Research Article Details
| Article ID: | A42202 |
| PMID: | 35247475 |
| Source: | J Ethnopharmacol |
| Title: | The Chinese medicine Fufang Zhenzhu Tiaozhi capsule protects against renal injury and inflammation in mice with diabetic kidney disease. |
| Abstract: | ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi capsule (FTZ) is a patented preparation of Chinese herbal medicine that has been used to treat hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and other glucolipid metabolic diseases (GLMDs) in the clinic for almost 10 years. However, how FTZ reduces albuminuria and attenuates diabetic kidney disease (DKD) progression is unknown. AIM OF THE STUDY: To clarify the effects of FTZ on DKD mice model and to explore the underlying mechanisms. MATERIALS AND METHODS: We used streptozotocin (STZ) (40 mg/kg/d, i.p. for 5 days, consecutively) combined with a high-fat diet (HFD) to induce a DKD mouse model, followed by FTZ (1, 2 g/kg/d, i.g.) treatment for 12 weeks. Losartan (30 mg/kg/d, i.g.) was used as a positive control. Measurements of 24 h proteinuria, serum creatinine (SCr), fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels and expression levels of fibronectin (FN), collagen IV, inflammatory cytokines, inflammatory cells, interleukin-17A (IL-17A) and the nuclear transcription factor-κB (NF-κB) signaling pathway in the kidney were examined. RESULTS: FTZ effectively decreased 24 h proteinuria, Scr, FBG, TC, TG, and LDL-C levels, inhibited mesangial cell expansion, reduced FN and collagen IV accumulation, and F4/80+ macrophage cell infiltration and Ly-6G+ neutrophil infiltration in glomerulus and tubulointerstitium. Furthermore, IL-17A production and the NF-κB signaling pathway were also downregulated after the administration of FTZ. CONCLUSION: FTZ might attenuate DKD progression, and inhibited kidney inflammation and fibrosis by inhibiting the expression of RORγT and IL-17A in vivo, offering novel insights for the clinical application of FTZ. |
| DOI: | 10.1016/j.jep.2022.115165 |
| 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 |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_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 |
| T21 | Diacylglycerol O-acyltransferase 2 | DGAT2 | inhibitor | Enzyme | Q96PD7 | DGAT2_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I07 | 1936 | Arteriosclerosis | Build-up of fatty material and calcium deposition in the arterial wall resulting in partial or complete occlusion of the arterial lumen.https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C35768 | disease of anatomical entity/cardiovascular system disease/ vascular disease/ artery 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 |
| D144 | FTZ | Chemical drug | -- | -- | -- | Under clinical trials | Details |
| D209 | Losartan | Chemical drug | DB00678 | AGTR1 antagonist&binder | Anti-fibrosis | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D413 | Zhenzhu Tiaozhi Capsule | Traditional medicine | -- | -- | -- | 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 |