Research Article Details
| Article ID: | A49338 |
| PMID: | 35784533 |
| Source: | Front Endocrinol (Lausanne) |
| Title: | Fufang Zhenzhu Tiaozhi Capsule Prevents Intestinal Inflammation and Barrier Disruption in Mice With Non-Alcoholic Steatohepatitis. |
| Abstract: | Nonalcoholic steatohepatitis (NASH) has become a major cause of liver transplantation and liver-associated death. Targeting the gut-liver axis is a potential therapy for NASH. The Fufang Zhenzhu Tiaozhi (FTZ) capsule, a traditional Chinese medicine commonly used in clinical practice, has recently emerged as a promising drug candidate for metabolic diseases such as NASH. The present study aimed to investigate whether FTZ exerts an anti-NASH effect by targeting the gut-liver axis. Mice were fed with a high-fat diet (HFD) for 20 weeks to induce NASH. HFD-fed mice were daily intragastrically administrated with FTZ at 10 weeks after tbe initiation of HFD feeding. The mRNA levels of genes associated with the intestinal tight junction, lipid metabolism, and inflammation were determined by the q-PCR assay. Hepatic pathology was evaluated by H&E staining. The gut microbiota was analyzed by 16S rRNA gene sequencing. FTZ attenuated HFD-induced obesity, insulin resistance, and hepatic steatosis in mice. FTZ treatment decreased the elevated levels of serum aminotransferases and liver triglyceride in NASH mice. Furthermore, FTZ treatment reduced hepatic inflammatory cell infiltration and fibrosis in mice. In addition, FTZ attenuated the intestinal inflammatory response and improved intestinal barrier function. Mechanistically, FTZ-treated mice showed a different gut microbiota composition compared with that in HFD-fed mice. Finally, we identified eight differential metabolites that may contribute to the improvement of NASH with FTZ treatment. In summary, FTZ ameliorates NASH by inhibiting gut inflammation, improving intestinal barrier function, and modulating intestinal microbiota composition. |
| DOI: | 10.3389/fendo.2022.864703 |
| 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 |
| 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 |
| 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 |
| S10 | Liver transplantation | -- | -- | -- | 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 |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | 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 |
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D144 | FTZ | Chemical drug | -- | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D413 | Zhenzhu Tiaozhi Capsule | Traditional medicine | -- | -- | -- | Under clinical trials | Details |