Mechanism of Zhigancao Tang Against Coronary Heart Disease： An Exploration Based on Thought of "Four in One" / 中国实验方剂学杂志

"Four in one" is a research idea of identifying the classic prescriptions from the following four dimensions： "nature， location， tendency， and syndrome". The multi-dimensional analysis of the mechanism of classic prescription Zhigancao Tang in treating coronary heart disease helps to understand the syndrome differentiation and treatment thoughts of ZHANG Zhong-jing. The coronary heart disease results from deficiency. The efficacy of Zhigancao Tang in treating coronary heart disease can be elucidated from the "nature，location，tendency， and syndrome". In terms of nature， Zhigancao Tang is pungent and sweet in flavor and warm in property， with the sweet responsible for tonifying deficiency， the pungent for dispersing Yang， resolving Yin， and eliminating surplus pathogen， and the warm for moving Yangqi， nourishing blood， and promoting blood circulation. In terms of location， Zhigancao Tang mainly acts on vessels for restoring the normal circulation of blood in the vessels and improving coronary artery stenosis and the resulting ischemia and anoxia. In terms of tendency， Zhigancao Tang tends to affect the upper and inner parts of the body to tonify deficiency in Zangfu organs， promote fluid production， nourish nutrient blood， and dissipate cold simultaneously， thus alleviating chest impediment. In terms of syndrome， Zhigancao Tang is applicable to fluid exhaustion with blood dryness and Yin-yang-qi-blood deficiency syndrome， manifested as regularly or irregularly intermittent pulse and severe palpitation. Zhigancao Tang has been widely used for the treatment of over 70 diseases classified into 10 systems， especially the cardiovascular diseases， in traditional Chinese medicine （TCM） and western medicine. As the “one” of “four in one”， Zhigancao Tang is composed of multiple Chinese herbs and its therapeutic effect is superior to the sum of its parts. It ameliorates the coronary heart disease by resisting inflammation， protecting against ischemia-reperfusion injury， adjusting the ion channels of myocardial cells， and participating in atrial remodeling and hematopoiesis. Its mechanism and clinical efficacy in the treatment of coronary heart disease have been verified by clinical and experimental studies. The utilization of the thought of "four in one" to analyze classical prescriptions enables the combination of prescriptions with syndromes， which is of great significance to the clinical application and modern development of classical prescriptions.

Effect of two Chinese medicinal compounds, blood-activating and water-draining medicine, on tumor necrosis factor α and nuclear factor κ B expressions in rats with intracerebral hemorrhage / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of blood-activating Chinese medicinal compounds and water-draining Chinese medicinal compounds on tumor necrosis factor alpha (TNF-α) and nuclear factor kappaB (NF-κ B) expressions in rats with intracerebral hemorrhage (ICH) at the acute stage, and to monitor their therapeutic effect and mechanism of action on inflammation and cerebral edema.</p><p><b>METHODS</b>A rat model of cerebral hemorrhage was achieved by injecting autologous arterial blood into the caudate nucleus. A total of 168 rats were randomly divided into 4 groups: blood-activating medicine group (n=42), water-draining medicine group (n=42), sham operated group (n=42), and the model group (n=42). A series of brain samples were obtained at days 1, 3 and 5 after ICH from rats in all groups. Protein expression levels of TNF-α and NF-κ B were measured by immunohistochemical staining and gene expression levels of TNF-α and NF-κ B were measured by real-time fluorescent PCR.</p><p><b>RESULTS</b>Compared to the sham operated group, protein expression levels of TNF-α and NF-κ B in the model group significantly increased (P<0.01). Protein and gene expressions of TNF-α from the blood-activating medicine group and water-draining medicine group significantly decreased when compared to those in the model group P<0.05). Meanwhile, compared to the model group, the expression of NF-κ B in the blood-activating medicine group significantly decreased (P<0.05), while expression of NF-κ B in the water-draining medicine group did not differ (P>0.05).</p><p><b>CONCLUSIONS</b>Blood-activating Chinese medicinal compounds and water-draining Chinese medicinal compounds can alleviate inflammation of peripheral tissue and cerebral edema. However, the blood-activating Chinese medicinal compounds were more effective than the water-draining Chinese medicinal compounds. The possible effective mechanism may be by means of inhibiting the activation of NF-κ B so as to suppress the transcription of target genes including gene expression of TNF-α.</p>

Effects of herbs capable of activating blood circulation or inducing diuresis on the expressions of tumor necrosis factor-alpha, nuclear factor-kappaB, and aquaporin-4 in rats with intracerebral hemorrhage / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effects of herbs capable of activating blood circulation or inducing diuresis on the expressions of tumor necrosis factor-alpha (TNF-alpha), nuclear factor-kappaB (NF-kappaB), and aquaporin-4 (AQP-4) in rats with intracerebral hemorrhage (ICH), and to study their possible mechanisms.</p><p><b>METHODS</b>The ICH rat model was established by injecting autologous arterial blood into the right caudate nucleus. The 168 male rats were randomly divided into four groups, the sham-operative group, the model group, the blood activating group, and the diuresis inducing group, 42 in each group. Chinese compound decoction (consisting of 0.2 g rhubarb, 0.02 g leech, and 0.3 g notoginseng in each milliliter decoction) was given to rats in the blood activating group by gastrogavage at the dose of 10 mL/kg, once daily. Chinese compound decoction (consisting of 0.2 g poria, 0.2 g water plantain tuber, and 0.2 g acori graninei in each milliliter decoction) was given to rats in the diuresis inducing group by gastrogavage at the dose of 10 mL/kg, once daily. 4.0 mL/kg normal saline was given to rats in the model group and the sham-operative group by gastrogavage, once daily. A series of brain samples were obtained on the 1st, 3rd, and 5th day, respectively. The mRNA and protein expressions of TNFalpha, NF-kappaB p65, and AQP-4 were determined by immunohistochemical staining and Real-time fluorescent quantitative PCR respectively.</p><p><b>RESULTS</b>After ICH, TNF-alpha, NF-KB, and AQP-4 protein positive cells in the brain tissue and their protein and mRNA expressions significantly increased in rats of the model group at each time point when compared with the sham-operative group (P < 0.01, P < 0.05). The gene and protein expressions of TNF-alpha and AQP-4 significantly decreased in the blood activating group and the diuresis inducing group at each time point when compared with the model group (PP < 0.05). The expression of NF-kappaB p65 in the blood activating group obviously decreased when compared with the model group (P < 0.05), but there was no statistical difference in the NF-KB expression when compared with the diuresis inducing group (P > 0.05). Compared with the model group, the water content of the brain tissue decreased to some degree in the blood activating group and the diuresis inducing group at each time point. There was statistical difference between the blood activating group and the diuresis inducing group (P < 0.05).</p><p><b>CONCLUSIONS</b>Chinese herbs capable of activating blood circulation or inducing diuresis could inhibit the release of TNF-alpha, down-regulate the expression of AQP-4, and alleviate the brain edema around hematoma. But the action strength and the effect links were different.</p>