太子参葛根淫羊藿复合物抗抑郁作用: 与NRSF/NRSE-TPH2 信号相关

doi:10.5246/jcps.2021.01.003

中国药学(英文版) ›› 2021, Vol. 30 ›› Issue (1): 27-41.DOI: 10.5246/jcps.2021.01.003

太子参葛根淫羊藿复合物抗抑郁作用: 与NRSF/NRSE-TPH2 信号相关

余煊¹, 王欣佩¹, 雷帆¹, 王玉刚¹, 王伟¹, 丁怡¹, 邢东明¹, 袁梽漪¹, 孙虹², 杜力军¹^,^*()

1. 清华大学生命科学学院药物药理实验室, 北京100084
2. 中国医学科学院北京协和医学院药用植物研究所, 北京 100094

收稿日期:2020-07-20 修回日期:2020-08-17 接受日期:2020-09-12 出版日期:2021-01-29 发布日期:2021-01-29
通讯作者: 杜力军
作者简介:
+ Tel.: +86-10-62796270, E-mail: lijundu@mail.tsinghua.edu.cn
基金资助:
The Student Research Training (SRT) Program of Tsinghua University (Grant No. 1522T0221) and the National Natural Science Foundation of China (Grant No. 81374006 and 81073092).

The antidepressive effect of the complex consisting of Radix Pseudostellariae, Radix Pueraria and Herba Epimedii: the involvement of NRSF/NRSE-TPH2 signaling

Xuan Yu¹, Xinpei Wang¹, Fan Lei¹, Yugang Wang¹, Wei Wang¹, Yi Ding¹, Dongming Xing¹, Zhiyi Yuan¹, Hong Sun², Lijun Du¹^,^*()

1 Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
2 Institute of Medicinal Plant and Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100094, China

Received:2020-07-20 Revised:2020-08-17 Accepted:2020-09-12 Online:2021-01-29 Published:2021-01-29
Contact: Lijun Du

摘要/Abstract

摘要：

抑郁症属于心理性疾病且无特效疗法。本文对由太子参多糖、葛根淫羊藿总黄酮组成的太子(TZ)胶囊的抗抑郁作用进行了实验研究。利用整体动物悬尾和强迫游泳方法观察TZ的抗抑郁药效, 构建了五羟色胺羟化酶2(TPH2, tryptophan hydroxylase-2)质粒对TZ进行体外实验研究, 利用qPCR和Western blot方法检测mRNA和蛋白的表达。结果显示TZ对小鼠和大鼠模型均具有抗抑郁作用, 能够升高脑内5-HT含量, 并通过抑制NRSF (neuron restrictive silencer factor)表达, 升高TPH2的mRNA和蛋白表达。而NRSF可以结合于TPH2基因转录启动区的NRS响应元件(NRSE, neuron restrictive silencer element)进而抑制抑郁症时TPH2基因转录。淫羊藿苷可以直接作用于NRSE阻断NRSF的结合, 从而解除NRSF对TPH2基因转录的抑制。因此, TZ具有潜在的抗抑郁作用, 能够改善实验动物的抑郁行为, 其相关机制与NRSF/NRSE-TPH2信号通路相关。淫羊藿苷是TZ抗抑郁作用的主要活性成分。本研究为中药抗抑郁作用提供了基于NRSF/NRSE-TPH2信号的新的机制。

关键词: 抑郁症, TPH2, NRSF, 淫羊藿苷, 太子参, 葛根, 淫羊藿

Abstract:

Depression is a psychological disease with no particularly effective therapy currently available. In the present study, we aimed to examine the antidepressive activity of a pharmaceutical Chinese medicine called TaiZi (TZ) capsule, consisting of total polysaccharides of Radix Pseudostellariae and total flavonoids of both Radix Pueraria and Herba Epimedii. A tail suspension test and forced swimming test were performed to assess the effect of TZ in vivo. A plasmid of TPH2 (tryptophan hydroxylase-2) was constructed to determine the exact target of TZ in vitro. In addition, mRNA expression was detected using a real-time PCR assay, and the protein expression was investigated using a Western blotting analysis. The results showed that TZ had an anti-depression effect in mouse and rat models with increased serotonin in the brain, and in the upregulation of mRNA and protein expression of TPH2 in the brain simultaneously by inhibition of NRSF (neuron restrictive silencer factor) expression because NRSF could bind to NRSE (neuron restrictive silencer element) to repress TPH2 transcription during the depression conditions. Icariin could bind to NRSE directly and block NRSF protein toward to NRSE for TPH2 inhibition. Therefore, we concluded that TZ had potential antidepressive effects because it could ameliorat the depression-like behavior in the animals, and the underlying mechanism of the effect was involved in NRSF/NRSE-TPH2 signaling. Icariin was identified as the active component of TZ. This study provided a new perspective for the development of antidepression drugs (Chinese medicines) based on NRSF/NRSE -TPH2 signaling.

Key words: Depression, TPH2, NRSF, Icariin, Pseudostellariae, Pueraria, Epimedii

Supporting:

余煊, 王欣佩, 雷帆, 王玉刚, 王伟, 丁怡, 邢东明, 袁梽漪, 孙虹, 杜力军. 太子参葛根淫羊藿复合物抗抑郁作用: 与NRSF/NRSE-TPH2 信号相关[J]. 中国药学(英文版), 2021, 30(1): 27-41.

Xuan Yu, Xinpei Wang, Fan Lei, Yugang Wang, Wei Wang, Yi Ding, Dongming Xing, Zhiyi Yuan, Hong Sun, Lijun Du. The antidepressive effect of the complex consisting of Radix Pseudostellariae, Radix Pueraria and Herba Epimedii: the involvement of NRSF/NRSE-TPH2 signaling[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(1): 27-41.

图/表 6

Figure 1. Chemical characteristics of TZ. (A) Structures of puerarin and icariin. (B) Chromatogram of TZ. (C) Chromatogram of puerarin and icariin. (D) UV spectrum of standard puerarin and icariin. (E) UV spectrum of puerarin and icariin of TZ. HPLC conditions: mobile phase consisted of acetonitrile and 0.1% phosphate water (pH 3, 25:75, v/v). The column temperature was controlled at 25 °C. A C18 reversal column (5.4 mm × 15 mm, Ф 0.45 μm) (Waters, U.S.) was employed. Waters Empover2 workstation consisting of 996 DAD and 2 × 515 pumps were employed for the experiment (Waters, USA). The flow rate was set at 1.0 mL/min. The volume of the injection was 10 μL.

Figure 2. Effect of TZ on the depression-like behavior of mice. (A)–(B) Tail suspension test. TZ significantly decreased the immobility time in mice in the tail suspension test. (C)–(D) Forced swimming test. TZ also significantly decreased the immobility time in mice in the forced swimming test. (E) Reserpine test. In the reserpine model, TZ showed antagonism. A lower number of mice showed ptosis and akinesia behavior in the TZ groups. All three TZ groups demonstrated a significantly reduced immobility time compared with the model groups, while the model groups showed an increased time compared with the control groups. (F) Unpredicted stress model in mice. TZ extract was used at 800, 400 and 200 mg/kg. Ami: amitriptyline, dose of 70 mg/kg. The data are presented as mean ± S.D. of 12 mice (n = 12). #P < 0.05, ##P < 0.01 vs. control groups, *P < 0.05 vs. model groups.

Figure 3. Effect of TZ on the depression-like behavior and cerebral neural transmitters of rats. (A) Prevention of depression-like behavior by forced swimming test. TZ extract significantly decreased the immobility time in rats. (B) Forced swimming test on day 5. (C)–(D): Neural transmitters of the brains of rats. TZ increased the 5-HT level while slowing the metabolism of 5-HT, where there was a reduction in the 5-HITT level. Additionally, TZ improved the noradrenaline level in rat brains, while it had no effect on the dopamine level. TZ was used at 400, 200 and 100 mg/kg. Ami: amitriptyline, dose of 35 mg/kg. The data are presented as mean ± S.D. of 10 rats (n = 10). #P <0 .05, ##P < 0.01 vs. control groups. NS: no significance.

