Andrographolide Exerts Chondroprotective Activity in Equine Cartilage Explant and Suppresses Interleukin-1 β -Induced MMP-2 Expression in Equine Chondrocyte Culture.
Abstract: Cartilage erosion in degenerative joint diseases leads to lameness in affected horses. It has been reported that andrographolide from Andrographis paniculata inhibited cartilage matrix-degrading enzymes. This study aimed to explore whether this compound protects equine cartilage degradation in the explant culture model and to determine its effect on matrix metalloproteinase-2 (MMP-2) expression, a matrix-degrading enzyme, in equine chondrocyte culture. Equine articular cartilage explant culture was induced by 25 ng/mL interleukin-1β, a key inducer of cartilage degeneration, in cultures with or without andrographolide ranging from 10 to 50 μM. After 3-21 days, they were analyzed for the markers of cartilage degradation. It was found that interleukin-1β increased the release of sulfated glycosaminoglycans and hyaluronan from the explants into the culture media consistently with the decrease in uronic acid and collagen content in the cartilage explants. These catabolic effects were inhibited when cotreated with interleukin-1β and andrographolide. In primary equine chondrocytes, andrographolide suppressed interleukin-1β-induced MMP-2 mRNA expression and MMP-2 activity in the culture medium. These results confirmed the in vitro potent chondroprotective activities of this compound which were performed in cartilage explants and on a cellular level. These may indicate the application of andrographolide for therapeutic use in equine degenerative joint diseases.
Publication Date: 2014-10-29 PubMed ID: 27379277PubMed Central: PMC4897368DOI: 10.1155/2014/464136Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research article investigates the potential for a compound, Andrographolide, from the plant Andrographis paniculata, to protect horse cartilage from degradation and reduce the effects of the enzyme MMP-2 on cartilage, which plays a key role in cartilage degeneration. The study also proves the protective properties of the compound both on a cellular level and in cartilage explants.
Background and Objectives
- The study looks into the degenerative joint diseases in horses that lead to lameness due to cartilage erosion. The cartilage degradation is induced by the activity of matrix metalloproteinase-2 (MMP-2), a matrix-degrading enzyme.
- The team sought to explore if andrographolide, derived from the plant Andrographis paniculata, can inhibit cartilage matrix-degrading enzymes and preserve cartilage integrity.
Research Methodology
- Researchers used an equine articular cartilage explant culture, which was triggered by interleukin-1β (a known inducer of cartilage degeneration). They employed varying levels of andrographolide (from 10 to 50 μM) in the cultures.
- The research involved analyzing markers of cartilage degradation between 3 to 21 days.
Key Findings
- The interleukin-1β resulted in an increased release of sulfated glycosaminoglycans and hyaluronan from the explants into the culture media. This was accompanied by a decrease in uronic acid and collagen content in the cartilage explants, evidencing degradation.
- This degradation was inhibited when the cultures were cotreated with interleukin-1β and andrographolide, meaning andrographolide interfered with the cartilage degradation process.
- In primary equine chondrocytes, andrographolide suppressed interleukin-1β-induced MMP-2 mRNA expression and MMP-2 activity in the culture medium, hence providing in vitro evidence of its chondroprotective potential.
Implication of Findings
- The results attest to the potent chondroprotective activities of the compound andrographolide. This offers potential application in treating degenerative joint diseases in horses, though further research and trials would undoubtedly be needed to confirm efficacy and safety in vivo.
Cite This Article
APA
Tangyuenyong S, Viriyakhasem N, Peansukmanee S, Kongtawelert P, Ongchai S.
(2014).
Andrographolide Exerts Chondroprotective Activity in Equine Cartilage Explant and Suppresses Interleukin-1 β -Induced MMP-2 Expression in Equine Chondrocyte Culture.
Int Sch Res Notices, 2014, 464136.
https://doi.org/10.1155/2014/464136 Publication
Researcher Affiliations
- Department of Companion Animal and Wildlife Clinic, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, Thailand.
- Thailand Excellence Centre for Tissue Engineering and Stem Cells, Department of Biochemistry and the Center of Excellence for Innovation in Chemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
- Department of Companion Animal and Wildlife Clinic, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, Thailand.
- Thailand Excellence Centre for Tissue Engineering and Stem Cells, Department of Biochemistry and the Center of Excellence for Innovation in Chemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
- Thailand Excellence Centre for Tissue Engineering and Stem Cells, Department of Biochemistry and the Center of Excellence for Innovation in Chemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
References
This article includes 41 references
- Krasnokutsky S, Samuels J, Abramson SB. Osteoarthritis in 2007.. Bulletin of the NYU Hospital for Joint Diseases 2007;65(3):222–228.
