Research Article Details
| Article ID: | A03317 |
| PMID: | 34047448 |
| Source: | Mol Nutr Food Res |
| Title: | Soyasaponin A2 Alleviates Steatohepatitis Possibly through Regulating Bile Acids and Gut Microbiota in the Methionine and Choline-Deficient (MCD) Diet-induced Nonalcoholic Steatohepatitis (NASH) Mice. |
| Abstract: | SCOPE: Nonalcoholic steatohepatitis (NASH) is a chronic progressive disease with complex pathogenesis of which the bile acids (BAs) and gut microbiota are involved. Soyasaponins (SS) exhibits many health-promoting effects including hepatoprotection, but its prevention against NASH is unclear. This study aims to investigate the preventive bioactivities of SS monomer (SS-A2 ) against NASH and further clarify its mechanism by targeting the BAs and gut microbiota. METHODS AND RESULTS: The methionine and choline deficient (MCD) diet-fed male C57BL/6 mice were intervened with obeticholic acid or SS-A2 for 16 weeks. Hepatic pathology is assessed by hematoxylin-eosin and Masson's trichrome staining. BAs in serum, liver, and colon are measured by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQMS). Gut microbiota in caecum are determined by 16S rDNA amplicon sequencing. In the MCD diet-induced NASH mice, SS-A2 significantly reduces hepatic steatosis, lobular inflammation, ballooning, nonalcoholic fatty liver disease activity score (NAS) scores, and fibrosis, decreases Erysipelotrichaceae (Faecalibaculum) and Lactobacillaceae (Lactobacillus) and increases Desulfovibrionaceae (Desulfovibrio). Moreover, SS-A2 reduces serum BAs accumulation and promotes fecal BAs excretion. SS-A2 changes the BAs profiles in both liver and serum and specifically increases the taurohyodeoxycholic acid (THDCA) level. Faecalibaculum is negatively correlated with serum THDCA. CONCLUSION: SS-A2 alleviates steatohepatitis possibly through regulating BAs and gut microbiota in the MCD diet-induced NASH mice. |
| DOI: | 10.1002/mnfr.202100067 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S06 | Regulating intestinal flora | intestine gut microbiota; gut microbiota | farnesoid X receptor (FXR); fibroblast growth factor-19 (FGF19) | Probiotics; Prebiotics; Rifaximin; Yaq-001; Cilofexor; EDP-305; EYP001a; INT-767 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T17 | Farnesoid X-activated receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T07 | Bile acid receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D075 | Choline | Supplement | DB00122 | PLD2 product of; PLD1 product of | -- | Under clinical trials | Details |
| D018 | Aspirin | Chemical drug | DB00945 | AKR1C1 inhibitor; PCNA downregulator | Enhance lipid metabolism | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |