Scutellarein Ameliorated Chondrocyte Inflammation and Osteoarthritis in Rats

Shao-ze Jing1(), Shu-han Yang1, Yun-kun Qu2, Hai-hu Hao1(), Hua Wu1,2()

PDF
Current Medical Science ›› 2024, Vol. 44 ›› Issue (2) : 355-368. DOI: 10.1007/s11596-024-2854-6

Scutellarein Ameliorated Chondrocyte Inflammation and Osteoarthritis in Rats

  • Shao-ze Jing1(), Shu-han Yang1, Yun-kun Qu2, Hai-hu Hao1(), Hua Wu1,2()
Author information +
History +

Abstract

Abstract
Objective

Osteoarthritis (OA) is a degenerative joint disorder characterized by the gradual degradation of joint cartilage and local inflammation. This study aimed to investigate the anti-OA effect of scutellarein (SCU), a single-unit flavonoid compound obtained from Scutellaria barbata D. Don, in rats.

Methods

The extracted rat chondrocytes were treated with SCU and IL-1β. The chondrocytes were divided into control group, IL-1β group, IL-1β+SCU 50 µmol/L group, and IL-1β+SCU 100 µmol/L group. Morphology of rat chondrocytes was observed by toluidine blue and safranin O staining. CCK-8 method was used to detect the cytotoxicity of SCU. ELISA, qRT-PCR, Western blotting, immunofluorescence, SAβ-gal staining, flow cytometry, and bioinformatics analysis were applied to evaluate the effect of SCU on rat chondrocytes under IL-1β intervention. Additionally, anterior cruciate ligament transection (ACL-T) was used to establish a rat OA model. Histological changes were detected by safranin O/fast green, hematoxylin-eosin (HE) staining, and immunohistochemistry.

Results

SCU protected cartilage and exhibited anti-inflammatory effects via multiple mechanisms. Specifically, it could enhance the synthesis of extracellular matrix in cartilage cells and inhibit its degradation. In addition, SCU partially inhibited the nuclear factor kappa-B/mitogen-activated protein kinase (NF-κB/MAPK) pathway, thereby reducing inflammatory cytokine production in the joint cartilage. Furthermore, SCU significantly reduced IL-1β-induced apoptosis and senescence in rat chondrocytes, further highlighting its potential role in OA treatment. In vivo experiments revealed that SCU (at a dose of 50 mg/kg) administered for 2 months could significantly delay the progression of cartilage damage, which was reflected in a lower Osteoarthritis Research Society International (OARSI) score, and reduced expression of matrix metalloproteinase 13 (MMP13) in cartilage.

Conclusion

SCU is effective in the therapeutic management of OA and could serve as a potential candidate for future clinical drug therapy for OA.

Keywords

scutellarein / osteoarthritis / apoptosis / mitogen-activated protein kinase (MAPK) / nuclear factor kappa-B (NF-κB)

Cite this article

Download citation ▾
Shao-ze Jing, Shu-han Yang, Yun-kun Qu, Hai-hu Hao, Hua Wu. Scutellarein Ameliorated Chondrocyte Inflammation and Osteoarthritis in Rats. Current Medical Science, 2024, 44(2): 355‒368 https://doi.org/10.1007/s11596-024-2854-6

