Chinese Traditional and Herbal Drugs 46 20 2015 10 3109 1, 2 1, 2 1* 1 1 1 1 3 1. 030006 2. 030006 3. 100050 2 R285 A 0253-2670(2015)20-3109 - 08 DOI: 10.7501/j.issn.0253-2670.2015.20.025 Research progress on antidepressive active ingredients of Xiaoyaosan and their mechanism LI Xiao 1, 2, GONG Wen-xia 1, 2, ZHOU Yu-zhi 1, GAO Li 1, GAO Xiao-xia 1, TIAN Jun-sheng 1, QIN Xue-mei 1, DU Guan-hua 3 1. Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China 2. College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China 3. Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China Abstract: The antidepressive effect of Xiaoyaosan is obvious, however, the active ingredients with potential antidepressive activity and their mechanism remain unclear. In this paper, by two ways of the effects to active ingredients and the active ingredients to mechanism, the antidepressive active ingredients and their mechanism of Xiaoyaosan are summarized. Xiaoyaosan as a classic antidepressant Chinese prescription is further confirmed with many advantages, such as multi-level, multi-channel, multi-target, and so on. Key words: Xiaoyaosan; antidepression; quercetin; liquiritin; saikoside; paeoniflorin; ferulic acid; curcumin 3.5 disability 2/3 [1] WHO 2020 2 MAOIs 5-5 5 [2-3] [4] 2015-05-13 2011DFA32630 2012ZX09103201-03520140313008- 142014091022 1990 Tel: 15735171967 E-mail: lixiaoedu@126.com Tel: (0351)7019178 E-mail: zhouyuzhi@sxu.edu.cn
3110 Chinese Traditional and Herbal Drugs 46 20 2015 10 30 g 30 g 30 g 30 g 30 g 15 g 10 g 10 g 8 [5-6] [7] [8] 60 90% [9] 32 90.16% [10] 60 [11] [12] 1 1.1 [13-16] [17] [12] 1.1.1 0.47% [18] [19] corticosterone PC12 0.125 μmol/l 1.25 μmol/l PC12 Bhutada [20] 20 mg/kg CRFKawabata [21] 50 mg/kg CRF mrna - - HPA Dimpfel [22] 10 mg/kg 1.1.2 Sloley [23] MAOIs IC 50 0.7 μmol/l MAOIs [24] MAOIs 1.1.3 2.05% 1.08% [25] [26] 10 mg/kg [27] Wang [28] 10 mg/kg FST TST 5-5-HTNA 1 2
Chinese Traditional and Herbal Drugs 46 20 2015 10 3111 1.1.4 0.12% [29] MAO IC 50 13.9 μmol/l [30] 1.2 A D [12] 1.2.1 A A 0.44% [31] [32] A [33] 1.25 mg/l A Glu [Ca 2+ ] -6 IL-6 Zhu [34] 12.5 μmol/l A MAPK -κb NF-κB 1.2.2 D D 0.57% [33] Li [35] D PC12 [36] 4 μmol/l D SH-SY5Y NO JNK A D 1.2.3 4.5% [37] 0.6 mmol/l Glu Bax mrna Bcl-2 mrna Glu PC12 [38] Glu PC12 0.6 mmol/l 1.2.4 1.65% [39] 100 mg/kg 5-HT [40-41] [42] 416.3 μmol/l N- -D- NMDA 10 μmol/l Glu PC12 Bax Bcl-2 [43-44] [45] 10 mg/kg NO/cGMP NO 1 μmol/l NGF PC12 [46] 40 10 1.2.5 0.42% [39] [47] 7 mg/kg 2.5 5.0 10.0 mg/kg Western blotting 5.0 10.0 mg/kg HPA [48] 1.3 1.3.1
3112 Chinese Traditional and Herbal Drugs 46 20 2015 10 [12] 0.06% [49] 0.004% [50] [51] 5-HT NA 5-HT MAOIs Glu [52-54] 1.3.2 0.15% [55] [56] HPA [57] 5-HT 5-HT NA DA Kulkarni [58] 5-HT NA DA [59] 20 d WBC ACTH -1β IL-1β WBC ACTH IL-1β HPA Xu [60] / GR mrna BDNF 12 A D [61] 2 2.1 5-HT NA 2 2 [62] MAOIs MAOIs NA 5-HT DA [23] [40-41] [57-58] A [32] [26] [26] 2.2 20 70 HPA HPA HPA ACTH TRH HPA [62] HPA
Chinese Traditional and Herbal Drugs 46 20 2015 10 3113 CRF mrna [19-21] ACYH [58-59] HPA [47-48] 2.3 [63-64] BDNF BDNF BDNF DG BDNF BDNF BDNF [52] [24] A [32-33] D [35-36] [38] [51-53] [59] BDNF [42] NGF A D 2.4 camp-pka-creb-bdnf NO-cGMP-PKG MAPK [64] A MAPK NF-κB [34] D SH-SY5Y NO JNK [36] NO/cGMP [45] A D 2.5 [65] A Glu IL-6 [33] IL-1β [58] A 2.6 [66] [27] PC12 [46] 14 1 3 8
3114 Chinese Traditional and Herbal Drugs 46 20 2015 10 A D NE DA IL-1 IL-6 Glu 5-HT GABA GSH MAPK NO-cGMP- PKG SOD CAT camp-pka-creb- BDNF NMDA EAAT A NGF AMPA BDNF GR HPA 1 Fig. 1 Antidepressive active ingredients of Xiaoyaosan and their mechanism [1] Ledford H. If depression were cancer [J]. Nature, 2014, 515(184): 182-184. [2]. [J]., 2005, 5(2): 81-84. [3],. [J]., 2011, 17(24): 3777-3779. [4],,,. [J]., 2014, 33(2): 88-90. [5]. [M]. :, 2003. [6],,. [J]., 2014, 20(2): 278-279. [7],. [M]. :, 2007. [8]. 60 [J]., 2011, 23(2): 179. [9]. 32 [J]., 2009, 50(6): 525. [10],. [J]., 2005, 18(2): 114. [11],. [J]., 2007, 24(1): 40-42. [12],,,. [J]., 2014, 45(14): 2100-2105. [13] Havsteen B H. The biochemistry and medical significance of the flavonoids [J]. Pharmacol Theraps, 2006, 96(2/3): 67-202. [14],,. [J]., 2008, 39(4): 623-628. [15] Pietta P G. Flavonoids as Antioxidants [J]. J Nat Prod, 2000, 63(7): 1035-1042. [16] Middleton E Jr, Kandaswami C, Theoharides T C. The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer [J]. Pharmacol Rev, 2000, 52(4): 673-751. [17],,,. [J]., 2011, 42(1): 195-200. [18],,,. HPLC [J]., 2012, 18(15): 76-79. [19],. PC12 [J]., 2009, 26(1): 47-49. [20] Bhutada P, Mundhada Y, Bansod K. Reversal by quercetin of corticotrophin releasing factor induced anxiety-and depression-like effect in mice [J]. Prog Neuro- Psychopharmacol Biol Psychiatry, 2010, 33(6): 955-960.
Chinese Traditional and Herbal Drugs 46 20 2015 10 3115 [21] Kawabata K, Kawai Y, Terao J. Suppressive effect of quercetin on acute stress-induced hypothalamic-pituitaryadrenal axis response in Wistar rats [J]. J Nutr Biochem, 2010, 21(5): 374-380. [22] Dimpfel W. Rat electropharmacograms of the flavonoids rutin and quercetin in comparison to those of moclobemide and clinically used reference drugs suggest antidepressive and/or neuroprotective action [J]. Phytomedicine, 2009, 16(4): 287-294. [23] Sloley B D, Urichuk L J, Morley P. Identification of kaemp ferol as a monoamine oxidase inhibitor and potential neuroprotectant in extracts of Ginkgo biloba leaves [J]. J Pharm Pharmacol, 2000, 52(4): 451-459. [24]. [M]. :, 2011. [25],,,. RP-HPLC [J]., 2004, 35(5): 576-577. [26],,,. [J]., 2006, 20(12): 787-790. [27],,,. [J]., 2006, 10(27): 69-72. [28] Wang W X, Hu X Y, Zhao Z Y. Antidepressant-like effects of liquiritin and isoliquiritin from Glycyrrhiza uralensis in the forced swimming test and tail suspension test in mice [J]. Prog Neuro-Psychopharmacol Biol Psychiatry, 2008, 32(5): 1179-1184. [29],. HPLC [J]., 2003, 34(7): 618-619. [30] Pan X, Kong L D, Zhang Y. In vitro inhibition of rat monoamine oxidase by liquiritigenin and isoliquiritigenin isol ated from Sinofranchetia chinensis [J]. Acta Pharmacol Sin, 2000, 21(10): 949-953. [31],,,. 3 [J]., 2010, 21(4): 103-105. [32],,,. A [J]., 2008, 29(8): 1535-1538. [33],,. a Ca 2+ IL-6 [J]., 2008, 31(11): 756-766. [34] Zhu J, Luo C Q, Wang P. Saikosaponin A mediates the inflammatory response by inhibiting the MAPK and NF-κB pathways in LPS-stimulated RAW 264.7 cells [J]. Exp Therap Med, 2013, 5(5): 1345-1350. [35] Li Z Y, Jiang Y M, Liu Y M. Saikosaponin D acts against corticosterone-induced apoptosis via regulation of mitochondrial GR translocation and a GR-dependent pathway [J]. Prog Neuro-Psychopharmacol Biol Psychiatry, 2014, 53: 80-89. [36],,. d SH-SY5Y JNK [J]., 2013, 42(9): 785-788. [37],,,. HPLC [J]., 2006, 28(2): 161-164. [38] Hou Y Y, Yang Y, Yao Y. Neuroprotection of glycyrrhizin against ischemic vascular dementia in vivo and glutamate-induced damage in vitro [J]. Chin Herb Med, 2010, 2(2): 125-131. [39],,. [J]., 2012, 10(2): 98-100. [40],,,. [J]., 2013, 53(19): 28-29. [41],. [J]., 2012, 18(12): 272-274. [42],,. [J]., 2001, 15(3): 164-168. [43],,. PCI2 [J]., 2006, 41(23): 1792-1794. [44] Sun R, Wang K, Wu D D. Protective effect of paeoniflorin against glutamate-induced neurotoxicity in PC12 cells via Bcl-2/Bax signal pathway [J]. Folia Neuropathol, 2012, 50(3): 270-276. [45],,,. NO/cGMP [J]., 2012, 3(1): 27-28. [46] Mao Q Q, Zhong X M, Qiu F M. Protective effects of paeoniflorin against corticosterone-induced neurotoxicity in PC12 cells [J]. Phytother Res, 2012, 26(7): 969-973. [47],,,. [J]., 2011, 2(6): 35-37. [48],,,. - - [J]., 2014, 28(3): 340-344. [49],,,. [J]., 2003, 38(11): 838-840.
3116 Chinese Traditional and Herbal Drugs 46 20 2015 10 [50],,. HPLC [J]., 2000, 22(5): 342-345. [51],,,. [J]., 2007, 16(7): 595-596. [52] Yu L J, Zhang Y P, Ma R D. Potent protection of fernlic acid against excitotoxic effects of maternal intragastrie administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain [J]. Eur Neuropsychopharmacol, 2006, 16: 170-177. [53] Zhang Y P, Yu L J, Ma R D. Potent protective effects of ferulic acid on glutamate-induced neurotoxicity in adult mice [J]. Chin Neural Med, 2008, 7(6): 596-599. [54],,. [J]., 2010, 32(6): 840-849. [55],,,. -HPLC [J]., 2008, 20(5): 859-862. [56],,,. - [J]., 2011, 22(7): 1637-1639. [57],,,. [J]., 2005, 44(9): 162-164. [58] Kulkarni S K, Bhutani M K, Bishnol M. Antidepressant activity of curcumin: involvement of serotonin and dopamine system [J]. Psychopharmacology, 2008, 201(3): 435-442. [59],,,. ACTH [J]. 2008, 38(1): 22-24. [60] Xu Y, Ku B S, Lu T, et al. Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB [J]. Brain Res, 2006, 1122(1): 56-64. [61] [S].. 2010. [62],,,. [J]., 2013, 30(2): 121-125. [63]. [J]., 2008, 33(4): 326-330. [64]. [D]. :, 2013. [65],. [J]., 2007, 33(9): 572-574. [66] Mattson M P, Gleichmann M, Cheng A. Mitochondria in neuroplasticity and neurological disorders [J]. Neuron, 2008, 60: 784-766.