中国药学(英文版) ›› 2023, Vol. 32 ›› Issue (5): 360-378.DOI: 10.5246/jcps.2023.05.031
李双1,4, 董明纲2,*(), 郭春燕1,3,*(), 李双双1, 尤斯涵1, 万叶1, 刘心星4
收稿日期:
2022-12-14
修回日期:
2023-01-10
接受日期:
2023-01-25
出版日期:
2023-06-02
发布日期:
2023-06-02
通讯作者:
董明纲, 郭春燕
作者简介:
基金资助:
Shuang Li1,4, Minggang Dong2,*(), Chunyan Guo1,3,*(), Shuangshuang Li1, Sihan You1, Ye Wan1, Xinxing Liu4
Received:
2022-12-14
Revised:
2023-01-10
Accepted:
2023-01-25
Online:
2023-06-02
Published:
2023-06-02
Contact:
Minggang Dong, Chunyan Guo
摘要:
帕金森氏病(PD)是一种进行性神经系统疾病, 以震颤和运动缓慢为特征。线粒体功能障碍和氨基酸代谢是PD疾病的重要机制。前期工作证实SH-SY5Y细胞中氨基酸含量的变化早于细胞活力的变化。本研究旨在探讨桃红四物配方颗粒(THSWDG)是否能够减轻鱼藤酮诱导的SH-SY5Y细胞毒性, 是否能够改善鱼藤酮诱导线粒体功能障碍及氨基酸代谢紊乱。用MTT法分析细胞存活率; JC-1染色法测定线粒体膜电位; 高效液相色谱法测定SH-SY5Y细胞中氨基酸的含量。采用主成分分析法分析氨基酸含量的变化趋势; 使用生物信息学工具进一步阐明其潜在机制。研究表明, SH-SY5Y细胞氨基酸含量的变化早于细胞活性的变化。THSWDG能显著提高细胞存活率, 改善鱼藤酮对线粒体膜电位的影响和氨基酸的异常代谢。生物信息分析结果表明, THSWDG的作用涉及9个生物学过程, 包括5个与PD疾病相关的氨基酸代谢调节过程和4个与氧化损伤相关的生物学过程。细胞氨基酸过程是一种常见的调节氨基酸代谢和氧化损伤的生物过程。提示THSWDG通过改善线粒体功能障碍和氨基酸代谢紊乱对鱼藤酮诱导的SH-SY5Y细胞损伤发挥保护作用。
Supporting:
李双, 董明纲, 郭春燕, 李双双, 尤斯涵, 万叶, 刘心星. 桃红四物汤颗粒通过改善线粒体功能障碍和氨基酸代谢紊乱缓解鱼藤酮诱导的SH-SY5Y细胞毒性作用[J]. 中国药学(英文版), 2023, 32(5): 360-378.
Shuang Li, Minggang Dong, Chunyan Guo, Shuangshuang Li, Sihan You, Ye Wan, Xinxing Liu. Taohong Siwu dispensing granules alleviate rotenone-induced SH-SY5Y cellular cytotoxicity by rescuing mitochondrial dysfunction and amino acid metabolism disarrangements[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(5): 360-378.
Figure 2. Effect of rotenone on the cell vitality of SH-SY5Y cells. SH-SY5Y cells were treated with rotenone at concentrations of 0, 50, 100, 150, 200, 250, 300, 350, 400, 450, and 500 nM for 24 h (A) or exposed to 150 nM rotenone at different times of 0, 3, 6, 12, 24, and 48 h (B). Cell survival was analyzed with MTT assay. Note: ##P < 0.01, ###P < 0.001, compared with the control group; NS: no significant difference.
Figure 3. Effect of THSWDG treatment alone on cell vitality of SH-SY5Y cells. SH-SY5Y cells were treated with THSWDG at concentrations of 0, 0.4, 2, 10, 50, and 250 μg/mL for 24 h (A) and 48 h (B). Cell survival was analyzed with MTT assay. NS: no significant difference compared with the control group.
