Journal of Alternative Complementary & Integrative Medicine Category: Medicine Type: Research Article

Application of Tongqiao Huoxue Decoction in the Treatment of Cerebrovascular Disease : A Review

Da-Yuan Zhong1 and Yi-Hui Deng1*
1 HuNan University Of Chinese Medicine, Changsha, China

*Corresponding Author(s):
Yi-Hui Deng
HuNan University Of Chinese Medicine, Changsha, China
Tel:+86 13787319813,
Email:644138330@qq.com

Received Date: Dec 24, 2020
Accepted Date: Dec 28, 2020
Published Date: Dec 31, 2020

Abstract

TongqiaoHuoxue Decoction (TONGQIAO HUOXUE DECOCTION) originated from the book "Medical Forest Correction" written by Wang Qingren in 1830. It is a prescription for activating blood circulation and dispersing stagnation, mainly for the faculties of the head and face. With more than one hundred years of clinical and experimental exploration by Chinese medicine researchers, the connotation of TONGQIAO HUOXUE DECOCTION has been enriched and developed. It can be used to treat many diseases, but it still focuses on head and face related diseases, especially cerebrovascular diseases. By collecting and sorting out the relevant literature on TONGQIAO HUOXUE DECOCTION, we systematically report the latest knowledge about TONGQIAO HUOXUE DECOCTION, mainly including the application of TONGQIAO HUOXUE DECOCTION in the treatment of cerebrovascular diseases and their secondary diseases.

INTRODUCTION

Tongqiao Huoxue Decoction (TONGQIAO HUOXUE DECOCTION) is derived from Wang Qingren's “Medical Forest Correction”, which consists of red peony root, peach kernel, safflower, ginger, chuanxiong, musk, green onion and red dates. Wang believes that it has the effects of activating blood and removing blood stasis, dredging collaterals and relieving pain, and fragrant and resuscitating, which can improve the blood stasis syndrome of the blood vessels of the head, face and limbs. However, with the in-depth understanding of TONGQIAO HUOXUE DECOCTION by Chinese medicine researchers, the application of TONGQIAO HUOXUE DECOCTION has become more and more extensive. At present, TONGQIAO HUOXUE DECOCTION has been applied to Ischemic Stroke (IS) [1], Hemorrhagic Stroke (hemorrhagic stroke) [2], Vertebrobasilar artery extension and Dilatation (VBD) [3], Vascular Dementia (VD) [4] and Posterior Circulation Ischemic Vertigo (PCIV) [5] and other diseases. The purpose of this article is to summarize the latest knowledge about TONGQIAO HUOXUE DECOCTION, mainly including the application of TONGQIAO HUOXUE DECOCTION in the treatment of cerebrovascular diseases and their secondary diseases.

APPLICATION OF TONGQIAO HUOXUE DECOCTION IN CEREBROVASCULAR DISEASES

IS 

China is one of the countries with the heaviest stroke burden in the world. The incidence of stroke disease is about 1.6%, of which IS accounts for 21.4% [6]. At present, the treatment of this disease is mainly through intravenous drug thrombolysis, arterial thrombolysis, non-stent mechanical thrombectomy and stent mechanical thrombectomy treatment [7]. Among them, the time of intravenous drug thrombolysis treatment is stricter (3∼4.5h in acute cerebrovascular occlusion), and the recanalization rate of large artery occlusion is low, and the treatment effect is relatively poor. The cerebral infarction secondary to acute cerebrovascular occlusion is mostly caused by the formation of a large number of thrombi on the basis of cerebral artery stenosis. Even if the blood vessel is recanalized after simple thrombolysis, it will often leave obvious stenosis and be prone to re-occlusion [8]. And because thrombolytic drugs [9,10] easily cause intracranial hemorrhage, the incidence of intravenous thrombolysis is about 6.4%, and the incidence of arterial thrombolysis is close to 10%, which exacerbates the deterioration of the disease. Therefore, the treatment effect is not particularly ideal. Traditional Chinese medicine believes that the incidence of ISis closely related to blood stasis [11], so the treatment mainly starts with promoting blood circulation and removing blood stasis [12]. Among the 6 traditional Chinese medicine compounds for promoting blood circulation and removing blood stasis, the results of a network meta-analysis [13] show that TONGQIAO HUOXUE DECOCTION and BuyangHuanwu Decoction are effective. Liu Yali et al., [14] found that the improvement of the Montreal Cognitive (MoCA) score and the Ability of Daily Living (ADL) score of patients taking TONGQIAO HUOXUE DECOCTION was significantly better than that of the control group. Han Sufang [15] found that after TONGQIAO HUOXUE DECOCTION treatment, the patient's Nihemorrhagic Stroke S score was significantly lower than that of the control group. HuoQiwen et al., [16] also found that TONGQIAO HUOXUE DECOCTION can effectively reduce the expression of serum Copeptin and BNP and improve the perfusion of the infarct center and nearby tissues. All the above evidences show that TONGQIAO HUOXUE DECOCTION can effectively improve the symptoms of IS and cerebral ischemia, and this has also been confirmed by evidence-based medicine [1]. Regarding the mechanism of TONGQIAO HUOXUE DECOCTION in the treatment of IS, there are currently several opinions, including inflammation [17], oxidative stress [18], autophagy [17], immunity [17] and apoptosis [17,19] and other functions.