Figure 4. Effect of TZ on TPH2. (A) TPH2 mRNA and protein levels in mouse brains. mRNA and protein of TPH2 in AMI group and TZ groups showed a significant increase compared with control groups. (B)–(C): TPH2 mRNA and protein levels of C17.2 cells. As a component of TZ, icariin increased the level of transcription. (D) MTT assay of icariin in C17.2 cells. (E) Effect of TZ on the TPH2 promoter. GFP mRNA level was up-regulated by TZ extract and icariin. NC: Negative control. C: Control. Dosages of puerarin (Puer.), icariin (Icar.) and polysaccharide (Polysac.) were 25 μg/mL. The data are presented as mean ± S.D. of 3 independent experiments (n = 3). #P < 0.05, ##P < 0.01 vs. control groups. NS: No significance.

Figure 5. The effect of icariin and TZ on NRSF in vitro and in vivo. (A) Schematic of plasmid NRSE. (B)–(C) mRNA and protein levels of recombinant plasmid GFP. Icariin up-regulated GFP transcription and expression of recombinant plasmid with a wild type mouse TPH2 promoter, which contains an NRSE (NRSE+) while showing no effect on GFP of an NRSE knock out TPH2 promoter plasmid (NRSE-). (D) NRSF protein level of mouse brain. The data are presented as mean ± S.D. of three independent experiments (n = 3) in vitro and 12 mice in vivo. #P < 0.05, ##P < 0.01 vs. control groups, *P < 0.05, * *P < 0.01 vs. model groups, NS: not significant.

Figure 6. Schematic representation of TPH2 transcription regulated by TZ and NRSF. Normally, the binding of NRSF to NRSE inhibits the transcription of TPH2 and reduces 5-HT consequently. TZ (Icariin) can downregulate NRSF expression and simultaneously bind to NRSE for blocking NRSF, thereby relieving the repression to TPH2 transcription and in result enhancing 5-HT. "–": inhibition.