Figure 4. Effect of THSWDG on cell vitality of SH-SY5Y cells. Cells were grouped as follows: the control group, the model group, and the THSWDG group. In the control group, cells were not treated with any drugs, and the final concentration of the medium solution containing DMSO was 0.025%. In the model group, cells were treated with 150 nM rotenone for 24 h to establish the PD cell model. In the THSWDG group, cells were exposed to 150 nM rotenone in the presence of 10, 50, and 250 μg/mL THSWDG (added immediately before rotenone) for 24 h. ###P < 0.001, compared with the control group; *P < 0:05, **P < 0.01, ***P < 0.001, compared with the model group.
Figure 5. Effects of THSWDG on MMP. Normal SH-SY5Y cells stained with the JC-1 dye emitted a mitochondrial orange-red fluorescence with a small amount of green fluorescence (A). After treatment with 10, 50, and 250 μg/mL THSWDG, the ratio of green/red fluorescence was significantly decreased (C–E). Scale bar = 20 μm.
Figure 6. Effects of THSWDG on SOD, GSH, and LDH. Cells were grouped as described above. The levels of SOD (A), GSH (B), and LDH (C) are shown. Compared with the control group, the SOD activity (A) and GSH level (B) were decreased significantly, while the LDH level (C) was increased significantly in the model group. THSWDG treatment dose-dependently elevated the SOD activity and GSH level but inhibited the rotenone-induced decrease of LDH level. The 10–250 μg/mL THSWDG was negatively correlated to the change of SOD, suggesting that the dosage of THSWDG must be controlled reasonably. However, this would not change the results that THSWDG could inhibit the oxidative damage induced by rotenone. ###P < 0.001, compared with the control group; *P < 0.05, **P < 0.01, ***P < 0.001, compared with the model group.
Figure 7. HPLC of AAs with pre-column DNFB derivatization reaction. Black: blank chromatogram containing derivative reagent; Blue: chromatogram of AA reference standards; Red: chromatogram of AAs in SH-SY5Y cells. DNFB: 2,4-dinitrofluorobenzene; E-glutamic acid; Q-glutamine; G-glycine; H-histidine; I-isoleucine; L-leucine; K-lysine; F-phenylalanine; P-proline; S-serine. Flow rate 1.0 mL/min; UV wavelength 360 nm; Injection volume 20 μL; Thermo BDS Hypersil column (5 μm, 4.6 mm × 250 mm); Column temperature 30 °C; Gradient elution; Run time: 35 min.
Figure 8. The PCA and PLS-DA of cells treated with rotenone for 3 and 24 h. PCA was performed to verify outliers (A-3 h; C-24 h). The 95% con?dence interval was indicated as an ellipse. The PLS-DA model discriminates control and model (B-3 h; D-24 h). E-Glutamic acid; Q-glutamine; G-glycine; H-histidine; I-isoleucine; L-leucine; K-lysine; F-phenylalanine; P-proline; S-serine. Variable importance in projection (VIP) scores are shown in brackets for amino acid metabolites. “↓” indicates metabolites (VIP > 1 and P < 0.05), which identified biomarkers for predicting PD with PLS-DA.
Figure 9. The PCA and PLS-DA of cells treated with THSWDG for 24 h. PCA was performed to verify outliers (A). The 95% CI was indicated as an ellipse. The PLS-DA model discriminates control, model, and THSWDG groups (B). E-Glutamic acid; Q-glutamine; G-glycine; H-histidine; I-isoleucine; L-leucine; K-lysine; F-phenylalanine; P-proline; S-serine.
Figure 10. The contents of AA biomarkers in different groups. ###P < 0.001, compared with the control group; **P < 0.01, ***P < 0.001, compared with the model group.
Figure 11. The AA-gene interaction network was constructed using Cytoscape software. The red nodes represent found differentially expressed AAs, the blue nodes represent associated gene targets, and the pink nodes represent related metabolites.
