Astragaloside IV ameliorates diet-induced hepatic steatosis in obese mice by inhibiting intestinal FXR via intestinal flora remodeling

Zhai, Yuanyuan; Zhou, Wenling; Yan, Xu; Qiao, Yuan; Guan, Lingling; Zhang, Zhichun; Líu, Hao; Jiang, Jizhi; Liu, Jiang; Peng, Liang

doi:10.1016/j.phymed.2022.154444

Cited by 18 publications

(10 citation statements)

References 46 publications

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“…Bidirectional crosstalk between gut microbiota and bile acids could impair the intestinal epithelial function, increasing the translocation of gut-derived endotoxins such as LPS to the blood and lymphatics to activate hepatic TLR-4/NF-κB signaling and promote NAFLD or NASH [108,109]. HFD-mediated changes in bile acids decreased FXR and TGR5 signaling and degraded the intestinal barrier [110,111].…”

Section: Non-alcoholic Fatty Liver Disease (Nafld)mentioning

confidence: 99%

Bile Acids, Intestinal Barrier Dysfunction, and Related Diseases

Shi

Jin

Huang

2023

Cells

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The intestinal barrier is a precisely regulated semi-permeable physiological structure that absorbs nutrients and protects the internal environment from infiltration of pathological molecules and microorganisms. Bile acids are small molecules synthesized from cholesterol in the liver, secreted into the duodenum, and transformed to secondary or tertiary bile acids by the gut microbiota. Bile acids interact with bile acid receptors (BARs) or gut microbiota, which plays a key role in maintaining the homeostasis of the intestinal barrier. In this review, we summarize and discuss the recent studies on bile acid disorder associated with intestinal barrier dysfunction and related diseases. We focus on the roles of bile acids, BARs, and gut microbiota in triggering intestinal barrier dysfunction. Insights for the future prevention and treatment of intestinal barrier dysfunction and related diseases are provided.

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Section: Non-alcoholic Fatty Liver Disease (Nafld)mentioning

confidence: 99%

Bile Acids, Intestinal Barrier Dysfunction, and Related Diseases

Shi

Jin

Huang

2023

Cells

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“…The investigators transplanted IBATi-treated mouse fecal microbiomes into AIMD mice and revealed that restoration of a-diversity and Firmicutes:Bacteroidetes was involved in the amelioration of disease-related metabolic dysregulation in MAFLD mice [ 324 ]. In recent times, such combinatorial microbiome-related and animal model approaches have been adopted for a multitude of interventional factors ranging from small-molecule drugs [ 325 ] and defined dietary supplements or compounds [ 326 , 327 , 328 , 329 ] to herbal extracts [ 330 , 331 , 332 ].…”

Section: Mafld Preclinical Modelsmentioning

confidence: 99%

Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm

Chua

Low

Cheam

et al. 2022

IJMS

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Fatty liver disease is an emerging contributor to disease burden worldwide. The past decades of work established the heterogeneous nature of non-alcoholic fatty liver disease (NAFLD) etiology and systemic contributions to the pathogenesis of the disease. This called for the proposal of a redefinition in 2020 to that of metabolic dysfunction-associated fatty liver disease (MAFLD) to better reflect the current understanding of the disease. To date, several clinical cohort studies comparing NAFLD and MAFLD hint at the relevancy of the new nomenclature in enriching for patients with more severe hepatic injury and extrahepatic comorbidities. However, the underlying systemic pathogenesis is still not fully understood. Preclinical animal models have been imperative in elucidating key biological mechanisms in various contexts, including intrahepatic disease progression, interorgan crosstalk and systemic dysregulation. Furthermore, they are integral in developing novel therapeutics against MAFLD. However, substantial contextual variabilities exist across different models due to the lack of standardization in several aspects. As such, it is crucial to understand the strengths and weaknesses of existing models to better align them to the human condition. In this review, we consolidate the implications arising from the change in nomenclature and summarize MAFLD pathogenesis. Subsequently, we provide an updated evaluation of existing MAFLD preclinical models in alignment with the new definitions and perspectives to improve their translational relevance.

