Study on potential effective components and mechanism of Zhishe Tongluo Capsules in treatment of ischemic stroke / 中国中药杂志

To explore the potential effective components and mechanism of Zhishe Tongluo Capsules in the treatment of ischemic stroke via network pharmacology, molecular docking and cellular experiment. The chemical constituents of Zhishe Tongluo Capsules were found by TCMSP, BATMAN-TCM and literatures. The constituents-target network was predicted by BATMAN-TCM database. Key words such as cerebral stroke, ischemic stroke and cerebral ischemic stroke were used to search ischemic stroke related targets, and then Venny Map was constructed based on the targets of traditional Chinese medicine and the targets of ischemic stroke. The overlapping targets were imported into STRING database to establish the interaction network. Furthermore, the core targets were screened out by Cytoscape software. Go and KEGG enrichment analysis were performed through DVIAD database. The results showed a total of 193 potential chemical constituents, 985 drug targets and 6 035 disease targets. There were 631 potential targets, 44 core targets and 55 potential active components for treating ischemic stroke through Venny mapping. GO enrichment analysis mainly involved response to hypoxia and positive regulation of ERK1/ERK2. KEGG pathway enrichment analysis mainly involved cholinergic synapse, cAMP signaling pathway, and calcium signaling pathway. Molecular docking data revealed that TP53, EGFR, IL6, INS, TNF and SRC had a good capability to bind with their corresponding active components. To ensure the protective effect Zhishe Tongluo Capsules on the inflammation reaction, an in vitro model of lipopolysaccharide(LPS)-induced RAW264.7 cells was built. The contents of IL-1α, IL-1β, IL-6 and TNF-α in the supernatant were significantly decreased by enzyme linked immunosorbent assay(ELISA). The findings suggested that Zhishe Tongluo Capsules could prevent the injury of ischemic stroke by inhibiting the inflammation.

Study on mechanism of Qinbaohong Oral Liquid in anti-inflammation, stopping cough, eliminating phlegm and relieving asthma based on network pharmacology / 中国中药杂志

This study aimed to investigate the anti-inflammatory, antitussive, expectorant, and anti-asthmatic effects of Qinbaohong Oral Liquid in mouse experiments and explore its action mechanism based on network pharmacology. The mouse auricle swelling was induced by xylene for detecting the anti-inflammatory effect of Qinbaohong Oral Liquid, whose antitussive effect was then examined in mice with cough after exposure to ammonium hydroxide. The expectorant effect was determined based on the excretion of phenol red into the mouse trachea. The mouse model of asthma induced by histamine phosphate and acetylcholine chloride was used to observe the anti-asthmatic effect. The chemical components of Qinbaohong Oral Liquid were retrieved from TCMSP and literature, followed by target prediction based on BATMAN-TCM. The targets of inflammation, cough, expectoration, and asthma collected from GeneCards were intersected with drug targets for GO and KEGG enrichment analysis using Metascape. The results were imported into STRING for exploring protein-protein interactions and screening the key targets. As demonstrated by our findings, Qinbaohong Oral Liquid at 4.5 and 9.0 mL·kg~(-1) obviously decreased the weight(P<0.05) and thickness(P<0.01) of the right swelling ear and also the weight diffe-rence(swelling degree) between the two ears(P<0.05), prolonged the incubation period of cough(P<0.05), reduced the frequency of cough within 3 min(P<0.05), and increased the excretion of phenol red into the mouse trachea(P<0.01). Qinbaohong Oral Li-quid at 2.3, 4.5, and 9.0 mL·kg~(-1) dramatically prolonged the incubation period of asthma(P<0.05). A total of 324 chemical components and 1 245 targets were harvested for the Qinbaohong Oral Liquid, together with 10 272 inflammation targets, 4 400 cough targets, 192 expectoration targets, and 7 533 asthma targets. Their intersection revealed that the anti-inflammatory, antitussive, expectorant and anti-asthmatic effects of Qinbaohong Oral Liquid were correlated with such GO biological processes as the regulation of ion transport and blood circulation and such KEGG pathways as cancer-related signaling pathways and neuroactive ligand-receptor interaction. Qinbaohong Oral Liquid has been confirmed by both experiments and network pharmacology analysis to be efficient in anti-inflammation, stopping cough, eliminating phlegm, and relieving asthma.

Pathological Mechanisms of Brain-Heart Mutual Damage and Treatment with Traditional Chinese Medicine: A review / 中国实验方剂学杂志

