Tubeimoside I improves survival of mice in sepsis by inhibiting inducible nitric oxide synthase expression.

Abstract

Sepsis is a disease with high mortality rate worldwide and inducible nitric oxide (iNOS) induced vascular hyporeactivity plays a key role in it. There is no effective drug to treat vascular hyporeactivity specifically. Tubeimoside I (TBM) is a triterpenoid saponin isolated from Rhizoma Bolbostemmatis. In this study, we found that 4 mg/kg TBM intraperitoneally injected 1 h before cecal ligation and puncture (CLP) partially improved survival, ameliorated mean arterial pressure (MAP) and enhanced vascular responsiveness to norepinephrine (NE) and KCl in wild-type septic mice. CLP activated TLR4-MyD88-NF-κB-iNOS pathway was also inhibited by TBM both in vitro and in vivo. However, iNOS gene knockout counteracted the protection provided by TBM. We conclude that TBM protects mice in sepsis by reducing excessive NO production through inhibiting the TLR4-MyD88-NF-κB-iNOS pathway. Our study suggests a possible therapeutic application of TBM in sepsis.

• Authors: Minghao Luo, Suxin Luo, Zhe Cheng, Xiyang Yang, Dingyi Lv, Xingbing Li, Yongzheng Guo, Chang Li, Jianghong Yan
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 126 Pg. 110083 (Jun 2020) ISSN: 1950-6007 [Electronic] France
• PMID: 32272432 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Biomarkers
• Drugs, Chinese Herbal
• Enzyme Inhibitors
• Saponins
• Triterpenes
• Vasoconstrictor Agents
• tubeimoside I
• Nitric Oxide
• Nitric Oxide Synthase
• Norepinephrine

Topics

• Animals
• Biomarkers
• Disease Models, Animal
• Drugs, Chinese Herbal (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Gene Expression
• Gene Expression Regulation (drug effects)
• Male
• Mesenteric Arteries (drug effects, metabolism)
• Mice
• Mice, Knockout
• Myocytes, Smooth Muscle (drug effects, metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (genetics)
• Norepinephrine (pharmacology)
• Prognosis
• Saponins (pharmacology)
• Sepsis (drug therapy, etiology, mortality)
• Signal Transduction (drug effects)
• Treatment Outcome
• Triterpenes (pharmacology)
• Vasoconstrictor Agents (pharmacology)