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Objective:To evaluate the clinical effect of treatment of activating blood and removing blood stasis, invigorating the spleen and soothing the liver for the patients with gastric collateral stasis syndrome and chronic atrophic gastritis (CAG).Methods:Randomized controlled trial. A total of 68 CAG patients admitted to the Huairou Hospital of Traditional Chinese Medicine from January 2018 to January 2021 who met the selection criteria were divided into 2 groups according to the random number table method, with 34 in each group. The control group received conventional western medicine treatment, such as inhibition of acid, protecting the gastric mucosa, and the observation group was treated with Traditional Chinese Medicine (TCM) herbal prescription of activating blood and removing blood stasis, invigorating the spleen and soothing the liver. Both groups were treated for 12 weeks. TCM symptom scores were performed before and after treatment. The serum level of pepsinogen Ⅰ(PG Ⅰ), pepsinogen Ⅱ (PGⅡ) were detected by ELISA, and the PG Ⅰ/PG Ⅱ ratio was calculated. Gastroscopic biopsy was performed to observe the changes of intestinal metaplasia of gastric mucosa and glandular atrophy, and to evaluate the clinical efficacy.Results:The total responsive rate was 85.3% (29/34) in the study group and 58.8% (20/34) in the control group. There was significant difference between the two groups ( χ2=9.35, P=0.030). After treatment, the scores of stomachache, fullness of feeling in the observation group were significantly lower than those in the control group ( t=2.97, 3.80, P<0.05). After treatment, the level of serum PG Ⅰ[(76.21 ± 17.35) mg/L vs. (66.8 ± 18.77) mg/L, t=2.15] and PG Ⅰ/PG Ⅱ [(4.67 ± 0.99) vs. (3.90± 1.25), t=2.81] in the study group were significantly higher than those in the control group ( P<0.05), and PG Ⅱ [(16.36 ± 1.85) mg/L vs. (17.42 ± 2.05) mg/L, t=2.24] was significantly lower than that of the control group ( P<0.05). After treatment, intestinal metaplasia and glandular atrophy was significantly more improved or reversed than those in the control group ( χ2=20.67,9.33, P<0.05). Conclusion:The methods of activating blood and removing blood stasis, invigorating the spleen and soothing the liver can reverse the precancerous lesions of patients with gastric collateral stasis syndrome of chronic atrophic gastritis and have a good prognosis.
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Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-β/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.
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Child , Humans , Female , Primary Ovarian Insufficiency/drug therapy , Phosphatidylinositol 3-Kinases/metabolism , Vascular Endothelial Growth Factor A , Medicine, Chinese Traditional , NF-kappa B , KidneyABSTRACT
Occupational silicosis features as irreversible pulmonary fibrosis, which is caused by long-term inhalation of free silica dust. The pathogenesis of silicosis is complex and there is no cure at present. Traditional Chinese medicine classifies silicosis fibrosis into the category of diseases as "pulmonary paralysis" and "pulmonary arthralgia", and its treatment is based on promoting blood circulation and activating qi. Traditional Chinese medicine for activating blood circulation is one of the commonly used medications, which has the effects of anti-oxidation, anti-inflammation, anti-fibrosis and immunomodulation, and has broad application prospect in the prevention and treatment of silicosis. At present, animal experiments and clinical studies have been carried out using the single Chinese herbs extracts that could activate blood circulation such as Salvia miltiorrhiza, Ligusticum chuanxiong Hort., Panax notoginseng, Curcuma longa L., peach kernel and Carthamus tinctorius L. as well as their compound herbs for the prevention and treatment of silicosis. The mechanisms of anti-pulmonary fibrosis and the efficacy and safety of treating silicosis and its complications were explored. There are also scholars studying Salvia miltiorrhiza, Curcuma longa L. and Danhong injection, Taohong Siwu Decoction and others for prevention and treatment of pulmonary fibrosis. Additionally, network pharmacological research, analyzing potential targets and pathways, were carried out to provide scientific rationale for prevention and treatment of silicosis. However, the effectiveness of research is still uncertain, and it cannot meet the clinical needs. In the future, it is necessary to explore the application of more high-quality active components of traditional Chinese medicine monomer or mixture of activating blood circulation in the prevention and treatment of silicosis, to provide new ideas and scientific basis for the prevention and treatment of silicosis using traditional Chinese medicine.
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Heart failure with high prevalence is the endpoint of many cardiovascular diseases. Once diagnosed， patients usually need lifelong medication， which seriously affects their quality of life. The drugs commonly used to treat heart failure include angiotensin-converting enzyme inhibitors， beta-blockers， aldosterone receptor antagonists， and diuretics. However， the long-term use of those drugs can lead to side effects such as hypotension， depletion of body fluid， and electrolyte imbalance and even increase mortality. According to the theory of traditional Chinese medicine （TCM）， Qi deficiency and blood stagnation is the major cause of heart failure and when Qi is not moving， blood is not flowing. Therefore， the TCM clinical treatment of heart failure uses the Chinese medicinal materials which replenish Qi， activate blood， and dispell stasis to treat both internal cause and external symptoms. Recent studies have demonstrated that Chinese herbal medicines such as Astragali Radix， Ginseng Radix et Rhizoma， Notoginseng Radix et Rhizoma， Salviae Miltiorrhizae Radix et Rhizoma， Angelicae Sinensis Radix， as well as the compound formulas such as Buyang Huanwutang， Simiao Yongantang， Qili Qiangxin capsules， and Qishen Yiqi drops， play a significant role in the prevention and treatment of heart failure via replenishing Qi， activating blood， and dispelling stasis. Inhibition of oxidative stress and inflammatory responses， mitigation of myocardial fibrosis， improvement of calcium cycling， and protection of mitochondrial function represent the key mechanisms for the treatment of heart failure with Chinese medicinal materials. Focusing on the pathogenic mechanisms and signaling pathways of heart failure， this paper systematically describes the pharmacological effects， molecular mechanisms， and research progress in the clinical application of Chinese medicinal herbs with effects of replenishing Qi， activating blood， and dispelling stasis and their compound formulas in the prevention and treatment of heart failure， aiming to provide scientific evidence for the development and clinical use of anti-heart failure Chinese medicinal materials.
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As China is about to enter an era of deep aging， the coexistence of multiple diseases is gradually increasing. Coronary heart disease （CHD） and cognitive dysfunction also show increasing incidence year by year. The two diseases affect and cause each other， becoming the major chronic diseases harmful to the health of the elderly. It is of great clinical significance to explore the methods integrating traditional Chinese and western medicine for the prevention and treatment of the two diseases. The relationship between CHD and cognitive dysfunction in traditional Chinese medicine （TCM） was first recorded in Huangdi’s Internal Classic （Huang Di Nei Jing）. As the understanding of CHD and cognitive dysfunction is deepening， the influences of stasis and toxin on both diseases have attracted increasing attention. According to the theories of TCM， CHD and cognitive dysfunction have common points in the etiology and pathogenesis. Therefore， the theory of treating different diseases with same method provides a theoretical basis for the clinical treatment of different diseases with the same pathogenesis. Moreover， this theory conforms to the principle of integrated and individualized prevention and treatment of multi-disease coexistence in modern medicine. This paper systematically proposed that the coexistence of stasis and toxin is a major pathogenesis of CHD and cognitive dysfunction. We then explored the possible mechanisms of the blood-activating and toxin-removing method in the treatment of CHD and cognitive dysfunction based on the theory of treating different diseases with same method. The mechanisms include the regulation of ceramide metabolism， activation of silent mating-type information regulation 2 homolog 1 （SIRT1）， inhibition of pyroptosis， regulation of mitogen-activated protein kinase/nuclear factor-κB （MAPK/NF-κB） signaling pathway， inhibition of mitochondrial division， and regulation of DNA methylation. We hope this paper will provide an idea for the future research on the prevention and treatment of CHD and cognitive dysfunction with TCM.
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The important pathogenesis of knee osteoarthritis (KOA) lies in kidney deficiency and blood stasis. Therefore, Traditional Chinese Medicine (TCM) for tonifying the kidney and activating blood circulation is widely used in clinical practise with high response. The existing literature mainly focuses on single medicine for tonifying the kidney and activating blood circulation, as well as TCM compounds, such as classic prescriptions Yougui Pill, Duhuo Jisheng Decoction, which contain TCMs for tonifying the kidney and activating blood circulation, or self-made empirical prescriptions Bushen Huoxue Recipe and Bushen Tongluo Recipe, which are based on the idea of tonifying the kidney and activating blood circulation. The above TCMs mainly regulate oxidative stress response, inflammatory cytokine level, no level, lymphatic function and microcirculation Inhibit chondrocyte apoptosis, regulate cartilage metabolism, protect and repair cartilage, and inhibit matrix degrading enzymes to play a therapeutic role.