Hemorrhagic stroke 

Hemorrhagic stroke is a disease caused by rupture of blood vessels that penetrates into the brain. It is associated with severe morbidity and high mortality [20]. It can be further divided into Intracerebral Hemorrhage (ICH) and subarachnoid hemorrhage (subarachnoid hemorrhage) [21]. Among them, ICH penetrates into the brain parenchyma, and Subarachnoid Hemorrhage penetrates into the subarachnoid space. There is no name for hemorrhagic stroke in the classics of traditional Chinese medicine. According to its symptoms, it is included in the categories of stroke, seizure syndrome, and true headache. Traditional Chinese medicine believes that the main causes of hemorrhagic stroke are wind, fire, phlegm, qi, blood, stasis, and deficiency. According to the different time of onset, “Chinese Medicine Internal Medicine” [22] divides hemorrhagic stroke into three stages: acute phase, recovery phase and sequelae phase. It is further divided into two categories: the meridian and the viscera for treatment based on syndrome differentiation. According to the order of onset time, Peng Weixian [23] subdivided hemorrhagic stroke into five periods: hyper acute, acute, subacute, recovery and sequelae. According to the pathological changes in each stage, it is proposed that the traditional Chinese medicine for promoting blood circulation and removing blood stasis can be used during the super-acute and acute phases while taking into account the symptoms and signs of the patient.

Cerebral Hemorrhage (CH) 

CH is defined as primary non-traumatic cerebral parenchymal hemorrhage, also known as spontaneous hemorrhage. In recent years, the incidence of CH has gradually increased among the Chinese population, especially among the middle-aged and elderly people [24,25]. CH has always been known for its high fatality rate and high disability rate [26]. In order to save the lives of patients and prevent the occurrence of disability, clinicians are required to deal with them as quickly as possible. Traditional Chinese medicine believes that the onset of CH is closely related to blood stasis, so TONGQIAO HUOXUE DECOCTION treatment is also feasible in this disease. GuohuaXi [27] believes that CH mainly occurs in the arteries, and NieZhiling [28] found that the main pathogenesis of CH is that long-term hypertension causes structural changes in the wall of deep perforating arteries, such as the growth of tiny aneurysms which rupture when blood pressure rises sharply. This indicates that the pathogenesis of hemorrhagic stroke is the change of blood vessel wall, and has nothing to do with the coagulation mechanism. Gao Huijuan et al., [29] observed the hemorheological indexes of 157 patients with CH and found that the indexes were significantly higher than those in the normal control group, suggesting that the blood of patients with CH was in a state of thick, sticky, coagulated and aggregated in the acute phase. Not only that, early studies [30-32] found that both acute CH and new ischemic lesions coexist. These factors lead to the destruction of the blood-brain barrier, cerebral edema, and hydrocephalus [33]. Different from the effects of anti-platelet aggregation drugs such as aspirin, traditional Chinese medicines that promote blood circulation and remove blood stasis will not induce vascular endothelial cell damage while reducing the level of platelets [34,35]. On the contrary, it may also protect vascular endothelial cells [36,37], such as the peach kernel [38], safflower [39], red peony [40] and other traditional Chinese medicines in TONGQIAO HUOXUE DECOCTION. Therefore, Gao Niuniu [41] believes that Chinese medicine for promoting blood circulation and removing blood stasis can be used reasonably in hemorrhagic stroke. Chen Qingren et al., [42] divided 94 patients with acute CH into TONGQIAO HUOXUE DECOCTION combined with conventional western medicine group and conventional western medicine group. The results showed that the IL-6, TNF-α and Nihemorrhagic stroke S scores of the observation group were significantly lower than those of the control group, ESS score and Barthel index Both were significantly higher than the control group. This result is basically consistent with the result of JinYumei [43]. These evidences suggest that TONGQIAO HUOXUE DECOCTION has the effect of improving the symptoms of patients with CH, and this effect may be related to the reduction of brain inflammation.

Subarachnoid Hemorrhage 

Subarachnoid Hemorrhage is a special subtype of intracranial hemorrhage. It includes two types. One is primary Subarachnoid Hemorrhage, such as aneurysmal subarachnoid hemorrhage [44]. The other is secondary subarachnoid hemorrhage, such as secondary subarachnoid hemorrhage after brain trauma [45]. In general, basal acute subarachnoid hemorrhage is common in cerebral aneurysm rupture, and cortical acute subarachnoid hemorrhage is common in brain trauma [44]. Aneurysm rupture subarachnoid hemorrhage [46] and traumatic subarachnoid hemorrhage [47] are critical and critical illnesses in neurology. Scientists have long believed that cerebral vasospasm is the main cause of delayed nervous system deterioration after aneurysmal subarachnoid hemorrhage [48] and traumatic subarachnoid hemorrhage [49]. Although the essence of subarachnoid hemorrhage and CH is different, the understanding of them in Chinese medicine is the same. Recent studies have found that there is vasospasm in deep cerebral veins after subarachnoid hemorrhage [50]. In addition, subarachnoid hemorrhage can also lead to the formation of micro thrombosis and microvascular stenosis [51-53], which suggests that subarachnoid hemorrhage is likely to be complicated by ischemic events. Therefore, the use of traditional Chinese medicine for promoting blood circulation and removing blood stasis, such as TONGQIAO HUOXUE DECOCTION, is allowed. XiongJiarui et al., [54] found that Tongqiao Huoxue Decoction had a poor prevention and treatment effect on early-onset cerebral vasospasm after subarachnoid hemorrhage, but had a significant effect on delayed-onset cerebral vasospasm (P<0.05). And the use of TONGQIAO HUOXUE DECOCTION does not increase the risk of bleeding in patients with subarachnoid hemorrhage [55]. Liu Changya et al., [56] found that the serum carbon monoxide and the mean blood flow Velocity of the Middle Cerebral Artery (VMCA) of the TONGQIAO HUOXUE DECOCTION group were higher than those of the control group, the serum endothelin vascular peptide, Serum Neurospecific Enolase (NSE) and serum Intracellular Adhesion Molecules -1 (ICAM-1) and Serum Interleukin-1β (IL-1β) were lower than those of the control group, and the above differences were statistically significant (P<0.05). This suggests that TONGQIAO HUOXUE DECOCTION can improve the symptoms of patients with subarachnoid hemorrhage, and this is not only limited to primary subarachnoid hemorrhage, TONGQIAO HUOXUE DECOCTION is also effective for patients with secondary Subarachnoid hemorrhage [57]. The main reason for the onset of TONGQIAO HUOXUE DECOCTION [58] may be related to the relief of vascular spasm.

APPLICATION OF TONGQIAO HUOXUE DECOCTION IN SECONDARY DISEASES OF CEREBROVASCULAR DISEASE

Post stroke Vascular Dementia (VD) 

According to estimates by the World Health Organization [59], there were approximately 35.6 million people suffering from dementia worldwide in 2012, and this number is expected to triple by 2050. VD is a group of heterogeneous brain diseases, accounting for about 20% of dementia cases [60], and its cognitive impairment is mainly due to cerebrovascular diseases. The CA1 area of the hippocampus is one of the most sensitive areas of cerebral ischemia. It plays a very important role in the storage, consolidation and extraction of information, and is an important part of high-level neural activities such as learning and memory [61]. There is a significant loss of neurons in the CA1 area of the hippocampus after cerebral ischemia, and the loss of neurons in this area is closely related to the changes in the learning and memory ability of patients with VD [62]. This suggests that the ischemia and hypoxia of hippocampal CA1 area caused by cerebral microcirculation is closely related to the occurrence of VD. The 2019 Chinese Guidelines for the Diagnosis and Treatment of Vascular Cognitive Impairment [63] divides the severity of VD into mild vascular cognitive impairment (mild VCI) and severe Vascular Cognitive Impairment (major VCI). Phthalin and nimodipine are included in the recommended list of anti-platelet aggregation and microcirculation drugs. Chinese medicine believes that VD belongs to the category of “Dai Bing” in Chinese medicine, and its disease is located in the brain. “JingyueQuanshu” believes that “everyone who has blood stasis in the heart and brain can also make forgetful”, which shows that blood stasis is closely related to the occurrence of dementia. As a famous prescription for promoting blood circulation and removing blood stasis, TONGQIAO HUOXUE DECOCTION can be used for the treatment of VD. The latest clinical research [64] results show that TONGQIAO HUOXUE DECOCTION can significantly improve the living ability and cognitive function of patient’s withVD, and can significantly reduce blood lipids, Hcy levels and arteriosclerosis. Evidence-based medicine [65] found that TONGQIAO HUOXUE DECOCTION has a certain effect in the treatment of VD, and its effect is related to the course of treatment. Animal experimental studies [66] showed that TONGQIAO HUOXUE DECOCTION can reduce the ratio of LC3II/LC3I and Beclin1 protein in CA1 area of VD rats. TONGQIAO HUOXUE DECOCTION can reduce the content of AchE and increase the content of ChAT in the hippocampus of VD rats [67]. Its regulation of the central cholinergic system may be one of the reasons for promoting the recovery of learning and memory in rats. The therapeutic effect of TONGQIAO HUOXUE DECOCTION onVD rats may be related to the up-regulation of the Ca2+/CaMKII/CREB pathway [67]. YQHXD can also significantly increase the content of cAMP and PKA in the serum of VD rats [68], significantly reduce the apoptosis rate of neurons in the hippocampal CA1 area, and increase the end-field excitatory postsynaptic potential 1h after hippocampal High Frequency Stimulation (HFS) (fEPSP) [69]. These studies have provided clinical evidence for TONGQIAO HUOXUE DECOCTION treatment of VD.

Post-Stroke Depression (PSD) 

PSD is one of the most common complications of cerebrovascular disease. The main manifestations are depression, loss of interest, loss of appetite, fatigue, slow thinking, pessimism and despair after stroke, and even suicide attempts and behaviors [70]. In recent years, the incidence of PSD has increased year by year. A large sample study conducted in Italy [71] indicates that the incidence of PSD is about 36%, and the incidence of mild depression is about 80%. Related studies conducted in China have found that the incidence of PSD in patients is about 41.8% [72]. The specific pathogenesis of PSD is currently unclear. The main theories include elevated monoamine system [73], abnormal Hypothalamus-Pituitary-Adrenal (HPA) axis [74], rupture of the prefrontal-subcortical circuit [75], neuroplasticity and the neurotransmission of glutamate [76] and excess pro-inflammatory cytokines [77]. However, Chinese medicine's understanding of PSD is not that complicated. Chinese medicine believes that PSD belongs to the category of “stagnation syndrome” and the pathogenesis is qi stagnation and blood stasis. The location of the disease is often in the brain and kidney [78] and the disease is mostly based on deficiency and excess. Among them, qi stagnation and blood stasis are the basic pathogenesis of the disease. Based on the three aspects of blood stasis, heart, and brain, TONGQIAO HUOXUE DECOCTION exactly corresponds to the pathogenesis of PSD, so TONGQIAO HUOXUE DECOCTION can be used in the treatment of this disease. A clinical trial conducted by Chu Caiyun [79] found that TONGQIAO HUOXUE DECOCTION can significantly improve the HAMD score of PSD patients, and its effect is better than that of fluoxetine hydrochloride (Prozac) group, which is consistent with the results of Liu Wei [80] and Zhang Yunxing [81]. Zhan Cuiqin et al., [82] found that in addition to significantly reducing BRMS and HAMD scores, TONGQIAO HUOXUE DECOCTION can also affect patients’ serum interleukin-4 (IL-4), interleukin-1β (IL-1β) and tumor necrosis factor- α (TNF-α) all had a significant effect. Kang et al., [83] found that increased levels of IL-6 and IL-18 after stroke are associated with depression. A systematic review carried out in 14 years [84] proved that anti-inflammatory treatment can reduce the symptoms of depression. These evidences suggest that the treatment of PSD by TONGQIAO HUOXUE DECOCTION may be related to anti-inflammatory response. Animal experiments [78] found that after high-dose TONGQIAO HUOXUE DECOCTION treatment, the Brain-Derived Neurotrophic Factor (BDNF) count in the hippocampal dentate gyrus of rats was higher than that in the model group (P<0.05). It is suggested that the effect of TONGQIAO HUOXUE DECOCTION on the expression of BDNF in the hippocampal dentate gyrus may be one of the factors that can improve the behavior of PSD rats.

OTHERS

In addition to the diseases mentioned above, TONGQIAO HUOXUE DECOCTION can also have a beneficial effect on other diseases. Such as stasis headache [85], sudden deafness [86], type 2 diabetes [87], diabetic optic neuropathy [88], oral lichen planus [89] and other diseases.

DISCUSSION

Although there are many studies confirming the therapeutic role of TONGQIAO HUOXUE DECOCTION in diseases, these studies have obvious limitations. 1 at present, the research of TONGQIAO HUOXUE DECOCTION is mainly concentrated in the field of vascular diseases, and the number of studies on other diseases is relatively small. 2 The research of TONGQIAO HUOXUE DECOCTION is mainly based on clinical research, and the number of experimental studies on the treatment mechanism is limited. This makes the mechanism of TONGQIAO HUOXUE DECOCTION treatment not clearly understood, and ultimately directly affects the secondary development of TONGQIAO HUOXUE DECOCTION. 3 TONGQIAO HUOXUE DECOCTION related clinical studies are of poor quality. These studies have basically never used blinding (including single-blind and double-blind) and lack of multi-center joint and double-blind randomized controlled trials to verify. 4 TONGQIAO HUOXUE DECOCTION -related clinical research includes fewer indicators for evaluation, and some include more subjective evaluation indicators (such as efficiency indicators), which is not conducive to a more comprehensive and objective evaluation of its efficacy. 5 TONGQIAO HUOXUE DECOCTION related research is mainly published in Chinese. Up to now, CNKI database (https://www.cnki.net/), has published 872 articles related to TONGQIAO HUOXUE DECOCTION, but PubMed database (https://pubmed.ncbi.nlm.nih.gov/) there are only 4 items. This suggests that the TONGQIAO HUOXUE DECOCTION research may have language publication bias. 6 TONGQIAO HUOXUE DECOCTION -related studies rarely mention adverse events, and it is impossible to evaluate the safety of TONGQIAO HUOXUE DECOCTION in the treatment process. Therefore, the treatment of TONGQIAO HUOXUE DECOCTION on cerebrovascular diseases needs more rigorous clinical research to verify. In addition, more detailed research on effective mechanisms must be carried out in a timely and effective manner.

DISCLOSURE

No conflicts of interest in this work.

FUNDING

This study was funded by the General Project of National Natural Science Foundation of China (81874416) and Open Fund for First-Class Disciplines of Integrated Chinese and Western Medicine at Hunan University of Traditional Chinese Medicine (2018ZXYJH36).

REFERENCES

  1. Zhong D-Y, Li H-Y, Li L, Ma R-M, Jiang C-T, et al. (2020) Effect of Tongqiao Huoxue Decoction Combined with Western Medicine on Ischemic Stroke: A Systematic Review. Evidence-Based Complementary and Alternative Medicine 2020: 8877998.
  2. Qingwei C, Zuoying Y, Shengjuan Z (2020) Effects of Tongqiao Huoxue Decoction on neurological function and quality of life in patients with acute cerebral hemorrhage. Chinese Journal of Traditional Chinese Medicine 2020: 1-9.
  3. Daopei Z, Feixiang L, Weitao W (2020) Effects of Jiawei TongqiaoHuoxue Decoction on Circulatory Blood Flow and Wall Shear Force of Vertebrobasilar Artery Prolongation and Expansion Syndrome of Blood Stasis Blocking Collateral Syndrome. Chinese Journal of Experimental Pharmacology 26: 35-41.
  4. Fenglin D (2020) Efficacy of TongqiaoHuoxue Decoction in the treatment of vascular dementia and its effect on blood lipids and homocysteine. Journal of Changchun University of Traditional Chinese Medicine 36: 309-311.
  5. Shixi L, Tao H (2020) Efficacy of BuzhongYiqi Decoction and TongqiaoHuoxue Decoction after treatment of circulatory ischemic vertigo and changes in TCD and serum ox-LDL and CML levels. Chinese Medicinal Materials 43: 224 -228.
  6. Wenzhi W, Bin J, Haixin S (2017) Prevalence, Incidence and Mortality of Stroke in China: Results from a Nationwide Population-Based Survey of 480,687 Adults. Circulation 135: 759-771.
  7. Gulati P, Singh N, Muthuraman A (2014) Pharmacologic evidence for role of endothelial nitric oxide synthase in neuroprotective mechanism of ischemic postconditioning in mice. Journal of Surgical Research 188: 349-360.
  8. Junping P (2017) Study on the efficacy and safety of the clinical treatment model of acute ischemic cerebrovascular disease in cerebral angiography. The Digest of World Latest Medical Information 17: 12-14.
  9. Lin W (2017) Clinical study of arterial thrombolysis combined with interventional methods for the treatment of elderly patients with acute cerebrovascular occlusion. Modern Diagnosis and Treatment 28: 1872-1873.
  10. Hu J, Pang Ws, Han J, Zhang K, Zhang J-Z, et al. (2018) GualouGuizhi decoction reverses brain damage with cerebral ischemic stroke, multi-component directed multi-target to screen calcium-overload inhibitors using combination of molecular docking and protein–protein docking. Journal of Enzyme Inhibition and Medicinal Chemistry 33: 115-125.
  11. Nanfang C, Feng T (2013) The pathogenesis of blood stasis and early treatment of blood stasis in apoplexy[J]. China Emergency in Traditional Chinese Medicine 22: 1668-1669.
  12. Keji C, Lianda L, Weiliang W (2005) Study on Blood Stasis Syndrome and Activating Blood to Remove Stasis. Journal of Integrated Traditional Chinese and Western Medicine Cardio-Cerebrovascular Disease 3: 1-2.
  13. Dayuan Z, Lan L, Chengting J, Yihui D (2019) Net Meta-analysis of 6 kinds of traditional Chinese medicine for promoting blood circulation and removing blood stasis combined with western medicine in the treatment of ischemic stroke. Journal of Hunan University of Traditional Chinese Medicine 39: 1114-1119.
  14. Yali L, Jian G, Weijuan S, Yanjie B, Ming Z, et al. (2020) Efficacy of TongqiaoHuoxue Decoction in the treatment of cognitive impairment after stroke. Chinese General Practice 18: 1560-1576.
  15. Sufang H (2020) Analysis of the effect of Tongqiao Huoxue Decoction on patients with cerebral infarction and its influence on neurological deficit score. Electronic Journal of Integrated Traditional Chinese and Western Medicine Cardiovascular Diseases 8: 170-171.
  16. Qiwen H, Feng T, Xuewen W, Yali L (2020) Effects of electroacupuncture combined with TongqiaoHuoxue Decoction on serum Copeptin and BNP expression and perfusion of infarct center and nearby tissues in patients with acute cerebral infarction. Lishizhen Medicine and Materia Medica Research 31: 1143-1146.
  17. Yong D, Gesheng W, Shumin Z (2020) Improving effect of Tongqiaohuoxue Decoction on brain injury in mice and its mechanism. Shandong Medicine 60: 48-52.
  18. Ying J (2016) Effects of TongqiaoHuoxue Decoction on neurotransmitters in rats with ischemic stroke. Chinese Journal of Clinical Pharmacology 32: 1307-1310.
  19. Yanju L, Fang JF, Junde C (2020) Clinical efficacy of TongqiaoHuoxue Decoction combined with conventional treatment on patients with cognitive dysfunction in acute ischemic stroke. Chinese Patent Medicine 42: 1959-1962.
  20. Chen S, Zeng L, Hu Z (2014) Progressing haemorrhagic stroke: categories, causes, mechanisms and managements. J Neurol 261: 2061-2078.
  21. Unnithan AKA, Mehta P (2020) Hemorrhagic Stroke. StatPearls Publishing, USA.
  22. Zhongying Z (2007) Traditional Chinese Medicine. Beijing: China Press of Traditional Chinese Medicine, China.
  23. Weixian P (2015) Probing into the treatment of hemorrhagic stroke by stage differentiation [J]. Chinese Emergency in Traditional Chinese Medicine 24: 468-470.
  24. Hongjian Y, Qiang S, Yunfeng Y (2019) Clinical study of ShilongQingxue Granules combined with edaravone in the treatment of hypertensive cerebral hemorrhage. Modern Medicine and Clinics 34: 2343-2346.
  25. Jianguo Q, Ye X, Ruiyu H (2019) Correlation analysis of serum CCCK-18 level and prognosis in patients with acute hypertensive cerebral hemorrhage. Journal of Brain and Nervous Diseases 27: 479-482.
  26. Peilun L, Wenhao J, Yingxin C (2019) Application of airway clearing plan based on PDCA circulation management model in ICU patients with cerebral hemorrhage. Qilu Journal of Nursing 25: 87-89.
  27. Xi G, Keep RF, Hoff JT (2006) Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurology 5: 53-63.
  28. Zhiling N, Teng Z (2012) The application of the method of promoting blood circulation to remove blood stasis in the acute phase of hemorrhagic stroke. Chinese Journal of Traditional Chinese Medicine 21: 1449-1450.
  29. Huijuan G, Yongqin H, Hongwei W (2005) Clinical study of hemorheological changes in patients with acute cerebral hemorrhage. Journal of Microcirculation 15: 48-51.
  30. Kang DW, Han MK, Kim HJ, Yun SC, Jeon SB, et al. (2012) New ischemic lesions coexisting with acute intracerebral hemorrhage. Neurology 79: 848-855.
  31. Gregoire SM, Charidimou A, Gadapa N, Dolan E, Antoun N, et al. (2011) Acute ischaemic brain lesions in intracerebral haemorrhage: multicentre cross-sectional magnetic resonance imaging study. Brain 134: 2376-2386.
  32. Menon RS, Burgess RE, Wing JJ, Gibbons MC, Shara NM, et al. (2012) Predictors of highly prevalent brain ischemia in intracerebral hemorrhage. Annals of Neurology 71: 199-205.
  33. Ziai WC (2013) Hematology and inflammatory signaling of intracerebral hemorrhage. Stroke 44: 74-78.
  34. Chen B, Zhao J, Zhang S, Wu W, Qi R (2012) Aspirin inhibits the production of reactive oxygen species by down-regulating Nox4 and inducible nitric oxide synthase in human endothelial cells exposed to oxidized low-density lipoprotein. J Cardiovasc Pharm 59: 405-412.
  35. Chen QQ, Liu WL, Guo X, Li YJ, Guo ZG (2007) Biphasic effect of aspirin on apoptosis of bovine vascular endothelial cells and aspirin on apoptosis of bovine vascular endothelial cells and its molecular mechanism. ActaPharmacol Sin 28: 353-358.
  36. Jiajie L, Zhen W, Li E (2017) Effects of panax notoginseng saponins combined with dual antiplatelet drugs on human umbilical vein endothelial cell injury and endothelial platelet adhesion. Pharmacology and Clinics of Chinese Materia Medica 33: 99-102.
  37. Shuo W, Zhenjie W, Feng Z (2011) Experimental study of the protective effect of Danshensu on oxidative stress injury of vascular endothelial cells. Modern Journal of Integrated Traditional Chinese and Western Medicine 20: 2493-2494.
  38. Min Y, Jiagang D, Erwei H, Xiliu Z, Hailing O, et al. (2013) Effects of peach kernels on endothelial cell apoptosis and related protein expression in rats with blood circulation disorders. Chinese Journal of Experimental Formulas 19: 178-182.
  39. Jinyi C, Lu L, Jialin D, Yongwu H, Yi Q, et al. (2019) Effects of Astragalus and Safflower Compatibility on Angiogenesis and Cav-1/VEGF Signaling Pathway in Rats after Cerebral Ischemia. Modern Biomedicine Progress 19: 1016-1019.
  40. Na L, Xue Z, Wenting F, Jinlian L, Yebin L, et al. (2019) Effects of red peony root, white peony root, paeoniflorin and paeoniflorin on hemorheology and vascular endothelial function in rats with acute blood stasis syndrome. Global Chinese Medicine 12: 1302-1307.
  41. Niuniu G, Yi M, Ru L, Chenyi Z (2017) Clinical application of promoting blood circulation and removing blood stasis drugs in acute phase of hemorrhagic stroke. Clinical Journal of Chinese Medicine 9: 140-142.
  42. Qingwei C, Zuoying Y, Shengjuan Z, Lemiao L (2020) Effects of TongqiaoHuoxue Decoction on neurological function and quality of life in patients with acute cerebral hemorrhage. Chinese Journal of Traditional Chinese Medicine 1-9.
  43. Yumei J (2019) Effects of Jiawei TongqiaoHuoxue Decoction combined with Xingnaojing injection on neurological function and quality of life in patients with acute cerebral hemorrhage. Henan Medical Research 28: 2241-2242.
