Silibinin làm giảm tổn thương DNA, rối loạn chức năng ti thể và apoptosis do căng thẳng oxy hóa trong các tế bào biểu mô sắc tố võng mạc người

Yung Hyun Choi1,2
1Anti‑Aging Research Center, Dong-eui University, Busan, Republic of Korea
2Department of Biochemistry, College of Korean Medicine, Dong-eui University, Busan, Republic of Korea

Tóm tắt

Silibinin, một loại flavonolignan, được biết đến với nhiều hoạt động dược lý khác nhau, bao gồm hoạt động chống oxy hóa, nhưng cơ chế chống oxy hóa của nó trong mắt vẫn chưa rõ ràng. Nghiên cứu này nhằm đánh giá liệu silibinin có thể bảo vệ các tế bào biểu mô sắc tố võng mạc người ARPE-19 khỏi tổn thương do oxy hóa hay không. Silibinin làm giảm sự suy giảm khả năng sống sót của tế bào và tổn thương DNA trong các tế bào ARPE-19 được điều trị bằng hydrogen peroxide (H2O2), đồng thời ức chế sản xuất các gốc tự do oxy phản ứng (ROS) trong tế bào và bảo tồn lượng glutathione (GSH) giảm. Silibinin cũng đối kháng với sự ức chế do H2O2 gây ra đối với biểu hiện và hoạt động của các enzym chống oxy hóa, như GSH peroxidase và mangan superoxide dismutase, điều này liên quan đến việc ức chế sản xuất ROS ở ti thể. Hơn nữa, silibinin đã cứu tế bào ARPE-19 khỏi sự apoptosis do H2O2 gây ra bằng cách phục hồi tỷ lệ Bcl-2/Bax giảm và giảm hoạt hóa caspase-3. Ngoài ra, silibinin đã ức chế sự giải phóng cytochrome c từ ti thể vào nội bào, điều này đạt được bằng cách can thiệp vào sự phá hủy màng ti thể. Những phát hiện này gợi ý rằng silibinin có hoạt động quét ROS mạnh mẽ với tiềm năng bảo vệ chống lại các bệnh về mắt do căng thẳng oxy hóa.

Từ khóa

#silibinin #DNA tổn thương #rối loạn chức năng ti thể #apoptosis #căng thẳng oxy hóa #tế bào ARPE-19

