[an error occurred while processing this directive]

Journal of Chinese Integrative Medicine ›› 2009, Vol. 7 ›› Issue (1): 25-33.doi: 10.3736/jcim20090104

• Original Clinical Research • Previous Articles     Next Articles

  • Herbs for calming liver and suppressing liver-yang in treatment of migraine with hyperactive liver-yang sydrome and its effects on lymphocyte protein expression: a randomized controlled trial

 Guang-wei Zhonga, Wei Lia, Yan-hong Luob, Guo-lin Chena, Zhen-jia Yia ,Jian-jun Hua, Ying Zhanga, Yao-hui Yina, Le Zhangc   

  1. a Research Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China
    b Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China
    c Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China
  • Received:2008-07-30 Accepted:2008-08-12 Online:2009-01-20 Published:2009-01-15

RichHTML

4

PDF (PC)

191

Like

Objective

To observe the efficacy of herbs for calming liver and suppressing liver-yang in treatment of migraine patients with hyperactivity of liver-yang syndrome and to investigate its effects on the lymphocyte protein expression. This approach may lay a foundation for the further investigation of pathogenic mechanisms in migraine with hyperactive liver-yang sydrome and the curative mechanisms of calming liver and suppressing liver-yang treatment.
Methods

A total of 32 migraine patients with hyperactivity of liver-yang syndrome were randomly divided into treatment group (16 cases) and control group (16 cases). The patients in the treatment group were treated with herbs for calming liver and suppressing liver-yang in accordance with traditional Chinese medicine (TCM) theory and the patients in the control group were treated with Flunarizine Capsules for two courses of treatment. The therapeutic effects, the score of TCM symptom and the changes of headache attack were observed in both groups before and after the treatment. The side effects were also observed in both groups. The level of differential protein expression was analyzed by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS).
Results

The herbs for calming liver and suppressing liver-yang had better effects on headache improvement than the Flunarizine Capsules (P<0.01). The cure rates in the treatment and control groups were 87.5% and 75.0% respectively. Vertigo, restlessness and tantrum, and prosopo-heat in the treatment group were also improved as compared with those in the control group (P<0.05). After treatment, the score of TCM symptom in the two groups were all decreased (P<0.01), and there was a significant difference between the treatment group and the control group (P<0.01). The herbs for calming liver and suppressing liver-yang had no side effects. The average protein spots in the blood lymphocyte of normal people, migraine patients with hyperactivity of liver-yang syndrome in the treatment group before and after the treatment were (534±42), (552±54) and (529±55) spots respectively. Six down-regulated protein expressions and 14 up-regulated protein expressions were obtained in the treatment group. Four strengthened protein expressions in the six down-regulated proteins and 11 low protein expressions in the 14 up-regulated proteins were also obtained after treatment. Ten of the total 12 differential protein spots were successfully identified by MALDI-TOF-MS. The functions of these proteins were involved in metabolism, energy generation, transportation, antioxidation, signal transduction and immune, etc. According to information provided by NCBI and MSDB database, there were some proteins closely related to migraine with hyperactivity of liver-yang syndrome, such as peroxiredoxin 2, heat shock protein 27 and annexin A1.
Conclusion

 Herbs for calming liver and suppressing liver-yang is effective in treating migraine, and can improve TCM symptoms. The effects on migraine patients with hyperactivity of liver-yang syndrome may be related to regulating the blood lymphocyte protein expression.

Key words: Calming the liver, Suppressing liver-yang, Liver-yang hyperactivity, Proteomics, Migraine disorder, Randomized controlled trials

Table 1

Attack of headache in the treatment and control groups (x±s)"

Group n Frequency (attacks/month) Persistence time (h)
Control
Before treatment 16 3.5±0.58 5.48±1.43
After treatment 16 1.8±0.34** 2.43±0.46**
Treatment
Before treatment 16 3.4±0.56 5.62±1.36
After treatment 16 1.2±0.37**△ 1.87±0.69**△

Table 2

Therapeutic effects on headache in the treatment and control groups [Cases (%)]"

Group n Cure Obvious effect Improvement No improvement Total obvious effect
Control 16 3 (18.75) 6 (37.50) 3 (18.75) 4 (25.00) 12 (75.00)
Treatment 16 5 (31.25) 7 (43.75) 2 (12.50) 2 (12.50) 14 (87.50)△△

Table 3

Main symptoms of hyperactivity of liver-yang syndrome in the treatment and control groups [Cases]"

Group n Headache Dry mouth Vertigo Restlessness and tantrum Prosopo-heat
Control
Before treatment 16 16 14 10 13 12
After treatment 16 4** 6** 6** 9** 8**
Treatment
Before treatment 16 16 13 11 14 13
After treatment 16 3** 7** 3**△ 6**△ 6**△

Table 4

Score of traditional Chinese medicine symptom in the treatment and control groups (x±s)"

Group n Score of traditional
Chinese medicine symptom
Control
Before treatment 16 20.82±7.28
After treatment 16 10.73±3.92**
Treatment
Before treatment 16 21.64±6.65
After treatment 16 7.21±3.18**△△

Figure 1

Two-dimensional electrophoresis map of human in the normal and treatment groups A: Normal group; B: Before treatment in the treatment group; C: After treatment in the treatment group."

Table 5

Relative intensity of protein expression in the normal and treatment groups"

SSP Normal group
(x±s, n=10)		 Before treatment in the
treatment group (x±s, n=10)		 Ratio After treatment in the treatment
group(x±s, n=10)		 Ratio
1016 784.1±24.5 2 124.6±26.5 2.71 937.2±38.2 0.44
1207 368.3±28.6 981.2±17.7 2.66 458.1±22.4 0.47
1318 16.2±3.5 171.6±21.2 10.60 62.5±19.3 0.36
1420 35.6±4.2 1 226.8±54.9 34.46 367.3±43.4 0.29
1625 109.8±35.7 763.5±58.5 6.95 654.7±61.4 0.85
1801 673.7±56.6 1 532.7±116.1 2.28 1 738.5±88.9 1.13
2019 484.7±43.6 1 491.1±83.6 3.08 586.1±43.6 0.39
2013 123.1±15.1 4 282.5±238.1 34.76 576.2±47.4 0.13
2209 357.2±23.2 1 091.5±71.1 3.06 735.6±57.7 0.67
2259 263.4±22.5 2 363.4±128.1 8.97 472.3±36.9 0.20
4204 1 281.6±112.2 2 831.4±121.6 2.21 1 153.8±138.2 0.41
5606 140.3±12.8 362.4±42.9 2.58 116.7±19.3 0.32
5625 20.6±4.1 1 517.7±111.5 73.67 367.9±41.6 0.24
7234 24.5±5.4 231.3±31.8 9.44 111.8±14.3 0.48
2225 1 073.5±42.3 461.9±34.8 0.43 964.2±67.5 2.09
2115 692.3±56.5 301.6±47.6 0.44 838.5±56.9 2.78
2350 992.9±65.6 178.3±26.5 0.18 392.7±43.6 2.22
2313 934.8±73.8 304.3±32.7 0.33 484.3±21.3 1.59
2374 2 200.7±87.1 387.1±65.5 0.18 326.8±30.1 0.84
2439 797.8±41.5 169.7±31.1 0.21 527.6±65.4 3.11

Figure 2

Peptide mass fingerprinting of sample 7 by MALDI-TOF-MS analysis"

Figure 3

Mascot search results of peptide mass fingerprinting of sample 7 in Swissport"

Table 6

Proteins identified by Mascot software"