- Lees P. Pharmacology of drugs used to treat osteoarthritis in veterinary practice.. Inflammopharmacology 2003;11(4–6):385–399.
- Wallin L, Strandberg E, Philipsson J, Dalin G. Estimates of longevity and causes of culling and death in Swedish warmblood and coldblood horses.. Livestock Production Science 2000;63(3):275–289.
- Goodrich LR, Nixon AJ. Medical treatment of osteoarthritis in the horse—a review.. The Veterinary Journal 2006;171(1):51–69.
- Goldring MB, Marcu KB. Cartilage homeostasis in health and rheumatic diseases.. Arthritis Research & Therapy 2009;11(3):p. 224.
- Kobayashi M, Squires GR, Mousa A. Role of interleukin-1 and tumor necrosis factor α in matrix degradation of human osteoarthritic cartilage.. Arthritis and Rheumatism 2005;52(1):128–135.
- Yaron M, Shirazi I, Yaron I. eAnti-interleukin-1 effects of diacerein and rhein in human osteoarthritic synovial tissue and cartilage cultures.. Osteoarthritis and Cartilage 1999;7(3):272–280.
- Lin BF, Chao WW, Kuo YH, Hsieh SL. Inhibitory effects of ethyl acetate extract of Andrographis paniculata on NF-κB trans-activation activity and LPS-induced acute inflammation in mice.. Evidence-Based Complementary and Alternative Medicine 2011;2011:9.
- Burgos RA, Hancke JL, Bertoglio JC. Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial.. Clinical Rheumatology 2009;28(8):931–946.
- Chao CY, Lii CK, Hsu YT. Induction of heme oxygenase-1 and inhibition of TPA-induced matrix metalloproteinase-9 expression by andrographolide in MCF-7 human breast cancer cells.. Carcinogenesis 2013;34(8):1843–1851.
- Parichatikanond W, Suthisisang C, Dhepakson P, Herunsalee A. Study of anti-inflammatory activities of the pure compounds from Andrographis paniculata (burm.f.) Nees and their effects on gene expression.. International Immunopharmacology 2010;10(11):1361–1373.
- Ding QH, Ji XW, Cheng Y, Yu YG, Qi YY, Wang XH. Inhibition of matrix metalloproteinases and inducible nitric oxide synthase by andrographolide in human osteoarthritic chondrocytes.. Modern Rheumatology 2013;23(6):1124–1132.
- Phitak T, Choocheep K, Pothacharoen P, Pompimon W, Premanode B, Kongtawelert P. The effects of p-hydroxycinnamaldehyde from Alpinia galanga extracts on human chondrocytes.. Phytochemistry 2009;70(2):237–243.
- Chaiwongsa R, Ongchai S, Tangyuenyong S, Kongtawelert P, Panthong A, Reutrakul V. Chondroprotective potential of bioactive compounds of Zingiber cassumunar Roxb. against cytokine-induced cartilage degradation in explant culture.. Journal of Medicinal Plants Research 2012;6(39):5204–5213.
- Kleiner DE, Stetler-Stevenson WG. Quantitative zymography: detection of picogram quantities of gelatinases.. Analytical Biochemistry 1994;218(2):325–329.
- Bondeson J, Wainwright SD, Lauder S, Amos N, Hughes CE. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis.. Arthritis Research and Therapy 2006;8, article R187.
- Jiang Z, Uboh CE, Chen J, Soma LR. Isolation of RNA from equine peripheral blood cells: comparison of methods.. SpringerPlus 2013;2, article 478.
- Glasel JA. Validity of nucleic acid purities monitored by 260nm/280nm absorbance ratios.. BioTechniques 1995;18(1):62–63.
- Fleige S, Pfaffl MW. RNA integrity and the effect on the real-time qRT-PCR performance.. Molecular Aspects of Medicine 2006;27(2-3):126–139.
- Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.. Journal of Immunological Methods 1983;65(1-2):55–63.
- Decker T, Lohmann-Matthes ML. A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity.. Journal of Immunological Methods 1988;115(1):61–69.
- Aigner T, Soeder S, Haag J. IL-1β and BMPS—interactive players of cartilage matrix degradation and regeneration.. European Cells and Materials 2006;12:49–56.
- Melchiorri C, Meliconi R, Frizziero L. Enhanced and coordinated in vivo expression of inflammatory cytokines and nitric oxide synthase by chondrocytes from patients with osteoarthritis.. Arthritis and Rheumatism 1998;41(12):2165–2174.
- Wojdasiewicz P, Poniatowski ŁA, Szukiewicz D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis.. Mediators of Inflammation 2014;2014:19.
