Assessment of the Impact of Curcumin on Cell Cultures Derived from the Primary Intervertebral Disc Tissue in Humans
Abstract
Aim: Degenerative disc disease in the lumbar spine is widely observed. Degenerative disc diseases are among the causes of low back pain in older age. Modern drug discovery studies have aimed to identify potential molecules that target multiple pathways with a safer profile against degeneration. This study aimed to evaluate the effects of curcumin, a natural phenolic compound, on primary cell cultures prepared using intervertebral disc (IVD) tissues resected during the surgeries of patients with lumbar disc herniation.
Materials and Methods: Primary cell cultures were prepared using human IVD tissues of eight patients. Untreated groups served as the control and curcumin-treated groups as the study sample. In-vitro cytotoxicity analyses were performed in all groups. Acridine orange (AO)/propidium iodide (PI) and Janus Green B staining were performed to evaluate cell surface morphologies. One-way analysis of variance and Tukey HSD, a multiple comparison test, were used to assess the obtained data.
Results: Proliferation slightly increased as of 24 h in the curcumin-treated samples, but decreased in the 48 and 72 hour curcumin-treated samples compared to the control samples. The obtained results were statistically significant (p<0.05). Additionally no cytotoxicity was observed according to morphological evaluations.
Conclusion: This research is an in-vitro experimental study. However, this natural and non-toxic pleiotropic agent can be targeted to cell-damaged sites through appropriate drug delivery systems. It may thus be a safe treatment option for the regeneration of degenerated lumbar IVD cells in the future.
Keywords
Annulus fibrosus Curcumin Cytotoxicity Nucleus pulposus Primary cell culture Proliferation.
References
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- 8. Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer.2005;41:1955-68.
- 9. He HJ, Xiong X, Zhou S, et al. Neuroprotective effects of curcumin via autophagy induction in 6 hydroxydopamine Parkinson's models. Neurochem Int.2022;155:105297.
- 10. Zhao P, Cheng J, Geng J, et al. Curcumin protects rabbit articular chondrocytes against sodium nitroprusside-induced apoptosis in vitro. Eur J Pharmacol.2018;828:146-53.
- 11. Brochard S, Pontin J, Bernay B, Boumediene K, Conrozier T, Baugé C. The benefit of combining curcumin, bromelain and harpagophytum to reduce inflammation in osteoarthritic synovial cells. BMC Complement Med Ther.2021;21:261.
- 12. Wang P, Ye Y, Yuan W, Tan Y, Zhang S, Meng Q. Curcumin exerts a protective effect on murine knee chondrocytes treated with IL-1β through blocking the NF-κB/HIF-2α signaling pathway. Ann Transl Med.2021;9:940.
- 13. Kang L, Xiang Q, Zhan S, et al. Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration. Oxid Med Cell Longev.2019;2019:7810320.
- 14. Hu Y, Tang JS, Hou SX, et al. Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS,COX-2, TGF-β1/2, MMP-9 and BDNF in a rat model. Mol Med Rep.2017;16:6864-9.
- 15. Somay H, Karaarslan N. Sequestrectomy or microdiscectomy in patients with lumbar disc herniation. Ann Med Res.2021;26,753-8.
- 16. Karaarslan N, Yilmaz I, Sirin DY, Ozbek H, Kaplan, Kaya Y E, et al. Pregabalin treatment for neuropathic pain may damage intervertebral disc tissue. Exp Ther Med.2018;16:1259-65.
- 17. Kaya YE, Akalan H, Yilmaz I, Karaarslan N, Yasar Sirin D, Ozbek H. Evaluation of the expression and proliferation of degenerative markers in primary cell cultures obtained from human intervertebral disc tissue. Ann Med Res.2020;27:711-6.
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- 29. Karaarslan N, Yilmaz I, Sirin DY. Toxicity of the acetyl-para-aminophenol group of medicines to intact intervertebral disc tissue cells. Exp Ther Med.2021;21:147.
- 30. Yilmaz I, Karaarslan N, Ozbek H. Practical Performance of Hippocampal Tissue Resection in Rats in Pharmacomolecular Research. Turk Neurosurg.2021;31(1):112-8.
