Skip to main content

Advertisement

SpringerLink
Log in

Baicalein inhibits IL-1β-induced extracellular matrix degradation with decreased MCP-1 expression in primary rat chondrocytes

  • Original Article
  • Published:
Toxicological Research Aims and scope Submit manuscript

Abstract

Baicalein is a flavonoid extracted from the roots of Scutellaria baicalensis and Scutellaria lateriflora. This compound exerts various biochemical activities, including antioxidant and anti-inflammatory effects. The study aimed to investigate the effect of baicalein on articular cartilage cells and elucidate its underlying mechanism. In primary rat chondrocyte cultures, treatment with baicalein demonstrated a reduction in the loss of proteoglycan and extracellular matrix degradation induced by interleukin (IL)-1β. Baicalein suppressed IL-1β-induced catabolic responses, including the expression and activation of matrix metalloproteinase (MMP)-13, MMP-3, and MMP-1. In addition, baicalein effectively reduced nitric oxide and prostaglandin E2 production, and it downregulated the expression of inducible nitric oxide synthase and cyclooxygenase-2 in primary rat chondrocytes. Furthermore, baicalein downregulated IL-1β-induced inflammatory chemokines and cytokines, such as GM-CSF and MCP-1. These findings suggest that baicalein could potentially mitigate the catabolic responses of IL-1β in chondrocytes, making it a promising candidate for both the prevention and treatment of osteoarthritis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

All data generated or analyzed during this study, including supplementary material files, are included in this article. For further inquiries, please contact the corresponding author.

References

  1. Hayami T, Pickarski M, Zhuo Y, Wesolowski GA, Rodan GA, Duong LT (2006) Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. Bone 38:234–243. https://doi.org/10.1016/j.bone.2005.08.007

    Article  PubMed  Google Scholar 

  2. van der Kraan PM (2018) Differential role of transforming growth factor-beta in an osteoarthritic or a healthy joint. J Bone Metab 25:65–72. https://doi.org/10.11005/jbm.2018.25.2.65

    Article  PubMed  PubMed Central  Google Scholar 

  3. Liu S, Deng Z, Chen K, Jian S, Zhou F, Yang Y, Fu Z, Xie H, Xiong J, Zhu W (2022) Cartilage tissue engineering: from proinflammatory and anti-inflammatory cytokines to osteoarthritis treatments (review). Mol Med Rep 25:99. https://doi.org/10.3892/mmr.2022.12615

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lu H, Jia C, Wu D, Jin H, Lin Z, Pan J, Li X, Wang W (2021) Fibroblast growth factor 21 (FGF21) alleviates senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the SIRT1-mTOR signaling pathway. Cell Death Dis 12:865. https://doi.org/10.1038/s41419-021-04157-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Park EH, Kim JS, Lee JS, Lee YJ, Song YW, Lee EY (2018) Compound K inhibits interleukin-1β-induced expression of inflammatory mediators and matrix metalloproteinases by inhibiting mitogen-activated protein kinase activation in chondrocytes. J Rheum Dis 25:188–196. https://doi.org/10.4078/jrd.2018.25.3.188

    Article  Google Scholar 

  6. Yang F, Chen Y, Lu Z, Xie W, Yan S, Yang J, Li Y (2021) Treatment of knee osteoarthritis with acupuncture combined with Chinese herbal medicine: a systematic review and meta-analysis. Ann Palliat Med 10:11430–11444. https://doi.org/10.21037/apm-21-2565

    Article  PubMed  Google Scholar 

  7. Chin KY (2016) The spice for joint inflammation: anti-inflammatory role of curcumin in treating osteoarthritis. Drug Des Dev Ther 10:3029–3042. https://doi.org/10.2147/DDDT.S117432

    Article  CAS  Google Scholar 

  8. Aggarwal BB, Gupta SC, Sung B (2013) Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers. Br J Pharmacol 169:1672–1692. https://doi.org/10.1111/bph.12131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bai C, Yang J, Cao B, Xue Y, Gao P, Liang H, Li G (2020) Growth years and post-harvest processing methods have critical roles on the contents of medicinal active ingredients of Scutellaria baicalensis. Ind Crops Prod 158:112985. https://doi.org/10.1016/j.indcrop.2020.112985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Li Y, Wang J, Song X, Bai H, Ma T, Zhang Z, Li X, Jiang R, Wang G, Fan X, Liu X, Gao L (2017) Effects of baicalein on IL-1β-induced inflammation and apoptosis in rat articular chondrocytes. Oncotarget 8:90781–90795. https://doi.org/10.18632/oncotarget.21796

    Article  PubMed  PubMed Central  Google Scholar 

  11. Cho IA, Kim TH, Lim H, Park JH, Kang KR, Lee SY, Kim CS, Kim DK, Kim HJ, Yu SK, Kim SG, Kim JS (2019) Formononetin antagonizes the interleukin-1beta-induced catabolic effects through suppressing inflammation in primary rat chondrocytes. Inflammation 42:1426–1440. https://doi.org/10.1007/s10753-019-01005-1

    Article  CAS  PubMed  Google Scholar 

  12. Lee GJ, Cho IA, Oh JS, Seo YS, You JS, Kim SG, Kim JS (2019) Anticatabolic effects of morin through the counteraction of interleukin-1beta-induced inflammation in rat primary chondrocytes. Cells Tissues Organs 207:21–33. https://doi.org/10.1159/000500323

    Article  CAS  PubMed  Google Scholar 

  13. Kim JS, Ellman MB, An HS, van Wijnen AJ, Borgia JA, Im HJ (2010) Insulin-like growth factor 1 synergizes with bone morphogenetic protein 7-mediated anabolism in bovine intervertebral disc cells. Arthritis Rheum 62:3706–3715. https://doi.org/10.1002/art.27733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Burrage PS, Mix KS, Brinckerhoff CE (2006) Matrix metalloproteinases: role in arthritis. Front Biosci 11:529–543. https://doi.org/10.2741/1817

