Oridonin protects hydrogen peroxide-induced human lens epithelial cell damage by regulating the NLRP3/NF-κB pathway and Nrf2-mediated oxidative stress
Main Article Content
Keywords
cataract, oridonin (ORI), oxidative stress, Nrf2, NLRP3, NF-κB
Abstract
Cataract is the clouding of eye lens, and is the leading cause of visual impairment and blindness worldwide. There is an urgent need to develop new drugs to combat this disease. Oridonin (ORI), isolated from Rabdosia rubescens, is a natural substance that has been studied as an activator of nuclear factor erythroid 2-related factor 2 (Nrf2) and covalent inhibitor of NLR family pyrin domain containing 3 (NLRP3). Whether ORI has a therapeutic effect on human lens’ epithelial cell injury needs further study. In this study, we used cataract lens epithelial cell lines HLE-B3 and SRA01/04. We found using the MTT assay that ORI treatment increased cell viability induced by hydrogen peroxide (H2O2). In addition, ORI suppressed the apoptosis of H2O2-induced HLE-B3 and SRA01/04 cells detected by flow cytometry and Western blot analysis. Our data further revealed that ORI regulated nuclear factor, erythroid 2 (NFE2) like bZIP transcription factor 2 (Nrf2)-mediated oxidative stress by enzyme-linked-immunosorbent serologic assay. We further found that ORI inhibited NLRP3/nuclear factor-κb (NF-κB) pathway in H2O2-induced HLE-B3 and SRA01/04 cells by Western blot analysis. Therefore, these results suggested that ORI could have the potential to serve as a promising drug to treat cataract.
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References
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Zhao, X.J., Zhu, H.Y., Wang, X.L., Lu, X.W., Pan, C.L., Xu, L., Liu, X., Xu, N. and Zhang, Z.Y., 2022b. Oridonin ameliorates traumatic brain injury-induced neurological damage by improving mitochondrial function and antioxidant capacity and suppressing neuroinflammation through the Nrf2 pathway. Journal of Neurotrauma 39(7–8): 530–543. 10.1089/neu.2021.0466
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Zhu, Y., Ruan, S., Shen, H., Guan, Q., Zhai, L., Yang, Y., 2021. Oridonin regulates the polarized state of Kupffer cells to alleviate nonalcoholic fatty liver disease through ROS-NF-kappa B. International Immunopharmacology 101(Pt B): 108290. 10.1016/j.intimp.2021.108290
Camilloni, A., Nati, G., Maggiolini, P., Romanelli, A., Latina, R., 2021. Chronic non-cancer pain in primary care: an Italian cross-sectional study. Signa Vitae 17(2): 54–62.
Chang, C.W., 2022. Habitual tea consumption and risk of cataracts: a longitudinal study. International Journal of Medical Sciences 19(10): 1596–1602. 10.7150/ijms.75774
Du, X., Que, W., Hu, X., Yu, X., Guo, W.Z., Zhang, S., Li, X.K., 2021. Oridonin prolongs the survival of mouse cardiac allografts by attenuating the NF-kappa B/NLRP3 pathway. Frontiers in Immunology 12: 719574. 10.3389/fimmu.2021.719574
Duan, D., Feng, X., Pan, D., Wang, L., Wang, Y., Wang, X., 2021. Oridonin induces oxidative stress-mediated cancer cells apoptosis via targeting thioredoxin reductase. Current Pharmaceutical Biotechnology 23(14): 1647–1657. 10.2174/1389201023666211217151955
Gajraj, M. and Mohan, A., 2022. Safety and efficacy of manual small-incision cataract surgery in patients with brunescent and black cataracts and other ocular comorbidities. Indian Journal of Ophthalmology 70(11): 3898–3903. 10.4103/ijo.IJO_1565_22
Hassan, A.Y., Yousaf, S., Levin, M.R., Saeedi, O.J., Riazuddin, S., Alexander, J.L., Ahmed, Z.M., 2021. Novel homozygous missense variant in GJA3 connexin domain causing congenital nuclear and cortical cataracts. International Journal of Medical Sciences 23(1): 240. 10.3390/ijms23010240
Hong, M.K., Liu, H.H., Chen, G.H., Zhu, J.Q., Zheng, S.Y., Zhao, D., Diao, J., Jia, H., Zhang, D.D., Chen, S.X., Gao, L., Li, J., 2021. Oridonin alters hepatic urea cycle via gut microbiota and protects against acetaminophen-induced liver injury. Oxidative Medicine and Cellular Longevity 2021: 3259238. 10.1155/2021/3259238
Hua, X., Wu, P., Gao, G.S., Ye, X.L, 2021. Combination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR5. International Journal of Ophthalmology 14(12): 1834–1842. 10.18240/ijo.2021.12.05
Kazantseva, L., Becerra, J., Santos-Ruiz, L., 2022. Oridonin enhances antitumor effects of doxorubicin in human osteosarcoma cells. Pharmacological Reports 74(1): 248–256. 10.1007/s43440-021-00324-1
Li, C., Zhu, Y., Wu, Y., Fu, M., Wu, Y., Wu, Y., Qiu, Y., Zhang, H., Ding, M., 2021a. Oridonin alleviates LPS-induced depression by inhibiting NLRP3 inflammasome via activation of autophagy. Frontiers in Medicine (Lausanne) 8: 813047. 10.3389/fmed.2021.813047
Li, H., Yan, L., Shi, L., 2021b. Discussion on infection prevention and control when media reporters enter into isolation wards during COVID-19 epidemic. Signa Vitae 17(1): 6–10.
