J Appl Biomed 14:307-314, 2016 | DOI: 10.1016/j.jab.2016.05.001
Carnosol ameliorates monosodium iodoacetate-induced osteoarthritis by targeting NF-κB and Nrf-2 in primary rat chondrocytes
- a Department of Joint Surgery, Weifang People's Hospital, Shandong Province 261041, China
- b Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250000, China
- c Department of Orthopedics, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250000, China
- d Department of Breast & Thyroid Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, China
- e Department of Medical Devices, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, China
Oxidative stress and NF-κB signaling plays a major role in pathogenesis of osteoarthritis. In the present study, we analyzed the potent role of carnosol against osteoarthritis in cells treated using monosodium iodoacetate (MIA) model through in vitro studies. MIA caused dose-dependent cell death and induced programmed cell death by increasing subG1 accumulation and caspase-3 expressions. MIA caused oxidative stress by increasing reactive oxygen species, lipid peroxidation and further induced NF-κB expression and down regulated Nrf-2 levels. Pre-treatment with carnosol significantly protected the cells by reducing the oxidative stress markers and improved the cell viability up to 98%. Further, carnosol down regulated NF-κB nuclear expression with a concomitant increase in Nrf-2 nuclear localization and up regulated the nuclear Nrf-2 levels. Carnosol also inhibited MIA-induced subG1 accumulation and caspase-3 activation. This study demonstrates that, carnosol might act as potent antioxidant and regulate MIA-induced oxidative stress, NF-κB signaling and programmed cell death by up regulating the Nrf-2 levels.
Keywords: Osteoarthritis; Oxidative stress; NF-κB; Nrf-2; Carnosol; ROS; Programmed cell death
Received: November 26, 2015; Revised: May 1, 2016; Accepted: May 4, 2016; Published: November 1, 2016 Show citation
ACS | AIP | APA | ASA | Harvard | Chicago | Chicago Notes | IEEE | ISO690 | MLA | NLM | Turabian | Vancouver |
References
- Aigner, T., Kim, H.A., Roach, H.I., 2004. Apoptosis in osteoarthritis. Rheum. Dis. Clin. 30, 639-653.
Go to original source...
Go to PubMed...
- Almonte-Becerril, M., Navarro-Garcia, F., Gonzalez-Robles, A., Vega-Lopez, M.A., Lavalle, C., Kouri, J.B., 2010. Cell death of chondrocytes is a combination between apoptosis and autophagy during the pathogenesis of osteoarthritis within an experimental model. Apoptosis 15, 631-638.
Go to original source...
Go to PubMed...
- Aruoma, O.I., Halliwell, B., Aeschbach, R., Löligers, J., 1992. Antioxidant and pro-oxidant properties of active rosemary constituents: carnosol and carnosic acid. Xenobiotica 22, 257-268.
Go to original source...
Go to PubMed...
- Aupperle, K.R., Bennett, B.L., Han, Z., Boyle, D.L., Manning, A.M., Firestein, G.S., 2001. NF-kB regulation by IkB kinase-2 in rheumatoid arthritis synoviocytes. J. Immunol. 166, 2705- 2711.
Go to original source...
Go to PubMed...
- Canter, P.H., Wider, B., Ernst, E., 2007. The antioxidant vitamins A, C, E and selenium in the treatment of arthritis: a systematic review of randomized clinical trials. Rheumatology 46, 1223-1233.
Go to original source...
Go to PubMed...
- Chen, C.-C., Chen, H.-L., Hsieh, C.-W., Yang, Y.-L., Wung, B.-S., 2011. Upregulation of NF-E2-related factor-2-dependent glutathione by carnosol provokes a cytoprotective response and enhances cell survival. Acta Pharmacol. Sin. 32, 62-69.
Go to original source...
Go to PubMed...
- Clegg, P.D., Mobasheri, A., 2003. Chondrocyte apoptosis, inflammatory mediators and equine osteoarthritis. Vet. J. 166, 3-4.
Go to original source...
Go to PubMed...
- Dossumbekova, A., Anghelina, M., Madhavan, S., He, L., Quan, N., Knobloch, T., Agarwal, S., 2007. Biomechanical signals inhibit IKK activity to attenuate NF-kB transcription activity in inflamed chondrocytes. Arthritis Rheum. 56, 3284-3296.
Go to original source...
Go to PubMed...
- Goldring, M.B., Goldring, S.R., 2007. Osteoarthritis. J. Cell. Physiol. 213, 626-634.
Go to original source...
Go to PubMed...
- Goldring, M.B., Marcu, K.B., 2009. Cartilage homeostasis in health and rheumatic diseases. Arthritis Res. Ther. 11, 224.
Go to original source...
Go to PubMed...
- Grossin, L., Cournil-Henrionnet, C., Pinzano, A., Gaborit, N., Dumas, D., Etienne, S., Stoltz, J.F., Terlain, B., Netter, P., Mir, L. M., Gillet, P., 2006. Gene transfer with HSP 70 in rat chondrocytes confers cytoprotection in vitro and during experimental osteoarthritis. FASEB J. 20, 65-75.
Go to original source...
Go to PubMed...
- Hashimoto, S., Ochs, R.L., Komiya, S., Lotz, M., 1998. Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis. Arthritis Rheum. 41, 1632-1638.
Go to original source...
- Healy, Z.R., Lee, N.H., Gao, X., Goldring, M.B., Talalay, P., Kensler, T.W., Konstantopoulos, K., 2005. Divergent responses of chondrocytes and endothelial cells to shear stress: cross-talk among COX-2, the phase 2 response, and apoptosis. Proc. Natl. Acad. Sci. U. S. A. 102, 14010-14015.
Go to original source...
Go to PubMed...
- Henrotin, Y.E., Bruckner, P., Pujol, J.P.L., 2003. The role of reactive oxygen species in homeostasis and degradation of cartilage. Osteoarthr. Cartil. 11, 747-755.
Go to original source...
Go to PubMed...
- Huang, M.-T., Ho, C.-T., Wang, Z.Y., Ferraro, T., Lou, Y.-R., Stauber, K., Ma, W., Georgiadis, C., Laskin, J.D., Conney, A.H., 1994. Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid. Cancer Res. 54, 701- 708.
- Ivanavicius, S.P., Ball, A.D., Heapy, C.G., Westwood, R.F., Murray, F., Read, S.J., 2007. Structural pathology in a rodent model of osteoarthritis is associated with neuropathic pain: increased expression of ATF-3 and pharmacological characterisation. Pain 128, 272-282.
Go to original source...
Go to PubMed...
- Jiang, L., Li, L., Geng, C., Gong, D., Jiang, L., Ishikawa, N., Kajima, K., Zhong, L., 2013. Monosodium iodoacetate induces apoptosis via the mitochondrial pathway involving ROS production and caspase activation in rat chondrocytes in vitro. J. Orthop. Res. 31, 364-369.
Go to original source...
Go to PubMed...
- Johnson, J.J., Syed, D.N., Heren, C.R., Suh, Y., Adhami, V.M., Mukhtar, H., 2008. Carnosol, a dietary diterpene, displays growth inhibitory effects in human prostate cancer PC3 cells leading to G2-phase cell cycle arrest and targets the 50 -AMPactivated protein kinase (AMPK) pathway. Pharm. Res. 25, 2125-2134.
Go to original source...
Go to PubMed...
- Kim, S.-J., Kim, J.-S., Cho, H.-S., Lee, H.J., Kim, S.Y., Kim, S., Lee, S.-Y., Chun, H.S., 2006. Carnosol, a component of rosemary (Rosmarinus officinalis L.) protects nigral dopaminergic neuronal cells. NeuroReport 17, 1729-1733.
Go to original source...
Go to PubMed...
- Kim, S.Y., Park, E., Park, J.A., Choi, B.-S., Kim, S., Jeong, G., Kim, C.-S., Kim, D.K., Kim, S.-J., Chun, H.S., 2010. The plant phenolic diterpene carnosol suppresses sodium nitroprusside-induced toxicity in C6 glial cells. J. Agric. Food Chem. 58, 1543-1550.
Go to original source...
Go to PubMed...
- Kobayashi, A., Kang, M.-I., Watai, Y., Tong, K.I., Shibata, T., Uchida, K., Yamamoto, M., 2006. Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of Keap1. Mol. Cell. Biol. 26, 221-229.
Go to original source...
Go to PubMed...
- Largo, R., Alvarez-Soria, M.A., Díez-Ortego, I., Calvo, E., SánchezPernaute, O., Egido, J., Herrero-Beaumont, G., 2003. Glucosamine inhibits IL-1b-induced NFkB activation in human osteoarthritic chondrocytes. Osteoarthr. Cartil. 11, 290-298.
Go to original source...
Go to PubMed...
- Li, W., Khor, T.O., Xu, C., Shen, G., Jeong, W.-S., Yu, S., Kong, A.N., 2008. Activation of Nrf2-antioxidant signaling attenuates NF-kB-inflammatory response and elicits apoptosis. Biochem. Pharmacol. 76, 1485-1489.
Go to original source...
Go to PubMed...
- Li, D., Xie, G., Wang, W., 2012. Reactive oxygen species: the 2edged sword of osteoarthritis. Am. J. Med. Sci. 344, 486-490.
Go to original source...
Go to PubMed...
- Lian, K.-C., Chuang, J.-J., Hsieh, C.-W., Wung, B.-S., Huang, G.-D., Jian, T.-Y., Sun, Y.-W., 2010. Dual mechanisms of NF-kB inhibition in carnosol-treated endothelial cells. Toxicol. Appl. Pharmacol. 245, 21-35.
Go to original source...
Go to PubMed...
- Lianxu, C., Hongti, J., Changlong, Y., 2006. NF-kBp65-specific siRNA inhibits expression of genes of COX-2, NOS-2 and MMP-9 in rat IL-1b-induced and TNF-a-induced chondrocytes. Osteoarthr. Cartil. 14, 367-376.
Go to original source...
Go to PubMed...
- Lo, A.-H., Liang, Y.-C., Lin-Shiau, S.-Y., Ho, C.-T., Lin, J.-K., 2002. Carnosol, an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-kB in mouse macrophages. Carcinogenesis 23, 983-991.
Go to original source...
Go to PubMed...
- Loeser, R.F., Forsyth, C.B., Samarel, A.M., Im, H.-J., 2003. Fibronectin fragment activation of proline-rich tyrosine kinase PYK2 mediates integrin signals regulating collagenase-3 expression by human chondrocytes through a protein kinase C-dependent pathway. J. Biol. Chem. 278, 24577-24585.
Go to original source...
Go to PubMed...
- Martin, D., Rojo, A.I., Salinas, M., Diaz, R., Gallardo, G., Alam, J., de Galarreta, C.M.R., Cuadrado, A., 2004. Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. J. Biol. Chem. 279, 8919-8929.
Go to original source...
Go to PubMed...
- Mengoni, E.S., Vichera, G., Rigano, L.A., Rodriguez-Puebla, M.L., Galliano, S.R., Cafferata, E.E., Pivetta, O.H., Moreno, S., Vojnov, A.A., 2011. Suppression of COX-2, IL-1b and TNF-a expression and leukocyte infiltration in inflamed skin by bioactive compounds from Rosmarinus officinalis L. Fitoterapia 82, 414-421.
Go to original source...
Go to PubMed...
- Mosmann, T., 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55-63.
Go to original source...
Go to PubMed...
- Poeckel, D., Greiner, C., Verhoff, M., Rau, O., Tausch, L., Hörnig, C., Steinhilber, D., Schubert-Zsilavecz, M., Werz, O., 2008. Carnosic acid and carnosol potently inhibit human 5lipoxygenase and suppress pro-inflammatory responses of stimulated human polymorphonuclear leukocytes. Biochem. Pharmacol. 76, 91-97.
Go to original source...
Go to PubMed...
- Rasband, W.S., 1997-2015. ImageJ. U. S. National Institutes of Health, Bethesda, MD, USA., http://imagej.nih.gov/ij/.
- Roman-Blas, J.A., Jimenez, S.A., 2006. NF-kB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthr. Cartil. 14, 839-848.
Go to original source...
Go to PubMed...
- Ronzière, M.-C., Aubert-Foucher, E., Gouttenoire, J., Bernaud, J., Herbage, D., Mallein-Gerin, F., 2005. Integrin a1b1 mediates collagen induction of MMP-13 expression in MC615 chondrocytes. Biochim. Biophys. Acta 1746, 55-64.
Go to original source...
Go to PubMed...
- Sharif, M., Whitehouse, A., Sharman, P., Perry, M., Adams, M., 2004. Increased apoptosis in human osteoarthritic cartilage corresponds to reduced cell density and expression of caspase-3. Arthritis Rheum. 50, 507-515.
Go to original source...
Go to PubMed...
- Singletary, K., MacDonald, C., Wallig, M., 1996. Inhibition by rosemary and carnosol of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumorigenesis and in vivo DMBA-DNA adduct formation. Cancer Lett. 104, 43-48.
Go to original source...
Go to PubMed...
- Taniguchi, S., Ryu, J., Seki, M., Sumino, T., Tokuhashi, Y., Esumi, M., 2012. Long-term oral administration of glucosamine or chondroitin sulfate reduces destruction of cartilage and upregulation of MMP-3 mRNA in a model of spontaneous osteoarthritis in Hartley guinea pigs. J. Orthop. Res. 30, 673- 678.
Go to original source...
Go to PubMed...
- Thomas, C.M., Fuller, C.J., Whittles, C.E., Sharif, M., 2007. Chondrocyte death by apoptosis is associated with cartilage matrix degradation. Osteoarthr. Cartil. 15, 27-34.
Go to original source...
Go to PubMed...
- Tomobe, K., Shinozuka, T., Kuroiwa, M., Nomura, Y., 2012. Agerelated changes of Nrf2 and phosphorylated GSK-3b in a mouse model of accelerated aging (SAMP8). Arch. Gerontol. Geriatr. 54, e1-e7.
Go to original source...
Go to PubMed...
- Ungvari, Z., Bailey-Downs, L., Sosnowska, D., Gautam, T., Koncz, P., Losonczy, G., Ballabh, P., de Cabo, R., Sonntag, W.E., Csiszar, A., 2011. Vascular oxidative stress in aging: a homeostatic failure due to dysregulation of NRF2-mediated antioxidant response. Am. J. Physiol. 301, H363-H372.
Go to original source...
Go to PubMed...
- Valdés, A., García-Cañas, V., Simó, C., Ibáñez, C., Micol, V., Ferragut, J.A., Cifuentes, A., 2014. Comprehensive foodomics study on the mechanisms operating at various molecular levels in cancer cells in response to individual rosemary polyphenols. Anal. Chem. 86, 9807-9815.
Go to original source...
Go to PubMed...
- Vergara, D., Simeone, P., Bettini, S., Tinelli, A., Valli, L., Storelli, C., Leo, S., Santino, A., Maffia, M., 2014. Antitumor activity of the dietary diterpene carnosol against a panel of human cancer cell lines. Food Funct. 5, 1261-1269.
Go to original source...
Go to PubMed...
- Wakabayashi, N., Slocum, S.L., Skoko, J.J., Shin, S., Kensler, T.W., 2010. When NRF2 talks, who's listening? Antioxid. Redox Signal. 13, 1649-1663.
Go to original source...
Go to PubMed...
- Zeng, H.H., Tu, P.F., Zhou, K., Wang, H., Wang, B.H., Lu, J.F., 2001. Antioxidant properties of phenolic diterpenes from Rosmarinus officinalis. Acta Pharmacol. Sin. 22, 1094-1098.
Go to PubMed...