Effect of Corynoline Isolated from &lt;i&gt;Corydalis bungeana&lt;/i&gt; Turcz on Lipopolysaccharides-Induced Sepsis &lt;i&gt;In vivo&lt;/i&gt; and &lt;i&gt;In vitro&lt;/i&gt;

Z He,Z Peng,L Jin,P Chen

doi:10.4314/tjpr.v13i1.12

Abstract

Purpose: To investigate the protective effect of corynoline isolated from Corydalis bungeana Turcz on lipopolysaccharides (LPS)-induced sepsis, and determine the possible mechanism of anti-sepsis effect of the isolated corynoline. Methods: Corynoline was extracted by column chromatography. LPS (100 ng/mL) was used to induce the release of TNF-α and IL-6 in RAW 264.7 cells, and the isolated corynoline was added. ELISA method was used to determine the levels of TNF-α and IL- 6. Furthermore, sepsis in mice was established by injection of LPS (2 mg/kg, i.v.), and the levels of TNF-α and IL-6 in plasma were determined by ELISA method. For survival rate test, LPS (15 mg/kg, i.v.) and heat-killed E. coli (1.0 ×10 11 CFU/kg, i.v.) were used to establish sepsis in mice model, and the mice were observed in 7 days. Results: The results indicate that corynoline significantly elevated the survival rate of septic mice induced by LPS and heat-killed E. coli, in a dose-dependent manner (p < 0.05). Corynoline decreased the release of TNF-α and IL-6 induced by LPS, in a dose-dependent manner (p < 0.05). Conclusion: Treatment with corynoline significantly inhibits the mortality of LPS-induced septic mice, and the mechanism of action is probably related to the decrease of TNF-α and IL-6 release. Thus corynoline has the potential to be developed as an effective and safe drug for treating sepsis.

Highlights

Sepsis, defined as the harmful or damaged systemic host response to infection induced by microorganisms, is a life-threatening disorder [1]
In the results of our present study, corynoline at doses of 20, 40 and 80 μg/mL significantly suppressed the expressions of TNF-α and IL-6 induced by LPS in RAW 264.7 (p < 0.05) (Figure 2B and C)
The sepsis mice induced by heat-killed E. coli was established, and the protective effect of corynoline on sepsis was further evaluate; the results revealed that the corynoline showed good protective effect on sepsis mice

Summary

INTRODUCTION

Sepsis, defined as the harmful or damaged systemic host response to infection induced by microorganisms, is a life-threatening disorder [1]. Far there have been no reports on the effects of corynoline on LPS-induced sepsis in mice and its possible mechanisms of action. Corynoline (20, 40, 80 μg/mL) added immediately after addition of 100 ng/mL LPS After incubation for another 4 h, the supernatants were collected to assess TNF-α and IL-6 levels using ELISA kits. To exclude the possibility that the inhibitory effects of corynoline on the pro-inflammatory cytokines production were due to the cytotoxcity of corynoline, MTT assay was performed, and when the RAW 264.7 cells were treated with corynoline and LPS, there was no obvious change in cell viability (Figure 2A). In the results of our present study, corynoline at doses of 20, 40 and 80 μg/mL significantly suppressed the expressions of TNF-α and IL-6 induced by LPS in RAW 264.7 (p < 0.05) (Figure 2B and C)

RESULTS

DISCUSSION

CONCLUSION