ReferenceID 2020
Selective STAT3 Inhibitor Alantolactone Ameliorates Osteoarthritis via Regulating Chondrocyte Autophagy and Cartilage Homeostasis
Front Pharmacol
Osteoarthritis (OA), which is identified by chronic pain, impacts the quality of life. Cartilage degradation and inflammation are the most relevant aspects involved in its development. Signal transducer and activator of
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 2020
- Evidence Id
- 18610
- Core Evidence Id
- 18610
- Source Reference Id
- 4050
- Herb2 Reference Id
- HBREF004847
- Subject Paper Key
- HBIN028928_34650433
- Pubmed Id
- 34650433
- Doi
- 10.3389/fphar.2021.730312
- Paper Title
- Selective STAT3 Inhibitor Alantolactone Ameliorates Osteoarthritis via Regulating Chondrocyte Autophagy and Cartilage Homeostasis
- Paper Abstract
- Osteoarthritis (OA), which is identified by chronic pain, impacts the quality of life. Cartilage degradation and inflammation are the most relevant aspects involved in its development. Signal transducer and activator of transcription 3(STAT3), a member of the STATs protein family, is associated with inflammation. Alantolactone (ALT), a sesquiterpene lactone compound, can selectively suppress the phosphorylation of STAT3. However, the pharmacological effect of ALT on OA is still imprecise. In this study, IL-1beta (10 ng/ml) was applied to cartilage chondrocytes, which were treated with different concentrations of Alantolactone for 24 h. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2(COX2), matrix metalloproteinases (MMPs) and thrombospondin motifs-5 (ADAMTS5) were detected by western blot. Protein expression of Collagen II was observed by western blot, safranin O staining and immunofluorescence. Manifestation of autophagy related proteins such as autophagy-related gene-5 (ATG5), P62, LC3II/I and PI3K/AKT/mTOR-related signaling molecules were measured by western blot and autophagic flux monitored by confocal microscopy. Expression of STAT3 and NF-kappaB-related signaling molecules were evaluated by western blot and immunofluorescence. In vivo, 2 mg/kg ALT or equal bulk of vehicle was engaged in the destabilization of medial meniscus (DMM) mouse models by intra-articular injection, the degree of cartilage destruction was classified by Safranin O/Fast green staining. Our findings reported that the enhance of inflammatory factors containing iNOS, COX2, MMPs and ADAMTS5 induced by IL-1beta could be ameliorated by ALT. Additionally, the diminish of Collagen II and autophagy which was stimulated by IL-1beta could be alleviated by ALT. Mechanistically, STAT3, NF-kappaB and PI3K/AKT/mTOR signal pathways might be involved in the effect of ALT on IL-1beta-induced mouse chondrocytes. In vivo, ALT protected cartilage in the DMM mouse model. Overall, this study illustrated that ALT attenuated IL-1beta-induced inflammatory responses, relieved cartilage degeneration and promoted impaired autophagy via restraining of STAT3 and NF-kappaB signal pathways, implying its auspicious therapeutical effect for OA.
- Journal
- Front Pharmacol
- Publish Year
- 2021
- Experiment Subject
- mouse; il-1beta-induced mouse chondrocytes
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Inflammation; Cartilage Degeneration; Osteoarthritis
- Paper Title Cn
- Paper Title En
- Selective STAT3 Inhibitor Alantolactone Ameliorates Osteoarthritis via Regulating Chondrocyte Autophagy and Cartilage Homeostasis
- Bilingual Status
- semi_complete