[an error occurred while processing this directive]

Journal of Chinese Integrative Medicine ›› 2010, Vol. 8 ›› Issue (2): 138-144.doi: 10.3736/jcim20100208

• Original Experimental Research • Previous Articles     Next Articles

Effects of Xiaotan Jieyu Recipe on behaviors of tumor-bearing rats with chronic mild stress and the mechanism

Li-juan Xiu, Pin-kang Wei,Hui-ming Lin, Bin Pang   

  1. Department of Traditional Chinese Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
  • Received:2009-10-09 Accepted:2009-12-10 Online:2010-02-20 Published:2010-02-15
  • Contact: Pin-kang Wei E-mail:czzyk73@163.com

RichHTML

1

PDF (PC)

101

Like

Objective

To investigate the effects of unpredictable chronic mild stress and Xiaotan Jieyu Recipe (XTJYR), a compound traditional Chinese herbal medicine, on the behaviors of Walker 256 tumor-bearing rats and to explore the mechanism.
Methods

Sixty Wistar rats were randomly divided into control group, stress group, tumor-bearing group, stress plus tumor-bearing group, fluoxetine group and XTJYR group. After treatment, sucrose solution consumption, score of ethology, body weight and serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected, expressions of Bcl-2 and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) proteins in hippocampus were detected by Western blotting method, and expression of Bcl-2 mRNA was measured by polymerase chain reaction method.
Results

Sucrose solution consumption, behavioral scores and body weight of rats were decreased in the stress group and the tumor-bearing group as compared with the control group. There were significant differences in expressions of Bcl-2 mRNA and Bcl-2 and p-ERK1/2 proteins in hippocampus and contents of serum TNF-α and IL-6 in the stress group and the tumor-bearing group as compared with those in the control group. XTJYR had the efficacy in improving behavioral scores of stress rats and tumor-bearing rats, down-regulating the contents of serum TNF-α and IL-6 and increasing the expressions of proteins of Bcl-2 and p-ERK1/2.
Conclusion

Tumor-bearing rats are prone to behave depressively after exposure to chronic mild stress and XTJYR can improve the behavioral scores of the rats. The mechanisms of XTJYR may relate to regulating contents of serum TNF-α and increasing the protein expressions of Bcl-2 and p-ERK1/2.

Key words: Tumor, Depression, Chronic mild stress, Drugs,Chinese herbal, Xiaotan Jieyu Decoction, Rats

Table 1

Primer sequence"

Gene Primer sequence Segment size (bp)
Bcl-2 Upper primer: 5'-GACGCGAAGTGCTATTGGT-3'
Reverse primer: 5'-CAGGCTGGAAGGAGAAGAT-3' 205
GAPDH Upper primer: 5'-TCCCTCAAGATTGTCAGCAA-3'
Reverse primer: 5'-AGATCCACAACGGATACATT-3' 308

Table 2

Sucrose solution consumption of rats in different groups before and after experiment ($\bar{x}±s$, mL/kg)"

Group n Sucrose solution consumption
Pre-experiment Post-experiment
Control 10 96.80±7.22 90.00±6.08
Tumor-bearing 10 94.00±2.92 77.80±11.48*△△
Stress 10 91.00±1.58 53.00±7.48**△△
Stress plus tumor-bearing 10 93.00±2.73 20.60±6.62**
Xiaotan Jieyu Recipe 10 92.00±5.15 66.00±6.44*△△
Fluoxetine 10 92.70±4.32 66.80±10.10*△△

Table 3

Behavioral test of rats in different groups before and after experiment ($\bar{x}±s$)"

Group n Crossing score Rearing score
Day 0 Day 28 Day 0 Day 28
Control 10 63.6±14.3 95.8±18.4 13.5±6.5 7.3±3.5
Tumor-bearing 10 57.5±24.8 53.4±22.4**△△ 9.0±3.8 5.0±3.6△△
Stress 10 68.6±17.9 45.5±14.1**△ 11.3±3.9 2.4±1.7**
Stress plus tumor-bearing 10 57.7±29.3 20.6±20.4** 10.0±4.2 1.4±1.8**
Xiaotan Jieyu Recipe 10 60.3±24.9 63.0±23.4**△△ 10.6±5.5 8.8±5.8△△
Fluoxetine 10 58.6±24.6 66.8±10.1**△△ 10.9±5.3 7.6±3.6△△

Table 4

Body weight of rats in different groups before and after experiment ($\bar{x}±s$, g)"

Group n Body weight
Pre-experiment Post-experiment Difference
Control 10 103.90±7.41 262.63±23.04 158.73±26.69
Tumor-bearing 10 109.30±5.31 209.30±9.15**△ 100.00±11.38*
Stress 10 105.40±5.38 211.40±22.74**△ 106.00±24.34*△
Stress plus tumor-bearing 10 105.40±4.77 194.70±7.86** 89.30±6.48*
Xiaotan Jieyu Recipe 10 107.20±4.62 209.70±10.11**△ 102.50±11.27*△
Fluoxetine 10 106.90±3.40 196.13±11.66** 89.23±13.08**

Table 5

Contents of serum TNF-α and IL-6 in rats in different groups after treatment ($\bar{x}±s$, ng/L)"

Group n TNF-α IL-6
Control 8 121.14±35.14 170.75±58.60
Tumor-bearing 8 181.45±20.14**△ 302.75±55.01**
Stress 8 172.17±9.92**△ 276.71±17.90*
Stress plus tumor-bearing 8 204.08±21.71** 323.00±37.95**
Xiaotan Jieyu Recipe 8 140.35±14.36*△△ 261.83±34.59*△
Fluoxetine 8 149.23±19.14*△△ 251.24±65.36*△

Table 6

Expressions of Bcl-2 mRNA and protein in hippocampus of rats in different groups ($\bar{x}±s$)"

Group n Bcl-2 protein Bcl-2 mRNA
Control 8 1.37±0.31 1.62±0.85
Tumor-bearing 8 1.20±0.23△△ 1.42±0.36△△
Stress 8 0.84±0.19**△ 0.63±0.29**
Stress plus tumor-bearing 8 0.54±0.26** 0.36±0.18**
Xiaotan Jieyu Recipe 8 1.59±1.02△△ 0.75±0.26**
Fluoxetine 8 1.13±0.30△ 1.22±0.22*△△

Figure 1

Expressions of Bcl-2 mRNA and protein in hippocampus of rats in different groupsA: Control group; B: Tumor-bearing group; C: Stress group; D: Stress plus tumor-bearing group; E: Xiaotan Jieyu Recipe group; F: Fluoxetine group."

Table 7

Expression of p-ERK1/2 protein in hippocampus of rats in different groups"

Group n p-ERK1/2 protein
Control 8 1.10±0.37
Tumor-bearing 8 0.86±0.33
Stress 8 0.62±0.43*
Stress plus tumor-bearing 8 0.52±0.45*
Xiaotan Jieyu Recipe 8 1.08±0.56△
Fluoxetine 8 1.40±0.20△△

Figure 2

Expression of p-ERK1/2 protein in hippocampus of rats in different groupsA: Control group; B: Tumor-bearing group; C: Stress group; D: Stress plus tumor-bearing group; E: Xiaotan Jieyu Recipe group; F: Fluoxetine group."