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Primary liver cancer is one of the common tumors in China， which seriously endangers human health. With the advancement in medical science and technology， some achievements have been made in the clinical treatment of liver cancer， but there is an urgent need to find a safe and effective solution for patients with advanced liver cancer. As a unique therapy in China， traditional Chinese medicine （TCM） has the characteristics of multiple targets and multiple pathways and plays a certain role in the treatment of malignancies. The present study aimed to clarify the mechanism of action of "dispelling pathogens" in the treatment of liver cancer through literature research. In TCM etiology and pathogenesis， deficient healthy Qi and exuberance of pathogenic Qi， such as phlegm， blood stasis， and toxins， lead to the development of liver cancer. The treatment should follow the principles of reinforcing healthy Qi and eliminating pathogens. It has been generally believed that tumor cell is the "pathogenic factor" and the immune function serves as the "healthy Qi". In the treatment of malignancies and the regulation of the immune function of patients， it is often advocated to reinforce healthy Qi to eliminate the accumulation. With the continuous updating of knowledge on tumors and tumor microenvironment， it is also recognized that there are "healthy Qi" and "pathogenic Qi" in the immune microenvironment of tumors. For example， the immune cells and immune factors that inhibit tumor growth can be classified as "healthy Qi" with TCM attributes， while those promoting tumor growth can be classified as "pathogenic Qi". Additionally， as proved by clinical data and experimental research， the elimination methods represented by "activating blood， resolving phlegm， and removing toxins" in the treatment of liver cancer can combat tumor cells and also regulate the "healthy Qi" and "pathogenic Qi" in the immune microenvironment of liver cancer to achieve the balance of Yin and Yang. Based on this， the present study reviewed from the TCM theory and the mechanisms of western medicine to provide theoretical support for the TCM treatment of malignancies by elimination methods and some ideas for TCM in tumor resistance.
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Stroke is the leading cause of death and disability. Therefore， it is critical to develop the approaches for improving recovery and neural repair after stroke. Recovery after stroke involves complex interrelated systems of neural repair. The whole process of neural repair requires a series of coordinated interactions， such as response of neuronal cell body to traumatic stimuli， neural stem cell proliferation and migration， axoplasmic transport of signaling molecules， construction of cytoskeleton， and formation of axonal growth cone， to achieve regeneration and growth. As a potential new target for the treatment of neurologic defects， neural remodeling has important research significance in both the specific mechanism of neural repair and the clinical treatment of neurologic defects. After brain injury， single therapy is often ineffective due to the complex mechanism of internal repair， and thus comprehensive therapy becomes the development direction to improve the brain repair. Invigorating qi and promoting blood can promote nerve function remodeling after injury through neural protection， angiogenesis， neurogenesis， loop reconstruction， and cytokine regulation， playing a key role in nerve repair after stroke. Its mechanism is associated with autophagy， immunomodulation， and microRNA regulation， which fully embodies the multi-pathway， multi-target， and overall regulation characteristics of invigorating Qi and activating blood. Therefore， it is of theoretical and guiding significance to study the brain function rehabilitation after stroke by invigorating qi and activating blood.
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Anxiety and depression are common comorbidities of coronary heart disease and are considered as independent risk factors in addition to traditional cardiovascular risk factors. Anxiety，depression and other mental abnormalities belong to the category of "depressive syndrome" of traditional Chinese medicine，which can lead to stasis of blood due to the lack of Qi flow. "Blood stasis" involves abnormal blood rheology， vascular endothelial dysfunction， chronic inflammatory response， abnormal lipid metabolism and other comprehensive pathological changes， and is the core pathogenesis of coronary heart disease in traditional Chinese medicine. "Depressive syndrome"can aggravate the development of coronary heart disease by promoting blood stasis in multiple ways. Prescriptions and herbs of promoting blood circulation and removing blood stasis can have a clinical effect by promoting blood circulation （improving physiological functions） and removing blood stasis （eliminating pathological changes）. In clinical practice， strengthening the screening of the mental and psychological status of patients with coronary heart disease and providing early and effective psychological interventions and combined Chinese and Western medicine drug treatment can significantly improve the clinical symptoms and prognosis of patients. This article was the first to put forward the academic view of "stasis caused by depression" for the first time，and discuss the modern biological research progress of "depression" in Chinese medicine that promotes blood stasis and aggravates coronary heart disease，in order to provide a basis for the subsequent development of Chinese medicine in the prevention and treatment of coronary heart disease. The aim is to provide a theoretical basis for the subsequent systematic research on the prevention and treatment of coronary heart disease with emotional abnormalities in Chinese medicine.
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Metastasis is the main cause of poor prognosis of malignant tumors， and intervention with metastasis is the key measure in the treatment of malignant tumors. Hematogenous metastasis， the most common tumor metastasis， falls into the category of "Chuanshe" in traditional Chinese medicine （TCM）， with Qi deficiency and blood stasis as the critical pathogenesis. In the fight against malignant tumors， TCM emphasizes the reinforcement of healthy Qi and the elimination of pathogenic factors， exhibiting its action advantages of multiple targets， multiple mechanisms， and multiple levels. Extensive clinical evidence has shown the exact efficacy of Chinese herbal compounds designed for invigorating Qi and activating blood in delaying the progression of tumor disease and prolonging the survival period of patients. In view of the important role of hematogenous metastasis in the prognosis of tumors， more and more studies have explored the effects and mechanisms of Chinese herbal compounds capable of invigorating Qi and activating blood in intervening in hematogenous metastasis. This paper summarized the relevant literature reports in China and abroad on the intervention of Chinese herbal compounds capable of invigorating Qi and activating blood in the hematogenous metastasis of malignant tumors， in order to provide a theoretical basis for the clinical application of Qi-invigorating and blood-activating therapy in the treatment of malignant tumors. It has been found that Chinese herbal compounds formulated for invigorating qi and activating blood are effective in hindering several key steps in hematogenous metastasis through various mechanisms， including regulating the expression of cell adhesion molecules， inhibiting extracellular matrix degradation and angiogenesis， enhancing the killing effect of immunity， and improving blood hypercoagulability and hyperviscosity. Furthermore， the combination of invigorating Qi and activating blood targets the pathogenesis essence （Qi deficiency and blood stasis， characterized by sthenia in origin and asthenia in superficiality） of malignant tumor much better. Some comparative studies have demonstrated that the anti-metastasis effect of Qi-invigorating and blood-activating therapy is significantly stronger than that of the Qi-invigorating or blood-activating therapy alone， and such combination avoids the possible risk of the metastasis of malignant tumors triggered by the use of either of them. This study has provided some reference for the current clinical application of TCM for improving the prognosis of malignant tumors.
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Angelicae Sinensis Radix excels in activating blood, but the scientific mechanism has not been systematically analyzed, thus limiting the development of the medicinal. This study employed the computer-aided drug design methods, such as structural similarity-based target reverse prediction, complex network analysis, molecular docking, binding free energy calculation, cluster analysis, and ADMET(absorption, distribution, metabolism, excretion, toxicity) calculation, and enzyme activity assay in vitro, to explore the components and mechanism of Angelicae Sinensis Radix in activating blood. Target reverse prediction and complex network analysis yielded 40 potential anticoagulant targets of the medicinal. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the targets mainly acted on the complement and coagulation cascade signaling pathway to exert the anticoagulant function. Among them, the key enzymes thrombin(THR) and coagulation factor Xa(FXa) in coagulation cascade and thrombosis were the drug targets for thromboembolic diseases. At the same time, molecular docking and cluster analysis showed that the medicinal had high selectivity for FXa. According to binding free energy score, 8 potential active components were selected for enzyme activity assay in vitro. The results demonstrated that 8 components inhibited THR and FXa, and the inhibition was stronger on FXa than on THR. The pharmacophore model of 8 active compounds was constructed, which suggested that the components had the common pharmacophore AAHH. The ADMET calculation result indicated that they had good pharmacokinetic properties and were safe. Based on target reverse prediction, complex network analysis, molecular docking and binding free energy calculation, anticoagulant activity in vitro, spatial binding conformation of molecules and targets, pharmacophore model construction, and ADMET calculation, this study preliminarily clarified the material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood from the perspective of big data, and calculated the pharmacology and toxicology parameters of the active components. Our study, for the first time, revealed that the medicinal had obvious selectivity and pertinence for different coagulation proteins, reflecting the unique effect of different Chinese medicinals and the biological basis. Therefore, this study can provide clues for precision application of Angelicae Sinensis Radix and the development of the blood-activating components with modern technology.
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Anticoagulants/pharmacology , Blood Coagulation , Drug Design , Drugs, Chinese Herbal/pharmacology , Molecular Docking SimulationABSTRACT
Derived from Curcuma plants, Curcumae Longae Rhizoma, Curcumae Rhizoma, Wenyujin Rhizoma Concisum, and Curcumae Radix are common blood-activating and stasis-resolving medicinals in clinical practice, which are mainly used to treat amenorrhea, dysmenorrhea, chest impediment and heart pain, and rheumatic arthralgia caused by blood stasis block. According to modern research, the typical components in medicinals derived from Curcuma plants, like curcumin, demethoxycurcumin, bisdemethoxycurcumin, curdione, germacrone, curcumol, and β-elemene, have the activities of hemorheology improvement, anti-platelet aggregation, anti-thrombosis, anti-inflammation, anti-tumor, and anti-fibrosis, thereby activating blood and resolving stasis. However, due to the difference in origin, medicinal part, processing, and other aspects, the efficacy and clinical application are different. The efficacy-related substances behind the difference have not yet been systematically studied. Thus, focusing on the efficacy-related substances, this study reviewed the background, efficacy and clinical application, efficacy-related substances, and "prediction-identification-verification" research method of blood-activating and stasis-resolving medicinals derived from Curcuma plants, which is expected to lay a theoretical basis for the future research on the "similarities and differences" of such medicinals based on integrated evidence chain and to guide the scientific and rational application of them in clinical practice.
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Curcuma , Curcumin , Drugs, Chinese Herbal , Plant Roots , Platelet Aggregation , RhizomeABSTRACT
Objective:To observe the effect of Tangtong formula on the expression of autophagy pathway proteins PI3K, Akt and mTOR in sciatic nerve of DPN rats, and to explore its mechanism. Methods:There were 60 male SD rats, 15 of which were randomly selected as the normal group, and the other rats were used to establish DPN model with STZ + ischemia-reperfusion method. Then they were divided into model group, Tangtong formula low-dose group and Tangtong formula high-dose group, with 15 rats in each group with random number table method. 36.67 g/kg Tangtong formula was administered by gavage in the high-dose group and 18.33 g/kg Tangtong formula was administered by gavage in the low-dose group, once a day. After 8 weeks of continuous gavage, the conduction velocity of sciatic nerve was detected. The mRNA and protein expression levels of PI3K, Akt and mTOR were detected by PCR and Western blot. The structure of sciatic nerve fibers was observed by HE staining. Results:Compared with the model group, the motor nerve conduction velocity, sensory nerve conduction velocity, muscle compound action potential and sensory nerve action potential in the low-dose Tangtong formula group and high-dose Tangtong formula group were increased ( P<0.05). The expression of PI3K mRNA(6.05±0.18, 3.36±0.29 vs. 11.57±1.93), Akt mRNA(1.26±0.13, 0.64±0.04 vs. 1.86±0.06), mTOR mRNA(1.82±0.11, 0.92±0.06 vs. 2.68±0.18) of sciatic nerve in rats of the low-dose and high-dose group were increased ( P<0.05). The expression of PI3K(0.40±0.00, 0.19±0.02 vs. 0.61±0.03), Akt(0.64±0.02, 0.45±0.01 vs. 0.83±0.02), mTOR(0.17±0.01, 0.09±0.00 vs. 0.34±0.01)of sciatic nerve in rats of the low-dose and high-dose group were increased ( P<0.05). The model group's nerve fibers were loose and swollen, myelin sheath became thin, and the axis Atresia, the neuromorphology of the low-dose and high-dose group tended to be normal, and the morphology of myelin sheath and axon were better. Conclusions:Tangtong formula could improve the conduction velocity and potential amplitude of sciatic nerve in DPN rats, reduce nerve injury and demyelinating changes, improve axon morphology and protect nerve fiber structure. Its mechanism might be related to activating PI3K/Akt/mTOR signal pathway and inhibiting excessive autophagy.