参考文献 58

[1]	Anthes, E. Depression: a change of mind. Nature. 2014, 515, 185–187.
[2]	Dafsari, F.S.; Jessen, F. Depression-an underrecognized target for prevention of dementia in Alzheimer’s disease. Transl. Psychiatry. 2020, 10, 160.
[3]	Krishnan, V.; Nestler, E.J. The molecular neurobiology of depression. Nature. 2008, 455, 894–902.
[4]	Pizzagalli, D.A. Depression, stress, and anhedonia: toward a synthesis and integrated model. Annu. Rev. Clin. Psychol. 2014, 10, 393–423.
[5]	Nabavi, S.M.; Daglia, M.; Braidy, N.; Nabavi, S.F. Natural products, micronutrients, and nutraceuticals for the treatment of depression: a short review. Nutr. Neurosci. 2017, 20, 180–194.
[6]	Li, S.S.; Chen, Z.C.; Wang, X.Q.; Zhang, C.L. Crude polysaccharides from Radix pseudostellariae improves exercise endurance and decreases oxidative stress in forced swimming rats. J. Food Agric. Environ. 2013, 11, 123–126.
[7]	Guo, R.; Wei, W.; Wang, Y.L.; Li, K.; Cui, X.B.; Zhu, C.L.; Shen, L.S. Protective effects of Radix Pseudostellariae extract against retinal laser injury. Cell Physiol. Biochem. 2014, 33, 1643–1653.
[8]	Lan, J.Q.; Yan, B.; Zhao, Y.N.; Wang, D.Y.; Hu, J.; Xing, D.M.; Du, L.J. Cerebral ischemia reperfusion exacerbates and pueraria flavonoids attenuate depressive responses to stress in mice. Tinshhua Sci. Technol. 2008, 13, 485–491.
[9]	Meng, X.; Zeng, N.; Zhang, Y.; Lai, X.; Ren, C.; Cheng, L. Effect of active constituents of Herba Epimedii on hypothalamic monoamine neurotransmitters and other brain functions in aging rats. Chin. J. Chin. Mat. Med. 1996, 21, 683–685.
[10]	Cai, J.; Zheng, T.; Zhang, L.; Tian, Y.; Yang, M.H.; Du, J. Effects of Herba Epimedii and Fructus Ligustri lucidi on the transcription factors in hypothalamus of aged rats. Chin. J. Integr. Med. 2011, 17, 758–763.
[11]	Patel, P.D.; Bochar, D.A.; Turner, D.L.; Meng, F.; Mueller, H.M.; Pontrello, C.G. Regulation of tryptophan hydroxylase-2 gene expression by a bipartite RE-1 silencer of transcription/neuron restrictive silencing factor (REST/NRSF) binding motif. J. Biol. Chem. 2007, 282, 26717–26724.
[12]	Gentile, M.T.; Nawa, Y.; Lunardi, G.; Florio, T.; Matsui, H.; Colucci-D’amato, L. Tryptophan hydroxylase 2 (TPH2) in a neuronal cell line: modulation by cell differentiation and NRSF/rest activity. J. Neurochem. 2012, 123, 963–970.
[13]	Chen, Y.Y.; Ding, Y.; Wang, W.; Wang, R.F.; Su, H.; Du, L.J. Determination of polysaccharide in radix pseudostellariae extract by size-exclusion high-performance liquid chromatography. Tinshhua Sci. Technol. 2007, 12, 389–393.
[14]	Shen, J.; Meng, Z.; Su, H.; Xing, D.M.; Ding, Y.; Du, L.J. Different kinetics of puerarin in plasma of normal and depressed rats after oral administration of Chinese medicine TZ18. Tinshhua Sci. Technol. 2007, 12, 394–399.
[15]	Zhang, L.J.; Ding, Y.; Chen, Y.Y.; Wang, W.H.; Wang, W.; Xing, D.M.; Du, L.J. Study of the process of polysaccharide from Radix Pseudostellariae. Chin. J. Chin. Mat. Med. 2004, 29, 1201–1203.
[16]	Lu, C.Y.; Wang, Y.; Zhang, Y.F. Light deprivation produces a sexual dimorphic effect on neural excitability and depression-like behavior in mice. Neurosci. Lett. 2016, 633, 69–76.
[17]	Kokras, N.; Antoniou, K.; Mikail, H.G.; Kafetzopoulos, V.; Papadopoulou-Daifoti, Z.; Dalla, C. Forced swim test: What about females? Neuropharmacology. 2015, 99, 408–421.
[18]	Bourin, M.; Poncelet, M.; Chermat, R.; Simon, P. The value of the reserpine test in psychopharmacology. Arzneimittelforschung. 1983, 33, 1173–1176.
[19]	Zhao, Y.N.; Ma, R.; Shen, J.; Su, H.; Xing, D.M.; Du, L.J. A mouse model of depression induced by repeated corticosterone injections. Eur. J. Pharmacol. 2008, 581, 113–120.
[20]	Gong, Q.; Yan, X.J.; Lei, F.; Wang, M.L.; He, L.L.; Luo, Y.Y.; Gao, H.W.; Feng, Y.L.; Yang, S.L.; Li, J.; Du, L.J. Proteomic profiling of the neurons in mice with depressive-like behavior induced by corticosterone and the regulation of berberine: pivotal sites of oxidative phosphorylation. Mol. Brain. 2019, 12, 1–14.
[21]	Yavich, L.; MacDonald, E. Dopamine release from pharmacologically distinct storage pools in rat striatum following stimulation at frequency of neuronal bursting. Brain Res. 2000, 870, 73–79.
