Lactobacillus casei Strain Shirota Enhances the Ability of Geniposide to Activate SIRT1 and Decrease Inflammation and Oxidative Stress in Septic Mice.

Chao Mai,Yong Zeng,Xingqin Tan,Li Qiu

doi:10.3389/fphys.2021.678838

Abstract

Gardenia jasminoides Ellis is rich in geniposide, which can be transformed into the anti-oxidant and anti-inflammatory agent genipin. Genipin exhibits greater efficacy than geniposide, but it is unstable and difficult to preserve. In this study, a mouse model for sepsis was established by cecal ligation and puncture, and then we explored the effects and mechanism of Lactobacillus casei strain Shirota (LcS) on the enhancement of the ability of geniposide to reduce sepsis and decrease inflammatory and oxidative levels in mice by the regulation of sirtuin type 1 (SIRT1). The mice were evaluated and analyzed by the open field test, Morris water maze test, flow cytometry, kit assay, qPCR, and western blot. The LcS + geniposide increased the survival rate in mice with sepsis, and increased the total travel distance, number of times the mice stood up, amount of time the mice spent grooming their fur, duration in the target quadrant, and crossing area number. The testing of mouse nerve cells showed that LcS + geniposide reduced the rate of nerve cell apoptosis caused by sepsis. LcS + geniposide also decreased the amount of inflammatory-related indicators of TNF-α, IL-6, and IL-1β, and the oxidation-related levels of malondialdehyde (MDA) in the hippocampi of septic mice, and it increased the oxidase activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, LcS + geniposide increased the SOD1, SOD2, and CAT mRNA expression in the hippocampi of mice with sepsis and decreased the expression of TNF-α, IL-1β, NF-κB, and p53 mRNA. LcS+geniposide also increased the SIRT1 protein expression and decreased the Ac-FOXO1, Ac-NF-κB, and Ac-p53 protein expression in the hippocampi of mice with sepsis. We also observed that LcS + geniposide decreased the inflammatory and oxidative damage in the mice with sepsis. The effect of LcS + geniposide was similar to that of the drug dexamethasone and stronger than the effect of geniposide utilized alone. LcS also enhanced the ability of geniposide to activate SIRT1 and decrease the inflammation and oxidative stress in the septic mice, and it achieved an effect same with that obtained by the use of the drug dexamethasone.

Highlights

Sepsis is an organ dysfunction syndrome caused by an imbalance in response to infection (Jackson, 2004)
After the completion of the surgical modeling, the mice in each group were treated daily, and normal saline (0.2 ml) was administered by gavage to the mice in the normal and model groups; the Lactobacillus casei strain Shirota (LcS) group mice were treated with LcS (5 × 107 colony-forming unit (CFU)/kg) by gavage; the geniposide group mice were treated with geniposide (50 mg/kg, purity 99.9%; Shanghai Yuanye Biotechnology Co., Ltd., Shanghai, China) by gavage; the LcS + geniposide group mice were treated with LcS (5 × 107 CFU/kg) and geniposide (50 mg/kg) by gavage; the dexamethasone group mice were treated with dexamethasone (1 mg/kg) by intraperitoneal injection and treated with normal saline (0.2 ml) by gavage; and all the treatments were administered for 1 week
Within 48 h, eight mice died in the model group, seven mice died in the LcS group, 6 mice died in the geniposide group, two mice died in the LcS + geniposide group, and three mice in the dexamethasone group died

Summary

Introduction

Sepsis is an organ dysfunction syndrome caused by an imbalance in response to infection (Jackson, 2004). The severity of sepsis can increase and develop into septic shock, which can endanger life by leading to organ dysfunction or failure. Sepsis can affect all main organs of the body, and its pathogenesis and developmental mechanism are complex (Rudiger and Singer, 2007). The disease shows the effects of memory loss, cognitive ability and action ability. These symptoms lead to the decline of patients’ quality of life and have a negative impact on society and family

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