Abstract
Leonurine hydrochloride (LH) has been reported to exhibit a number of biological properties such as suppression of inflammation. This study aimed to examine whether the progression of osteoarthritis (OA) could be delayed by the administration of LH in an OA model. Rat chondrocytes were treated with LH under the condition of TNF-α-induced inflammation. After that, real-time PCR and Western blotting were conducted to evaluate relative gene/protein expression levels. For the in vivo study, rats were randomly allocated to a control group (anterior cruciate ligament transection (ACLT) surgery, treatment with saline) and LH group (ACLT surgery, treatment with LH). Articular cartilage degeneration was assessed by histological evaluation. It was found that LH significantly suppressed the expression of MMP-1, MMP-3, MMP-13, IL-6, and ADAMTS-5 in cells via the NF-κB signaling pathway. In addition, it is revealed that intra-articular injection of LH significantly ameliorated cartilage degeneration in a rat OA model. Taken together, these results indicate that LH attenuates progression of OA by inhibition of inflammation via the NF-κB signaling pathway and represents a potential preventive therapy for OA.
Similar content being viewed by others
References
French, H.P., R. Galvin, N.F. Horgan, and R.A. Kenny. 2016. Prevalence and burden of osteoarthritis amongst older people in Ireland: findings from The Irish LongituDinal Study on Ageing (TILDA). European Journal of Public Health 26: 192–198.
Bijlsma, J.W., F. Berenbaum, and F.P. Lafeber. 2011. Osteoarthritis: an update with relevance for clinical practice. Lancet 377: 2115–2126.
Benito, M.J., D.J. Veale, O. FitzGerald, W.B. van den Berg, and B. Bresnihan. 2005. Synovial tissue inflammation in early and late osteoarthritis. Annals of the Rheumatic Diseases 64: 1263–1267.
Haq, S.A., F. Davatchi, S. Dahaghin, N. Islam, A. Ghose, J. Darmawan, A. Chopra, Z.Q. Yu, L.F. Dans, and J.J. Rasker. 2010. Development of a questionnaire for identification of the risk factors for osteoarthritis of the knees in developing countries. A pilot study in Iran and Bangladesh. An ILAR-COPCORD phase III study. International Journal of Rheumatic Diseases 13: 203–214.
Davies, M.A.M., Z.Y. Kerr, J.D. DeFreese, N.K. Arden, S.W. Marshall, K.M. Guskiewicz, et al. 2019. Prevalence of and risk factors for total hip and knee replacement in retired national football league athletes. The American Journal of Sports Medicine 363546519870804.
Mikkelsen, S., E.B. Pedersen, C. Brauer, K.L. Moller, T. Alkjaer, H. Koblauch, et al. 2019. Knee osteoarthritis among airport baggage handlers: a prospective cohort study. American Journal of Industrial Medicine.
Rai, M.F., X. Duan, J.D. Quirk, N. Holguin, E.J. Schmidt, N. Chinzei, et al. 2017. Post-traumatic osteoarthritis in mice following mechanical injury to the synovial joint. Scientific Reports 7: 45223.
Ozler, K., E. Aktas, C. Atay, B. Yilmaz, M. Arikan, and S. Gungor. 2016. Serum and knee synovial fluid matrixmetalloproteinase-13 and tumor necrosis factor-alpha levels in patients with late stage osteoarthritis. Acta Orthopaedica et Traumatologica Turcica 50: 670–673.
Chen, C., J. Xie, R. Rajappa, L. Deng, J. Fredberg, and L. Yang. 2015. Interleukin-1beta and tumor necrosis factor-alpha increase stiffness and impair contractile function of articular chondrocytes. Acta Biochimica et Biophysica Sinica 47: 121–129.
Basu, A., B.T. Kurien, H. Tran, B. Byrd, J. Maher, J. Schell, E. Masek, J.R. Barrett, T.J. Lyons, N.M. Betts, and R. Hal Scofield. 2018. Strawberries decrease circulating levels of tumor necrosis factor and lipid peroxides in obese adults with knee osteoarthritis. Food & Function 9: 6218–6226.
Canas, C.A., C.J. Osorio, N. Coronel, M.C. Cepeda, J.H. Izquierdo, and F. Bonilla-Abadia. 2014. Efficacy and safety of oral low-dose glucocorticoids in patients with estrogen-dependent primary osteoarthritis. Rheumatology International 34: 733–735.