References

[1]
Glyn-Jones S, Palmer AJ, Agricola R, et al. Osteoarthritis. Lancet, 2015,386(9991):376–387
[2]
Barnett R. Osteoarthritis. Lancet, 2018,391(10134):1985
[3]
Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet, 2019,393(10182):1745–1759
[4]
Kapoor M, Martel-Pelletier J, Lajeunesse D, et al. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol, 2011,7(1):33–42
[5]
Armendáriz-Barragán B, Zafar N, Badri W, et al. Plant extracts: from encapsulation to application. Expert Opin Drug Deliv, 2016,13(8):1165–75
[6]
Liu D, Zhang C, Hu M, et al. Scutellarein relieves the death and inflammation of tubular epithelial cells in ischemic kidney injury by degradation of COX-2 protein. Int Immunopharmacol, 2021,101(Pt A):108193
[7]
Park MY, Ha SE, Kim HH, et al. Scutellarein Inhibits LPS-Induced Inflammation through NF-κB/MAPKs Signaling Pathway in RAW264.7 Cells. Molecules, 2022,27(12):3782
[8]
Lang X, Chen Z, Yang X, et al. Scutellarein induces apoptosis and inhibits proliferation, migration, and invasion in ovarian cancer via inhibition of EZH2/FOXO1 signaling. J Biochem Mol Toxicol, 2021,35(10):e22870
[9]
Guo F, Yang F, Zhu YH. Scutellarein from Scutellaria barbata induces apoptosis of human colon cancer HCT116 cells through the ROS-mediated mitochondria-dependent pathway. Nat Prod Res, 2019,33(16):2372–2375
[10]
Ha SE, Kim SM, Lee HJ, et al. Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells. Nutrients, 2019,11(2):263
[11]
Ding Q, Zhang R, Sheng G, et al. Dioscin alleviates the progression of osteoarthritis: an in vitro and in vivo study. J Inflamm (Lond), 2023,20(1):14
[12]
Liu X, Ouyang S, Yu B, et al. PharmMapper server: a web server for potential drug target identification using pharmacophore mapping approach. Nucleic Acids Res, 2010,38(Web Server issue):W609–W614
[13]
Bardou P, Mariette J, Escudié F, et al. Jvenn: an interactive Venn diagram viewer. BMC Bioinformatics, 2014,15(1):293
[14]
Gu Z, Gu L, Eils R, et al. circlize implements and enhances circular visualization in R. Bioinformatics, 2014,30(19):2811–2812
[15]
Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systemslevel datasets. Nat Commun, 2019,10(1):1523
[16]
Chu X, You H, Yuan X, et al. Protective effect of lentivirus-mediated siRNA targeting ADAMTS-5 on cartilage degradation in a rat model of osteoarthritis. Int J Mol Med, 2013,31(5):1222–1228
[17]
Sun K, Luo J, Jing X, et al. Hyperoside ameliorates the progression of osteoarthritis: An in vitro and in vivo study. Phytomedicine, 2021,80:153387
[18]
Lu R, Wang YG, Qu Y, et al. Dihydrocaffeic acid improves IL-1β-induced inflammation and cartilage degradation via inhibiting NF-κB and MAPK signalling pathways. Bone Joint Res, 2023,12(4):259–273
[19]
Aydelotte MB, Kuettner KE. Differences between subpopulations of cultured bovine articular chondrocytes. I. Morphology and cartilage matrix production. Connect Tissue Res, 1988,18(3):205–222
[20]
Rim YA, Nam Y, Ju JH. The Role of Chondrocyte Hypertrophy and Senescence in Osteoarthritis Initiation and Progression. Int J Mol Sci, 2020,21(7):2358
[21]
Tu C, Huang X, Xiao Y, et al. Schisandrin A Inhibits the IL-1β-Induced Inflammation and Cartilage Degradation via Suppression of MAPK and NF-κB Signal Pathways in Rat Chondrocytes. Front Pharmacol, 2019,10:41
[22]
Richards MM, Maxwell JS, Weng L, et al. Intraarticular treatment of knee osteoarthritis: from anti-inflammatories to products of regenerative medicine. Phys Sportsmed, 2016,44(2):101–108
[23]
Katz JA. COX-2 inhibition: what we learned—a controversial update on safety data. Pain Med, 2013,14(Suppl1):S29–S34
[24]
Lin S, Lu J, Chen Q, et al. Plantamajoside suppresses the activation of NF-κB and MAPK and ameliorates the development of osteoarthritis. Int Immunopharmacol, 2023,115:109582
[25]
Wang X, Guo Z, Lin J, et al. Indirubin protects chondrocytes and alleviates OA by inhibiting the MAPK and NF-κB pathways. Int Immunopharmacol, 2023,115:109624
[26]
Huang XW, Xu Y, Sui X, et al. Scutellarein suppresses Aβ-induced memory impairment via inhibition of the NF-κB pathway in vivo and in vitro. Oncol Lett, 2019,17(6):5581–5589
[27]
Fu F, Shao S, Wang Z, et al. Scutellarein inhibits RANKL-induced osteoclast formation in vitro and prevents LPS-induced bone loss in vivo. J Cell Physiol, 2019,234(7):11951–11959
[28]
Sun S, Yan Z, Shui X, et al. Astilbin prevents osteoarthritis development through the TLR4/MD-2 pathway. J Cell Mol Med, 2020, 24(22):13104–13114
[29]
Mobasheri A, Rayman MP, Gualillo O, et al. The role of metabolism in the pathogenesis of osteoarthritis. Nat Rev Rheumatol, 2017,13(5):302–311
[30]
Motta F, Barone E, Sica A, et al. Inflammaging and Osteoarthritis. Clin Rev Allergy Immunol, 2023,64(2):222–238
[31]
Wan J, He Z, Peng R, et al. Injectable photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered exosomes for osteoarthritis therapy. J Nanobiotechnology, 2023,21(1):284
[32]
Guo Q, Chen X, Chen J, et al. STING promotes senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the NF-κB signaling pathway. Cell Death Dis, 2021,12(1):13
[33]
Liu Y, Zhang Z, Li T, et al. Senescence in osteoarthritis: from mechanism to potential treatment. Arthritis Res Ther, 2022,24(1):174
[34]
Qu Y, Wang Y, Wang S, et al. A comprehensive analysis of single-cell RNA transcriptome reveals unique SPP1+ chondrocytes in human osteoarthritis. Comput Biol Med, 2023,160:106926
[35]
Mobasheri A, Matta C, Zákány R, et al. Chondrosenescence: definition, hallmarks and potential role in the pathogenesis of osteoarthritis. Maturitas, 2015,80(3):237–244
[36]
Duli? V, Beney GE, Frebourg G, et al. Uncoupling between phenotypic senescence and cell cycle arrest in aging p21-deficient fibroblasts. Mol Cell Biol, 2000,20(18):6741–6754
[37]
Chai B, Zheng ZH, Liao X, et al. The protective role of omentin-1 in IL-1β-induced chondrocyte senescence. Artif Cells Nanomed Biotechnol, 2020,48(1):8–14
[38]
Huang H, Lei H, Yang F, et al. Activation of the bile acid receptor GPBAR1 (TGR5) ameliorates interleukin-1β (IL-1β)-induced chondrocytes senescence. Biomed Pharmacother, 2018,106:1713–1719
[39]
Hwang HS, Kim HA. Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis. Int J Mol Sci, 2015,16(11):26035–26054
[40]
Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage, 2013,21(1):16–21
PDF

Accesses

Citations

Detail

Sections
Recommended

/