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Saponin fraction from Astragalus membranaceus roots protects mice against polymicrobial sepsis induced by cecal ligation and puncture by inhibiting inflammation and upregulating protein C pathway

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Abstract

Sepsis remains the leading cause of death in intensive care units. Uncontrolled systemic inflammation and an impaired protein C pathway are two important contributors to sepsis pathophysiology. Based on the beneficial effects of the saponin fraction from Astragalus membranaceus roots (SAM) against inflammation, liver dysfunction, and endothelium injury, we investigated the potential protective roles and underlying mechanisms of SAM on polymicrobial sepsis induced by cecal ligation and puncture (CLP) in mice. SAM, orally administered 1 h before and after CLP, significantly elevated the survival rate of mice. At 96 h after CLP operation, all mice in the model group died, whereas 33.3% of mice in the SAM (400 mg/kg)-treated group survived. SAM attenuated both inflammatory factors and their abilities to induce tissue dysfunction, which was mainly evidenced by decreased infiltration of polymorphonuclear leukocytes, tissue edema, and lung wet-to-dry weight ratio, lowered levels of myeloperoxidase (MPO), nitric oxide (NO), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in serum, as well as downregulated expressions of iNOS and IL-1β mRNA in livers. Furthermore, we addressed the effects of SAM on the protein C (PC) pathway, closely linked with sepsis. In CLP-induced septic mice, SAM elevated the impaired expression of PC mRNA in livers. In vitro, SAM reversed the decreased expressions of thrombomodulin (TM) and endothelial PC receptor (EPCR) mRNA induced by lipopolysaccharide (LPS) in endothelial cells. These findings suggest that SAM is able to restore the impaired protein C pathway. Taken together, the current study demonstrates that SAM has protective effects on polymicrobial sepsis in mice. The mechanisms of action involve anti-inflammation and upregulation of the PC pathway.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 30600821), the Natural Science Foundation of Anhui Province (No. 050431004), the postgraduate innovation project of Jiangsu Province.

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Authors and Affiliations

  1. Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 1 Shennong Road, 210038, Nanjing, China

    Xing-hua Gao, Xian-xiang Xu, Rong Pan, Ying Li, Yu-bin Luo & Yue Dai

  2. Department of Analysis of Chinese Materia Medica, China Pharmaceutical University, 1 Shennong Road, 210038, Nanjing, China

    Yu-feng Xia

  3. School of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan

    Kazuya Murata & Hideaki Matsuda

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  1. Xing-hua Gao
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Correspondence to Yue Dai.

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Gao, Xh., Xu, Xx., Pan, R. et al. Saponin fraction from Astragalus membranaceus roots protects mice against polymicrobial sepsis induced by cecal ligation and puncture by inhibiting inflammation and upregulating protein C pathway. J Nat Med 63, 421–429 (2009). https://doi.org/10.1007/s11418-009-0348-2

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  • DOI: https://doi.org/10.1007/s11418-009-0348-2

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