Figure 14. ClueGO analysis of the biological process. A functionally grouped network of enriched categories was generated for the genes/proteins. GO terms are represented as nodes, and the node size represents the enrichment significance. The node pie charts showed the most important biological processes. All of these results were filtered by P ≤ 0.05. The five biological processes of GLUL, MPO, and DDC were screened by ClueGO (A). The four biological processes of SOD, GSH, and LDH were screened by ClueGO (B).
[1] |
Chiu, C.C.; Yeh, T.H.; Lu, C.S.; Huang, Y.C.; Cheng, Y.C.; Huang, Y.Z.; Weng, Y.H.; Liu, Y.C.; Lai, S.C.; Chen, Y.L.; Chen, Y.J.; Chen, C.L.; Chen, H.Y.; Lin, Y.W.; Wang, H.L. PARK14 PLA2G6 mutants are defective in preventing rotenone-induced mitochondrial dysfunction, ROS generation and activation of mitochondrial apoptotic pathway. Oncotarget. 2017, 8, 79046–79060.
|
[2] |
Zhou, J.X.; Zhang, Y.; Li, S.Y.; Zhou, Q.; Lu, X.F.; Shi, J.S.; Liu, J.; Wu, Q.; Zhou, S.Y. Dendrobium nobile Lindl. alkaloids-mediated protection against CCl4-induced liver mitochondrial oxidative damage is dependent on the activation of Nrf2 signaling pathway. Biomed. Pharmacother. 2020, 129, 110351.
|
[3] |
Parkinson, J. An essay on the shaking palsy. 1817. J. Neuropsychiatry Clin. Neurosci. 2002, 14, 223–236, 222.
|
[4] |
Zhang, Y.; Wang, J.; Zuo, C.; Chen, W.; Zhu, Q.; Guo, D.; Wu, H.; Wang, H.; Peng, D.; Han, L. Protective effect of Taohong siwu decoction on abnormal uterine bleeding induced by incomplete medical abortion in rats during early pregnancy. Chem. Pharm. Bull. Tokyo. 2018, 66, 708–713.
|
[5] |
Liu, L.; Duan, J.A.; Su, S.L.; Liu, P.; Tang, Y.P.; Qian, D.W. Siwu series decoctions for treating primary dysmenorrea of gynecology blood stasis syndrome: research progress of Taohong Siwu decoction. China J. Chin. Materia Medica. 2015, 40, 814–821.
|
[6] |
Zheng, C.S.; Xu, X.J.; Ye, H.Z.; Wu, G.W.; Li, X.H.; Xu, H.F.; Liu, X.X. Network pharmacology-based prediction of the multi-target capabilities of the compounds in Taohong Siwu Decoction, and their application in osteoarthritis. Exp. Ther. Med. 2013, 6, 125–132.
|
[7] |
Luo, Z.R.; Li, H.; Xiao, Z.X.; Shao, S.J.; Zhao, T.T.; Zhao, Y.; Mou, F.F.; Yu, B.; Guo, H.D. Taohong siwu decoction exerts a beneficial effect on cardiac function by possibly improving the microenvironment and decreasing mitochondrial fission after myocardial infarction. Cardiol. Res. Pract. 2019, 2019, 5198278.
|
[8] |
Zhou, J.; Yang, D.; Zhou, S.H.; Wang, J.P.; Liu, Y.S.; Wang, S.L. Clinical efficacy and safety of bathing with Chinese medicine Taohong siwu decoction for treatment of diffuse cutaneous systemic sclerosis: a randomized placebo-controlled trial. Chin. J. Integr. Med. 2018, 24, 185–192.
|
[9] |
Tao, T.; He, T.; Mao, H.; Wu, X.; Liu, X. Non-targeted metabolomic profiling of coronary heart disease patients with Taohong siwu decoction treatment. Pharmacol. 2020, 11, 651.
|
[10] |
Chen, G.; Xie, Y.; Liu, Y.; Jin, S.; Chen, Z.; Zhang, P.; Shi, P.; Zhu, J.; Deng, J.; Liang, H.; Zhou, C. Taohong Siwu Decoction for femoral head necrosis: a protocol for systematic review. Med. Baltim. 2020, 99, e19368.
|
[11] |
Liu, T.H.; Chen, W.H.; Chen, X.D.; Liang, Q.E.; Tao, W.C.; Jin, Z.; Xiao, Y.; Chen, L.G. Network pharmacology identifies the mechanisms of action of TaohongSiwu Decoction against essential hypertension. Med. Sci. Monit. 2020, 26, e920682.
|
[12] |
Duan, X.; Pan, L.; Bao, Q.; Peng, D. UPLC-Q-TOF-MS study of the mechanism of THSWD for breast cancer treatment. Pharmacol. 2019, 10, 1625.
|
[13] |
Li, L.; Yang, N.; Nin, L.; Zhao, Z.; Chen, L.; Yu, J.; Jiang, Z.; Zhong, Z.; Zeng, D.; Qi, H.; Xu, X. Chinese herbal medicine formula Tao Hong si wu decoction protects against cerebral ischemia-reperfusion injury via PI3K/Akt and the Nrf2 signaling pathway. J. Nat. Med. 2015, 69, 76–85.
|
[14] |
Zhang, X.; Du, L.D.; Zhang, W.; Yang, Y.L.; Zhou, Q.M.; Du, G.H. Therapeutic effects of baicalein on rotenone-induced Parkinson’s disease through protecting mitochondrial function and biogenesis. Sci. Rep. 2017, 7, 9968.
|
[15] |
Tatulli, G.; Mitro, N.; Cannata, S.M.; Audano, M.; Caruso, D.; D’Arcangelo, G.; Lettieri-Barbato, D.; Aquilano, K. Intermittent fasting applied in combination with rotenone treatment exacerbates dopamine neurons degeneration in mice. Front. Cell Neurosci. 2018, 12, 4.
|
[16] |
Yu, T.; Zhen, M.; Li, J.; Zhou, Y.; Ma, H.; Jia, W.; Wang, C. Anti-apoptosis effect of amino acid modified gadofullerene via a mitochondria mediated pathway. Dalton Trans. Camb. Engl. 2019, 48, 7884–7890.
|
[17] |
Kim, H.; Perentis, R.J.; Caldwell, G.A.; Caldwell, K.A. Gene-by-environment interactions that disrupt mitochondrial homeostasis cause neurodegeneration in C. elegans Parkinson’s models. Cell Death Dis. 2018, 9, 555.
|
[18] |
Papada, E.; Forbes, A.; Amerikanou, C.; Torović, L.; Kalogeropoulos, N.; Tzavara, C.; Triantafillidis, J.K.; Kaliora, A.C. Antioxidative efficacy of a pistacia lentiscus supplement and its effect on the plasma amino acid profile in inflammatory bowel disease: a randomised, double-blind, placebo-controlled trial. Nutrients. 2018, 10, E1779.
|
[19] |
Martis, R.M.; Knight, L.J.; Donaldson, P.J.; Lim, J.C. Identification, expression, and roles of the cystine/glutamate antiporter in ocular tissues. Oxid. Med. Cell Longev. 2020, 2020, 4594606.
|
[20] |
Michel, M.; Dubowy, K.O.; Entenmann, A.; Karall, D.; Adam, M.G.; Zlamy, M.; Odri Komazec, I.; Geiger, R.; Niederwanger, C.; Salvador, C.; Müller, U.; Laser, K.T.; Scholl-Bürgi, S. Targeted metabolomic analysis of serum amino acids in the adult Fontan patient with a dominant left ventricle. Sci. Rep. 2020, 10, 8930.
|
[21] |
Wang, M.; Gui, X.; Wu, L.; Tian, S.; Wang, H.; Xie, L.; Wu, W. Amino acid metabolism, lipid metabolism, and oxidative stress are associated with post-stroke depression: a metabonomics study. BMC Neurol. 2020, 20, 250.