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Astragali Radix-Angelicae Sinensis Radix （AA） is a basic pair of drugs mainly targeting the syndrome characteristics of Qi and blood diseases. LI Dong-yuan's Danggui Buxuetang （DBT） is composed of AA， which is mainly used to tonify Qi and generate blood， with main indications of Qi deficiency and blood deficiency， blood heat and so on. It is favored by doctors because of its refined prescription and remarkable curative effect. However， there are many compatibility ratios of AA in different prescriptions in ancient books， and their efficacy and indications are also slightly different. This research showed that DBT also had the effect of invigorating Qi and activating blood， and the previous study of the group showed that 3∶1 compatibility ratio of the two herbs in the total amount of 36 g had more obvious effect of invigorating Qi and activating blood. By consulting the relevant literature， it was found that the drug pair had a certain effect of invigorating Qi and activating blood in various compatibility ratios such as 1∶1， 3∶1， 1∶5， 3∶2， 2∶1， 5∶1. The corresponding pharmacological effect mainly included regulating the energy metabolism of substances， regulating immune function， reducing blood viscosity， anti-oxidation stress， anti-inflammation， lowering blood lipids， lowering blood sugar， protecting heart function， protecting blood vessel wall， intervening angiogenesis， fighting against organ tissue fibrosis and so on. Regardless of the AA single-medicine's activating blood effect and the theory that "Qi circulation leads to blood circulation" or the drug pair's manifestation in modern pharmacological effects， all of these have confirmed that AA's effect of invigorating Qi and activating blood does exist， and the difference of action performance caused by different ratios of AA is closely related to dosage and proportion， which needs further study. Based on the study focusing on the effect of tonifying Qi and generating blood， it is easy to ignore the effect of invigorating Qi and activating blood， which limits the clinical application of the latter. Therefore， the tonifying Qi and activating blood circulation effect of the drug pair is reviewed in this paper， so as to provide a theoretical basis for its clinical rational drug use and related research.
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The traditional Chinese medicines(TCM) for activating blood circulation and the TCM for regulating Qi are often used in combination in clinical practice. However, their mechanisms are still unclear. The activity spectrum of targets can fuse the active components, targets and intensity of action, which provides support for the discussion of efficacy targets. The chemical components of common TCM sets for activating blood circulation and regulating Qi, as well as the negative sets not for activating blood circulation and re-gulating Qi were obtained from the database of TCM. By the similarity analysis of chemical components in TCM for activating blood circulation and DrugBank database, the predicted targets of chemical components in TCM for activating blood circulation were obtained, and the similarity value of the two was taken as the activity value of the active components and predicted targets. Then, the component-target activity value was weighted. The activity values of herb acting on the same target were fused to construct activity spectra of targets of the herbs for activating blood circulation, herbs for regulating Qi and negative herbs. The targets whose activity values of activating blood circulation and regulating Qi were higher than those of negative herbs were selected as potential targets of efficacy. Protein-protein interaction networks were constructed for topological, GO and KEGG enrichment analysis to determine the key targets of efficacy of activating blood circulation and regulating Qi. The component-target activity information collected from DrugBank database contained 4 499 compounds, 627 targets and 11 295 action relationships. The activating blood function protein-protein interaction network contained 206 nodes and 1 728 edges, while the regulating Qi function protein-protein interaction network contained 230 nodes and 986 edges. The enrichment analysis of topology, GO and KEGG showed that TCM for activating blood circulation mainly exerted its anti-inflammatory, neuroprotective and angiogenic effects on signaling cascade pathway mediated by VEGF/VEGFR2, ERK signaling pathway, calcium signaling pathway and PI3 K-AKT signaling pathway, and the key targets included mitogen activated protein kinases 3(MAPK3), proto-oncogene tyrosine-protein kinase Src(SRC), mitogen activated protein kinases 1(MAPK1), epidermal growth factor receptor(EGFR), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform(PIK3 CA), peroxisome proliferators-activated receptor gamma(PPARG), nitric oxide synthase 3(NOS3), prostaglandin G/H synthetase 2(PTGS2), matrix metalloproteinase-9(MMP9), and vascular endothelial growth factor A(VEGFA). TCM for regulating Qi mainly exerted anti-inflammatory and neuroprotective effects by acting on MAPK signaling pathway and PI3 K-AKT signaling pathway, and the key targets included mitogen activated protein kinases 8(MAPK8), SRC, mitogen activated protein kinases 14(MAPK14), and RAC-alpha serine/threonine-protein kinase(AKT1), mitogen activated protein kinases 3(MAPK3). Based on the activity spectrum of targets, the targets of the TCM for activating blood and the targets of the TCM for regulating Qi were analyzed to provide reference for the study of efficacy targets of TCM, and also provide some scientific basis for clinical application.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional , Protein Interaction Maps , Qi , Vascular Endothelial Growth Factor AABSTRACT
The traditional Chinese medicine(TCM) syndrome of blood stasis refers to blood stagnation in meridians and viscera, with the main symptoms of pain, mass, bleeding, purple tongue, and unsmooth pulse. Cardiovascular and cerebrovascular diseases are among the major chronic diseases seriously harming the health of the Chinese. Among the coronary heart disease and stroke patients, most demonstrate the blood stasis syndrome. Platelet is considered to be one of the necessary factors in thrombosis, which closely relates to the TCM syndrome of blood stasis and the occurrence of cardiovascular and cerebrovascular diseases. The clinical and laboratory research on platelet activation and aggregation has been paid more and more attention. Its purpose is to treat and prevent blood stasis syndrome. In this study, the authors analyzed the research on the dysfunctions of platelets in blood stasis syndrome, biological basis of TCM blood stasis syndrome, and the effect of blood-activating stasis-resolving prescriptions on platelets, aiming at providing a reference for exploring the mechanism of platelet intervention in the treatment of TCM blood stasis syndrome and the pathways and targets of Chinese medicine in the prevention and treatment of the syndrome.
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Humans , Blood Platelets , Coronary Disease , Medicine, Chinese Traditional , Platelet Activation , SyndromeABSTRACT
Heart failure is a complex clinical syndrome，which is the final result of compensatory failure of heart injury caused by various reasons. Long-term persistent cardiac stress leads to mitochondrial dysfunction，which in turn further damages cardiomyocytes and leads to disease progression. Timely removal of damaged mitochondria in cardiomyocytes and maintaining a good living environment of viable mitochondria is not only an effective means to protect cardiomyocytes，but also a new way to prevent and treat heart failure and ventricular remodeling. Mitochondrial quality control is a series of cellular activities for mitochondria to maintain their structural and functional stability，including oxidative stress response，regulation of mitochondrial dynamics，mitochondrial autophagy，intracellular calcium regulation and so on. Traditional Chinese medicine（TCM） mostly uses drugs of replenishing Qi and activating blood circulation in the treatment of chronic heart failure，and Qi and mitochondria are similar in function. According to TCM，the performance of the body as "static，descending and inhibitory" in the case of Qi deficiency can also be compared with the energy defect of mitochondria. The classical method of tonifying qi and activating blood circulation in TCM can be applied here. In recent years，TCM takes mitochondria as the target and carries out many related experimental studies from the point of view of myocardial energy supply. It is found that Chinese herbs for replenishing Qi and activating blood circulation can participate in regulating the quality control mechanism of intracellular mitochondria with multiple targets and links. It is proved by experiments that Chinese herbs for replenishing Qi and activating blood circulation can exert myocardial protective effect through this mechanism.
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Objective To explore the possible mechanism of activating blood circulation and removing blood stasis herbs in the treatment of endometriosis (EM) with network pharmacology approach. Methods Seven kinds of commonly used activating blood circulation and removing blood stasis herbs, such as: peach kernel, safflower, zeilan, salvia miltiorrhiza, leonuri, radix cyathulae, and wang buliuxing were selected as the research subjects. TCMSP platform, a database of traditional Chinese medicine chemical ingredients, was used to retrieve the effective ingredients of 7 herbs. The targets of the effective ingredients were obtained through the Targets information software. GeneCards database was used to collect EM related target genes. Venn diagram tool was used to obtain the target genes of active ingredients of activating blood circulation and removing blood stasis herbs. Cytoscape 3.6.0 software was used to construct the active ingredient-target-disease network. KEGG database was used to analyze the signal pathways of target gene enrichment. Results A total of 94 active ingredients and 119 targets of 7 herbs were screened. Quercetin, luteolin and kaempferol were the key active components. PTGS2, PTGS1, NCOA2 and NCOA1 were the key targets. The 7 herbs have 20 related KGEE pathways, involving sex hormones, inflammation, apoptosis and angiogenesis. PI3K-Akt signaling pathway, IL-17 signaling pathway, TNF signaling pathway were the main pathways. Conclusion The treatment of EM with activating blood circulation and removing blood stasis herbs has the characteristics of multiple components, multiple targets and multiple pathways, which can relieve the pain, inflammation and menstrual disorders symptoms of EM.
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Objective: To evaluate the therapeutic effect of Toutongning Dropping Pills in the treatment of migraine in various experimental models. Methods: The experimental model of nitroglycerin-induced migraine in rats was used to observe the preventive effect of Toutongning Dropping Pills. The analgesic effect of Toutongning Dropping Pills was observed by chemical stimulation, thermal stimulation in mice, mechanical stimulation and formalin stimulation in rats. The sedative effect of Toutongning Dropping Pills was observed by using the mice convulsion model induced by strychnine nitrate and the model of spontaneous activity in normal mice. The blood-activating effects of Toutongning Dropping Pills were observed in rats with hyperviscosity and mice with microcirculation disorder. Results: Five days after Toutongning Dropping Pills were given, compared with the model group, 1 g/kg and 2 g/kg drug dose group significantly reduced the number of climbing cage and scratching head in migraine rats, and shortened the fading time of pink ears. Toutongning Dropping Pills 1.5 g/kg and 3 g/kg dose group significantly reduced the number of writhing induced by acetic acid in mice; While it had no obvious effect on the thermal stimulation model. Toutongning Dropping Pills 1 g/kg and 2 g/kg dose group could significantly improve pain threshold of the mechanical stimulation of rats, and shorten the phase II time of formalin pain in rats; 1.5 g/kg and 3 g/kg drug dose group could significantly prolong the incubation period of convulsion and reduce the number of spontaneous activities in mice; 0.5 g/kg and 1 g/kg and 2 g /kg drug dose group significantly inhibited the increase of whole blood viscosity in rats; 1.5 g/kg and 3 g/kg drug dose group significantly improved the blood flow pattern in mice, reduced erythrocyte aggregation, and increased the number of capillary intersection points. Conclusion: Toutongning Dropping Pills have obvious analgesic, sedative, blood-activating functions, and have therapeutic effects on experimental migraine.
ABSTRACT
Objective: To establish a biological potency assay for Xiaojin Pills against platelet aggregation in vitro, evaluate the quality consistency of Xiaojin Pills, and screen traditioanal Chinese medicines which play the role of promoting blood circulation in Xiaojin Pills. Methods: Xiaojin Pills and ten Chinese medicines [artificial musk, Momordica cochinchinensis, Aconitum kusnezoffii, Liquidambar formosana, Boswellia carterii, Commiphora myrrha, Faeces Trogopterori, Angelica sinensis, Pheretima aspergillum, Fragrant Ink] in its formula were extracted by ultrasound in 40% methanol. The antiplatelet aggregation rate of the extract was measured by platelet aggregation meter. The platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were prepared from abdominal aorta of rats. The platelet aggregation was induced by adenosine diphosphate (ADP). With sodium ferulate as a standard reference material, the biological potency of antiplatelet aggregation of Xiaojin Pills was calculated by the simplified probit principle. Results: The results showed that the biological potency of Xiaojin Pills was between 0.598 and 1.338 U/mg among different manufacturers and batches. In Xiaojin Pills group, Pheretima, Faeces Trogopterori, and Momordicae Semen had stronger inhibitory effects on platelet aggregation with inhibition rates of 70.87%, 31.83% and 67.52%, respectively. Conclusion: The quality consistency of Xiaojin Pills from different manufacturers and batches is poor, and Pheretima, Faeces Trogopterori, and Momordicae Semen may be the key drugs for Xiaojin Pills to play the role of promoting blood circulation.