- Kamm JL, Nixon AJ, Witte TH. Cytokine and catabolic enzyme expression in synovium, synovial fluid and articular cartilage of naturally osteoarthriticequine carpi.. Equine Veterinary Journal 2010;42(8):693–699.
- Busschers E, Holt JP, Richardson DW. Effects of glucocorticoids and interleukin-1β on expression and activity of aggrecanases in equine chondrocytes.. American Journal of Veterinary Research 2010;71(2):176–185.
- Stabellini G, de Mattei M, Calastrini C. Effects of interleukin-1β on chondroblast viability and extracellular matrix changes in bovine articular cartilage explants.. Biomedicine & Pharmacotherapy 2003;57(7):314–319.
- Heinegård D. Proteoglycans and more—from molecules to biology.. International Journal of Experimental Pathology 2009;90(6):575–586.
- Heinegård D, Saxne T. The role of the cartilage matrix in osteoarthritis.. Nature Reviews Rheumatology 2011;7(1):50–56.
- Phitak T, Pothacharoen P, Kongtawelert P. Comparison of glucose derivatives effects on cartilage degradation.. BMC Musculoskeletal Disorders 2010;11, article 162.
- Butler GS, Butler MJ, Atkinson SJ. The TIMP2 membrane type 1 metalloproteinase “receptor” regulates the concentration and efficient activation of progelatinase A. A kinetic study.. The Journal of Biological Chemistry 1998;273(2):871–880.
- Fietz S, Einspanier R, Hoppner S, Hertsch B, Bondzio A. Determination of MMP-2 and -9 activities in synovial fluid of horses with osteoarthritic and arthritic joint diseases using gelatin zymography and immunocapture activity assays.. Equine Veterinary Journal 2008;40(3):266–271.
- Song H, Ki SH, Kim SG, Moon A. Activating transcription factor 2 mediates matrix metalloproteinase-2 transcriptional activation induced by p38 in breast epithelial cells.. Cancer Research 2006;66(21):10487–10496.
- Kumar B, Koul S, Petersen J. p38 Mitogen-activated protein kinase-driven MAPKAPK2 regulates invasion of bladder cancer by modulation of MMP-2 and MMP-9 activity.. Cancer Research 2010;70(2):832–841.
- Brown KK, Heitmeyer SA, Hookfin EB. P38 MAP kinase inhibitors as potential therapeutics for the treatment of joint degeneration and pain associated with osteoarthritis.. Journal of Inflammation 2008;5, article 22.
- Wang W, Wang J, Dong SF. Immunomodulatory activity of andrographolide on macrophage activation and specific antibody response.. Acta Pharmacologica Sinica 2010;31(2):191–201.
- Zhu T, Wang DX, Zhang W. Andrographolide Protects against LPS-Induced Acute Lung Injury by Inactivation of NF-κB.. PLoS ONE 2013;8(2).
- Shen T, Yang WS, Yi YS. AP-1/IRF-3 targeted anti-inflammatory activity of andrographolide isolated from Andrographis paniculata .. Evidence-Based Complementary and Alternative Medicine 2013;2013:16.
- Tetlow LC, Adlam DJ, Woolley DE. Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes.. Arthritis and Rheumatism 2001;44(3):585–594.
- Hardy MM, Seibert K, Manning PT. Cyclooxygenase 2-dependent prostaglandin E2 modulates cartilage proteoglycan degradation in human osteoarthritis explants.. Arthritis and Rheumatism 2002;46(7):1789–1803.
- Firestein GS, Alvaro-Garcia JM, Maki R. Quantitative analysis of cytokine gene expression in rheumatoid arthritis.. Journal of Immunology 1990;144(9):3347–3353.
Citations
This article has been cited 3 times.- Wu X, Fu Y, Ma J, Wang H, Li C, Zhu Y, Wang Q, Guo X, Zhang T, He A. Blocking calcium-MYC regulatory axis inhibits early dedifferentiation of chondrocytes and contributes to cartilage regeneration. Stem Cell Res Ther 2025 Jul 15;16(1):372.
- Kulsirirat T, Honsawek S, Takeda-Morishita M, Sinchaipanid N, Udomsinprasert W, Leanpolchareanchai J, Sathirakul K. The Effects of Andrographolide on the Enhancement of Chondrogenesis and Osteogenesis in Human Suprapatellar Fat Pad Derived Mesenchymal Stem Cells. Molecules 2021 Mar 24;26(7).
- Ongchai S, Somnoo O, Kongdang P, Peansukmanee S, Tangyuenyong S. TGF-β1 upregulates the expression of hyaluronan synthase 2 and hyaluronan synthesis in culture models of equine articular chondrocytes. J Vet Sci 2018 Nov 30;19(6):735-743.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