Tài liệu tham khảo

Aamani N, Bagheri A, Masoumi Qajari N, Malekzadeh Shafaroudi M, Khonakdar-Tarsi A (2022) JNK and p38 gene and protein expression during liver ischemia-reperfusion in a rat model treated with silibinin. Iran J Basic Med Sci 25:1373–1381 Anupama C, Shettar A, Ranganath SH, Srinivas SP (2023) Experimental oxidative stress breaks down the barrier function of the corneal endothelium. J Ocul Pharmacol Ther 39:70–79 Baeeri M et al (2018) Molecular and biochemical evidence on the protective role of ellagic acid and silybin against oxidative stress-induced cellular aging. Mol Cell Biochem 441:21–33 Bock FJ, Tait SWG (2020) Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol 21:85–100 Cao M, Fan B, Zhen T, Das A, Wang J (2023) Ruthenium biochanin-a complex ameliorates lung carcinoma through the downregulation of the TGF-β/PPARγ/PI3K/TNF-α pathway in association with caspase-3-mediated apoptosis. Toxicol Res 39:455–475 Chaudhary MR et al (2023) Aging, oxidative stress and degenerative diseases: mechanisms, complications and emerging therapeutic strategies. Biogerontology 24:609–662 Chen CL, Chen JT, Liang CM, Tai MC, Lu DW, Chen YH (2017) Silibinin treatment prevents endotoxin-induced uveitis in rats in vivo and in vitro. PLoS ONE 12:e0174971 Chen YH, Lin H, Wang Q, Hou JW, Mao ZJ, Li YG (2020) Protective role of silibinin against myocardial ischemia/reperfusion injury-induced cardiac dysfunction. Int J Biol Sci 16:1972–1988 Clementi ME, Pizzoferrato M, Bianchetti G, Brancato A, Sampaolese B, Maulucci G, Tringali G (2022) Cytoprotective effect of idebenone through modulation of the intrinsic mitochondrial pathway of apoptosis in human retinal pigment epithelial cells exposed to oxidative stress induced by hydrogen peroxide. Biomedicines 10:503 Cordelli E, Bignami M, Pacchierotti F (2021) Comet assay: A versatile but complex tool in genotoxicity testing. Toxicol Res (camb) 10:68–78 Dammak A et al (2023) Oxidative stress in the anterior ocular diseases: diagnostic and treatment. Biomedicines 11:292 Demine S, Renard P, Arnould T (2019) Mitochondrial uncoupling: a key controller of biological processes in physiology and diseases. Cells 8:795 Enns GM, Cowan TM (2017) Glutathione as a redox biomarker in mitochondrial disease-implications for therapy. J Clin Med 6:50 Goswami DG, Kant R, Tewari-Singh N, Agarwal R (2018) Efficacy of anti-inflammatory, antibiotic and pleiotropic agents in reversing nitrogen mustard-induced injury in ex vivo cultured rabbit cornea. Toxicol Lett 293:127–132 Guo H, Wang Y, Liu D (2020) Silibinin ameliorate H2O2-induced apoptosis and oxidative stress response by activating Nrf2 signaling in trophoblast cells. Acta Histochem 122:151620 Hahm JY, Park J, Jang ES, Chi SW (2022) 8-Oxoguanine: from oxidative damage to epigenetic and epitranscriptional modification. Exp Mol Med 54:1626–1642 Hernandez M et al (2021) Anti-inflammatory and anti-oxidative synergistic effect of vitamin D and nutritional complex on retinal pigment epithelial and endothelial cell lines against age-related macular degeneration. Nutrients 13:1423 Hsueh YJ, Chen YN, Tsao YT, Cheng CM, Wu WC, Chen HC (2022) The pathomechanism, antioxidant biomarkers, and treatment of oxidative stress-related eye diseases. Int J Mol Sci 23:1255 Islam A, Mishra A, Siddiqui MA, Siddiquie S (2021) Recapitulation of evidence of phytochemical, pharmacokinetic and biomedical application of silybin. Drug Res (stuttg) 71:489–503 Kalemci S et al (2015) Silibinin attenuates methotrexate-induced pulmonary injury by targeting oxidative stress. Exp Ther Med 10:503–507 Kiraz Y, Adan A, Kartal Yandim M, Baran Y (2016) Major apoptotic mechanisms and genes involved in apoptosis. Tumor Biol 37:8471–8486 Kopp B, Khoury L, Audebert M (2019) Validation of the γH2AX biomarker for genotoxicity assessment: a review. Arch Toxicol 93:2103–2114 Křen V, Valentová K (2022) Silybin and its congeners: From traditional medicine to molecular effects. Nat Prod Rep 39:1264–1281 Lalier L, Vallette F, Manon S (2022) Bcl-2 family members and the mitochondrial import machineries: the roads to death. Biomolecules 12:162 Li W et al (2023) Silibinin exerts neuroprotective effects against cerebral hypoxia/reoxygenation injury by activating the GAS6/Axl pathway. Toxicology 495:153598 Lin CH et al (2013) Silibinin inhibits VEGF secretion and age-related macular degeneration in a