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“…A number of studies have shown that saponins possess the ability to alleviate NAFLD/NASH by modulating the gut microbiota. [ 11,21 ] Zhai et al. [ 21 ] reported that astragaloside IV ameliorated NAFLD through inhibiting the BAs deconjugation via the regulation of gut microbiota.…”

Section: Introductionmentioning

confidence: 99%

“…[ 11,21 ] Zhai et al. [ 21 ] reported that astragaloside IV ameliorated NAFLD through inhibiting the BAs deconjugation via the regulation of gut microbiota. Yang et al.…”

Section: Introductionmentioning

confidence: 99%

“…[20] A number of studies have shown that saponins possess the ability to alleviate NAFLD/NASH by modulating the gut microbiota. [11,21] Zhai et al [21] reported that astragaloside IV ameliorated NAFLD through inhibiting the BAs deconjugation via the regulation of gut microbiota. Yang et al [22] found that Akebia saponin D alleviated NAFLD via remodeling gut microbiota and maintaining the intestinal barrier function.…”

Section: Introductionmentioning

confidence: 99%

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Gut Microbiota Plays Essential Roles in Soyasaponin's Preventive Bioactivities against Steatohepatitis in the Methionine and Choline Deficient (MCD) Diet‐Induced Non‐Alcoholic Steatohepatitis (NASH) Mice

Su,

Wang,

Luo

et al. 2024

Molecular Nutrition Food Res

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ScopeGut microbiota (GM) is involved in nonalcoholic steatohepatitis (NASH) development. Phytochemicals soyasaponins can prevent NASH possibly by modulating GM. This study aims to investigate the preventive bioactivities of soyasaponin monomers (SS‐A1 and SS‐Bb) against NASH and explores the mechanisms by targeting GM.Methods and resultsMale C57BL/6 mice are fed with methionine and choline deficient (MCD) diet containing SS‐A1, SS‐Bb, or not for 16 weeks. Antibiotics‐treated pseudo germ‐free (PGF) mice are fed with MCD diet containing SS‐A1, SS‐Bb, or not for 8 weeks. GM is determined by 16S rRNA amplicon sequencing. Bile acids (BAs) are measured by UPLC‐MS/MS. In NASH mice, SS‐A1 and SS‐Bb alleviate steatohepatitis and fibrosis, reduce ALT, AST, and LPS in serum, decrease TNF‐α, IL‐6, α‐SMA, triglycerides, and cholesterol in liver. SS‐A1 and SS‐Bb decrease Firmicutes, Erysipelotrichaceae, unidentified‐Clostridiales, Eggerthellaceae, Atopobiaceae, Aerococcus, Jeotgalicoccus, Gemella, Rikenella, increase Proteobacteria, Verrucomicrobia, Akkermansiaceae, Romboutsia, and Roseburia. SS‐A1 and SS‐Bb alter BAs composition in liver, serum, and feces, activate farnesoid X receptor (FXR) in liver and ileum, increase occludin and ZO‐1 in intestine. However, GM clearance abrogates the preventive bioactivities of SS‐A1 and SS‐Bb against NASH.ConclusionGM plays essential roles in soyasaponin's preventive bioactivities against steatohepatitis in MCD diet‐induced NASH mice.

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Astragaloside IV ameliorates diet-induced hepatic steatosis in obese mice by inhibiting intestinal FXR via intestinal flora remodeling

Cited by 18 publications

References 46 publications

Bile Acids, Intestinal Barrier Dysfunction, and Related Diseases

Bile Acids, Intestinal Barrier Dysfunction, and Related Diseases

Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm

Gut Microbiota Plays Essential Roles in Soyasaponin's Preventive Bioactivities against Steatohepatitis in the Methionine and Choline Deficient (MCD) Diet‐Induced Non‐Alcoholic Steatohepatitis (NASH) Mice

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