigated the effects of SalB on sepsis.

Experimental approach: The model of sepsis via caecal ligation puncture (CLP) was established in male C57BL/6 mice. Therapeutic effects of SalB on hepatic and pulmonary injury, inflammatory responses and microcirculatory disturbances in sepsis were evaluated. Platelet aggregation and adhesion were measured via flow cytometry and an adhesion test. After overexpression of platelet-related activating molecules by 293T cells, the efficient binding of SalB and platelet CD226 molecules was further evaluated. Finally, neutralizing antibody experiments were used to assess the mechanism of SalB in alleviating the progression of sepsis.

Key results: SalB mitigated hepatic and pulmonary impairments, reduced inflammatory cytokine levels and enhanced mesenteric microvascular blood flow in septic mice. SalB enhanced CLP-induced reduction of platelet count and platelet pressure cumulative volume. SalB reduced platelet adhesion to endothelial cells and platelet aggregation to leukocytes. A high binding efficiency was observed between SalB and the platelet adhesion molecule CD226. Ex vivo, interactions between SalB and platelets from CD226-knockout mice were markedly decreased. In vivo administration of CD226 neutralizing Antibodies significantly delayed disease progression and enhanced mesenteric microcirculation in septic mice.

Conclusion and implications: In our murine model of sepsis, treatment with SalB improved the microcirculatory disturbance and hindered the progression of sepsis by inhibiting platelet CD226 function. Our results suggest SalB is a promising therapeutic approach to the treatment of sepsis.

Keywords

adhesion molecule; microcirculatory dysfunction; platelet; salvianolic acid B; sepsis.

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