Research Article Details
| Article ID: | A01787 |
| PMID: | 34618611 |
| Source: | Immunopharmacol Immunotoxicol |
| Title: | Capillin protects against non-alcoholic steatohepatitis through suppressing NLRP3 inflammasome activation and oxidative stress. |
| Abstract: | BACKGROUND: Non-alcoholic steatohepatitis (NASH) is an extreme form of non-alcoholic fatty liver disease. The present study concentrated on the role of Capillin, a polyacetylene compound isolated from Artemisia capillaris Thunb., in NASH development. MATERIALS AND METHODS: Palmitic acid (PA) was treated with FL83B hepatocytes, and high-fat diet was given to mouse to construct the NASH model in vivo. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, flow cytometry, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were carried out to measure the viability and apoptosis of FL83B hepatocytes. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to measure the mRNA expressions of infiltration markers (Cd11c, Ccr2, and Ly6c), fibrosis genes (Tgfβ1, Col1a1, and Timp1), and alpha-smooth muscle actin (α-SMA). Western blot, immunofluorescence, and Enzyme-linked immunosorbent assay (ELISA) were implemented to examine the proteins of Caspase-3, Bcl2, Nrf2, HO-1, NLRP3, ASC, and Caspase-1, the ROS level, and oxidative stress markers (MDA, GSH-ST, SOD, and GSH-Px), and the lipid peroxidation level, respectively. Moreover, HE staining was manipulated to observe the histopathological changes in liver tissue. RESULTS: Capillin hampered PA-mediated hepatocytes apoptosis and enhanced cell viability. Furthermore, Capillin suppressed PA-mediated oxidative stress in hepatocytes, promoted Nrf2/HO-1 expression, and repressed NLRP3-ASC-Caspase1 inflammasome. The in vivo studies indicated that Capillin vigorously improves liver fat accumulation, oxidative stress, and liver injury in NASH mice. Mechanistically, Capillin repressed NLRP3-ASC-Caspase1 inflammasome and up-regulated the Nrf2-HO-1 pathway in the liver. CONCLUSION: Capillin ameliorates hepatocyte injury by dampening oxidative stress and repressing NLRP3 inflammasome in NASH mice. |
| DOI: | 10.1080/08923973.2021.1984520 |
| 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T24 | C-C chemokine receptor type 2 | CCR2 | antagonist | GPCR | P41597 | CCR2_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T11 | Caspase-3 | CASP3 | inhibitor | Enzyme | P42574 | CASP3_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 |
| D558 | Yinchenhao decoction | Traditional medicine | -- | -- | -- | Under clinical trials | Details |
| D401 | A mixture of Huangqi, Huanglian, Zexie, Yujin, Zhidahuang, Shanzha, Maiya, Zhizhi, Huangqin and Yincheng | Herbal medicine | -- | -- | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D158 | Glutathione | Chemical drug | DB00143 | MGST3; HPGDS; GSTM2; GSTM5; GPX7 cofactor; MGST2; GSS; GSTM1; GSTK1; GSTM3; GSTM4; GPX1 cofactor; GPX2 cofactor; GPX3 cofactor | -- | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |