目的 研究和厚朴酚对急慢性应激小鼠的抗抑郁作用及其机制。方法 采用强迫游泳急性应激小鼠模型(FST)及慢性应激小鼠模型。急性应激小鼠随机分为对照组、氟西汀组(3.3 mg·kg-1)、和厚朴酚组(2.5,5,10 mg·kg-1);慢性应激小鼠随机分为空白组、模型组、氟西汀组(3.3 mg·kg-1)、和厚朴酚组(2.5,5,10 mg·kg-1),观察小鼠强迫游泳不动时间,采用Elisa试剂盒检测小鼠脑组织中5-羟色胺(5-HT)及吲哚2,3-双加氧酶(IDO)含量。采用实时荧光定量PCR检测慢性应激小鼠脑组织中IDO mRNA的表达情况。结果 急慢性应激小鼠各给药组强迫游泳不动时间明显缩短(P<0.05);和厚朴酚中、高剂量组可增加FST小鼠模型脑5-HT含量(P<0.05,P<0.01),高剂量组明显减少FST小鼠模型脑IDO含量(P<0.05);和厚朴酚低、中、高剂量组明显增加慢性应激小鼠脑组织5-HT含量,减少脑组织IDO含量,明显降低IDO mRNA表达水平,与模型组相比具有统计学差异(P<0.05)。结论 和厚朴酚可以改善小鼠抑郁行为,具有一定抗抑郁作用,其主要作用机制与降低色氨酸通路限速酶IDO含量及基因表达水平,促进色氨酸转化为5HT,增加大脑中5-HT水平有关。
Abstract
OBJECTIVE To abserve the antidepressant effect and mechanism of honokiol on acute and chronic stress mouse. METHODS Forced swimming model of acute stress (FST) and chronic stress mice model were used. The acute stress mouse were randomized into a control group, a fluoxetine group (3.3 mg·kg-1), honokiol groups (2.5,5,10 mg·kg-1). The chronic stress mouse were randomized into a blank group, a model group, a fluoxetine group(3.3 mg·kg-1), honokiol groups (2.5,5,10 mg·kg-1). Then, the immobility time of forced swimming, 5-hydroxytryptamine (5-HT) and 2,3- indole dioxygenase (IDO) contents in mouse brain tissue by Elisa Kit, and the expression of IDO mRNA in brain tissue used by quantitative real-time PCR were studied. RESULTS ①After acute stress, the immobility time of forced swimming in each treatment group was significantly shorter than that in the model group (P<0.05). The 5-HT content of fluoxetine and honokiol medium and high dose group was significantly higher than that of model group (P<0.05, P<0.01). The IDO content of honokiol high dose group was significantly higher than that of model group (P<0.05). ②After chronic stress, the immobility time of the model group were significantly higher than the blank group (P<0.01). The 5-HT content in brain tissue of the model group was significantly lower than that of the blank group (P<0.01), the IDO content in brain tissue and its expression level of mRNA increased comparing with the normal group (P<0.01). For each treatment group, the immobility time of forced swimming, IDO content and the expression level of IDO mRNA was significantly decreased, and the 5-HT content was significantly increased, comparing with the model group with significant difference (P<0.05). CONCLUSION Honokiol can relieve the depression behavior of mouse and have certain antidepressant effect. The main mechanism may be associated with the increase of 5-HT, reduction of the tryptophan pathway enzyme IDO content and its gene expression level.
关键词
和厚朴酚 /
抗抑郁 /
作用机制
{{custom_keyword}} /
Key words
honokiol /
antidepressant /
mechanism
{{custom_keyword}} /
中图分类号:
R965
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] LI D H. Research progress of Magnolia officinalis[J]. J Liaoning Univ Tradit Chin Med(辽宁中医药大学学报), 2012,14(9):220-222.
[2] GUO C H, LI J J, LIU Y R, et al. Antidepressant effect of banxia magnoliae officinalis decoction [J]. Sci Technol Eng(科学技术与工程), 2014, 14(24):191-194.
[3] MA Z Q, LI R P, LI Y B, et al. Antidepressant-like effects of banxia houpu decoction by improving the state of oxidative stress in the brain [J]. Pharm Clin Res(药学与临床研究), 2014, 22(3):205-208.
[4] LONG F, HAN X Q, LONG S J,et al. Preliminary study on antidepressant effect of leaves of Magnolia officinalis Rehd. et Wils[J]. J Chengdu Univ Tradit Chin Med(成都中医药大学学报), 2014, 37(1):39-41.
[5] FU Q, MA Z Q, YANG W,et al. Antidepressant effect of magnolol on chronic mild stress model of depression in the mice [J]. Pharmacol Clin Chin Mater Med(中药药理与临床), 2013(2):47-51.
[6] KURIBARA H, KISHI E, HATTORI N, et al. The anxiolytic effect of two oriental herbal drugs in Japan attributed to honokiol from magnolia bark[J]. J Pharm Pharmacol, 2000, 52(11):1425-1429.
[7] LI T, WANG X, WANG Y, et al. Antidepressant-like effects of monarch drug compatibility in[J]. Chin J Nat Med(中国天然药物), 2010, 8(5):362-369.
[8] KNORR U, VINBERG M, GETHER U, et al. The effect of escitalopram versus placebo on perceived stress and salivary cortisol in healthy first-degree relatives of patients with depression—A randomised trial[J]. Psych Res, 2012, 200(2-3):354-360.
[9] XU Y J, SHENG H, NI X. The research progress of pathogenesis in depression [J]. Acta Univ Med Anhui(安徽医科大学学报), 2012, 47(3):323-326.
[10] ELHWUEGI A S. Central monoamines and their role in major depression[J]. Progr Neuro-psychopharmacol Biol Psych, 2004, 28(3): 435-437.
[11] OCONNOR J C, SALAZAR A, GONZALEZ-RIVERA B L, et al. Indoleamine 2,3-dioxygenase mediates anhedonia and anxiety-like behaviors caused by peripheral lipopolysaccharide immune challenge[J]. Horm Behav, 2012, 62(3):202-209.
[12] OXENKRUG G F. Metabolic syndrome, age-associated neuroendocrine disorders, and dysregulation of tryptophan—kynurenine metabolism[J]. Annals New York Acad Sci, 2010, 1199(1):1-14.
[13] SAVITZ J, DANTZER R, WURFEL B E, et al. Neuroprotective kynurenine metabolite indices are abnormally reduced and positively associated with hippo- campal and amygdalar volume in bipolar disorder[J]. Psychoneuroendocrinology, 2015, 52(52):200-211.
[14] BAY-RICHTER C, LINDERHOLM K R, CHAI K L, et al. A role for inflammatory metabolites as modulators of the glutamate N-methyl-d-aspartate receptor in depression and suicidality[J]. Brain Behav Immun, 2015, 43(11):110-117.
[15] CHOI K H, JEONG S I, LEE J H, et al. Pharmacological mechanism responsible for the Atractylodes japonica-induced distal colonic contraction in rats[J]. Phytomedicine, 2011, 18(5):408-413.
[16] KIMURA Y, SUMIYOSHI M. Effects of an Atractylodes lancea, rhizome extract and a volatile component β-eudesmol on gastrointestinal motility in mice[J]. J Ethnopharmacol, 2012, 141(1):530-536.
[17] SHISHKINA G T, KALININA T S, DYGALO N N. Up-regulation of tryptophan hydroxylase-2 mRNA in the rat brain by chronic fluoxetine treatment correlates with its antidepressant effect[J]. Neuroscience, 2008, 150(2):404-412.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
国家自然科学基金资助项目(81373584)
{{custom_fund}}