[22]	Espejo, E.F.; Miñano, F.J. Prefrontocortical dopamine depletion induces antidepressant-like effects in rats and alters the profile of desipramine during Porsolt’s test. Neuroscience. 1999, 88, 609–615.
[23]	D’Aquila, P.S.; Collu, M.; Gessa, G.L.; Serra, G. The role of dopamine in the mechanism of action of antidepressant drugs. Eur. J. Pharmacol. 2000, 405, 365–373.
[24]	Wang, B.; Jedlicka, S.; Cheng, X.H. Maintenance and neuronal cell differentiation of neural stem cells C17.2 correlated to medium availability sets design criteria in microfluidic systems. PLoS One. 2014, 9, e109815.
[25]	Yan, X.; Chai, Y.; Lei, F.; Xing, D.; du, L. Blockage of p53 reduces acute alcohol-induced neuronal apoptosis. J. Chin. Pharmaceut. Sci. 2016, 25, 57–65.
[26]	Wang, Y.G.; Lei, F.; Wang, X.K.; Hu, J.; Zhan, H.L.; Xing, D.M.; Du, L.J. Regulatory effects of Wuzhuyutang (Evodiae prescription) and its consisting herbs on TPH2 promoter. Chin. J. Chin. Mat. Med. 2009, 34, 2261–2264.
[27]	Xie, X.Y.; Mathias, J.R.; Smith, M.A.; Walker, S.L.; Teng, Y.; Distel, M.; Köster, R.W.; Sirotkin, H.I.; Saxena, M.T.; Mumm, J.S. Silencer-delimited transgenesis: NRSE/RE1 sequences promote neural-specific transgene expression in a NRSF/REST-dependent manner. BMC Biol. 2012, 10, 1–21.
[28]	Xu, H.; Cheng, J.; Wang, X.B.; Liu, H.Q.; Wang, S.Y.; Wu, J.X.; Xu, B.L.; Chen, A.H.; He, F. Resveratrol pretreatment alleviates myocardial ischemia/reperfusion injury by inhibiting STIM1-mediated intracellular calcium accumulation. J. Physiol. Biochem. 2019, 75, 607–618.
[29]	Lu, X.; Yuan, Z.Y.; Yan, X.J.; Lei, F.; Jiang, J.F.; Yu, X.; Yang, X.W.; Xing, D.M.; Du, L.J. Effects of Angelica dahurica on obesity and fatty liver in mice. Chin. J. Nat. Med. 2016, 14, 641–652.
[30]	Pratelli, M.; Pasqualetti, M. Serotonergic neurotransmission manipulation for the understanding of brain development and function: Learning from Tph2 genetic models. Biochimie. 2019, 161, 3–14.
[31]	Thompson, R.; Chan, C. NRSF and its epigenetic effectors: new treatments for neurological disease. Brain Sci. 2018, 8, 226.
[32]	Chmielewska, N.; Wawer, A.; Maciejak, P.; Turzyńska, D.; Sobolewska, A.; Skórzewska, A.; Osuch, B.; Płaźnik, A.; Szyndler, J. The role of REST/NRSF, TrkB and BDNF in neurobiological mechanisms of different susceptibility to seizure in a PTZ model of epilepsy. Brain Res. Bull. 2020, 158, 108–115.
[33]	Planchez, B.; Surget, A.; Belzung, C. Animal models of major depression: drawbacks and challenges. J. Neural Transm. 2019, 126, 1383–1408.
[34]	Gururajan, A.; Reif, A.; Cryan, J.F.; Slattery, D.A. The future of rodent models in depression research. Nat. Rev. Neurosci. 2019, 20, 686.
[35]	Zhang, L.L.; Yang, Z.Y.; Ren, J.N.; Fan, G.; Pan, S.Y. Dietary essential oil from navel orange alleviates depression in reserpine-treated mice by monoamine neurotransmitters. Flavour Fragr. J. 2019, 34, 252–259.
[36]	Furmark, T.; Marteinsdottir, I.; Frick, A.; Heurling, K.; Tillfors, M.; Appel, L.; Antoni, G.; Hartvig, P.; Fischer, H.; Långström, B.; Eriksson, E.; Fredrikson, M. Serotonin synthesis rate and the tryptophan hydroxylase-2: G-703T polymorphism in social anxiety disorder. J. Psychopharmacol. 2016, 30, 1028–1035.
[37]	Yuan, Z.Y.; Lu, X.; Lei, F.; Chai, Y.S.; Wang, Y.G.; Jiang, J.F.; Feng, T.S.; Wang, X.P.; Yu, X.; Yan, X.J.; Xing, D.M.; Du, L.J. TATA boxes in gene transcription and poly (A) tails in mRNA stability: New perspective on the effects of berberine. Sci. Rep. 2015, 5, 18326.
[38]	Song, Z.Q.; Zhao, D.M.; Zhao, H.J.; Yang, L.F. NRSF: an angel or a devil in neurogenesis and neurological diseases. J. Mol. Neurosci. 2015, 56, 131–144.
[39]	Zhang, J.; Wang, S.H.; Yuan, L.; Yang, Y.X.; Zhang, B.W.; Liu, Q.B.; Chen, L.; Yue, W.; Li, Y.H.; Pei, X.T. Neuron-restrictive silencer factor (NRSF) represses cocaine- and amphetamine-regulated transcript (CART) transcription and antagonizes cAMP-response element-binding protein signaling through a dual NRSE mechanism. J. Biol. Chem. 2012, 287, 42574–42587.
[40]	Huang, Y.F.; Myers, S.J.; Dingledine, R. Transcriptional repression by REST: recruitment of Sin3A and histone deacetylase to neuronal genes. Nat. Neurosci. 1999, 2, 867.