  44. Gijn J, Kerr RS, Rinkel GJ (2007) Subarachnoid haemorrhage. Lancet 369: 306-318.
  45. Pujari R, Hutchinson PJ, Kolias AG (2018) Surgical management of traumatic brain injury. Journal of Neurosurgical Sciences 62: 584-592.
  46. Rinkel GJ (2016) Management of patients with aneurysmal subarachnoid hemorrhage. CurrOpinNeurol 29: 37-41.
  47. Eisenberg HM, Gary HE, Aldrich EF, Saydjari C, Turner B, et al. (1990) Initial CT findings in 753 patients with severe head injury. A report from the NIH Traumatic Coma Data Bank. Journal of Neurosurgery 73: 688- 698.
  48. Macdonald RL, Pluta RM, Zhang JH (2007) Cerebral vasospasm after subarachnoid hemorrhage: the emerging revolution. Nature Clinical Practice Neurology 3: 256-263.
  49. Modi N, Agrawal M, Sinha VD (2016) Post-traumatic subarachnoid hemorrhage: A review. Neurology India 64: 8.
  50. Dai Z, Deng X, Zhang Z (2012) MRI study of deep cerebral veins after subarachniod hemorrhage in rabbits. Chinese Journal of Clinical Anatomy 30: 176-180.
  51. Friedrich B, Müller F, Feiler S, Schöller K, Plesnila N (2012) Experimental subarachnoid hemorrhage causes early and long-lasting microarterial constriction and microthrombosis: an in-vivo microscopy study. Journal of Cerebral Blood Flow and Metabolism 32: 447-455.
  52. El Otmani H, Moutaouakil F, Fadel H, Slassi I (2012) Subarachnoid hemorrhage induced by cerebral venous thrombosis. Journal des Maladies Vasculaires 37: 323-325.
  53. Shad A, Rourke TJ, Jahromi AH, Green AL (2008) Straight sinus stenosis as a proposed cause of perimesencephalic non-aneurysmal haemorrhage. Journal of Clinical Neuroscience 15: 839-841.
  54. Jiarui X, Hongfa S, Qingxuan W (2002) Prevention and treatment of TongqiaoHuoxue Decoction on delayed cerebral vasospasm in dogs. Chinese Journal of Clinical Neurosurgery 2002: 49-50.
  55. Jiarui X, Benhan W, Chuanzhi D (2005) Clinical effect of TongqiaoHuoxue Decoction on patients with delayed ischemic brain damage after subarachnoid hemorrhage. Chinese Journal of Cerebrovascular Disease 2005: 212-214.
  56. Changya L, Xuebin H (2018) The mechanism of TongqiaoHuoxue Decoction on early brain injury of subarachnoid hemorrhage. Lishizhen Medicine and Materia Medica Research 29: 2443-2444.
  57. Zebiao X, Zhenyuan H, Weibin L (2014) Therapeutic effect of TongqiaoHuoxue Decoction on patients with subarachnoid hemorrhage and cerebral vasospasm after acute craniocerebral injury. Journal of Integrated Traditional Chinese and Western Medicine 6: 10-12.
  58. Jiarui X, Chuanzhi D, Qiujing W (2006) Experimental study of TongqiaoHuoxue Decoction in preventing delayed cerebral vasospasm. Practical Medical Journal 2006: 1477-1479.
  59. World Health Organization (2012) Dementia A Public Health Priority. World Health Organization, Geneva, Switzerland.
  60. Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, et al. (2011) Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke 42: 2672-2713.
  61. Liu CL, Chen H, Jiang Y, Tu PF, Zhong M, et al. (2013) Effects of echinacoside on extracellular acetylcholine and choline levels of hippocampus and striatum of cerebral ischemia rats. ActaPharmaceutica Sinica 48: 790-793.
  62. Kril JJ, Patel S, Harding AJ, Halliday GM (2002) Patients with vascular dementia due to microvascular pathology have significant hippocampal neuronal loss. Journal of Neurology Neurosurgery and Psychiatry 72: 747-751.
  63. Chinese Medical Journal (2019) Guidelines for the diagnosis and treatment of vascular cognitive impairment in China in 2019. Chinese Medical Journal 2019: 2737-2744.
  64. Fenglin D (2020) Efficacy of TongqiaoHuoxue Decoction in the treatment of vascular dementia and its effect on blood lipids and homocysteine. Journal of Changchun University of Traditional Chinese Medicine 36: 309-311.
  65. Jinghao L, Xiaoqiong Z, Dongqiao L (2020) Meta-analysis of the efficacy and safety of Tongqiaohuoxue Decoction in the treatment of vascular dementia. Journal of Practical Traditional Chinese Internal Medicine 34: 55-61.
  66. Yufen W, Zheyi Z, Linglu D (2019) Effects of TongqiaoHuoxue Decoction on autophagy-related proteins LC3 and Beclin-1 in hippocampal CA1 area of vascular dementia rats. Liaoning Journal of Traditional Chinese Medicine 46: 1547- 1550.
  67. Xinming W (2016) Based on Ca~(2+)-CaMKII-CREB pathway to study the mechanism of TongqiaoHuoxue Decoction on rats with vascular dementia. Anhui Medical University.
  68. Yufen W, Changjun L, Linglu D (2016) Regulation of Tongqiaohuoxue Decoction on the expression of cAMP and PKA in vascular dementia rats. Journal of Rehabilitation 26: 40-49.
  69. Bingxin W, Changjun L, Guocheng L (2018) Effects of TongqiaoHuoxue Decoction on learning and memory ability and hippocampal synaptic plasticity in vascular dementia rats. Journal of Liaoning University of Traditional Chinese Medicine 20: 28-31.
  70. Wu C, Zhang J, Chen Y (2015) Study on the behavioral changes of poststroke depression rat model Exp Ther Med 10: 159-163.
  71. Paolucci S, Gandolfo C, Provinciali L, Torta R, Toso V (2006) The Italian multicenter observational study on post - stroke depression (DESTRO). J Neurol 253: 556-5562.
  72. Shuhua YU, Lidong W (2007) Analysis of clinical characteristics of 92 cases of post-stroke depression. Journal of Regional Anatomy and Surgery 16: 41.
  73. Li W, Ling S, Yang Y, Hu Z, Davies H, et al. (2014) Systematic hypothesis for post-stroke depression caused inflammation and neurotransmission and resultant on possible treatments. Neuro endocrinol Lett 35: 104-109.
  74. Aström M, Olsson T, Asplund K (1993) Different linkage of depression to hypercortisolism early versus late after stroke: A 3-year longitudinal study. Stroke 24: 52-57.
  75. Taylor WD, Aizenstein HJ, Alexopoulos GS (2013) the vascular depression hypothesis: mechanisms linking vascular disease with depression. Mol Psychiatry 18: 963-974.
  76. Noonan K, Carey LM, Crewther SG (2013) Meta-analyses indicate associations between neuroendocrine activation, deactivation in neurotrophic and neuroimaging markers in depression after stroke. J Stroke Cerebrovasc Dis 22: 124-135.
  77. Spalletta G, Bossù P, Ciaramella A, Caltagirone C, Robinson RG (2006) The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines. Mol Psychiatry 11: 984-91.
  78. Zheyi Z, Nannan Y, Linglu D (2019) Effects of TongqiaoHuoxue Decoction on hippocampal behavior and BDNF of hippocampal dentate gyrus in rats with post-ischemic stroke depression[J].Lishizhen Medicine and Materia Medica Research 30: 2571-2574.
  79. Clinical study of tongqiao huoxue decoction and mahuang fuzixixin decoction in the treatment of post-stroke depression (blood stagnation syndrome). Nanjing University of Traditional Chinese Medicine, Nanjing, China.
  80. Liu Wei (2007) Clinical study of tongqiao huoxue decoction on post-stroke depression. Hunan University of Traditional Chinese Medicine, Nanjing China.
  81. Yuxing Z (2016) Ditan Decoction combined with TongqiaoHuoxue Decoction in the treatment of 30 cases of post-stroke depression. Yunnan Journal of Traditional Chinese Medicine and Materia Medica 37: 89-90.
  82. Cuiqin Z, Qianyun Z (2019) Jiawei tongqiao huoxue decoction combined with valproate in the treatment of bipolar disorder manic episode. Journal of Changchun University of Traditional Chinese Medicine, Nanjing China 35: 1080-1084.
  83. Kang HJ, Bae KY, Kim SW, Kim JT, Park MS, et al. (2016) Effects of interleukin-6, interleukin-18, and statin use, evaluated at acute stroke, on post-stroke depression during 1-year follow-up. Psychoneuroendocrinology 72: 156-160.
  84. Kohler O, Benros ME, Nordentoft M, Farkouh ME, Iyengar RL, et al. (2104) Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA psychiatry 71: 1381-1391.
  85. Taohong Z (2020) Clinical curative effect analysis of tongqiao huoxue decoction in the treatment of internal trauma and blood stasis headache. Shenzhen Journal of Integrated Traditional Chinese and Western Medicine 30: 48-49.
  86. Wei C, Zhongnan HU, Zhaojun T (2019) Analysis of the effect of tongqiao huoxue decoction on young and middle-aged patients with sudden deafness and changes in hemorheology. Information on Traditional Chinese Medicine 36: 45-48.
  87. Yingchun W, Xueming H, Xiaohui Z (2020) Clinical effect of acupuncture combined with tongqiao huoxue decoction in the treatment of type 2 diabetes with hyperlipidemia. Inner Mongolia Traditional Chinese Medicine 39: 135-137.
  88. Jie Q, Ji Z, Jiangen S (2018) The protective effect of tongqiao huoxue decoction combined with buyang Huanwu decoction on the optic nerve of diabetic patients and its mechanism. Sichuan Traditional Chinese Medicine 36: 103-106.
  89. Qiaoqun D, Fangping S, Yin W (2019) Clinical efficacy analysis of tongqiao huoxue decoction combined with narrow-band UV in the treatment of oral lichen planus. Chinese Journal of Traditional Chinese Medicine 37: 337-339.

Citation: Zhong D-Y, Deng Y-H (2020) Application of Tongqiao Huoxue Decoction in the Treatment of Cerebrovascular Disease?A Review. J Altern Complement Integr Med 6: 139.

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