Lactobacillus casei Strain Shirota Enhances the Ability of Geniposide to Activate SIRT1 and Decrease Inflammation and...

Area of Science:

• Pharmacology
• Microbiology
• Immunology

Background:

• Geniposide, derived from Gardenia jasminoides, is a precursor to the antioxidant and anti-inflammatory agent genipin.
• Genipin is more potent than geniposide but suffers from instability and preservation challenges.
• Sepsis involves significant inflammatory and oxidative stress, leading to organ damage and reduced survival rates.

Purpose of the Study:

• To investigate the synergistic effects of Lactobacillus casei strain Shirota (LcS) and geniposide in a mouse model of sepsis.
• To elucidate the underlying mechanism involving the regulation of sirtuin type 1 (SIRT1) in mitigating sepsis-induced inflammation and oxidative damage.
• To compare the efficacy of the LcS + geniposide combination therapy with geniposide alone and the drug dexamethasone.

Main Methods:

• Establishment of a mouse sepsis model using cecal ligation and puncture.
• Administration of LcS and geniposide, followed by comprehensive physiological and molecular analyses.
• Evaluation of cognitive function, apoptosis, inflammatory markers (TNF-α, IL-6, IL-1β), oxidative stress markers (MDA, SOD, CAT), and SIRT1 pathway components (SIRT1, Ac-FOXO1, Ac-NF-κB, Ac-p53) via various assays including qPCR and Western blot.

Main Results:

• LcS + geniposide significantly increased survival rates and improved cognitive and behavioral parameters in septic mice.
• The combination therapy markedly reduced apoptosis, inflammatory cytokine levels, and oxidative stress markers in the hippocampus.
• LcS + geniposide upregulated SIRT1 expression and downregulated key inflammatory and apoptotic pathway proteins, demonstrating a potent anti-sepsis effect comparable to dexamethasone.

Conclusions:

• Lactobacillus casei strain Shirota enhances the therapeutic potential of geniposide in managing sepsis.
• The LcS + geniposide combination effectively reduces inflammation and oxidative stress in sepsis, primarily through the activation of the SIRT1 pathway.
• This synergistic approach offers a promising therapeutic strategy for sepsis, potentially superior to geniposide alone and comparable to conventional treatments.