中国药学(英文版) ›› 2023, Vol. 32 ›› Issue (2): 85-100.DOI: 10.5246/jcps.2023.02.007
• 【研究论文】 • 下一篇
王昭景, 许青霞, 许京, 徐嵬, 杨秀伟*(
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>收稿日期:2022-10-07
修回日期:2022-10-16
接受日期:2022-11-27
出版日期:2023-02-28
发布日期:2023-02-28
通讯作者:
杨秀伟
作者简介:基金资助:
Zhaojing Wang, Qingxia Xu, Jing Xu, Wei Xu, Xiuwei Yang*()
Received:2022-10-07
Revised:2022-10-16
Accepted:2022-11-27
Online:2023-02-28
Published:2023-02-28
Contact:
Xiuwei Yang
摘要：
氧化损伤和神经炎症与许多神经系统疾病相关。近年来, 研究发现中药补骨脂能够改善中枢神经系统损伤。本研究旨在评价两个来自补骨脂的化合物: 补骨脂宁和补骨脂定的神经保护作用, 并揭示其作用机制。实验结果表明, 补骨脂宁和补骨脂定能够抑制过氧化氢(H2O2)诱导的小鼠海马神经原代细胞(HT22)活性氧(ROS)的生成, 抑制脂多糖(LPS)诱导的小鼠神经小胶质细胞(BV2)一氧化氮(NO)的生成。由于补骨脂宁在低剂量即表现出活性, 且在高剂量时未表现出细胞毒, 因此进一步研究其潜在的神经保护作用机制。在H2O2诱导的HT22细胞中, 补骨脂宁显著增加过氧化氢酶(CAT)、超氧化物歧化酶(SOD)活性, 促进谷胱甘肽(GSH)分泌, 抑制线粒体膜电位(MMP)降低。同时上调Nrf2和HO-1蛋白在HT22细胞中的表达。在LPS诱导的BV2细胞中, 补骨脂宁显著抑制炎症因子IL-1β、IL-6和TNF-α的分泌, 并能够特异性抑制NF-κB p65转移入核。分子对接结果显示: 补骨脂宁能够进入Keap 1和NF-κB蛋白的疏水口袋, 结合良好。本研究证实, 补骨脂宁能够改善H2O2诱导的氧化损伤和LPS诱导的神经炎症, 其作用机制可能与Nrf2/HO-1和NF-κB信号通路有关。
Supporting:
王昭景, 许青霞, 许京, 徐嵬, 杨秀伟. 补骨脂宁通过激活Nrf2/HO-1并抑制NF-κB信号通路在过氧化氢诱导的HT22细胞和脂多糖诱导的BV2细胞上发挥抗氧化和抗神经炎症作用[J]. 中国药学(英文版), 2023, 32(2): 85-100.
Zhaojing Wang, Qingxia Xu, Jing Xu, Wei Xu, Xiuwei Yang. Anti-oxidative and anti-neuroinflammatory effects of corylin in H2O2-induced HT22 cells and LPS-induced BV2 cells by activating Nrf2/HO-1 and inhibiting NF-κB pathways[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(2): 85-100.
2-85/img_1.jpg)
Figure 1. Cytotoxicity of corylin and psoralidin on BV2 (A) and HT22 (B) cells. H2O2-induced cell damage in HT22 cells (C). Cell viability was assessed through the MTT method, and the results were expressed as a percentage of viable cells vs. control when control was considered as 100% cell viability. The structures of corylin (D) and psoralidin (E) were shown. Data are presented as mean ± SEM. n = 3, ###P < 0.001 vs. control group.
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Figure 2. Corylin reduces H2O2-induced intracellular ROS generation without cytotoxicity in HT22 cells. HT22 cells were pretreated with or without corylin (5, 10, and 20 μM) for 1 h, followed by exposure to H2O2 (250 μM) for 3 h, the intracellular ROS generation was detected using CM-H2DCFDA (10 μM), and images were obtained using a fluorescence microscope (A). The average fluorescence intensity was measured using flow cytometry (B?C). Statistical analysis of ROS generation (D). Curcumin (10 μM, Cur) was used as a positive control. Data are presented as mean ± SEM. n = 3, ###P < 0.001 vs. control group, **P < 0.01 and ***P < 0.001 vs. H2O2 group.
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Figure 3. Psoralidin reduces H2O2-induced intracellular ROS generation with cytotoxicity in HT22 cells. HT22 cells were pretreated with or without psoralidin (1, 3, and 10 μM) for 1 h, followed by exposure to H2O2 (250 μM) for 3 h, the intracellular ROS generation was detected using CM-H2DCFDA (10 μM), and images were obtained using a fluorescence microscope (A). The average fluorescence intensity was measured using flow cytometry (B?C). Statistical analysis of ROS generation (D). Curcumin (10 μM, Cur) was used as a positive control. Data are presented as mean ± SEM. n = 3, ###P < 0.001 vs. control group, **P < 0.01 and ***P < 0.001 vs. H2O2 group.
2-85/img_4.jpg)
Figure 4. Effect of corylin (A) and psoralidin (B) on NO production and cell viability in LPS-induced BV2 cells. BV2 cells were pretreated with or without corylin and psoralidin (2.5, 5, 10, 20, 25, and 50 μM) for 30 min, followed by exposure to LPS (2 μg/mL) 24 h, and then detected by Griess reagent. L-NIL (10 μM) was used as a positive drug. The results of cell viability were expressed as a percentage of viable cells versus control, with control considered 100% cell viability. Data are presented as mean ± SEM. n = 3, ###P < 0.001 vs. control group, ***P < 0.001 vs. LPS group.
2-85/img_5.jpg)
Figure 5. Corylin enhances both CAT (A) and SOD (B) activities and GSH (C) content in H2O2-induced HT22 cells. HT22 cells were pretreated with or without corylin (5, 10, and 20 μM) for 1 h, followed by exposure to H2O2 (250 μM) for 3 h. Cur (10 μM) was used as a positive control. Data are presented as mean ± SEM. n = 3, ###P < 0.001 vs. control group, *P < 0.05, **P < 0.01 and ***P < 0.001 vs. H2O2 group.
2-85/img_6.jpg)
Figure 6. Corylin improves H2O2-induced MMP loss in HT22 cells. HT22 cells were pretreated with or without corylin (5, 10, and 20 μM) for 1 h, followed by exposure to H2O2 (250 μM) for 3 h, the MMP was detected using JC-1, and images were obtained using a fluorescence microscope (A). Detection of MMP by flow cytometry (B). Quantitative analysis of the ratio of the cells with normal MMP (C). Cur (10 μM) was used as a positive control. Data are presented as mean ± SEM. n = 3, ###P < 0.001 vs. control group, *P < 0.05, **P < 0.01 and ***P < 0.001 vs. H2O2 group.
2-85/img_7.jpg)
Figure 7. Corylin inhibits the expressions of proinflammatory cytokines, IL-1β (A), IL-6 (B), and TNF-α (C), in LPS-induced BV2 cells. BV2 cells were pretreated with or without corylin (20 and 40 μM) for 30 min, followed by exposure to LPS (2 μg/mL) overnight, and then measured by mouse ELISA Kit. Data are presented as mean ± SEM. n = 3, ###P < 0.001 vs. control group, *P < 0.05, **P < 0.01 and ***P < 0.001 vs. LPS group.
2-85/img_8.jpg)
Figure 8. Corylin activates Nrf2/HO-1 pathway in H2O2-induced HT22 cells. HT22 cells were pretreated with or without corylin (5, 10, and 20 μM) for 1 h, followed by exposure to H2O2 (250 μM) for 3 h. Then cell lysates containing equal amounts of protein were collected for immunoblotting (A?B). Predicted docking pose of corylin in complex with Keap1 (PDB: 1X2J, C). Data are presented as mean ± SEM. n = 3, ##P < 0.01 and #P < 0.05 vs. control group, *P < 0.05 and **P < 0.01 vs. H2O2 group.
2-85/img_9.jpg)
Figure 9. Corylin inhibits the NF-κB pathway in LPS-induced BV2 cells. BV2 cells were pretreated with or without corylin (20 and 40 μM) for 30 min, followed by exposure to LPS (2 μg/mL) for 1 h. Then cell lysates containing equal amounts of protein were collected for immunoblotting (A?B), and the effect of corylin (40 μM) on nuclear translocation of NF-κB p65 was observed by immunofluorescence (C). Predicted docking pose of corylin in complex with NF-κB (PDB: 1VKX, D). Data are presented as mean ± SEM. n = 3, ###P < 0.001 vs. control group, **P < 0.01 and ***P < 0.001 vs. LPS group.
| [1] |
Leng, F.D.; Edison, P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat. Rev. Neurol. 2021, 17, 157–172.
|
| [2] |
Piancone, F.; La Rosa, F.; Marventano, I.; Saresella, M.; Clerici, M. The role of the inflammasome in neurodegenerative diseases. Molecules. 2021, 26, 953.
|
| [3] |
Merelli, A.; Repetto, M.; Lazarowski, A.; Auzmendi, J. Hypoxia, oxidative stress, and inflammation: three faces of neurodegenerative diseases. J. Alzheimers Dis. 2021, 82, S109–S126.
|
| [4] |
Dionísio, P.A.; Amaral, J.D.; Rodrigues, C.M.P. Oxidative stress and regulated cell death in Parkinson's disease. Ageing Res. Rev. 2021, 67, 101263.
|
| [5] |
Bouvier, E.; Brouillard, F.; Molet, J.; Claverie, D.; Cabungcal, J.H.; Cresto, N.; Doligez, N.; Rivat, C.; Do, K.Q.; Bernard, C.; Benoliel, J.J.; Becker, C. Nrf2-dependent persistent oxidative stress results in stress-induced vulnerability to depression. Mol. Psychiatry. 2017, 22, 1795.
|
| [6] |
Li, W.F.; Ali, T.; He, K.W.; Liu, Z.Z.; Shah, F.A.; Ren, Q.G.; Liu, Y.; Jiang, A.L.; Li, S.P. Ibrutinib alleviates LPS-induced neuroinflammation and synaptic defects in a mouse model of depression. Brain Behav. Immun. 2021, 92, 10–24.
|
| [7] |
Qu, S.; Liu, M.; Cao, C.; Wei, C.; Meng, X.E.; Lou, Q.; Wang, B.; Li, X.; She, Y.; Wang, Q.; Song, Z.; Han, Z.; Zhu, Y.; Huang, F.; Duan, J.A. Chinese medicine formula Kai-Xin-San ameliorates neuronal inflammation of CUMS-induced depression-like mice and reduces the expressions of inflammatory factors via inhibiting TLR4/IKK/NF-κB pathways on BV2 cells. Front. Pharmacol. 2021, 12, 626949.
|
| [8] |
Behl, C. Effects of glucocorticoids on oxidative stress-induced hippocampal cell death: implications for the pathogenesis of Alzheimer’s disease. Exp. Gerontol. 1998, 33, 689–696.
|
| [9] |
Lin, S.P.; Hu, J.; Wei, J.X.; Ye, S.; Bu, J.; Xu, W.; Chen, S.; Wu, Y.; Wu, G.; Zhu, L.; Lin, P.Y.; Chen, X.H. Silencing of circFoxO3 protects HT22 cells from glutamate-induced oxidative injury via regulating the mitochondrial apoptosis pathway. Cell Mol. Neurobiol. 2020, 40, 1231–1242.
|
| [10] |
Woodburn, S.C.; Bollinger, J.L.; Wohleb, E.S. The semantics of microglia activation: neuroinflammation, homeostasis, and stress. J. Neuroinflammation. 2021, 18, 258.
|
| [11] |
Hickman, S.; Izzy, S.; Sen, P.; Morsett, L.; El Khoury, J. Microglia in neurodegeneration. Nat. Neurosci. 2018, 21, 1359–1369.
|
| [12] |
Calsolaro, V.; Edison, P. Neuroinflammation in Alzheimer’s disease: current evidence and future directions. Alzheimers Dement. 2016, 12, 719–732.
|
| [13] |
Kushairi, N.; Phan, C.W.; Sabaratnam, V.; David, P.; Naidu, M. Lion’s mane mushroom, Hericium erinaceus (bull.: Fr.) pers. suppresses H2O2-induced oxidative damage and LPS-induced inflammation in HT22 hippocampal neurons and BV2 microglia. Antioxid. Basel Switz. 2019, 8, E261.
|
| [14] |
Sivandzade, F.; Prasad, S.; Bhalerao, A.; Cucullo, L. NRF2 and NF-қB interplay in cerebrovascular and neurodegenerative disorders: molecular mechanisms and possible therapeutic approaches. Redox Biol. 2019, 21, 101059.
|
| [15] |
Meng, Y.; Feng, R.; Yang, Z.; Liu, T.T.; Huo, T.G.; Jiang, H. Oxidative stress induced by realgar in neurons: p38 MAPK and ERK1/2 perturb autophagy and induce the p62-Keap1-Nrf2 feedback loop to activate the Nrf2 signalling pathway. J. Ethnopharmacol. 2022, 282, 114582.
|
| [16] |
Yang, L.; Palliyaguru, D.L.; Kensler, T.W. Frugal chemoprevention: targeting Nrf2 with foods rich in sulforaphane. Semin. Oncol. 2016, 43, 146–153.
|
| [17] |
Xue, E.X.; Lin, J.P.; Zhang, Y.; Sheng, S.R.; Liu, H.X.; Zhou, Y.L.; Xu, H. Pterostilbene inhibits inflammation and ROS production in chondrocytes by activating Nrf2 pathway. Oncotarget. 2017, 8, 41988–42000.
|
| [18] |
Dinkova-Kostova, A.T.; Abramov, A.Y. The emerging role of Nrf2 in mitochondrial function. Free Radic. Biol. Med. 2015, 88, 179–188.
|
| [19] |
O’Neill, L.A.J.; Kaltschmidt, C. NF-kB: a crucial transcription factor for glial and neuronal cell function. Trends Neurosci. 1997, 20, 252–258.
|
| [20] |
Shih, R.H.; Wang, C.Y.; Yang, C.M. NF-kappaB signaling pathways in neurological inflammation: a mini review. Front. Mol. Neurosci. 2015, 8, 77.
|
| [21] |
Ju, I.G.; Huh, E.; Kim, N.; Lee, S.; Choi, J.G.; Hong, J.; Oh, M.S. Artemisiae Iwayomogii Herba inhibits lipopolysaccharide-induced neuroinflammation by regulating NF-κB and MAPK signaling pathways. Phytomedicine. 2021, 84, 153501.
|
| [22] |
Chen, Y.; Wang, H.D.; Xia, X.; Kung, H.F.; Pan, Y.; Kong, L.D. Behavioral and biochemical studies of total furocoumarins from seeds of Psoralea corylifolia in the chronic mild stress model of depression in mice. Phytomedicine. 2007, 14, 523–529.
|
| [23] |
Im, A.R.; Chae, S.W.; Zhang, G.J.; Lee, M.Y. Neuroprotective effects of Psoralea corylifolia Linn seed extracts on mitochondrial dysfunction induced by 3-nitropropionic acid. BMC Complement. Altern. Med. 2014, 14, 370.
|
| [24] |
Yang, Y.F.; Zhang, Y.B.; Chen, Z.J.; Zhang, Y.T.; Yang, X.W. Plasma pharmacokinetics and cerebral nuclei distribution of major constituents of Psoraleae fructus in rats after oral administration. Phytomedicine. 2018, 38, 166–174.
|
| [25] |
Huang, M.Y.; Tu, C.E.; Wang, S.C.; Hung, Y.L.; Su, C.C.; Fang, S.H.; Chen, C.S.; Liu, P.L.; Cheng, W.C.; Huang, Y.W.; Li, C.Y. Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3 inflammasome in microglia. BMC Complement. Altern. Med. 2018, 18, 221.
|
| [26] |
Kim, Y.J.; Lim, H.S.; Lee, J.; Jeong, S.J. Quantitative analysis of Psoralea corylifolia linne and its neuroprotective and anti-neuroinflammatory effects in HT22 hippocampal cells and BV-2 microglia. Molecules. 2016, 21, 1076.
|
| [27] |
Wang, Z.J.; Tang, H.H.; Yang, L.L.; Li, Y.M.; Wu, H.L. Tanshinone IIA, a melanogenic ingredient basis of Salvia miltiorrhiza Bunge. Dermatol. Sin. 2021, 39, 33.
|
| [28] |
Xu, Q.X.; Zhang, Y.B.; He, Z.C.; Liu, Z.Y.; Zhang, Y.T.; Xu, W.; Yang, X.W. Constituents promoting osteogenesis from the fruits of Psoralea corylifolia and their structure-activity relationship study. Phytochemistry. 2022, 196, 113085.
|
| [29] |
Zgorzynska, E.; Dziedzic, B.; Walczewska, A. An overview of the Nrf2/ARE pathway and its role in neurodegenerative diseases. Int. J. Mol. Sci. 2021, 22, 9592.
|
| [30] |
Gruber, H.E.; Hoelscher, G.L.; Bethea, S.; Hanley, E.N. Jr. Mitochondrial membrane potential and nuclear and gene expression changes during human disc cell apoptosis: In vitro and In vivo annulus findings. Spine. 2015, 40, 876–882.
|
| [31] |
Wakabayashi, N.; Dinkova-Kostova, A.T.; Holtzclaw, W.D.; Kang, M.I.; Kobayashi, A.; Yamamoto, M.; Kensler, T.W.; Talalay, P. Protection against electrophile and oxidant stress by induction of the phase 2 response: fate of cysteines of the Keap1 sensor modified by inducers. Proc. Natl. Acad. Sci. USA. 2004, 101, 2040–2045.
|
| [32] |
Wulczyn, F.G.; Krappmann, D.; Scheidereit, C. The NF-kappa B/Rel and I kappa B gene families: mediators of immune response and inflammation. J. Mol. Med. Berl. 1996, 74, 749–769.
|
| [33] |
Falabella, M.; Vernon, H.J.; Hanna, M.G.; Claypool, S.M.; Pitceathly, R.D.S. Cardiolipin, mitochondria, and neurological disease. Trends Endocrinol. Metab. 2021, 32, 224–237.
|
| [34] |
Tang, M.M.; Liu, T.; Jiang, P.; Dang, R.L. The interaction between autophagy and neuroinflammation in major depressive disorder: from pathophysiology to therapeutic implications. Pharmacol. Res. 2021, 168, 105586.
|
| [35] |
Yan, A.J.; Liu, Z.H.; Song, L.; Wang, X.J.; Zhang, Y.; Wu, N.; Lin, J.Y.; Liu, Y.; Liu, Z.G. Idebenone alleviates neuroinflammation and modulates microglial polarization in LPS-stimulated BV2 cells and MPTP-induced Parkinson’s disease mice. Front. Cell Neurosci. 2019, 12, 529.
|
| [36] |
Winter, A.N.; Ross, E.K.; Daliparthi, V.; Sumner, W.A.; Kirchhof, D.M.; Manning, E.; Wilkins, H.M.; Linseman, D.A. A cystine-rich whey supplement (immunocal®) provides neuroprotection from diverse oxidative stress-inducing agents In vitro by preserving cellular glutathione. Oxidative Med. Cell Longev. 2017, 2017, 3103272.
|
| [37] |
Kang, S.M.; Cha, S.H.; Ko, J.Y.; Kang, M.C.; Kim, D.; Heo, S.J.; Kim, J.S.; Heu, M.S.; Kim, Y.T.; Jung, W.K.; Jeon, Y.J. Neuroprotective effects of phlorotannins isolated from a brown alga, Ecklonia cava, against H2O2-induced oxidative stress in murine hippocampal HT22 cells. Environ. Toxicol. Pharmacol. 2012, 34, 96–105.
|
| [38] |
Li, C.; Zhao, B.; Lin, C.; Gong, Z.; An, X. TREM2 inhibits inflammatory responses in mouse microglia by suppressing the PI3K/NF-κB signaling. Cell Biol. Int. 2019, 43, 360–372.
|
| [39] |
Fão, L.; Mota, S.I.; Rego, A.C. Shaping the Nrf2-ARE-related pathways in Alzheimer’s and Parkinson’s diseases. Ageing Res. Rev. 2019, 54, 100942.
|
| [40] |
Yoo, J.M.; Lee, B.D.; Sok, D.E.; Ma, J.Y.; Kim, M.R. Neuroprotective action of N-acetyl serotonin in oxidative stress-induced apoptosis through the activation of both TrkB/CREB/BDNF pathway and Akt/Nrf2/Antioxidant enzyme in neuronal cells. Redox Biol. 2017, 11, 592–599.
|
| [41] |
Ali, T.; Kim, T.; Rehman, S.U.; Khan, M.S.; Amin, F.U.; Khan, M.; Ikram, M.; Kim, M.O. Natural dietary supplementation of anthocyanins via PI3K/Akt/Nrf2/HO-1 pathways mitigate oxidative stress, neurodegeneration, and memory impairment in a mouse model of Alzheimer’s disease. Mol. Neurobiol. 2018, 55, 6076–6093.
|
| [42] |
Seo, E.J.; Fischer, N.; Efferth, T. Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer’s disease. Pharmacol. Res. 2018, 129, 262–273.
|
| [43] |
Zusso, M.; Lunardi, V.; Franceschini, D.; Pagetta, A.; Lo, R.; Stifani, S.; Frigo, A.C.; Giusti, P.; Moro, S. Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-kB pathway. J. Neuroinflammation. 2019, 16, 148.
|
| [44] |
Chen, C.C.; Li, H.Y.; Leu, Y.L.; Chen, Y.J.; Wang, C.J.; Wang, S.H. Corylin inhibits vascular cell inflammation, proliferation and migration and reduces atherosclerosis in ApoE-deficient mice. Antioxid. Basel Switz. 2020, 9, E275.
|
| [45] |
Chen, C.C.; Kuo, C.H.; Leu, Y.L.; Wang, S.H. Corylin reduces obesity and insulin resistance and promotes adipose tissue browning through SIRT-1 and β3-AR activation. Pharmacol. Res. 2021, 164, 105291.
|
| [46] |
Yang, L.H.; Yao, Y.L.; Bai, Y.; Zheng, D.D.; Zhou, F.; Chen, L.Y.; Hu, W.L.; Xiang, Y.Q.; Zhao, H.Y.; Liu, Z.G.; Wang, L.X.; Huang, X.Y.; Zhao, C.G. Effect of the isoflavone corylin from cullen corylifolium on colorectal cancer growth, by targeting the STAT3 signaling pathway. Phytomedicine. 2021, 80, 153366.
|
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