- 31. Ashinsky B, Smith HE, Mauck RL, Gullbrand SE. Intervertebral disc degeneration and regeneration: a motion segment perspective. Eur Cell Mater.2021;41:370-80.
- 32. Hartman RA, Yurube T, Ngo K, et al. Biological responses to flexion/extension in spinal segments ex-vivo. J Orthop Res.2015;33:1255-64.
- 33. Kamali A, Ziadlou R, Lang G, et al. Small moleculebased treatment approaches for intervertebral disc degeneration: Current options and future directions. Theranostics.2021;11:27-47.
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- 37. Xie C, Shi Y, Chen Z, et al. Apigenin Alleviates Intervertebral Disc Degeneration via Restoring Autophagy Flux in Nucleus Pulposus Cells. Front Cell Dev Biol.2022;9:787278.
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İnsan Primer İntervertebral Disk Dokusundan Elde Edilen Hücre Kültürleri Üzerinde Curcumin'in Etkisinin Değerlendirilmesi
Abstract
Amaç
Lomber omurga bölgesinde dejeneratif disk hastalığı yaygın olarak gözlemlenmektedir. Dejeneratif disk hastalıkları, yaşlılıkta bel ağrısının nedenlerinden biridir. Modern ilaç keşfi çalışmaları, daha güvenli bir profille dejenerasyona karşı çoklu yolları hedefleyebilen potansiyel molekülleri tanımlamayı amaçlamıştır. Bu çalışmanın amacı, doğal bir fenolik bileşik olan kurkuminin, lomber disk herniasyonu olan hastaların cerrahileri sırasında çıkarılan intervertebral disk (IVD) dokuları kullanılarak hazırlanan primer hücre kültürleri üzerindeki etkilerini değerlendirmektir.
Materyal ve Metotlar
Sekiz hastanın insan IVD dokuları kullanılarak primer hücre kültürleri hazırlandı. Tedavi edilmemiş gruplar kontrol grubu olarak hizmet etti, kurkumin tedavisi uygulanan gruplar ise çalışma örneği olarak kullanıldı. Tüm gruplarda in-vitro sitotoksisite analizleri yapıldı. Hücre yüzey morfolojilerini değerlendirmek için Akrin Orange (AO)/Propidyum İodür (PI) ve Janus Green B boyaması yapıldı. Elde edilen verileri değerlendirmek için tek yönlü varyans analizi ve çoklu karşılaştırma testi olarak Tukey HSD kullanıldı.
Bulgular
Kurkumin tedavisi uygulanan örneklerde 24 saat sonra hafif bir şekilde çoğalma görülürken, 48 ve 72 saatlik kurkumin tedavisi uygulanan örneklerde kontrol örneklerine kıyasla azaldı. Elde edilen sonuçlar istatistiksel olarak anlamlıydı (p<0.05). Ayrıca morfolojik değerlendirmelere göre sitotoksisite gözlenmedi.
Sonuç
Bu araştırma in-vitro deneysel bir çalışmadır. Ancak, bu doğal ve toksik olmayan çok yönlü ajan uygun ilaç taşıma sistemleri aracılığıyla hücre hasarlı bölgelere yönlendirilebilir. Bu nedenle gelecekte dejeneratif lomber IVD hücrelerinin rejenerasyonu için güvenli bir tedavi seçeneği olabilir.
References
- 1. Degot P, Huber V, Touraud D, Kunz W. Curcumin extracts from Curcuma Longa - Improvement of concentration, purity, and stability in food-approved and water-soluble surfactant-free microemulsions. Food Chem.2021; 339:128140.
- 2. Mohammadian Haftcheshmeh S, Khosrojerdi A, Aliabadi A, Lotfi S, Mohammadi A, Momtazi-Borojeni AA. Immunomodulatory Effects of Curcumin in Rheumatoid Arthritis: Evidence from Molecular Mechanisms to Clinical Outcomes. Rev Physiol Biochem Pharmacol.2021;179:1-29.
- 3. Meena R, Kumar S, Kumar R, Gaharwar US, Rajamani P. PLGA-CTAB curcumin nanoparticles: Fabrication, characterization and molecular basis of anticancer activity in triple negative breast cancer cell lines (MDA-MB-231 cells). Biomed Pharmacother.2017;94:944-54.