Liu, J., Xie, S., Shao, X., Xue, S., Du, P., Wu, H., Xu, S., Chen, Z.S., Yang, D.H., Xu, J., Yao, H., 2022. Identification of new potent anticancer derivatives through simplifying the core structure and modification on their 14-hydroxyl group from oridonin. European Journal of Medicinal Chemistry 231: 114155. 10.1016/j.ejmech.2022.114155
Sritrakoon, N., 2021. Bilateral cataracts extraction by lens aspiration and foldable intraocular lens implantation in a black kite (Milvus migrans). Open Veterinary Journal 11(3): 441–446. 10.5455/OVJ.2021.v11.i3.17
Twum, K., Bhattacharjee, A., Laryea, E.T., Esposto, J., Omolloh, G., Mortensen, S., Jaradi, M., Stock, N.L., Schileru, N., Elias, B., Pszenica, E., McCormick, T.M., Martic, S., Beyeh, N.K., 2021. Functionalized resorcinarenes effectively disrupt the aggregation of alphaA66-80 crystallin peptide related to cataracts. RSC Medicinal Chemistry 12(12): 2022–2030. 10.1039/D1MD00294E
Wang, F. and Ren, Y., 2023. Nanofluorescence probe in detection of miR-187 and its correlation with oxidative stress response in cataracts. Alternative Therapies in Health and Medicine 29(1):73–79
Wang, Y., Lv, H., Dai, C., Wang, X., Yin, Y., Chen, Z., 2021. Oridonin dose-dependently modulates the cell senescence and apoptosis of gastric cancer cells. Evidence-Based Complementary and Alternative Medicine 2021: 5023536. 10.1155/2021/5023536
Wei, Q., Luo, L., Qiu, W., Gong, Y., Jiang, Y., 2022. Metabolomic study of eyeball rupture and patients with cataracts in aqueous humor. Experimental and Therapeutic Medicine 24(5): 657. 10.3892/etm.2022.11593
Yasuda, S., Horinaka, M., Iizumi, Y., Goi, W., Sukeno, M., Sakai, T., 2022. Oridonin inhibits SASP by blocking p38 and NF-kappaB pathways in senescent cells. Biochemical and Biophysical Research Communications 590: 55–62. 10.1016/j.bbrc.2021.12.098
Yin, X.H., Wang, Z.Q., Guo, Q.H., Wu, H., Shi, M., 2017. Overexpressed LEDGF is a novel biomarker of poor prognosis in patients with cervical cancer. European Journal of Gynaecological Oncology (EJGO) 38(2): 245–250.
Zhang, T., Yi, X., Lu, J., Fu, A.Y., 2017. Clinical evaluation of MRI in the differential diagnosis between benign and malignant ovarian tumors. European Journal of Gynaecological Oncology (EJGO) 38(2): 257–262.
Zhao, X., Liu, Y., Wang, L., Yan, C., Liu, H., Zhang, W., Zhao, H., Cheng, C., Chen, Z., Xu, T., Li, K., Cai, J., Qiao, T., 2022a. Oridonin attenuates hind limb ischemia-reperfusion injury by modulating Nrf2-mediated oxidative stress and NLRP3-mediated inflammation. Journal of Ethnopharmacology 292: 115206. 10.1016/j.jep.2022.115206
Zhao, X.J., Zhu, H.Y., Wang, X.L., Lu, X.W., Pan, C.L., Xu, L., Liu, X., Xu, N. and Zhang, Z.Y., 2022b. Oridonin ameliorates traumatic brain injury-induced neurological damage by improving mitochondrial function and antioxidant capacity and suppressing neuroinflammation through the Nrf2 pathway. Journal of Neurotrauma 39(7–8): 530–543. 10.1089/neu.2021.0466
Zhou, C., Zhang, J., Liu, H., Tian, Y., Liu, Y., Wang, Y., Zheng, Z., Wang, N., Wang, Z., Xu, X., Liu, H., Ke, Y., 2022. Synthesis, biological evaluation and cellular localization study of fluorescent derivatives of Jiyuan Oridonin A. European Journal of Medicinal Chemistry 229: 114048. 10.1016/j.ejmech.2021.114048
Zhu, Y., Ruan, S., Shen, H., Guan, Q., Zhai, L., Yang, Y., 2021. Oridonin regulates the polarized state of Kupffer cells to alleviate nonalcoholic fatty liver disease through ROS-NF-kappa B. International Immunopharmacology 101(Pt B): 108290. 10.1016/j.intimp.2021.108290
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Published
Jan 13, 2023
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