Research Article Details
| Article ID: | A04060 |
| PMID: | 33773192 |
| Source: | Phytomedicine |
| Title: | Si Miao Formula attenuates non-alcoholic fatty liver disease by modulating hepatic lipid metabolism and gut microbiota. |
| Abstract: | BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with few therapeutic options available currently. Traditional Chinese Medicine (TCM) has been practiced for thousands of years in China and Asian countries, and regarded as an important source for identifying novel medicines for diseases. Si Miao Formula (SMF) is a classical TCM formula for the treatment of gout disease by reducing serum uric acid concentrations, while high concentration of uric acid is also an independent risk factor for NAFLD. PURPOSE: To investigate the protective effect of SMF on NAFLD in a mouse model induced by a high fat/high sucrose (HFHS) diet. METHODS: Mice received a HFHS diet over a 16-week period to induce NAFLD with or without SMF intervention. Lipid levels were measured in both the liver and serum. Histopathological staining was used to evaluate the extent of hepatic lipid accumulation. Liver transcriptomics was used to enrich differentially expressed genes and to predict regulatory pathways after gene set enrichment analysis. 16S rRNA gene sequencing was used to determine the microbial composition. Genes of liver lipid metabolism, inflammation and intestinal tight junctions were detected by qRT-PCR analysis. RESULTS: SMF attenuated hepatic steatosis, reduced body weight gain and lipid concentrations, improved sensitivity to insulin and also tolerance to glucose, in mice fed an HFHS diet. Hepatic transcriptomics showed that SMF downregulated the biosynthesis of fatty acids and stimulated the insulin secretion pathway. SMF significantly altered the gut microbiota composition and in particular increased the proportion of Akkermansia muciniphila. In agreement with liver transcriptomics, SMF downregulated the expression of genes implicated in the metabolism of lipids (Acly, Fas, Acc, Scd-1) and pro-inflammatory cytokines (Il-1β, Nlrp-3) in the livers. CONCLUSION: The results indicate that SMF attenuates HFHS diet-induced NAFLD and regulates hepatic lipid metabolism pathways. The anti-NAFLD effect of SMF was linked to modulation of the gut microbiota composition and in particular an increased relative abundance of Akkermansia muciniphila. |
| DOI: | 10.1016/j.phymed.2021.153544 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | 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 | |
|---|---|---|---|---|---|---|---|
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T46 | ATP-citrate synthase | ACLY | inhibitor | Transferase | P53396 | ACLY_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_HUMAN | Details |
| T22 | Stearoyl-CoA desaturase | SCD | inhibitor | Enzyme | O00767 | SCD_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I15 | 1290 | Bone disease | A connective tissue disease that affects the structure or development of bone or causes an impairment of normal bone function. http://en.wikipedia.org/wiki/Bone_disease | disease of anatomical entity/ musculoskeletal system disease/connective tissue disease | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |