Shuxuetong injection, composed of hirudo and pberetima, is commonly used in TCM for the treatment of ischemic cerebrovascular events. Shuxuetong affects blood rheology, and may prolong clotting time, reduce platelet adhesion, increase arterial blood flow, and inhibit thrombosis. Shuxuetong inhibits BCL-2-associated X protein and caspase-3 induced nerve cell death by promoting BCL-2 expression. In addition, Shuxuetong reduces inflammation as assessed by levels of high-sensitivity C-reactive protein and homocysteine. Hirudo and pberetima are widely used in traditional medicine to promote blood circulation and remove blood stasis.
The potential mechanisms were as follows: stroke is neurological condition resulting from local vascular abnormalities. Neural cells in the center of the injury region may suffer irreversible injury and cell death. Oxygen-free radicals are produced in the ischemic penumbra, and reperfusion of the area results in the death of additional neurons. The Chinese herbal medicines Honghua and Danshen, the main components in BuchangNaoxintong, are used clinically to activate blood circulation and dissipate blood stasis.
Traditional Chinese medicine treatment of poststroke recovery has several challenges, including dialectical complexity, multiple prescriptions, and lack of uniformity of drugs. Therefore, we prefer to use standardized Chinese patent medicines to treat complications of stroke. There are few randomized clinical trials (RCTs) that have evaluated the combination of Chinese patent medicine on the treatment of stroke sequelae. Further clinical studies of Chinese medicine, using modern medical research methods, could provide more reliable results.
We did not analyze stroke patients in acute phase because the main purpose of acute phase treatment is to reduce the mortality and disability rate. The purpose of acute phase treatment is to rapidly reduce intracranial pressure, reduce cerebral edema, prevent infection, and provide symptomatic treatment. Chinese herbal medicine is mainly used to protect nervous system function and is not the main treatment for an acute stroke.
The individualized treatment model, rather than the model generalized to the population, was always used for patients receiving Chinese herbal medicines. In the current study, the treatment effect was evaluated by comparing patients treated with Chinese herbal patent medicines with patients who did not receive Chinese herbal patent medicine. For other individualized treatments model was balanced between intervention and control group. Although potential confounders may influence the treatment effect, we describe a systematic and comprehensive review for the treatment effect of Chinese herbal medicines on poststroke recovery.
The double-blind randomized placebo-controlled study is an important study design to evaluate the effectiveness of medical interventions. In the past, Chinese scientists had a lower level of knowledge of study design, especially in tested patients. Thus, well-designed RCTs are not common in China. In addition, it is complicated to design a placebo control for Chinese medicine and other natural medicines. The color, smell, and taste are difficult to simulate with nontherapeutic ingredient. However, Chinese scientists have explored creating placebo herbal drugs. Dilution of the drugs or removal of the effective components can result in a placebo that retains the original appearance and smell, with minimal therapeutic effect. Placebo preparation of natural drugs for use in clinical trials is an urgent issue for Chinese scientists.
This study has several limitations. First, the results were based on previous studies, not on an individual patient level. Second, the outcome assessments have a relatively high degree of subjectivity. Third, due to the variety of herbal medicines, we could not classify the drugs based on their composition. Fourth, we did not analyze Chinese medicine formulae and nonpatent drugs. Fifth, although some studies did not distinguish between ischemic or hemorrhagic stroke, treatment using TCM is relative similar for both types of stroke and is based on identifying TCM syndromes. Further studies are needed to clarify the effective ingredients of Chinese herbal medicine. Sixth, data from Taiwan, Japan, and Korea were not included due to language restricted. Seventh, the criteria for significant improvement were different among the included studies, this could introduce uncontrolled biases and affect treatment effect for poststroke recovery. Finally, we originally intended to evaluate subgroup analysis based on life style; however, these data were not available.
. Teasell R, Rice D, Richardson M, et al. The next revolution in stroke care. Expert Rev Neurother 2014;14:1307–14.
. Rehm J, Taylor B. Alcohol consumption, stroke and public health—an overlooked relation? Addiction 2006;101:1679–81.
. Wu X, Zhu B, Fu L, et al. Prevalence, incidence, and mortality of stroke in the Chinese island populations: a systematic review. PLoS One 2013;8:e78629.
. Malcolm MP, Vaughn HN, Greene DP. Inhibitory and excitatory motor cortex dysfunction persists in the chronic poststroke recovery phase. J Clin Neurophysiol 2015;32:251–6.
. Coull AJ, Lovett JK, Rothwell PM. Population based study of early risk of stroke after transient ischaemic attack or minor stroke: implications for public education and organisation of services. BMJ 2004;328:326.
. Chen CL, Venketasubramanian N, Lee CF, et al. Effects of MLC601 on early vascular events in patients after stroke: the CHIMES study. Stroke 2013;44:3580–3.
. Venketasubramanian N, Lee CF, Wong KS, et al. The value of patient selection in demonstrating treatment effect in stroke recovery
trials: lessons from the CHIMES study of MLC601 (NeuroAiD). J Evid Based Med 2015;8:149–53.