- 4. Zhu G, Shen Q, Jiang H, Ji O, Zhu L, Zhang L. Curcumin inhibited the growth and invasion of human monocytic leukaemia SHI-1 cells in vivo by altering MAPK and MMP signalling. Pharm Biol.2020;58:25-34.
- 5. Zia A, Farkhondeh T, Pourbagher-Shahri AM, Samarghandian S. The role of curcumin in aging and senescence: Molecular mechanisms. Biomed Pharmacother.2021;134: 111119.
- 6. Khan K, Quispe C, Javed Z, et al. Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/ mTOR pathway: go four better to treat bladder cancer. Cancer Cell Int.2020; 20:560.
- 7. Daugherty DJ, Marquez A, Calcutt NA, Schubert D. A novel curcumin derivative for the treatment of diabetic neuropathy. Neuropharmacology. 2018;129:26-35.
- 8. Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer.2005;41:1955-68.
- 9. He HJ, Xiong X, Zhou S, et al. Neuroprotective effects of curcumin via autophagy induction in 6 hydroxydopamine Parkinson's models. Neurochem Int.2022;155:105297.
- 10. Zhao P, Cheng J, Geng J, et al. Curcumin protects rabbit articular chondrocytes against sodium nitroprusside-induced apoptosis in vitro. Eur J Pharmacol.2018;828:146-53.
- 11. Brochard S, Pontin J, Bernay B, Boumediene K, Conrozier T, Baugé C. The benefit of combining curcumin, bromelain and harpagophytum to reduce inflammation in osteoarthritic synovial cells. BMC Complement Med Ther.2021;21:261.
- 12. Wang P, Ye Y, Yuan W, Tan Y, Zhang S, Meng Q. Curcumin exerts a protective effect on murine knee chondrocytes treated with IL-1β through blocking the NF-κB/HIF-2α signaling pathway. Ann Transl Med.2021;9:940.
- 13. Kang L, Xiang Q, Zhan S, et al. Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration. Oxid Med Cell Longev.2019;2019:7810320.
- 14. Hu Y, Tang JS, Hou SX, et al. Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS,COX-2, TGF-β1/2, MMP-9 and BDNF in a rat model. Mol Med Rep.2017;16:6864-9.
- 15. Somay H, Karaarslan N. Sequestrectomy or microdiscectomy in patients with lumbar disc herniation. Ann Med Res.2021;26,753-8.
- 16. Karaarslan N, Yilmaz I, Sirin DY, Ozbek H, Kaplan, Kaya Y E, et al. Pregabalin treatment for neuropathic pain may damage intervertebral disc tissue. Exp Ther Med.2018;16:1259-65.
- 17. Kaya YE, Akalan H, Yilmaz I, Karaarslan N, Yasar Sirin D, Ozbek H. Evaluation of the expression and proliferation of degenerative markers in primary cell cultures obtained from human intervertebral disc tissue. Ann Med Res.2020;27:711-6.
- 18. Xiao L, Ding M, Fernandez A, Zhao P, Jin L, Li X. Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors. Eur Cell Mater.2017;33:279-93.
- 19. Akgun FS, Sirin DY, Yilmaz I, et al. Investigation of the effect of dipyrone on cells isolated from intervertebral disc tissue. Exp Ther Med.2019;18:216-24.
- 20. Karaarslan N, Yilmaz I, Ozbek H, et al. Are radiocontrast agents commonly used in discography toxic to the intact intervertebral disc tissue cells? Basic Clin Pharmacol Toxicol.2019;124:181-9.
- 21. Ahmad F, Alamoudi W, Haque S, Salahuddin M, Alsamman K. Simple, reliable, and time-efficient colorimetric method for the assessment of mitochondrial function and toxicity. Bosn J Basic Med Sci.2018;18:367-74.
- 22. Yilmaz I, Karaarslan N. Examining the effects of HMGCoA reductase inhibitors on anabolic and catabolic signaling pathway proteins associated with degenerative disc diseaseEur Rev Clin Pharmacol Sci.2022;26:2990- 3000.
- 23. Fança-Berthon P, Tenon M, Bouter-Banon SL, et al. Pharmacokinetics of a Single Dose of Turmeric Curcuminoids Depends on Formulation: Results of a Human Crossover Study. J Nutr.2021;151:1802-16.
- 24. Tan JH, Li ZP, Liu LL, Liu H, Xue JB. IL-17 in intervertebral disc degeneration: Mechanistic insights and therapeutic implications. Cell Biol Int.2022;46:535-47.
- 25. Kakiuchi Y, Yurube T, Kakutani K, et al. Pharmacological inhibition of mTORC1 but not mTORC2 protects against human disc cellular apoptosis, senescence, and extracellular matrix catabolism through Akt and autophagy induction. Osteoarthritis Cartilage.2019;27:965-76.
- 26. Cherif H, Bisson DG, Jarzem P, Weber M, Ouellet JA, Haglund L. Curcumin and o-Vanillin Exhibit Evidence of Senolytic Activity in Human IVD Cells In Vitro. J Clin Med.2019;8:433.
- 27. Ma T, Guo CJ, Zhao X, Wu L, Sun SX, Jin QH. The effect of curcumin on NF-κB expression in rat with lumbar intervertebral disc degeneration. Eur Rev Med Pharmacol Sci.2015;19:1305-14.
- 28. Nowroozi N, Faraji S, Nouralishahi A, Shahrousvand M. Biological and structural properties of grapheneoxide/curcumin nanocomposite incorporated chitosan as a scaffold for wound healing application. Life Sci.2021;264:118640.
- 29. Karaarslan N, Yilmaz I, Sirin DY. Toxicity of the acetyl-para-aminophenol group of medicines to intact intervertebral disc tissue cells. Exp Ther Med.2021;21:147.
- 30. Yilmaz I, Karaarslan N, Ozbek H. Practical Performance of Hippocampal Tissue Resection in Rats in Pharmacomolecular Research. Turk Neurosurg.2021;31(1):112-8.
- 31. Ashinsky B, Smith HE, Mauck RL, Gullbrand SE. Intervertebral disc degeneration and regeneration: a motion segment perspective. Eur Cell Mater.2021;41:370-80.
- 32. Hartman RA, Yurube T, Ngo K, et al. Biological responses to flexion/extension in spinal segments ex-vivo. J Orthop Res.2015;33:1255-64.
- 33. Kamali A, Ziadlou R, Lang G, et al. Small moleculebased treatment approaches for intervertebral disc degeneration: Current options and future directions. Theranostics.2021;11:27-47.
- 34. Zhang S, Liang W, Abulizi Y, et al. Quercetin Alleviates Intervertebral Disc Degeneration by Modulating p38 MAPKMediated Autophagy. Biomed Res Int.2021;2021:6631562.
- 35. Chen Y, Zheng Z, Wang J, et al. Berberine suppresses apoptosis and extracellular matrix (ECM) degradation in nucleus pulposus cells and ameliorates disc degeneration in a rodent model. Int J Biol Sci.2018;14:682-92.
- 36. Bai X, Jiang M, Wang J, et al. Cyanidin attenuates the apoptosis of rat nucleus pulposus cells and the degeneration of intervertebral disc via the JAK2/STAT3 signal pathway in vitro and in vivo. Pharm Biol.2022;60:427-36.
- 37. Xie C, Shi Y, Chen Z, et al. Apigenin Alleviates Intervertebral Disc Degeneration via Restoring Autophagy Flux in Nucleus Pulposus Cells. Front Cell Dev Biol.2022;9:787278.
- 38. Brown GN, Sattler RL, Guo XE. Experimental studies of bone mechanoadaptation: bridging in vitro and in vivo studies with multiscale systems. Interface Focus.2016;6:20150071.
- 39. Vareed SK, Kakarala M, Ruffin MT, et al. Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomarkers Prev.2008;17:1411-17.
Details
| Primary Language | English |
|---|---|
| Subjects | Orthopaedics |
| Journal Section | Research Article |
| Authors | |
| Publication Date | August 31, 2023 |
| Submission Date | August 11, 2023 |
| Published in Issue | Year 2023 Volume: 15 Issue: 2 |
