Saikosaponin A-Induced Gut Microbiota Changes Attenuate Severe Acute Pancreatitis Through the Activation of Keap1/Nrf2-ARE Antioxidant Signaling

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2020 Nov 18

PMID 33204401

Citations 12

Authors

Jing Li

Jinfeng Han

Juan Lv

Shiji Wang

Lai Qu

Yanfang Jiang

Affiliations

Soon will be listed here.

Abstract

Objective: Severe acute pancreatitis (SAP) is a serious and life-threatening disease associated with multiple organ failure and a high mortality rate and is accompanied by distinct oxidative stress and inflammatory responses. Saikosaponin A has strong antioxidant properties and can affect the composition of gut microbiota. We sought to determine the effects of Saikosaponin A interventions on SAP by investigating the changes of gut microbiota and related antioxidant signaling.

Methods: A SAP model was established in Sprague-Dawley (SD) rats through the injection of sodium taurocholate into the biliopancreatic duct and confirmed by elevated levels of serum lipase and amylase. The model was fed a standard diet either with saline solution or with Saikosaponin A. Fecal microbiota transplantation (FMT) from Saikosaponin A-induced rats into the rat model was performed to test the effects of gut microbiota. The composition of gut microbiota was analyzed by using 16S rRNA gene sequencing. We measured apoptotic status, inflammatory biomarkers, and Keap1-Nrf2-ARE ((Kelch-like ECH-associated protein 1) nuclear factor erythroid 2-related factor 2-antioxidant response element) antioxidant signaling.

Results: Saikosaponin A intervention attenuated SAP lesions and reduced the levels of serum amylase and lipase, oxidative stress, and inflammatory responses by reducing pathological scores and affecting the serum level of oxidative and inflammatory factors. Meanwhile, the expression of Keap1-Nrf2-ARE was increased. Saikosaponin A intervention improved microbiota composition by increasing the relative abundance of Lactobacillus and Prevotella species. FMT resulted in similar results as those caused by the Saikosaponin A intervention, suggesting Saikosaponin A may exert its function via the improvement of gut microbiota composition.

Conclusions: Saikosaponin A-induced gut microbiota changes attenuate SAP progression in the rat model and may be a potential natural drug for adjuvant treatment of SAP. Further work is needed to clear up the points.

Citing Articles

Saikosaponin A alleviates depressive-like behavior induced by reserpine in mice by regulating gut microflora and inflammatory responses.

Wang M, Li H, Zhang W, Zhang L, Wang S, Jia M PLoS One. 2025; 20(2):e0311207.

PMID: 39928658 PMC: 11809902. DOI: 10.1371/journal.pone.0311207.

Fecal Microbiota Transplantation Activity of Polysaccharides and Their Protective Effect on Cyclophosphamide-Induced Immunosuppression and Intestinal Injury in Mice.

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Pharmacology, medical uses, and clinical translational challenges of Saikosaponin A: A review.

Sun X, Chai Y, Bai X, Li H, Xi Y Heliyon. 2024; 10(22):e40427.

PMID: 39641011 PMC: 11617869. DOI: 10.1016/j.heliyon.2024.e40427.

The causal relationship between the gut microbiota and acute pancreatitis: A 2-sample Mendelian randomization study.

He L, Luo H, Li Y, Zhang Y, Peng L, Xu Y Medicine (Baltimore). 2024; 103(22):e38331.

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The role of gut microbiome and its metabolites in pancreatitis.

Pan L, Yin N, Duan M, Mei Q, Zeng Y mSystems. 2024; 9(10):e0066524.

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