. Borchers AT, Hackman RM, Keen CL, et al. Complementary medicine: a review of immunomodulatory effects of Chinese herbal
medicines. Am J ClinNutr 1997;66:1303–12.
. Sucher NJ. Insights from molecular investigations of traditional Chinese herbal
stroke medicines: implications for neuroprotective epilepsy therapy. Epilepsy Behav 2006;8:350–62.
. Zhang Z, Peng D, Zhu H, et al. Experimental evidence of Ginkgo bilobaextract EGB as a neuroprotective agent in ischemia stroke rats. Brain Res Bull 2012;87:193–8.
. Liu J. The use of Ginkgo biloba extract in acute ischemic stroke. Explore (NY) 2006;2:262–3.
. Rastogi V, Santiago-Moreno J, Dore S. Ginseng: a promising neuroprotectivestrategy in stroke. Front Cell Neurosci 2014;8:457.
. Hildebrandt JP, Lemke S. Small bite, large impact-saliva and salivary molecules in the medicinal leech, Hirudomedicinalis. Naturwissenschaften 2011;98:995–1008.
. Ji XY, Tan BK, Zhu YZ. Salvia miltiorrhiza and ischemic diseases. ActaPharmacol Sin 2000;21:1089–94.
. Adams JD, Wang R, Yang J, et al. Preclinical and clinical examinations of Salvia miltiorrhiza and its tanshinones in ischemic conditions. Chin Med 2006;1:3.
. Junhua Z, Menniti-Ippolito F, Xiumei G, et al. Complex traditional Chinese medicine for poststroke motor dysfunction: a systematic review. Stroke 2009;40:2797–804.
. Lu L, Li HQ, Fu DL, et al. Rhubarb root and rhizome-based Chinese herbal
prescriptions for acute ischemic stroke: a systematic review and meta-analysis
. Complement Ther Med 2014;22:1060–70.
. Ni X, Liu S, Guo X. Medium- and long-term efficacy of ligustrazine plus conventional medication on ischemic stroke: a systematic review and meta-analysis
. J Tradit Chin Med 2013;33:715–20.
. Gonzalez-Fraile E, Martin-Carrasco M, Ballesteros J. Efficacy of MLC601 on functional recovery after stroke: a systematic review and meta-analysis
of randomized controlled trials. Brain Inj 2016;30:267–70.
. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097.
. Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928.
. Ades AE, Lu G, Higgins JP. The interpretation of random-effects meta-analysis
in decision models. Med Decis Making 2005;25:646–54.
. Stuck AE, Rubenstein LZ, Wieland D. Bias in meta-analysis
detected by a simple, graphical test. Asymmetry detected in funnel plot was probably due to true heterogeneity. BMJ 1998;316:469.
. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088–101.
. Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis
. Biometrics 2000;56:455–63.
. White IR, Barrett JK, Jackson D, et al. Consistency and inconsistency in network meta-analysis
: model estimation using multivariate meta-regression. Res Synth Methods 2012;3:111–25.
. Li D, Wang T, Shen S, et al. Effects of fluroquinolones in newly diagnosed, sputum-positive tuberculosis therapy: a systematic review and network meta-analysis
. PLoS One 2015;10:e0145066.
. Trinquart L, Chatellier G, Ravaud P. Adjustment for reporting bias in network meta-analysis
of antidepressant trials. BMC Med Res Methodol 2012;12:150.
. Goto H, Satoh N, Hayashi Y, et al. A chinese herbal
medicine, tokishakuyakusan, reduces the worsening of impairments and independence after stroke: a 1-year randomized, controlled trial. Evid Based Complement Alternat Med 2011;2011:194046.
. Yang R, Wang H. Curative effect observation of combination of acupuncture with medicine therapy for stroke. J Clin Acupuncture Moxibustion 1997;12–3. [In Chinese].
. Liu G, Wu Y. Comprehensive treatment of 80 cases of cerebral infarction sequela. J Pract Traditional Chin Med 2003;19:415[In Chinese].
. Huang J, Zeng H, Xu J. Observation on the therapeutic effect of acupuncture combined with intravenous infusion in the treatment of apoplexy sequelae. Chin Gen Pract 2005;8:1193–4. [In Chinese].
. Wang C. Observation of 30 cases of acute cerebral vascular disease with the treatment of acute cerebral vascular disease with the combination of Shen Mai injection and acupuncture. J Pract Traditional Chin Med 2005;21:73[In Chinese].
. Wu Yanyang. Clinical observation on the treatment of 60 cases of sequela of apoplexy by acupuncture and massage together with medicine. Guiding J Traditional Chin Med 2006;12:41–2. [In Chinese].
. Kong KH, Wee SK, Ng CY, et al. A double-blind, placebo-controlled, randomized phase II pilot study to investigate the potential efficacy of the traditional Chinese medicine Neuroaid (MLC 601) in enhancing recovery after stroke (TIERS). Cerebrovasc Dis 2009;28:514–21.
. Harandi AA, Abolfazli R, Hatemian A, et al. Safety and efficacy of MLC601 in Iranian patients after stroke: a double-blind, placebo-controlled clinical trial. Stroke Res Treat 2011;2011:721613.
. Bavarsad Shahripour R, Shamsaei G, Pakdaman H, et al. The effect of NeuroAiD (MLC601) on cerebral blood flow velocity in subjects’ post brain infarct in the middle cerebral artery territory. Eur J Intern Med 2011;22:509–13.
. Liang J. To observe the clinical efficacy of Naoxintong Capsule in the treatment of stroke recovery
period. Shenzhen J Integr Traditional Chin Western Med 2014;24:50–1. [In Chinese].
. Yao L. The clinical curative effect of 43 cases of recovery of Buchangnaoxintong capsule in the treatment of stroke. Tianjin Pharmacy 2010;22:31–2. [In Chinese].
. Cao X, Zhou X, Zhuang H. Clinical observation on the treatment of dengzhanshengmai capsule in the recovery stage of ischemic wind-stroke. Global Traditional Chin Med 2012;05:56–7. [In Chinese].
. Lin L, Peng X, Shi H, et al. Clinical observation on the treatment of Butylphthalide Soft Capsules plus Naoxintong Capsule in the recovery stage of qi deficiency and blood stasis syndrome cerebral infarction: a report of 60 cases. Guiding J Traditional Chin Med Pharmacy 2015;59–61. [In Chinese].
. Ying W. Therapeutic effect of Puerarin Injection on the treatment of cerebral infarction. Zhejiang J Integr Traditional Chin Western Med 2002;12:690[In Chinese].
. Wei C. Clinical analysis on prevention and treatment of Apoplexy by HuaTuo reconstruction pill. Health Care Today b 2013;[In Chinese].
. Zhang J, Guo A. Curative effect observation on the treatment of 130 cases of Apoplexy by HuaTuo reconstruction pill. Guangdong Med J 2009;30:296[In Chinese].
. Mai L, Huang L, Qian H, et al. Effect of Huangqi Injection on the change of 24-hour dynamic blood pressure in elderly patients with cerebral infarction at convalescent stage. Chin J Clin Rehabil 2006;10:30[In Chinese].
. Tan Z, Li P, Sun G. Capsule combined western medicine treatment of cerebral stroke recovery
QDBS Observation of 76 Cases. Popular Sci Technol 2013;132–3. [In Chinese].
. Lin X. Clinical observations of Naomaitai Capsules plus compound cerebroproteinhydrolysate tablets on old patients with convalescing cerebral infarction. Chin J Exp Traditional Med Formulae 2013;19:314–6. [In Chinese].
. Ma Y, Lan R. Clinical observation on 35 cases of recovery phase of ischemic apoplexy treated by the combination of cerebral embolism and rehabilitation training. Liaoning J Traditional Chin Med 2011;394–5. [In Chinese].
. Li W. Pei-yuan brain capsule, acupuncture combined with western medicine stroke recovery
randomized parallel group study treatment. J Pract Traditional Chin Internal Med 2015;167–70. [In Chinese].
. Zheng X. Clinical observation of Shuxuetong injection in the treatment of ischemic stroke (recovery). Gansu J TCM 2008;21:15[In Chinese].
. Yuan S, Li F. Clinical observation of the effect of Tongsaimai Tablets Combined with rehabilitation training on stroke hemiplegia. J New Chin Med 2009;57–8. [In Chinese].
. Lei W, Wu Y, Huang L. Effect of Tongxinluo capsule on ability of activities of daily living of old reconvalescent with cerebral infarction. Hebei J TCM 2007;29:739–41. [In Chinese].
. Wang W. The effects of tongxinluo capsule on patients with convalescent brain infarction. Chin J Difficult Complicated Cases 2006;5:331–3. [In Chinese].
. Niu X, Zou W, Zhao Y, et al. XixianTongshuan capsule combined with aspirin in the treatment of ischemic stroke recovery
of phlegm and blood stasis syndrome in 56 cases. J Traditional Chin Med 2013;54:1056–7. [In Chinese].
. Ge X, Jin Y, Wang Y, et al. Combined acupuncture and medicine in treating 60 cases of apoplexy sequelae. China's Naturopathy 2009;17:30[In Chinese].
. Yu R, Chen C, He S. Summarization on 98 cases of ischemic apoplexy convalescent period treated by combination of TCM and western medicine. Guiding J TCM 2006;12:26[In Chinese].
. Qiao H, Dong L, Zhang X, et al. Protective effect of luteolin in experimental ischemic stroke: upregulated SOD1, CAT, Bcl-2 and claudin-5, down-regulated MDA and Bax expression. Neurochem Res 2012;37:2014–24.
. Ran X, Diao JX, Sun XG, et al. Huangzhi oral liquid prevents arrhythmias by upregulating caspase-3 and apoptosis network proteins in myocardial ischemia-reperfusion injury in rats. Evid Based Complement Alternat Med 2015;2015:518926.
. Hu HQ. Recent development of Chinese therapies for apoplexy sequel. J Henan Coll Traditional Chin Med 2003;18:83–5. [In Chinese].