The brain and heart has a tight relationship upon physiology and pathology during the development of cardiovascular and cerebrovascular diseases with clinical conditions interacting with each other and complex pathological mechanisms. Clinical studies prove that cerebral diseases such as stroke usually happen with cardiac diseases as complications， and cardiac diseases such as atrial fibrillation can also cause cerebral diseases， which can even aggravate brain atrophy and lead to cognitive impairment. Traditional Chinese medicine （TCM） also believes that “the substance of Shenming is located in the brain and the function in the heart.” Specifically， Yuanshen is in the brain and Shishen is in the heart， which thus makes the heart and brain closely related. If Shenming in any of them is impaired， the other one would also be injured. Therefore， the pathological mechanisms of brain-heart mutual damage have become one of the current research hotspots. This paper， combined with the clinical research status of the brain-heart mutual damage， summarized its pathological mechanisms from the perspectives of inflammatory responses， dysregulation of autonomic nervous system， apoptosis， energy metabolism and oxidative stress. The necessity of “brain-heart concurrent regulation” was proposed and the research progress on the treatment of cerebral and cardiac diseases with TCM represented by Naoxintong capsule was profiled in the light of heart and brain function described by TCM and the holistic concept of TCM treating cerebral and cardiac diseases. This paper reviews the pathological mechanisms of brain-heart mutual damage and the research progress on its treatment with TCM， which can provide reference for the prevention and treatment of cardiovascular and cerebrovascular diseases and further research on them.

Usage of ethnomedicine on COVID-19 in China / 中国中药杂志

In December 2019, an outbreak of viral pneumonia began in Wuhan, Hubei Province, which caused the spread of infectious pneumonia to a certain extent in China and neighboring countries and regions, and triggered the epidemic crisis. The coronavirus disease 2019(COVID-19) is an acute respiratory infectious disease listed as a B infectious disease, which is managed according to standards for A infectious disease. Traditional Chinese medicine and integrated traditional Chinese and Western medicine have played an active role in the prevention and control of this epidemic. China's ethnomedicine has recognized infectious diseases since ancient times, and formed a medical system including theory, therapies, formula and herbal medicines for such diseases. Since the outbreak of the COVID-19 epidemic, Tibet Autonomous Region, Qinghai Province, Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region and Chuxiong Autonomous Prefecture of Yunnan, Qiandongnan Autonomous Prefecture of Guizhou have issued the prevention and control programs for COVID-19 using Tibetan, Mongolian, Uygur, Yi and Miao medicines. These programs reflect the wisdom of ethnomedicine in preventing and treating diseases, which have successfully extracted prescriptions and preventive measures for the outbreak of the epidemic from their own medical theories and traditional experiences. In this paper, we summarized and explained the prescriptions and medicinal materials of ethnomedicine in these programs, and the origin of Tibetan medicine prescriptions and Mongolian medicine prescriptions in ancient books were studied. These become the common characteristics of medical prevention and treatment programs for ethnomedicine to formulate therapeutic programs under the guidance of traditional medicine theories, recommend prescriptions and prevention and treatment methods with characteristics of ethnomedicine, and focus on the conve-nience and standardization. However, strengthening the support of science and technology and the popularization to the public, and improving the participation of ethnomedicine in national public health services and the capacity-building to deal with sudden and critical diseases are key contents in the development of ethnomedicine in the future.

Mechanisms and Components Identification of Naoxintong Intestinal Absorption Liquid Protecting Cardiac Injury Induced by H2O2 / 中国实验方剂学杂志

Objective: Intestinal absorption liquid as medicine carriers, one or more kinds of traditional Chinese medicine protecting cardiac injury in Naoxintong capsule will be found through separation and combination of prescription. This study also can expand protecting mechanisms of Naoxintong capsule. Method: Naoxintong intestinal absorption liquids of single, combination and total prescription were prepared. H9c2 cell line exposed to H2O2 was established. Cell survival rate was determined with methyl thiazolyl tetrazolium(MTT). Cell apoptosis rate was examined by Annexin Ⅴ-FITC/PI staining with a flow cytometer. Aquaporin1(AQP1) expression was detected by Western blot. One or more kinds of traditional Chinese medicine in Naoxintong capsule which exerted protective effect from cardiac injury were screened through separation and combination of prescription. Result: As compared with control group, the protein expression level of AQP1 was significantly increased(PPPPPPConclusion: Naoxintong capsule acts as a protective role in myocardial injury through decreasing AQP1 expression and inhibiting cell apoptosis. Salviae Miltiorrhizae Radix et Rhizoma, Pheretima, Scorpio are important components in Naoxintong capsule.

Analysis on "component-target-pathway" of Paeonia lactiflora in treating cardiac diseases based on data mining / 中国中药杂志

Based on the literature review and modern application of Paeonia lactiflora in heart diseases, this article would predict the target of drug and disease by intergrative pharmacology platform of traditional Chinese medicine (TCMIP, http://www.tcmip.cn), and then explore the molecular mechanism of P. lactiflora in treatment of heart disease, providing theoretical basis and method for further studies on P. lactiflora. According to the ancient books, P. lactiflora with functions of "removing the vascular obstruction, removing the lumps, relieving pain, diuretic, nutrient qi" and other effects, have been used for many times to treat heart disease. Some prescriptions are also favored by the modern physicians nowadays. With the development of science, the chemical components that play a role in heart disease and the interrelation between these components and the body become the research hotspot. In order to further reveal the pharmacological substance base and molecular mechanism of P. lactiflora for the treatment of such diseases, TCM-IP was used to obtain multiple molecular targets and signaling pathways in treatment of heart disease. ATP1A1, a common target of drug and disease, was related to energy, and HDAC2 mainly regulated cardiomyocyte hypertrophy gene and cardiomyocyte expression. Other main drug targets such as GCK, CHUK and PRKAA2 indirectly regulated heart disease through many pathways; multiple disease-associated signaling pathways interfered with various heart diseases including coronary heart disease, myocardial ischemia and myocardial hypertrophy through influencing energy metabolism, enzyme activity and gene expression. In conclusion, P. lactiflora plays a role in protecting heart function by regulating the gene expression of cardiomyocytes directly. Meanwhile, it can indirectly intervene in other pathways of heart function, and thus participate in the treatment of heart disease. In this paper, the molecular mechanism of P. lactiflora for treatment of heart disease was in computer prediction analysis level, and the specific mechanism of action still needs further experimental verification.

