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Effect of luteolin on apoptosis, MAPK and JNK signaling pathways in guinea pig chondrocyte with osteoarthritis
Corresponding Author(s) : Jianli Xue
Cellular and Molecular Biology,
Vol. 65 No. 6: Issue 6
Abstract
Osteoarthritis (OA) is a degenerative joint disease usually seen in the elderly, which incidence increases with age. Its pathogenesis and underlying mechanism are still unclear. The disease severely affects the physical health and life quality of patients, thereby constituting a huge economic burden to family and society. Luteolin (LUT) is a natural flavonoid with multiple pharmacological properties. Many plants containing LUT have been applied in the treatment of several inflammation-related diseases due the relatively strong anti-inflammatory effects of LUT. The present study investigated the influence of LUT on cell apoptosis and inflammatory reactions in cartilage of OA guinea pigs, and its underlying mechanism. It was found that LUT effectively inhibited proliferation of OA cartilage cells, down-regulated the expressions of JNK and p38MAPK in cartilage cells of OA, and downregulated NO, TNF-α and IL-6. Thus, it alleviated inflammatory reactions, protected cartilage cells, and delayed cartilage degeneration.
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- Sandell LJ, Aigner T. Articular cartilage and changes in arthritis: cell biology of osteoarthritis. Arthritis Res 2001; 3: 107.
- Li M, Xiao R, Li J, Zhu Q. Regenerative approaches for cartilage repair in the treatment of osteoarthritis. Osteoarthritis Cartilage 2017; 25: 1577-1587.
- Berenbaum F. New horizons and perspectives in the treatment of osteoarthritis. Arthritis Res Ther 2008; 10: 1.
- Katiyar C, Gupta A, Kanjilal S, Katiyar S. Drug discovery from plant sources: An integrated approach. Ayu 2012; 33: 10.
- Jeong D, Yi YS, Sung GH, Yang WS, Park JG, Yoon K, et al. Anti-inflammatory activities and mechanisms of Artemisia asiatica ethanol extract. J Ethnopharmacol 2014; 152: 487-496.
- Zang MD, Hu L, Fan ZY, Wang HX, Zhu ZL, Cao S, et al. Luteolin suppresses gastric cancer progression by reversing epithelial-mesenchymal transition via suppression of the Notch signaling pathway. J Transl Med 2017; 15: 52.
- Luo Y, Shang P, Li D. Luteolin: A flavonoid that has multiple cardio-protective effects and its molecular mechanisms. Front Pharmacol 2017; 8: 692.
- Zang M, Hu L, Zhang B, Zhu Z, Li J, Zhu Z, et al. Luteolin suppresses angiogenesis and vasculogenic mimicry formation through inhibiting Notch1-VEGF signaling in gastric cancer. Biochem Biophys Res Commun 2017; 490: 913-919.
- Farzaei MH, Abbasabadi Z, Ardekani MRS, Rahimi R, Farzaei F. Parsley: a review of ethnopharmacology, phytochemistry and biological activities. J Tradit Chin Med 2013; 33: 815-826.
- Seelinger G, Merfort I, Schempp CM. Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin. Planta Med 2008; 74: 1667-1677.
- Park SJ, Jung NJ, Na SS. The effects of exercise on the GAP-43 expression in the spinal cord of arthritis-induced rats. J Phys Ther Sci 2016; 28: 2921-2923.
- Yu J, Liang F, Huang H, Pirttiniemi P, Yu D. Effects of loading on chondrocyte hypoxia, HIF"1α and VEGF in the mandibular condylar cartilage of young rats. Orthod Craniofac Res 2018; 21: 41-47.
- Attoub S, Hassan AH, Vanhoecke B, Iratni R, Takahashi T, Gaben AM, et al. Inhibition of cell survival, invasion, tumor growth and histone deacetylase activity by the dietary flavonoid luteolin in human epithelioid cancer cells. Eur J Pharmacol 2011; 651: 18-25.
- Chen Z, Zhang B, Gao F, Shi R. Modulation of G2/M cell cycle arrest and apoptosis by luteolin in human colon cancer cells and xenografts. Oncol Lett 2018; 15: 1559-1565.
- Cook MT. Mechanism of metastasis suppression by luteolin in breast cancer. Breast Cancer (Dove Med Press) 2018; 10: 89.
- Komori T. Cell death in chondrocytes, osteoblasts, and osteocytes. Int J Mol Sci 2016; 17: 2045.
- Zahoor T, Mitchell R, Bhasin P, Guo Y, Paudel S, Schon L, et al. Effect of low-intensity pulsed ultrasound on joint injury and post-traumatic osteoarthritis: an animal study. Ultrasound Med Biol 2018; 44: 234-242.
- Chowdhury T, Salter D, Bader D, Lee DA. Signal transduction pathways involving p38 MAPK, JNK, NFκB and AP-1 influences the response of chondrocytes cultured in agarose constructs to IL-1β and dynamic compression. Inflamm Res 2008; 57: 306-313.
- Prasadam I, Mao X, Wang Y, Shi W, Crawford R, Xiao Y. Inhibition of p38 pathway leads to OA-like changes in a rat animal model. Rheumatology (Oxford) 2012; 51: 813-823.
- Stoddart MJ, Grad S, Eglin D, Alini M. Cells and biomaterials in cartilage tissue engineering. Regen Med 2009; 4: 81-98.