Sample Database ID Protein name Molecular
weight		 Isoelectric
point		 Matched
peptides		 Sequence
coverage		 Expression
1 Q71V49_HUMAN Alcohol dehydrogenase 3 1 217 9.52 5 30% ↓
2 S26788 Immunoglobulin heavy
chain Ⅴ region		 12 472 8.01 7 33% ↑
3 E980237 Heat shock protein-27 22 427 7.83 5 78% ↑
4 DEF4_HUMAN Neutrophil defensin
4 precursor		 10 839 8.31 5 40% ↑
5 MAGE2_HUMAN Melanoma-associated
antigen E2		 12 344 6.63 4 35% ↑
6 Q8IUS2_HUMAN LOC339483 protein 11 303 6.67 7 33% ↑
7 P04083_HUMAN Annexin-A1 38 583 6.64 5 59% ↑
8 AAB06412_HUMAN Immunoglobulin heavy
chain variable region (Fragment)		 13 424 8.57 3 41% ↑
9 P35704_HUMAN Peroxiredoxin-2 21 956 5.34 8 49% ↑
10 Q9UC96_HUMAN MU class glutathione
S-transferase (Fragment)		 3 544 5.50 5 40% ↓
[1] Stang P, Sternfeld B, Sidney S . Migraine headache in a prepaid health plan: ascertainment, demographics, physiological, and behavioral factors[J]. Headache, 1996,36(2):69-76
doi: 10.1046/j.1526-4610.1996.3602069.x
[2] Zhou S, Yang WH, Sun ZQ, Bu XC . Clinical effect of Pinggantonyluo Granules on migraine with liver-wind and blood stasis symptom[J]. Zhong Chen Yao, 2003,25(1):46-48
周慎, 杨维华, 孙兆泉, 卜献春 . 平肝通络颗粒治疗偏头痛肝风血瘀证的临床及实验研究[J]. 中成药, 2003,25(1):46-48
[3] Kuang PG . Migraine[J]. Zhongguo Teng Tong Yi Xue Za Zhi, 2002,8(2):46-48
匡培根 . 偏头痛[J]. 中国疼痛医学杂志, 2002,8(2):46-48
[4] Jin YQ. Modern research and clinical practice of theories about the liver in traditional Chinese medicine[M]. Beijing: People's Medical Publishing House,2002 237-238
金益强 . 中医肝脏象现代研究与临床[M]. 北京: 人民卫生出版社,2002 237-238
[5] Li LW, Fan LQ, Zhu WB, Nie HC, Sun BL, Luo KL, Liao TT, Tang L, Lu GX . Establishment of a high-resolution 2-D reference map of human spermatozoal proteins from 12 fertile sperm-bank donors[J]. Asian J Androl, 2007,9(3):321-329
doi: 10.1111/ajan.2007.9.issue-3
[6] Fernandez J, Gharahdaghi F, Mische SM . Routine identification of proteins from sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) gels or polyvinyl difluoride membranes using matrix assisted laser desorption/ionization-time of flight-mass spectrometry(MALDI-TOF-MS)[J]. Electrophoresis, 1998,19(6):1036-1045
doi: 10.1002/(ISSN)1522-2683
[7] Zhang SB, Wang JG . Progress of integrated traditional Chinese and Western medicine in treating migraine[J]. Tianjin Zhong Yi Xue Yuan Xue Bao, 2006,25(1):55-56
张树彪, 王景阁 . 偏头痛的中西医治疗进展[J]. 天津中医学院学报, 2006,25(1):55-56
[8] Yoshimoto M, Sato M, Yoshimoto N, Nakao K . Liposomal encapsulation of yeast alcohol dehydrogenase with cofactor for stabilization of the enzyme structure and activity[J]. Biotechnol Prog, 2006,24(3):576-582
[9] Macleod RJ, Hamilton JR, Bateman A, Belcourt D, Hu J, Bennett HP, Solomon S . Corticostatic peptides cause nifedipine-sensitive volume reduction in jejunal villus enterocytes[J]. Proc Natl Acad Sci, 1991,88(2):552-556
doi: 10.1073/pnas.88.2.552
[10] Lencer WI, Cheung G, Strohmeier GR, Currie MG, Ouellette AJ, Selsted ME, Madara JL . Induction of epithelial chloride secretion by channel-forming cryptdins 2 and 3[J]. Proc Natl Acad Sci, 1997,94(16):8585-8589
doi: 10.1073/pnas.94.16.8585
[11] Junker H, Suofu Y, Venz S, Sascau M, Herndon JG, Kessler C, Walther R, Popa-Wagner A . Proteomic identification of an upregulated isoform of annexin A3 in the rat brain following reversible cerebral ischemia[J]. Glia, 2007,55(16):1630-1637
doi: 10.1002/glia.v55:16
[12] Evgrafov OV, Mersiyanova I, Irobi J, Van Den Bosch L, Dierick I, Leung CL, Schagina O, Verpoorten N, Van Impe K, Fedotov V, Dadali E, Auer-Grumbach M, Windpassinger C, Wagner K, Mitrovic Z, Hilton-Jones D, Talbot K, Martin JJ, Vasserman N, Tverskaya S, Polyakov A, Liem RK, Gettemans J, Robberecht W, De Jonghe P, Timmerman V .Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy[J]. Nat Genet, 2004,36(6):602-606
doi: 10.1038/ng1354
[13] Damdimopoulos AE, Miranda-Vizuete A, Pelto-Huikko M, Gustafsson JA, Spyrou G . Human mitochondrial thioredoxin. Involvement in mitochondrial membrane potential and cell death[J]. J Biol Chem, 2002,277(36):33249-33257
doi: 10.1074/jbc.M203036200
[14] Yan YP, Yi ZJ, Li W, Li ZY, Wang SE, Zhong GW, Zhou LY, Li Z . Analysis of hypothalamuses in the spontaneous hypertension rats with hyperactivity of liver-yang using two-dimensional electrophosis[J]. Zhongguo Yi Shi Za Zhi, 2006,8(3):330-333
颜永平, 易振佳, 李炜, 李臻琰, 王素娥, 钟广伟, 周凌燕, 李智 . 高血压大鼠肝阳上亢证的下丘脑双向凝胶电泳分析[J]. 中国医师杂志, 2006,8(3):330-333
[1] Jing-lin Shi, Wan-hong Miao. Effects of acupuncture on lactoferrin content in tears and tear secretion in patients suffering from dry eyes: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(9): 1003-1008.
[2] Ming T. Tan , Jian-ping Liu , Lixing Lao. Adequate application of quantitative and qualitative statistic analytic methods in acupuncture clinical trials. Journal of Chinese Integrative Medicine, 2012, 10(8): 847-852.
[3] Lu Yu, Shui-miao Lin, Ru-qian Zhou, Wei-jun Tang, Pin-xian Huang, Ying Dong, Jian Wang, Zhi-hua Yu, Jiu-lin Chen, Li Wei, San-li Xing, Hui-juan Cao, Hong-bin Zhao. Chinese herbal medicine for patients with mild to moderate Alzheimer disease based on syndrome differentiation: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(7): 766-776.
[4] Hui Luo, Jian-ping Liu, Qing Li. Methodological issues and suggestions for improvement in randomized controlled trials of Chinese herbal medicine for recurrent miscarriage. Journal of Chinese Integrative Medicine, 2012, 10(6): 604-614.
[5] Peng Fu , Xue-qiang Huang, Ai-hong Yuan, Guang Yu, Xiao-bin Mei, Ruo-lan Cu. Effects of salvianolate combined with alprostadil and reduced glutathione on progression of chronic renal failure in patients with chronic kidney diseases: a long-term randomized controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(6): 641-646.
[6] Shui-qiu Deng, Xue-nong Ouyang, Zong-yang Yu, Xi-hu Dai, Xi Chen, Fang-zheng Fang, Wen-wu Wang, Zhi-zhen Liu. Influence of Chinese herbal medicine Feitai Capsule on completion or delay of chemotherapy in patients with stage ⅢB/Ⅳ non-small-cell lung cancer: a Randomized controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(6): 635-640.
[7] Ming-xing Zhao, Zhen-hua Dong, Zhong-hai Yu, Shi-yuan Xiao, Ya-ming Li . Effects of Ginkgo biloba extract in improving episodic memory of patients with mild cognitive impairment: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(6): 628-634.
[8] Ying-chun Miao , Jin-zhou Tian , Jing Shi , Min Mao. Effects of Chinese medicine for tonifying the kidney and resolving phlegm and blood stasis in treating patients with amnestic mild cognitive impairment: A randomized, double-blind and parallel-controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(4): 390-397.
[9] Xiao-hui Sun, Sheng Liu . External Chinese medical therapy for pain associated with hyperplastic disease of the breast: Study protocol of a randomized, double-blind, multicenter, controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(4): 384-389.
[10] Zhu Yan-feng, Luo Hai-ming, Deng Zhong-long, Fu De-yu, Yao Wang, Dai Jian. Effects of the Chinese patent medicine, Honghua Injection, on platelet glycoprotein Ⅱb/Ⅲa receptors in patients with acute coronary syndrome: a randomized controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(3): 318-323.