[41]	Naruse, Y.; Aoki, T.; Kojima, T.; Mori, N. Neural restrictive silencer factor recruits mSin3 and histone deacetylase complex to repress neuron-specific target genes. Proc. Natl. Acad. Sci. USA. 1999, 96, 13691–13696.
[42]	Lunyak, V.V.; Burgess, R.; Prefontaine, G.G.; Nelson, C.; Sze, S.H.; Chenoweth, J.; Schwartz, P.; Pevzner, P.A.; Glass, C.; Mandel, G.; Rosenfeld, M.G. Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science. 2002, 298, 1747–1752.
[43]	Huang, X.M.; Chen, G.M.; Lin, J. Study on the teratogenicity of radix pseudostellariae in rats. Chin. J. Health Lab. Technol. 2013, 23, 2262–2264.
[44]	Li, B.; Duan, X.H.; Xu, C.Q.; Wu, J.F.; Liu, B.J.; Du, Y.J.; Luo, Q.L.; Jin, H.L.; Gong, W.Y.; Dong, J.C. Icariin attenuates glucocorticoid insensitivity mediated by repeated psychosocial stress on an ovalbumin-induced murine model of asthma. Int. Immunopharmacol. 2014, 19, 381–390.
[45]	Wu, J.F.; Du, J.; Xu, C.Q.; Le, J.J.; Xu, Y.Z.; Liu, B.J.; Dong, J.C. Icariin attenuates social defeat-induced down-regulation of glucocorticoid receptor in mice. Pharmacol. Biochem. Behav. 2011, 98, 273–278.
[46]	Zhang, L.; Shen, C.; Chu, J.; Zhang, R.Y.; Li, Y.L.; Li, L. Icariin decreases the expression of APP and BACE-1 and reduces the β-amyloid burden in an APP transgenic mouse model of Alzheimer's disease. Int. J. Biol. Sci. 2014, 10, 181–191.
[47]	Li, F.; Dong, H.X.; Gong, Q.H.; Wu, Q.; Jin, F.; Shi, J.S. Icariin decreases both APP and Aβ levels and increases neurogenesis in the brain of Tg2576 mice. Neuroscience. 2015, 304, 29–35.
[48]	Huang, J.H.; Cai, W.J.; Zhang, X.M.; Shen, Z.Y. Icariin promotes self-renewal of neural stem cells: an involvement of extracellular regulated kinase signaling pathway. Chin. J. Integr. Med. 2014, 20, 107–115.
[49]	Xiong, D.Q.; Deng, Y.Y.; Huang, B.; Yin, C.X.; Liu, B.; Shi, J.S.; Gong, Q.H. Icariin attenuates cerebral ischemia-reperfusion injury through inhibition of inflammatory response mediated by NF-κB, PPARα and PPARγ in rats. Int. Immunopharmacol. 2016, 30, 157–162.
[50]	Sun, X.H.; Ding, J.P.; Li, H.; Pan, N.; Gan, L.; Yang, X.L.; Xu, H.B. Activation of large-conductance calcium-activated potassium channels by puerarin: the underlying mechanism of puerarin-mediated vasodilation. J. Pharmacol. Exp. Ther. 2007, 323, 391–397.
[51]	Wu, X.D.; Wang, C.; Zhang, Z.Y.; Fu, Y.; Liu, F.Y.; Liu, X.H. Puerarin attenuates cerebral damage by improving cerebral microcirculation in spontaneously hypertensive rats. Evid. Based Complement Alternat. Med. 2014, 2014, 1–7.
[52]	Yan, B.; Wang, D.Y.; Xing, D.M.; Ding, Y.; Wang, R.F.; Lei, F.; Du, L.J. The antidepressant effect of ethanol extract of radix puerariae in mice exposed to cerebral ischemia reperfusion. Pharmacol. Biochem. Behav. 2004, 78, 319–325.
[53]	Li, J.M.; Wang, G.; Liu, J.C.; Zhou, L.; Dong, M.X.; Wang, R.; Li, X.Y.; Li, X.M.; Lin, C.R.; Niu, Y.C. Puerarin attenuates amyloid-beta-induced cognitive impairment through suppression of apoptosis in rat hippocampus in vivo. Eur. J. Pharmacol. 2010, 649, 195–201.
[54]	Zou, Y.; Hong, B.; Fan, L.; Zhou, L.; Liu, Y.; Wu, Q.; Zhang, X.; Dong, M. Protective effect of puerarin against beta-amyloid-induced oxidative stress in neuronal cultures from rat hippocampus: involvement of the GSK-3β/Nrf2 signaling pathway. Free. Radic. Res. 2013, 47, 55–63.
[55]	Zhao, J.; Luo, D.; Liang, Z.H.; Lao, L.X.; Rong, J.H. Plant natural product puerarin ameliorates depressive behaviors and chronic pain in mice with spared nerve injury (SNI). Mol. Neurobiol. 2017, 54, 2801–2812.
[56]	Chen, Z.C.; Li, S.S.; Wang, X.Q.; Zhang, C.L. Protective effects of Radix Pseudostellariae polysaccharides against exercise-induced oxidative stress in male rats. Exp. Ther. Med. 2013, 5, 1089–1092.
[57]	Gong, M.J.; Han, B.; Wang, S.M.; Liang, S.W.; Zou, Z.J. Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats. J. Pharm. Biomed. Anal. 2016, 123, 63–73.
[58]	Liu, B.; Xu, C.; Wu, X.; Liu, F.; Du, Y.; Sun, J.; Tao, J.; Dong, J. Icariin exerts an antidepressant effect in an unpredictable chronic mild stress model of depression in rats and is associated with the regulation of hippocampal neuroinflammation. Neuroscience. 2015, 294, 193–205.