hypoxia-dependent manner through the PI-3 kinase/Akt/mTOR pathway. Br J Pharmacol 168:920–931 Liu M, Sun X, Chen B, Dai R, Xi Z, Xu H (2022) Insights into manganese superoxide dismutase and human diseases. Int J Mol Sci 23:15893 Lou MF (2022) Glutathione and glutaredoxin in redox regulation and cell signaling of the lens. Antioxidants (basel) 11:1973 Mao YX et al (2018) RAGE-dependent mitochondria pathway: A novel target of silibinin against apoptosis of osteoblastic cells induced by advanced glycation end products. Cell Death Dis 9:674 Marazita MC, Dugour A, Marquioni-Ramella MD, Figueroa JM, Suburo AM (2016) Oxidative stress-induced premature senescence dysregulates VEGF and CFH expression in retinal pigment epithelial cells: Implications for age-related macular degeneration. Redox Biol 7:78–87 Mukherjee S, Park JP, Yun JW (2022) Carboxylesterase3 (Ces3) Interacts with bone morphogenetic protein 11 and promotes differentiation of osteoblasts via Smad1/5/9 pathway. Biotechnol Bioprocess Eng 27:1–16 Munro D, Treberg JR (2017) A radical shift in perspective: mitochondria as regulators of reactive oxygen species. J Exp Biol 220:1170–1180 Nawaz A, Zaib S, Khan I, Ahmed A, Shahzadi K, Riaz H (2023) Silybum marianum: An overview of its phytochemistry and pharmacological activities with emphasis on potential anticancer properties. Anticancer Agents Med Chem 23:1519–1534 Palma FR et al (2020) Mitochondrial superoxide dismutase: What the established, the intriguing, and the novel reveal about a key cellular redox switch. Antioxid Redox Signal 32:701–714 Park J, Choi C (2012) Contribution of mitochondrial network dynamics to intracellular ROS signaling. Commun Integr Biol 5:81–83 Park C et al (2023) Nrf2-mediated activation of HO-1 is required in the blocking effect of compound K, a ginseng saponin metabolite, against oxidative stress damage in ARPE-19 human retinal pigment epithelial cells. J Ginseng Res 47:311–318 Singh M et al (2023) A systematic review of the protective effects of silymarin/silibinin against doxorubicin-induced cardiotoxicity. Cancer Cell Int 23:88 Sozen H, Celik OI, Cetin ES, Yilmaz N, Aksozek A, Topal Y, Cigerci IH, Beydilli H (2015) Evaluation of the protective effect of silibinin in rats with liver damage caused by itraconazole. Cell Biochem Biophys 71:1215–1223 Sukjamnong S, Chen H, Saad S, Santiyanont R (2022) Fimbristylis ovata and Artemisia vulgaris extracts inhibited AGE-mediated RAGE expression, ROS generation, and inflammation in THP-1 cells. Toxicol Res 38:331–343 Takke A, Shende P (2019) Nanotherapeutic silibinin: an insight of phytomedicine in healthcare reformation. Nanomedicine 21:102057 Tie F, Fu Y, Hu N, Wang H (2022) Silibinin protects against H2O2-induced oxidative damage in SH-SY5Y cells by improving mitochondrial function. Antioxidants (basel) 11:1101 Tong Y, Zhang Z, Wang S (2022) Role of mitochondria in retinal pigment epithelial aging and degeneration. Front Aging 3:926627 Wadhwa K, Pahwa R, Kumar M, Kumar S, Sharma PC, Singh G, Verma R, Mittal V, Singh I, Kaushik D, Jeandet P (2022) Mechanistic insights into the pharmacological significance of silymarin. Molecules 27:5327 Wang X, Zhang Z, Wu SC (2020) Health benefits of Silybum marianum: phytochemistry, pharmacology, and applications. J Agric Food Chem 68:11644–11664 Yan J, Jiang J, He L, Chen L (2020) Mitochondrial superoxide/hydrogen peroxide: An emerging therapeutic target for metabolic diseases. Free Radic Biol Med 152:33–42 Yang F, Jia M, Deng C, Xiao B, Dai R, Xiang Y (2022) Silibinin ameliorates cisplatin-induced acute kidney injury via activating Nfe2l1-mediated antioxidative response to suppress the ROS/MAPK signaling pathway. J Mol Histol 53:729–740 Zappavigna S et al (2019) Silybin-induced apoptosis occurs in parallel to the increase of ceramides synthesis and miRNAs secretion in human hepatocarcinoma cells. Int J Mol Sci 20:2190 Zhang SM, Fan B, Li YL, Zuo ZY, Li GY (2023) Oxidative stress-involved mitophagy of retinal pigment epithelium and retinal degenerative diseases. Cell Mol Neurobiol 43:3265–3276 Zia A, Farkhondeh T, Pourbagher-Shahri AM, Samarghandian S (2022) The roles of mitochondrial dysfunction and reactive oxygen species in aging and senescence. Curr Mol Med 22:37–49 Zou GP et al (2023) Lactate protects against oxidative stress-induced retinal degeneration by activating autophagy. Free Radic Biol Med 194:209–219