Jung, S.Y., E.J. Jang, S. Choi, S.G. Im, D. Kim, S.K. Cho, et al. 2019. The effect of a nationwide real-time drug utilization review system on duplicated non-steroid anti-inflammatory drugs prescription in Korea. Arthritis Care & Research.
Zhang, R., L. Li, B. Chen, H. Liu, J. Liu, L. Zhang, et al. 2019. Acupotomy versus nonsteroidal anti-inflammatory drugs for knee osteoarthritis: protocol for a systematic review and meta-analysis. Medicine 98: e17051.
Berman, B.M., L. Lao, M. Greene, R.W. Anderson, R.H. Wong, P. Langenberg, and M.C. Hochberg. 1995. Efficacy of traditional Chinese acupuncture in the treatment of symptomatic knee osteoarthritis: a pilot study. Osteoarthritis and Cartilage 3: 139–142.
Hou, P.W., P.K. Fu, H.C. Hsu, and C.L. Hsieh. 2015. Traditional Chinese medicine in patients with osteoarthritis of the knee. Journal of Traditional and Complementary Medicine 5: 182–196.
Lo, P.C., F.C. Lin, Y.C. Tsai, and S.K. Lin. 2019. Traditional Chinese medicine therapy reduces the risk of total knee replacement in patients with knee osteoarthritis. Medicine 98: e15964.
Yang, L., G. Liu, K. Lian, Y. Qiao, B. Zhang, X. Zhu, Y. Luo, Y. Shang, and X.L. Gu. 2019. Dietary leonurine hydrochloride supplementation attenuates lipopolysaccharide challenge-induced intestinal inflammation and barrier dysfunction by inhibiting the NF-kappaB/MAPK signaling pathway in broilers. Journal of Animal Science 97: 1679–1692.
Zhang, L., H.X. Li, W.S. Pan, F.U. Khan, C. Qian, F.R. Qi-Li, et al. 2019. Novel hepatoprotective role of leonurine hydrochloride against experimental non-alcoholic steatohepatitis mediated via AMPK/SREBP1 signaling pathway. Biomedicine & Pharmacotherapy 110: 571–581.
Yang, L., G. Liu, X. Zhu, Y. Luo, Y. Shang, and X.L. Gu. 2019. The anti-inflammatory and antioxidant effects of leonurine hydrochloride after lipopolysaccharide challenge in broiler chicks. Poultry Science 98: 1648–1657.
Xi, L., C. Wang, P. Chen, Q. Yang, R. Hu, H. Zhang, et al. 2017. Expressions of IL-6, TNF-alpha and NF-kappaB in the skin of Chinese brown frog (Rana dybowskii). European Journal of Histochemistry 61: 2834.
Xu, B., R. Xing, Z. Huang, S. Yin, X. Li, L. Zhang, L. Ding, and P. Wang. 2019. Excessive mechanical stress induces chondrocyte apoptosis through TRPV4 in an anterior cruciate ligament-transected rat osteoarthritis model. Life Sciences 228: 158–166.
Xue, S., L. Zhu, C. Wang, Y. Jiang, H. Lu, Y. Liu, Q. Shao, B. Xue, W. Sang, and J. Ma. 2019. CDK9 attenuation exerts protective effects on catabolism and hypertrophy in chondrocytes and ameliorates osteoarthritis development. Biochemical and Biophysical Research Communications 517: 132–139.
Zeng, Y.F., R. Wang, Y. Bian, W.S. Chen, and L. Peng. 2019. Catalpol attenuates IL-1beta induced matrix catabolism, apoptosis and inflammation in rat chondrocytes and inhibits cartilage degeneration. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research 25: 6649–6659.
Sun, F.F., P.F. Hu, Y. Xiong, J.P. Bao, J. Qian, and L.D. Wu. 2019. Tricetin protects rat chondrocytes against IL-1beta-induced inflammation and apoptosis. Oxidative Medicine and Cellular Longevity 2019: 4695381.