太子参葛根淫羊藿复合物抗抑郁作用: 与NRSF/NRSE-TPH2 信号相关

The antidepressive effect of the complex consisting of Radix Pseudostellariae, Radix Pueraria and Herba Epimedii: the involvement of NRSF/NRSE-TPH2 signaling

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[4]	宋玮, 李艳姣, 乔雪, 钱薏, 叶敏. 中药葛根的化学成分研究进展[J]. 中国药学(英文版), 2014, 23(6): 347-360.
[5]	李艳姣, 刘慧敏, 党晓芳, 张硕峰, 吴金英, 贾占红, 韩立炜^*. HPLC方法研究葛根素混合胶束在Beagle犬体内的药代动力学[J]. , 2012, 21(4): 327-332.
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[8]	宋丽军, 谭晓梅, 赵文昌, 罗佳波^*. HPLC-DAD法同时定量分析葛根芩连微丸中12种活性成分[J]. , 2010, 19(6): 464-470.
[9]	胡道德*, 姚慧娟, 顾磊, 王松坡, 刘皋林. 淫羊藿总黄酮对大鼠肝微粒体CYP1A2、CYP3A4和CYP2E1活性的影响[J]. , 2008, 17(2): 167-169.
[10]	王秋娟^*, 潘志伟, 王玉, 杨涓, 贾莹, 孔令义. 淫羊藿苷对血管紧张素II诱导人脐静脉内皮细胞损伤的保护作用[J]. , 2008, 17(1): 16-21.
[11]	斯建勇, 常琪, 沈连钢, 陈迪华^*. 野葛化学成分研究[J]. , 2006, 15(4): 248-250.
[12]	刘火安, 王伯初, 戴传云^*, 邵志勇, 何从林, 贾云. 利用大孔树脂从葛根中分离纯化总黄酮[J]. , 2006, 15(2): 121-126.
[13]	郭圣荣^*, 郭丽. PVP K30对葛根黄豆苷元溶解度和溶出的影响[J]. , 2004, 13(1): 42-48.
[14]	马元春, 罗迈, Sarah Wittenberg, Clive Barwell, 周玉新^*, 魏璐雪. 高效液相色谱法对淫羊藿及人参复方产品的定性定量分析[J]. , 2003, 12(1): 6-10.
[15]	翟光喜^*, 娄红祥, 毕殿洲, 邹立家. 固体分散体中葛根素与磷脂的相互作用[J]. , 2003, 12(1): 36-40.