[11] Li Min, Yang Ming-hui, Liu Yi. Effects of Chinese herbal medicine Bushen Huoxue Granule on quality of life of patients with Parkinson disease: a randomized, double-blinded and placebo-controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(3): 310-317.
[12] Paula de Sousa Fragoso Ana, de Sá Ferreira Arthur. Evaluation of the immediate effects of manual acupuncture on brachial bicep muscle function in healthy individuals and poststroke patients: a study protocol of a parallel-group randomized clinical trial. Journal of Chinese Integrative Medicine, 2012, 10(3): 303-309.
[13] Li-xin Ma, Yu-yi Wang, Xin-xue Li, Jian-ping Liu . Systematic review on methodology of randomized controlled trials of post-marketing Chinese patent drugs for treatment of type 2 diabetes. Journal of Chinese Integrative Medicine, 2012, 10(3): 279-292.
[14] Wang Yun-fei, Que Hua-fa, Xu Jie-nan, Tang Han-jun, Xiang Huan-yu, Liu Xiao-dong, Zhang Zhen, Xing Jie, Shen Liang, Shan Wei, Liu An-min, Qiu Lian-yin, Deng Da-yi, Gao Dan. Assessment of external methods of traditional Chinese medicine in patients with chronic ulcer of the lower extremities: study protocol of a multicenter, randomized, parallel-group, prospective trial. Journal of Chinese Integrative Medicine, 2012, 10(2): 166-175.
[15] Liu Jian, Gao Ying, Kan Bao-hong, Zhou Li. Systematic review and meta-analysis of randomized controlled trials of Chinese herbal medicine in treatment of multiple sclerosis. Journal of Chinese Integrative Medicine, 2012, 10(2): 141-153.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[2] Hai-feng Wei, Bai-liu Ya, Ling Zhao, Cui-fei Ye, Li Zhang, Lin Li. Evaluation of tongue manifestation of blood stasis syndrome and its relationship with blood rheological disorder in a rat model of transient brain ischemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 73-76
[3] Xi Lin, Jian-ping Liu. Herbal medicines for viral myocarditis. Journal of Chinese Integrative Medicine, 2008, 6(1): 76
[4] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[5] Liang-ping Hu, Hui Gao. Discrimination of errors in statistical analysis of medical papers published in the first issue of 2006 in Journal of Chinese Integrative Medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 98-106
[6] Yan-bo Zhu , Qi Wang, Cheng-yu Wu, Guo-ming Pang, Jian-xiong Zhao, Shi-lin Shen, Zhong-yuan Xia , Xue Yan . Logistic regression analysis on relationships between traditional Chinese medicine constitutional types and overweight or obesity. Journal of Chinese Integrative Medicine, 2010, 8(11): 1023-1035
[7] Wei Xu, Meng Shi, Jian-gang Liu, Cheng-long Wang . Collagen protein expressions in ischemic myocardium of rats with acute myocardial infarction and effects of qi-tonifying, yin-tonifying and blood-activating herbs and detoxifying and blood-activating herbs. Journal of Chinese Integrative Medicine, 2010, 8(11): 1041-1047
[8] Tao Wang , Feng Qin. Effects of Chinese herbal medicine Xiaoyao Powder on monoamine neurotransmitters in hippocampus of rats with postpartum depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1075-1079
[9] Ying Xu , Chang-chun Zeng , Xiu-yu Cai , Rong-ping Guo , Guang Nie , Ying Jin. Chromaticity and optical spectrum colorimetry of the tongue color in different syndromes of primary hepatic carcinoma. Journal of Chinese Integrative Medicine, 2012, 10(11): 1263-1271
[10] Xiang-ying Mao , Qin Bian , Zi-yin Shen. Analysis of the osteogenetic effects exerted on mesenchymal stem cell strain C3H10T1/2 by icariin via MAPK signaling pathway in vitro. Journal of Chinese Integrative Medicine, 2012, 10(11): 1272-1278
[an error occurred while processing this directive]