Wen, Z.H., Y.Y. Lin, Y.C. Chang, C.C. Tang, S.P. Hsieh, H.P. Lee, et al. 2019. The COX-2 inhibitor etoricoxib reduces experimental osteoarthritis and nociception in rats: The roles of TGF-beta1 and NGF expressions in chondrocytes. European Journal of Pain.
Murata, K., T. Kokubun, K. Onitsuka, Y. Oka, T. Kano, Y. Morishita, K. Ozone, N. Kuwabara, J. Nishimoto, T. Isho, K. Takayanagi, and N. Kanemura. 2019. Controlling joint instability after anterior cruciate ligament transection inhibits transforming growth factor-beta-mediated osteophyte formation. Osteoarthritis and Cartilage 27: 1185–1196.
Dong, H.C., P.N. Li, C.J. Chen, X. Xu, H. Zhang, G. Liu, L.J. Zheng, and P. Li. 2019. Sinomenine attenuates cartilage degeneration by regulating miR-223-3p/NLRP3 inflammasome signaling. Inflammation 42: 1265–1275.
Feng, K., Y. Ge, Z. Chen, X. Li, Z. Liu, H. Li, et al. 2019. Curcumin inhibits the PERK-eIF2alpha-CHOP pathway through promoting SIRT1 expression in oxidative stress-induced rat chondrocytes and ameliorates osteoarthritis progression in a rat model. Oxidative Medicine and Cellular Longevity 2019: 8574386.
Bjordal, J. 2006. NSAIDs in osteoarthritis: irreplaceable or troublesome guidelines? British Journal of Sports Medicine 40: 285–286 discussion 286.
Baraf, H.S., F.M. Gloth, H.R. Barthel, M.S. Gold, and R.D. Altman. 2011. Safety and efficacy of topical diclofenac sodium gel for knee osteoarthritis in elderly and younger patients: pooled data from three randomized, double-blind, parallel-group, placebo-controlled, multicentre trials. Drugs & Aging 28: 27–40.
Paul, S., N. Das, and S. Ghosh. 2009. The effects of aceclofenac and nabumetone in osteoarthritis. JNMA; Journal of the Nepal Medical Association 48: 121–125.
Mackenzie, I.S., and T.M. MacDonald. 2010. Treatment of osteoarthritis in hypertensive patients. Expert Opinion on Pharmacotherapy 11: 393–403.
Yuan, F.L., R.S. Xu, D.L. Jiang, X.L. He, Q. Su, C. Jin, and X. Li. 2015. Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated with estrogen deficiency by inhibiting the NF-kappaB and PI3K/Akt signaling pathways. Bone 75: 128–137.
Gierman, L.M., B. van El, F. van der Ham, A. Koudijs, R. Stoop, J.H. Verheijen, et al. 2013. Profiling the secretion of soluble mediators by end stage osteoarthritis synovial tissue explants reveals a reduced responsiveness to an inflammatory trigger. PLoS One 8: e62634.
Rai, M.F., and L.J. Sandell. 2011. Inflammatory mediators: tracing links between obesity and osteoarthritis. Critical Reviews in Eukaryotic Gene Expression 21: 131–142.
Neuhold, L.A., L. Killar, W. Zhao, M.L. Sung, L. Warner, J. Kulik, J. Turner, W. Wu, C. Billinghurst, T. Meijers, A.R. Poole, P. Babij, and L. DeGennaro. 2001. Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice. The Journal of Clinical Investigation 107: 35–44.
Verma, P., and K. Dalal. 2011. ADAMTS-4 and ADAMTS-5: key enzymes in osteoarthritis. Journal of Cellular Biochemistry 112: 3507–3514.
Glasson, S.S., R. Askew, B. Sheppard, B. Carito, T. Blanchet, H.L. Ma, C.R. Flannery, D. Peluso, K. Kanki, Z. Yang, M.K. Majumdar, and E.A. Morris. 2005. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 434: 644–648.
Funding
This study was supported by National Natural Science Foundation of China (81572142).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interests
The authors declare that they have no conflict of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Chen, C., Zhu, Z., Hu, N. et al. Leonurine Hydrochloride Suppresses Inflammatory Responses and Ameliorates Cartilage Degradation in Osteoarthritis via NF-κB Signaling Pathway. Inflammation 43, 146–154 (2020). https://doi.org/10.1007/s10753-019-01104-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10753-019-01104-z