|
[22] |
Kim, S.H.; Kim, K.Y.; Park, S.G.; Yu, S.N.; Kim, Y.W.; Nam, H.W.; An, H.H.; Kim, Y.W.; Ahn, S.C. Mitochondrial ROS activates ERK/autophagy pathway as a protected mechanism against deoxypodophyllotoxin-induced apoptosis. Oncotarget. 2017, 8, 111581–111596.
|
[23] |
Figura, M.; Kuśmierska, K.; Bucior, E.; Szlufik, S.; Koziorowski, D.; Jamrozik, Z.; Janik, P. Serum amino acid profile in patients with Parkinson’s disease. PLoS One. 2018, 13, e0191670.
|
[24] |
Pasini, E.; Corsetti, G.; Aquilani, R.; Romano, C.; Picca, A.; Calvani, R.; Dioguardi, F. Protein-amino acid metabolism disarrangements: the hidden enemy of chronic age-related conditions. Nutrients. 2018, 10, 391.
|
[25] |
Hopkins, A.L. Network pharmacology: the next paradigm in drug discovery. Nat. Chem. Biol. 2008, 4, 682–690.
|
[26] |
Gao, L.; Wang, K.X.; Zhou, Y.Z.; Fang, J.S.; Qin, X.M.; Du, G.H. Uncovering the anticancer mechanism of Compound Kushen Injection against HCC by integrating quantitative analysis, network analysis and experimental validation. Sci. Rep. 2018, 8, 624.
|
[27] |
Du, X.Y.; Xie, X.X.; Liu, R.T. The role of α-synuclein oligomers in Parkinson's disease. Int. J. Mol. Sci. 2020, 21, E8645.
|
[28] |
Zhao, J.; Yu, S.; Zheng, Y.; Yang, H.; Zhang, J. Oxidative modification and its implications for the neurodegeneration of Parkinson’s disease. Mol. Neurobiol. 2017, 54, 1404–1418.
|
[29] |
Zhu, Z.; Yang, C.; Iyaswamy, A.; Krishnamoorthi, S.; Sreenivasmurthy, S.G.; Liu, J.; Wang, Z.; Tong, B.C.; Song, J.; Lu, J.; Cheung, K.H.; Li, M. Balancing mTOR signaling and autophagy in the treatment of Parkinson’s disease. Int. J. Mol. Sci. 2019, 20, E728.
|
[30] |
Rocha, E.M.; De, M.B.; Sanders, L.H. Alpha-synuclein: pathology, mitochondrial dysfunction and neuroinflammation in Parkinson’s disease. Neurobiol. Dis. 2018, 109, 249–257.
|
[31] |
Iovino, L.; Tremblay, M.E.; Civiero, L. Glutamate-induced excitotoxicity in Parkinson’s disease: the role of glial cells. J. Pharmacol. Sci. 2020, 144, 151–164.
|
[32] |
Bastiaan, R.B.; Michael, S.O.; Christine, K. Parkinson’s disease. Lancet. 2021, 397, 2284–2303.
|
[33] |
Espay, A.J.; Morgante, F.; Merola, A.; Fasano, A.; Marsili, L.; Fox, S.H.; Bezard, E.; Picconi, B.; Calabresi, P.; Lang, A.E. Levodopa-induced dyskinesia in Parkinson disease: current and evolving concepts. Ann Neurol. 2018, 84, 797–811.
|
[34] |
Baig, F.; Kelly, M.J.; Lawton, M.A.; Ruffmann, C.; Rolinski, M.; Klein, J.C.; Barber, T.; Lo, C.; Ben-Shlomo, Y.; Okai, D.; Hu, M.T. Impulse control disorders in Parkinson disease and RBD: a longitudinal study of severity. Neurology. 2019, 93, e675–e687.
|
[35] |
Pahwa, R.; Tanner, C.M.; Hauser, R.A.; Isaacson, S.H.; Nausieda, P.A.; Truong, D.D.; Agarwal, P.; Hull, K.L.; Lyons, K.E.; Johnson, R.; Stempien, M.J. ADS-5102 (amantadine) extended-release capsules for levodopa-induced dyskinesia in parkinson disease (EASE LID study): a randomized clinical trial. J. Park. Dis. 2017, 74, 941–949.
|
[36] |
Klaus, S.; Chaudhuri, K.R.; Miguel, C.; Susan, H.F.; Regina, K.; Santiago, P.L.; Daniel, W.; Cristina, S. Update on treatments for nonmotor symptoms of Parkinson’s disease-an evidence-based medicine review. Movement disorders: Official Journal of The Movement Disorder Society. 2019, 34, 180–198.
|
[37] |
Li, S.; Le, W. Parkinson’s disease in traditional Chinese medicine. Lancet Neurol. 2021, 20, 262.
|
[38] |
Dalangin, R.; Kim, A.; Campbell, R.E. The role of amino acids in neurotransmission and fluorescent tools for their detection. Int. J. Mol. Sci. 2020, 21, E6197.
|
[39] |
Li, X.; Wang, W.; Yan, J.; Zeng, F. Glutamic acid transporters: targets for neuroprotective therapies in Parkinson’s disease. Front. Neurosci. 2021, 15, 678154.
|
[40] |
Giffard, R.G.; Xu, L.; Zhao, H.; Carrico, W.; Ouyang, Y.; Qiao, Y.; Sapolsky, R.; Steinberg, G.; Hu, B.; Yenari, M.A. Chaperones, protein aggregation, and brain protection from hypoxic/ischemic injury. J. Exp. Biol. 2004, 207, 3213–3220.
|
[41] |
Zhang, Q.; Gao, Y.; Zhang, J.; Li, Y.; Chen, J.; Huang, R.; Ma, G.; Wang, L.; Zhang, Y.; Nie, K.; Wang, L. L-asparaginase exerts neuroprotective effects in an SH-SY5Y-A53T model of Parkinson’s disease by regulating glutamine metabolism. Front. Mol. Neurosci. 2020, 13, 563054.
|
[42] |
Yuan, S.; Zhang, Z.W.; Li, Z.L. Cell death-autophagy loop and glutamate-glutamine cycle in amyotrophic lateral sclerosis. Front. Mol. Neurosci. 2017, 10, 231.
|
[43] |
Park, H.; Kim, J.E. Deletion of P2X7 receptor decreases basal glutathione level by changing glutamate-glutamine cycle and neutral amino acid transporters. Cells. 2020, 9, E995.
|
[44] |
Raj, A.; Kaushal, A.; Datta, I. Impact of monomeric and aggregated wild-type and A30P/A53T double-mutant α-synuclein on antioxidant mechanism and glutamate metabolic profile of cultured astrocytes. J. Neurosci. Res. 2022, 100, 681–706.
|
[45] |
Huang, S.Q.; Wan, J.Y.; Du, T.T.; Gong, T.; Zhang, J.; Jiang, X.H. The relationship between the contents of 13 amino acids in brain tissues and the progression of NAFLD via C57BL/6 model mice. J. Chin. Pharm. Sci. 2022, 31, 441.
|
[46] |
Havelund, J.F.; Heegaard, N.H.H.; Færgeman, N.J.K.; Gramsbergen, J.B. Biomarker research in Parkinson’s disease using metabolite profiling. Metabolites. 2017, 7, E42.
|
[47] |
Backe, M.B.; Jin, C.Y.; Andreone, L.; Sankar, A.; Agger, K.; Helin, K.; Madsen, A.N.; Poulsen, S.S.; Bysani, M.; Bacos, K.; Ling, C.; Perone, M.J.; Holst, B.; Mandrup-Poulsen, T. The lysine demethylase KDM5B regulates islet function and glucose homeostasis. J. Diabetes Res. 2019, 2019, 1–15.
|
[48] |
Komaniecki, G.; Lin, H. Lysine fatty acylation: regulatory enzymes, research tools, and biological function. Front. Cell Dev. Biol. 2021, 9, 717503.
|
[49] |
Zhao, D.L.; Shen, D.W.; Chi, Y.T.; Liu, F.; Zou, L.B.; Zhu, H.B. Liriodendrin protects SH-SY5Y cells from dopamine-induced cytotoxicity. J. Chin. Pharm. Sci. 2007, 294–299.
|
[1] | 黄素琼, 万敬员, 杜婷婷, 龚涛, 张静, 蒋心惠. C57BL/6小鼠脑组织中13种氨基酸含量与NAFLD疾病进展的关系[J]. 中国药学(英文版), 2022, 31(6): 441-451. |
[2] | 许士琪, 朱礼岩, 郝超, 刘文倩, 陈成龙, 陈泳怡, 刘爱芹. 一种新型含氨基酸基团替加氟前药的合成及其抗肿瘤活性评价[J]. 中国药学(英文版), 2021, 30(9): 743-753. |
[3] | 北京大学药学院 天然药物及仿生药物国家重点实验室. 刘涛研究员团队在《Nature Chemical Biology》上发表非天然氨基酸调控的胰岛素分泌细胞治疗系统[J]. 中国药学(英文版), 2021, 30(11): 937-938. |
[4] | 程士轩, 马迎聪, 刘瑜洁, 庞宁, 李骥, 沙勐, 任汝通, Nuramatjan Ablat, 曹静, 孙懿, 蒲小平, 叶敏, 齐宪荣. 红花抗帕金森病有效成分滴丸的制备和表征[J]. 中国药学(英文版), 2019, 28(1): 27-39. |
[5] | 石亚娟, 管清华, 吴艳芬, 王超. 含砷氨基酸的合成及其在多肽化学中的应用[J]. 中国药学(英文版), 2017, 26(5): 372-378. |
[6] | 郭涌斐, 王辰, 李婉, 张珂, 雷慧, 孙懿, 蒲小平, 赵欣. 紫红獐牙菜𠮿酮提取物对MPTP所致的帕金森小鼠的神经保护作用[J]. 中国药学(英文版), 2016, 25(5): 357-365. |
[7] | 王萌萌, 杜望春, 沈杰*, 董毅, 魏文石, 宋钟娟. 高效液相色谱荧光检测法测定小鼠脑组织中氨基酸类神经递质[J]. , 2013, 22(3): 239-243. |
[8] | 吕丽, 王江, 丁晓, 林岱宗, 赵临襄, 蒋华良, 柳红*. 镍螯合物(II) Suzuki 偶联反应诱导的α-取代β-氨基酸的合成[J]. , 2012, 21(6): 561-568. |
[9] | 李刚, 刘玉鹏, 雷蒙, 王欣*, 程铁明, 李润涛*. 以氨基酸甲酯和异硫氰酸酯为原料碱性Al2O3为载体合成硫代乙内酰脲的有效方法[J]. , 2012, 21(2): 136-141. |
[10] | 赵欣, 王欣, 余克富, 段瑀, 李捷思, 赵炳祥, 张烜*, 张强. 二氯醋酸钠激活C6细胞线粒体代谢途径的体外作用[J]. , 2011, 20(5): 460-465. |
[11] | 杨颖, 王超*. 多巯基功能性保护氨基酸的合成[J]. , 2011, 20(2): 195-198. |
[12] | 赵大龙, 申大伟, 迟玉涛, 刘方, 邹莉波, 朱海波*. Liriodendrin对多巴胺所致SH-SY5Y 细胞损伤的保护作用[J]. , 2007, 16(4): 294-299. |
[13] | 苗艳丽, 方富永, 宋文东*. 中药菲牛蛭化学成分的分析 [J]. , 2007, 16(3): 223-226. |
[14] | 方亚南, 林茂, 刘耕陶* . 异丹叶大黄素在体外对Cu2+介导的人低密度脂蛋白过氧化的抑制作用[J]. , 2004, 13(1): 63-67. |
[15] | 肖艳丽*, 董志, 傅洁民, 周岐新, 廖红. 莫达非尼对1-甲基-4苯基-1,2,3,6-四氢吡啶所致的帕金森病的神经保护作用[J]. , 2003, 12(3): 148-153. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||