Identification of effective components from Naoxintong Capsules intestinal absorption liquid in inhibiting ADP-induced platelet aggregation / 中国中药杂志

Intestinal absorption liquid was prepared by using everted intestinal sac method; meanwhile, its recipes were decomposed or restructured. Platelet aggregation activity was examined by biochemical tests and a microplate reader. One or more kinds of Chinese medicines which displayed inhibiting activity in Naoxintong Capsules were screened through separation and combination of prescription. The results showed that Naoxintong Capsules could inhibit ADP-induced platelet aggregation. Recipe decomposition and restructuring results showed that Salviae Miltiorrhizae Radix et Rhizoma, Paeoniae Radix Rubra, Cinnamomi Ramulus and Hirudo were the main effective medicines in inhibiting platelet aggregation. Furthermore, Cinnamomi Ramulus played a vital role in inhibiting activity among those four kinds of Chinese medicines. Coumarin derived from intestinal absorption liquid of Cinnamomi Ramulus had inhibiting activity in the range of 50-200 μmol·L⁻¹, and other ingredients such as cinnamyl alcohol and cinnamaldehyde also had inhibiting activities. In conclusion, Salviae Miltiorrhizae Radix et Rhizoma, Paeoniae Radix Rubra, Cinnamomi Ramulus and Hirudo are the main components for inhibiting ADP-induced platelet aggregation, and Cinnamomi Ramulus has the most strongest inhibiting activity in Naoxintong Capsules.

Evaluation of effect of supplementing Qi and activating blood decoction based on combined model of "intestinal out-cardiac muscle cells" and discussion of its mechanism / 中国中药杂志

This research firstly establishes the oxidative damage model of H9c2 induced by H2O2 and screens the concentration range of intestines absorption liquid of Qi benefiting and blood circulation activating formula which possess external myocardium protection function. Then, the thesis chooses 4 dosages to conduct experiments：examining the protection function of intestines absorption liquid of Qi benefiting and blood circulation activating formula on H9c2 to provide reference for clinical prevention and curing of relative heart diseases of oxidative stress injury; as well as examining the H9c2 cardiac muscle cell vigour, cellular morphology, SOD, MDA and other indexes to primarily evaluate and discuss the functional mechanism of intestines absorption liquid of Qi benefiting and blood circulation activating formula. The results show that the intestines absorption liquid of Qi benefiting and blood circulation activating formula has relatively better protection function toward the H9c2 cardiac muscle cell damage induced by H2O2 and presents concentration dependency to some extent. The intestines absorption liquid of Qi benefiting and blood circulation activating formula can increase SOD vigour, and decrease MDA emission, thus decreasing the formation of abnormal cell and strengthening the oxidation resistance of cardiac muscle cell. The intestines absorption liquid of Qi benefiting and blood circulation activating formula has protection function to some extent.

Molecular mechanism research on simultaneous therapy of brain and heart based on data mining and network analysis / 中国中药杂志

<p><b>OBJECTIVE</b>The theory of treating heart and brain simultaneously is from the theory of traditional Chinese medicine, and there aren't enough explanations for this theory from the perspective of molecular mechanism. As one successful case of this theory, the Chinese medicine formula--Buchang Naoxintong can achieve the goal of treating coronary heart disease and stroke at the same time. To illustrate the mechanism of the theory of treating heart and brain simultaneously, it is necessary to find out the molecular mechanism of this formula.</p><p><b>METHOD</b>Using the network analysis method, together with two data mining methods-clustering and apriori algorithm, the frequent gene combinations interfered by the chemicals of the formula based on the protein-protein interaction networks related with coronary heart disease and stroke disease were figured out respectively. To find out the molecular mechanism of the theory of treating heart and brain simultaneously, the results got from two diseases were compared and analyzed.</p><p><b>RESULT</b>Based on comparing two results from these two different diseases, the mechanism of the theory of treating heart and brain simultaneously was explained from molecular level by finding out key genes targeted by the components of this formula for both diseases and some particular genes interfered by the components for each disease. In addition, genes interfered indirectly by the chemicals for different diseases were found out based on the protein-protein interaction network.</p><p><b>CONCLUSION</b>It can help to explain the molecular mechanism of the theory by our methods. By finding out the molecular mechanism of this theory, it can promote the progress of combination of Chinese traditional and Western medicine.</p>