- Murphy G, Knäuper V, Atkinson S, Butler G, English W, Hutton M, et al. Matrix metalloproteinases in arthritic disease. Arthritis Res 2002; 4: 39.
- Wang H, Wang Z, Chen J, Wu J. Apoptosis induced by NO via phosphorylation of p38 MAPK that stimulates NF"κB, p53 and caspase"3 activation in rabbit articular chondrocytes. Cell Biol Int 2007; 31: 1027-1035.
- Malemud CJ, Islam N, Haqqi TM. Pathophysiological mechanisms in osteoarthritis lead to novel therapeutic strategies. Cells Tissues Organs 2003; 174: 34-48.
References
Sandell LJ, Aigner T. Articular cartilage and changes in arthritis: cell biology of osteoarthritis. Arthritis Res 2001; 3: 107.
Li M, Xiao R, Li J, Zhu Q. Regenerative approaches for cartilage repair in the treatment of osteoarthritis. Osteoarthritis Cartilage 2017; 25: 1577-1587.
Berenbaum F. New horizons and perspectives in the treatment of osteoarthritis. Arthritis Res Ther 2008; 10: 1.
Katiyar C, Gupta A, Kanjilal S, Katiyar S. Drug discovery from plant sources: An integrated approach. Ayu 2012; 33: 10.
Jeong D, Yi YS, Sung GH, Yang WS, Park JG, Yoon K, et al. Anti-inflammatory activities and mechanisms of Artemisia asiatica ethanol extract. J Ethnopharmacol 2014; 152: 487-496.
Zang MD, Hu L, Fan ZY, Wang HX, Zhu ZL, Cao S, et al. Luteolin suppresses gastric cancer progression by reversing epithelial-mesenchymal transition via suppression of the Notch signaling pathway. J Transl Med 2017; 15: 52.
Luo Y, Shang P, Li D. Luteolin: A flavonoid that has multiple cardio-protective effects and its molecular mechanisms. Front Pharmacol 2017; 8: 692.
Zang M, Hu L, Zhang B, Zhu Z, Li J, Zhu Z, et al. Luteolin suppresses angiogenesis and vasculogenic mimicry formation through inhibiting Notch1-VEGF signaling in gastric cancer. Biochem Biophys Res Commun 2017; 490: 913-919.
Farzaei MH, Abbasabadi Z, Ardekani MRS, Rahimi R, Farzaei F. Parsley: a review of ethnopharmacology, phytochemistry and biological activities. J Tradit Chin Med 2013; 33: 815-826.
Seelinger G, Merfort I, Schempp CM. Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin. Planta Med 2008; 74: 1667-1677.
Park SJ, Jung NJ, Na SS. The effects of exercise on the GAP-43 expression in the spinal cord of arthritis-induced rats. J Phys Ther Sci 2016; 28: 2921-2923.
Yu J, Liang F, Huang H, Pirttiniemi P, Yu D. Effects of loading on chondrocyte hypoxia, HIF"1α and VEGF in the mandibular condylar cartilage of young rats. Orthod Craniofac Res 2018; 21: 41-47.
Attoub S, Hassan AH, Vanhoecke B, Iratni R, Takahashi T, Gaben AM, et al. Inhibition of cell survival, invasion, tumor growth and histone deacetylase activity by the dietary flavonoid luteolin in human epithelioid cancer cells. Eur J Pharmacol 2011; 651: 18-25.
Chen Z, Zhang B, Gao F, Shi R. Modulation of G2/M cell cycle arrest and apoptosis by luteolin in human colon cancer cells and xenografts. Oncol Lett 2018; 15: 1559-1565.
Cook MT. Mechanism of metastasis suppression by luteolin in breast cancer. Breast Cancer (Dove Med Press) 2018; 10: 89.
Komori T. Cell death in chondrocytes, osteoblasts, and osteocytes. Int J Mol Sci 2016; 17: 2045.
Zahoor T, Mitchell R, Bhasin P, Guo Y, Paudel S, Schon L, et al. Effect of low-intensity pulsed ultrasound on joint injury and post-traumatic osteoarthritis: an animal study. Ultrasound Med Biol 2018; 44: 234-242.
Chowdhury T, Salter D, Bader D, Lee DA. Signal transduction pathways involving p38 MAPK, JNK, NFκB and AP-1 influences the response of chondrocytes cultured in agarose constructs to IL-1β and dynamic compression. Inflamm Res 2008; 57: 306-313.
Prasadam I, Mao X, Wang Y, Shi W, Crawford R, Xiao Y. Inhibition of p38 pathway leads to OA-like changes in a rat animal model. Rheumatology (Oxford) 2012; 51: 813-823.
Stoddart MJ, Grad S, Eglin D, Alini M. Cells and biomaterials in cartilage tissue engineering. Regen Med 2009; 4: 81-98.
Murphy G, Knäuper V, Atkinson S, Butler G, English W, Hutton M, et al. Matrix metalloproteinases in arthritic disease. Arthritis Res 2002; 4: 39.
Wang H, Wang Z, Chen J, Wu J. Apoptosis induced by NO via phosphorylation of p38 MAPK that stimulates NF"κB, p53 and caspase"3 activation in rabbit articular chondrocytes. Cell Biol Int 2007; 31: 1027-1035.
Malemud CJ, Islam N, Haqqi TM. Pathophysiological mechanisms in osteoarthritis lead to novel therapeutic strategies. Cells Tissues Organs 2003; 174: 34-48.