[1] Chochinov HM . Depression in cancer patients[J]. Lancet Oncol, 2001,2(8):499-505
doi: 10.1016/S1470-2045(01)00456-9
[2] Iconomou G, Mega V, Koutras A, Iconomou AV, Kalofonos HP . Prospective assessment of emotional distress, cognitive function, and quality of life in patients with cancer treated with chemotherapy[J]. Cancer, 2004,101(2):404-411
doi: 10.1002/(ISSN)1097-0142
[3] Irwin MR, Miller AH . Depressive disorders and immunity: 20 years of progress and discovery[J]. Brain Behav Immun, 2007,21(4):374-383
doi: 10.1016/j.bbi.2007.01.010
[4] Reiche EM, Nunes SO, Morimoto HK . Stress, depression, the immune system, and cancer[J]. Lancet Oncol, 2004,5(10):617-625
doi: 10.1016/S1470-2045(04)01597-9
[5] Spiegel D, Giese-Davis J . Depression and cancer: mechanisms and disease progression[J]. Biol Psychiatry, 2003,54(3):269-282
doi: 10.1016/S0006-3223(03)00566-3
[6] O'Mahony S Goulet J, Kornblith A, Abbatiello G, Clarke B, Kless-Siegel S, Breitbart W, Payne R. Desire for hastened death, cancer pain and depression: report of a longitudinal observational study[J]. J Pain Symptom Manage, 2005,29(5):446-457
doi: 10.1016/j.jpainsymman.2004.08.010
[7] Greer JA, Pirl WF, Park ER, Lynch TJ, Temel JS . Behavioral and psychological predictors of chemotherapy adherence in patients with advanced non-small cell lung cancer[J]. J Psychosom Res, 2008,65(6):549-552
doi: 10.1016/j.jpsychores.2008.03.005
[8] Wang SH, Zhang ZJ, Guo YJ, Teng GJ, Chen BA . Hippocampal neurogenesis and behavioural studies on adult ischemic rat response to chronic mild stress[J]. Behav Brain Res, 2008,189(1):9-16
doi: 10.1016/j.bbr.2007.11.028
[9] MacMaster FP, Mirza Y, Szeszko PR, Kmiecik LE, Easter PC, Taormina SP, Lynch M, Rose M, Moore GJ, Rosenberg DR . Amygdala and hippocampal volumes in familial early onset major depressive disorder[J]. Biol Psychiatry, 2008,63(4):385-390
doi: 10.1016/j.biopsych.2007.05.005
[10] Murray F, Smith DW, Hutson PH . Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice[J]. Eur J Pharmacol, 2008,583(1):115-127
doi: 10.1016/j.ejphar.2008.01.014
[11] Dranovsky A, Hen R . Hippocampal neurogenesis: regulation by stress and antidepressants[J]. Biol Psychiatry, 2006,59(12):1136-1143
doi: 10.1016/j.biopsych.2006.03.082
[12] Yang YX, Wei PK, Xiu LJ, Zhao Y, Shi J, Li YX, Yu S, Wu F . Effect of Bailong Jieyu granules on quality of life of patients with cancer-related depression[J]. Zhongguo Zhong Yi Yao Xin Xi, 2009,36(5):35-37
杨玉兴, 魏品康, 修丽娟, 赵颖, 施俊, 李宇欣, 俞珊, 武峰 . 白龙解郁颗粒对67例肿瘤相关性抑郁患者生活质量的影响[J]. 中国中医药信息, 2009,36(5):35-37
[13] Xiu LJ, Wei PK, Liu L, Lu Y, Wu F, Yang ZH . Influence of traditional Chinese recipe Xiaotanjieyu Decoction on behavior of mice after chronic swimming stress and on expression of 5-HT1A receptor mRNA in their hippocampus[J]. Di Er Jun Yi Da Xue Xue Bao, 2007,28(10):1126-1128
修丽娟, 魏品康, 刘龙, 陆烨, 武峰, 杨志慧 . 消痰解郁方对慢性强迫游泳应激后小鼠行为学及其海马组织5-HT1A受体mRNA表达的影响[J]. 第二军医大学学报, 2007,28(10):1126-1128
[14] Kodama M, Fujioka T, Duman RS . Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat[J]. Biol Psychiatry, 2004,56(8):570-580
doi: 10.1016/j.biopsych.2004.07.008
[15] Casarotto PC, Andreatini R . Repeated paroxetine treatment reverses anhedonia induced in rats by chronic mild stress or dexamethasone[J]. Eur Neuropsychopharmacol, 2007,17(11):735-742
doi: 10.1016/j.euroneuro.2007.03.001
[16] Jayatissa MN, Bisgaard C, Tingstrom A, Papp M, Wiborg O . Hippocampal cytogenesis correlates to escitalopram-mediated recovery in a chronic mild stress rat model of depression[J]. Neuropsychopharmacology, 2006,31(11):2395-2404
doi: 10.1038/sj.npp.1301041
[17] Banasr M, Valentine GW, Li XY, Gourley SL, Taylor JR, Duman RS . Chronic unpredictable stress decreases cell proliferation in the cerebral cortex of the adult rat[J]. Biol Psychiatry, 2007,62(5):496-504
doi: 10.1016/j.biopsych.2007.02.006
[18] Grønli J, Bramham C, Murison R, Kanhema T, Fiske E, Bjorvatn B, Ursin R, Portas CM . Chronic mild stress inhibits BDNF protein expression and CREB activation in the dentate gyrus but not in the hippocampus proper[J]. Pharmacol Biochem Behav, 2006,85(4):842-849
doi: 10.1016/j.pbb.2006.11.021
[19] Willner P . Chronic mild stress(CMS) revisited: consistency and behaviourial-neurobiological concordance in the effects of CMS[J]. Neuropsychobiology, 2005,52(2):90-110
doi: 10.1159/000087097
[20] Cui YZ, Han YG, Luo RC, Yang HQ, Jiang D . Establishment of an rat model of tumor-associated depression[J]. Nan Fang Yi Ke Da Xue Xue Bao, 2006,26(10):1513-1514
崔彦芝, 韩亚光, 罗荣城, 杨海青, 姜达 . 肿瘤相关性抑郁动物模型的建立[J]. 南方医科大学学报, 2006,26(10):1513-1514
[21] Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS . Hippocampal volume reduction in major depression[J]. Am J Psychiatry, 2000,157(1):115-118
doi: 10.1176/ajp.157.1.115
[22] Colla M, Kronenberg G, Deuschle M, Meichel K, Hagen T, Bohrer M, Heuser I . Hippocampal volume reduction and HPA-system activity in major depression[J]. J Psychiatr Res, 2007,41(7):553-560
doi: 10.1016/j.jpsychires.2006.06.011
[23] Tada E, Parent JM, Lowenstein DH, Fike JR . X-irradiation causes a prolonged reduction in cell proliferation in the dentate gyrus of adult rats[J]. Neuroscience, 2000,99(1):33-41
doi: 10.1016/S0306-4522(00)00151-2
[24] Dwivedi Y, Rizavi HS, Roberts RC, Conley RC, Tamminga CA, Pandey GN . Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects[J]. J Neurochem, 2001,77(3):916-928
doi: 10.1046/j.1471-4159.2001.00300.x
[25] Xu Z, Wang BR, Ding YQ, Kuang F, Wang X, Duan XL, Jiao XY, Ju G . Extracellular signal-regulated kinases1/2 in neurons of the dorsal motor nucleus of the vagus nerve and nucleus of the solitary tract are activated by noxious visceral stimulus in mice[J]. Neurosci Lett, 2002,334(2):103-106
doi: 10.1016/S0304-3940(02)01113-8
[26] Shirayama Y, Chen AC, Nakagawa S, Russell DS, Duman RS . Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression[J]. J Neurosci, 2002,22(8):3251-3261
doi: 10.1523/JNEUROSCI.22-08-03251.2002
[27] Branchi I, Francia N, Alleva E . Epigenetic control of neurobehavioural plasticity: the role of neurotrophins[J]. Behav Pharmacol, 2004,15(5-6):353-362
doi: 10.1097/00008877-200409000-00006
[28] Reif A, Schmitt A, Fritzen S, Chourbaji S, Bartsch C, Urani A, Wycislo M , M-ssner R, Sommer C, Gass P, Lesch KP.Differential effect of endothelial nitric oxide synthase(NOS-Ⅲ) on the regulation of adult neuroge-nesis and behaviour[J]. Eur J Neurosci, 2004,20(4):885-895
doi: 10.1111/ejn.2004.20.issue-4
[29] Schieper OJ, Wichers MC, Maes M . Cytokines and major depression[J]. Prog Neuropsychopharmacol Bio Psychiatry, 2005,29(2):201-217
doi: 10.1016/j.pnpbp.2004.11.003
[1] Na Wu , Lu Song , Xin-xin Yang, Jiang-lei Wei , Zhen-guo Liu. Effects of Chinese herbal medicine Tianqi Pingchan Granule on G protein-coupled receptor kinase 6 involved in the prevention of levodopa-induced dyskinesia in rats with Parkinson disease. Journal of Chinese Integrative Medicine, 2012, 10(9): 1018-1024.
[2] Avijit Paul, Kausik Bishayee, Samrat Ghosh, Avinaba Mukherjee, Sourav Sikdar, Debrup Chakraborty, Naoual Boujedaini, Anisur Rahman Khuda-Bukhsh. Chelidonine isolated from ethanolic extract of Chelidonium majus promotes apoptosis in HeLa cells through p38-p53 and PI3K/AKT signalling pathways. Journal of Chinese Integrative Medicine, 2012, 10(9): 1025-1038.
[3] Lawrence A. Olatunji, Taofeek O. Usman, Joseph O. Adebayo, Victoria A. Olatunji . Effects of aqueous extract of Hibiscus sabdariffa on renal Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities in Wistar rats. Journal of Chinese Integrative Medicine, 2012, 10(9): 1049-1055.
[4] Chan Chen, Chang-xun Chen, Xi-min Wu, Rui Wang, Yi-ming Li. Effects of extracts of Radix Scrophulariae on blood pressure in spontaneously hypertensive rats and the underlying mechanisms. Journal of Chinese Integrative Medicine, 2012, 10(9): 1009-1017.
[5] Dhirender Kaushik, Ajay Kumar, Pawan Kaushik, Avatar C. Rana. Anticonvulsant activity of alcoholic extract of bark of Pinus roxburghii Sarg. Journal of Chinese Integrative Medicine, 2012, 10(9): 1056-1060.
[6] Jian-sheng Li, Ya Li, Su-yun Li, Yuan-yuan Wang, Li Deng, Yan-ge Tian, Su-li Jiang , Ying Wang. Long-term effects of Tiaobu Feishen therapies on systemic and local inflammation responses in rats with stable chronic obstructive pulmonary disease. Journal of Chinese Integrative Medicine, 2012, 10(9): 1039-1048.
[7] Karuna A. Talpate, Uma A. Bhosale, Mandar R. Zambare. Clitorea ternatea, a herb from Indian folklore, improves streptozotocin-induced diabetes and diabetes-induced cognitive decline in rats. Journal of Chinese Integrative Medicine, 2012, 10(8): 939-947.
[8] Samuel Joshua Pragasam, Vachana Murunikara, Evan Prince Sabina, Mahaboobkhan Rasool. Antiperoxidative potential of p-coumaric acid, a common dietary phenol, in adjuvant-induced arthritis in rats. Journal of Chinese Integrative Medicine, 2012, 10(8): 932-938.
[9] Zi-hui Li, Jian Wang, Rong-lin Cai, You-wen Wang, Jian-peng Hu. Establishment and evaluation of a rat model of ulcerative colitis with syndrome of dampness stagnancy due to spleen deficiency. Journal of Chinese Integrative Medicine, 2012, 10(8): 918-924.
[10] Meng Li, Ling Hu, Rong-lin Cai, Zi-jian Wu, Ke-ming Wang. Effects of electro-acupuncture at PC6 and BL15 on nerve electrical activity in spinal dorsal root and norepinephrine and dopamine contents in paraventricular nucleus of hypothalamus in rats with acute myocardial ischemia. Journal of Chinese Integrative Medicine, 2012, 10(8): 874-879.
[11] Hong Wang , Jing-tian Ou , Xin Zhao , Ying Guoz , Hao-ping Mao. Vasodilator effect of oroxylin A on thoracic aorta isolated from rats. Journal of Chinese Integrative Medicine, 2012, 10(8): 880-885.
[12] Yong Zhang, Xiao-wen Sun, Jian-hua Xu, Hai Lu, Zhong-ze Fan, Jue Sun, Xiao-xiao Zhang. Effects of medicated serum prepared with Chinese herbal medicine Changweiqing on pharmacokinetics of oxaliplatin in colon cancer cells. Journal of Chinese Integrative Medicine, 2012, 10(8): 901-910.
[13] Xin-min Li, Hui Chen, Yan-yan Ren, Yan-li Lu. Effects of Chinese herbal medicine Xifeng Capsule on multidrug resistance-associated protein 1 expression in hippocampus and cortex of rats with lithium-pilocarpine-induced epilepsy. Journal of Chinese Integrative Medicine, 2012, 10(8): 911-917.
[14] Wei-hua Xu, Ze-huai Wen, Wei-xiong Liang, Qi Wang. A review of research on the development of instruments for therapeutic efficacy evaluation of traditional Chinese medicine. Journal of Chinese Integrative Medicine, 2012, 10(7): 726-737.
[15] C. Mouli Kalla, Vijaya Tartte, Dattatreya Rao Sirpurkar. Effectiveness of flavonoid-rich leaf extract of Acalypha indica in reversing experimental myocardial ischemia: biochemical and histopathological evidence. Journal of Chinese Integrative Medicine, 2012, 10(7): 784-792.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] Wei-xiong Liang. Problems-solving strategies in clinical treatment guideline for traditional Chinese medicine and integrative medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 1-4
[2] Zhao-guo Li. Discussion on English translation of commonly used sentences in traditional Chinese medicine: part one. Journal of Chinese Integrative Medicine, 2008, 6(1): 107-110
[3] Jun Hu, Jian-ping Liu. Non-invasive physical treatments for chronic/recurrent headache. Journal of Chinese Integrative Medicine, 2008, 6(1): 31
[4] Xue-mei Liu, Qi-fu Huang, Yun-ling Zhang, Jin-li Lou, Hong-sheng Liu, Hong Zheng. Effects of Tribulus terrestris L. saponion on apoptosis of cortical neurons induced by hypoxia-reoxygenation in rats. Journal of Chinese Integrative Medicine, 2008, 6(1): 45-50
[5] . Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing for biomedical publication (Chinese version, part two). Journal of Chinese Integrative Medicine, 2010, 8(11): 1001-1005
[6] Daniel Weber, Janelle M Wheat, Geoffrey M Currie. Inflammation and cancer: Tumor initiation, progression and metastasis,and Chinese botanical medicines. Journal of Chinese Integrative Medicine, 2010, 8(11): 1006-1013
[7] Hong Liu , Guo-liang Zhang, Li Shen , Zhen Zeng, Bao-luo Zhou, Cheng-hai Liu, Guang Nie . Application and evaluation of a pseudotyped virus assay for screening herbs for anti-H5Nl avian influenza virus. Journal of Chinese Integrative Medicine, 2010, 8(11): 1036-1040
[8] Zhao-guo Li . A discussion of English translation of 1995 and 1997 Chinese National Standards of Traditional Chinese Medical Terminologies for Clinical Diagnosis and Treatment. Journal of Chinese Integrative Medicine, 2010, 8(11): 1090-1096
[9] Rui Jin, Bing Zhang. A complexity analysis of Chinese herbal property theory: the multiple formations of herbal property (Part 1). Journal of Chinese Integrative Medicine, 2012, 10(11): 1198-1205
[10] Hui-min Liu, Xian-bo Wang, Yu-juan Chang, Li-li Gu. Systematic review and meta-analysis of randomized controlled trials of integrative medicine therapy for treatment of chronic severe hepatitis. Journal of Chinese Integrative Medicine, 2012, 10(11): 1211-1228
[an error occurred while processing this directive]