    Article  CAS  PubMed  Google Scholar 

  15. Kobayashi M, Squires GR, Mousa A, Tanzer M, Zukor DJ, Antoniou J, Feige U, Poole AR (2005) Role of interleukin-1 and tumor necrosis factor alpha in matrix degradation of human osteoarthritic cartilage. Arthritis Rheum 52:128–135. https://doi.org/10.1002/art.20776

    Article  CAS  PubMed  Google Scholar 

  16. Jenei-Lanzl Z, Meurer A, Zaucke F (2019) Interleukin-1beta signaling in osteoarthritis—chondrocytes in focus. Cell Signal 53:212–223. https://doi.org/10.1016/j.cellsig.2018.10.005

    Article  CAS  PubMed  Google Scholar 

  17. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H (2011) Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 7:33–42. https://doi.org/10.1038/nrrheum.2010.196

    Article  CAS  PubMed  Google Scholar 

  18. Gong WY, Zhao ZX, Liu BJ, Lu LW, Dong JC (2017) Exploring the chemopreventive properties and perspectives of baicalin and its aglycone baicalein in solid tumors. Eur J Med Chem 126:844–852. https://doi.org/10.1016/j.ejmech.2016.11.058

    Article  CAS  PubMed  Google Scholar 

  19. McInnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365:2205–2219. https://doi.org/10.1056/NEJMra1004965

    Article  CAS  PubMed  Google Scholar 

  20. Neuhold LA, Killar L, Zhao W, Sung ML, Warner L, Kulik J, Turner J, Wu W, Billinghurst C, Meijers T, Poole AR, Babij P, DeGennaro LJ (2001) Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice. J Clin Investig 107:35–44. https://doi.org/10.1172/JCI10564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Dave M, Attur M, Palmer G, Al-Mussawir HE, Kennish L, Patel J, Abramson SB (2008) The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production. Arthritis Rheum 58:2786–2797. https://doi.org/10.1002/art.23799

    Article  PubMed  Google Scholar 

  22. Wojdasiewicz P, Poniatowski LA, Szukiewicz D (2014) The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediat Inflamm 2014:561459. https://doi.org/10.1155/2014/561459

    Article  CAS  Google Scholar 

  23. Kang KA, Zhang R, Piao MJ, Chae S, Kim HS, Park JH, Jung KS, Hyun JW (2012) Baicalein inhibits oxidative stress-induced cellular damage via antioxidant effects. Toxicol Ind Health 28:412–421. https://doi.org/10.1177/0748233711413799

    Article  CAS  PubMed  Google Scholar 

  24. Aragay AM, Mellado M, Frade JM, Martin AM, Jimenez-Sainz MC, Martinez AC, Mayor F Jr (1998) Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2. Proc Natl Acad Sci USA 95:2985–2990. https://doi.org/10.1073/pnas.95.6.2985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Xu YK, Ke Y, Wang B, Lin JH (2015) The role of MCP-1-CCR2 ligand-receptor axis in chondrocyte degradation and disease progress in knee osteoarthritis. Biol Res 48:64. https://doi.org/10.1186/s40659-015-0057-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zeng Q, Zhang Y, Zhang W, Guo Q (2020) Baicalein suppresses the proliferation and invasiveness of colorectal cancer cells by inhibiting Snail-induced epithelial-mesenchymal transition. Mol Med Rep 21:2544–2552. https://doi.org/10.3892/mmr.2020.11051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hsieh CJ, Hall K, Ha T, Li C, Krishnaswamy G, Chi DS (2007) Baicalein inhibits IL-1beta- and TNF-alpha-induced inflammatory cytokine production from human mast cells via regulation of the NF-kappaB pathway. Clin Mol Allergy 5:5. https://doi.org/10.1186/1476-7961-5-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Li J, Ma J, Wang KS, Mi C, Wang Z, Piao LX, Xu GH, Li X, Lee JJ, Jin X (2016) Baicalein inhibits TNF-alpha-induced NF-kappaB activation and expression of NF-kappaB-regulated target gene products. Oncol Rep 36:2771–2776. https://doi.org/10.3892/or.2016.5108

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to extend their sincere thanks to Suk-Gyun Park and Seung Hee Kwon for their technical assistance.

Funding

This work was supported by National Research Foundation of Korea (NRF) grants (NRF-2019R1A6A3A01090239, NRF-2019R1A5A2027521) and a Korean Fund for Regenerative Medicine (KFRM) grant (Ministry of Science and ICT, Ministry of Health and Welfare, 22A0104L1).

Author information

Authors and Affiliations

  1. Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea

    InA Cho & Jeong-Tae Koh

  2. Hard-Tissue Biointerface Research Center, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea

    InA Cho, Young Kim & Jeong-Tae Koh

  3. Department of Preventive and Public Health Dentistry, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea

    Ki-Ho Chung & Choong-Ho Choi

  4. Department of Oral Pathology, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea

    Young Kim

Authors
  1. InA Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ki-Ho Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Young Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Choong-Ho Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jeong-Tae Koh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Choong-Ho Choi or Jeong-Tae Koh.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 91 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cho, I., Chung, KH., Kim, Y. et al. Baicalein inhibits IL-1β-induced extracellular matrix degradation with decreased MCP-1 expression in primary rat chondrocytes. Toxicol Res. 40, 237–246 (2024). https://doi.org/10.1007/s43188-024-00225-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43188-024-00225-4

Keywords

Search

Navigation