Research on Anti-aging Guided by Qiluo Doctrine / 中国实验方剂学杂志

Along with increasing degree of population aging globally， senility， good health and long life have become the focus of the world. Guided by Qiluo doctrine， an essence， Qi and spirit theory is proposed as below， essence is the origin of life， Qi is the impetus of life and spirit is the embodiment of life. Based on holistic view of kidney deficiency involving the five internal organs and injuries of the five internal organs definitely affecting the kidney， a mechanism of aging is proposed as below， deficiency of kidney essence is the foundation of aging， deficiency of promordial Qi is the key of aging and physical and spiritual loss is the manifestation of aging. It provides a theoretical guidance for anti-aging study of rejuvenating the elderly and making the strong person stronger. By virtue of the experiences in kidney-tonifying medication accumulated for more than two thousand years， Bazi Bushen capsules has been developed， which has anti-aging efficacy， including tonifying kidney， replenishing essence， coordinating Yin and Yang， supplementing primordial Qi and nourishing body and spirit. Experimental researches have demonstrated that Bazi Bushen capsules can improve overall aging and systemic aging， as well as prevent and treat aging related diseases. Preliminary clinical studies demonstrate that this capsules can enhance athletic ability and improve sexual function， and is expected to become a representative Chinese patent medicine of anti-aging. This paper addresses aging and anti-aging on the basis of Qiluo doctrine， in the hope of helping prevention and treatment of aging related diseases.

Bazi Bushen Capsules on Anti-aging： A Review / 中国实验方剂学杂志

The decline of body function and senile diseases caused by aging seriously affect human health and life span， which is an important topic in the field of life science. Bazi Bushen capsules is a representative Chinese patent medicine for tonifying essence， invigorating Qi and anti-aging， guided by Qiluo doctrine， and essence， Qi and spirit theory. Previous pharmacological and clinical studies have confirmed that this preparation has the comprehensive advantages of anti-aging， and prevention and treatment of aging-related diseases. Among them， pharmacological studies showed that Bazi Bushen capsules had the effect of improving the appearance status of mice， improving the level of sex hormones， inhibiting the formation of atherosclerosis， improving cardiac function， improving learning and memory cognitive ability， improving neurological function， improving osteoporosis and muscle function， improving sperm count and quality. The mechanism was related to the up-regulation of the recombinant sirtuin （SIRT6） level， down-regulation of the levels of aging-related proteins p53 and p16， up-regulation of telomerase reverse transcriptase level， and alleviation of inflammation and oxidative response. Clinical studies have proved that it can improve the symptoms of patients with kidney essence deficiency， improve exercise ability， and improve the sexual function of impotence patients. Anti-aging research of Bazi Bushen capsules based on Qiluo doctrine fully embodies the new mode of academic innovation and transformation of traditional Chinese medicine （TCM） with the combination of "theory-new drug-experiment-clinic"， which has made a demonstration for the anti-aging research of TCM.

Analysis of Pathogenesis and Treatment of Chronic Coronary Syndrome Based on Vessel-collateral Theory / 中国实验方剂学杂志

Based on the syndrome and treatment system of collateral disease， and inheriting the development of the bloodline theory of traditional Chinese medicine （TCM）， academician WU Yi-ling systematically constructed the vessel-collateral theory of TCM and proposed that its core theory was the theory of Yingwei， that is， "Ying in the vein， and Wei outside the vein" （Huangdi Neijing·Lingshu·Yingwei Shenghui）， "obstructing of Yingwei， congelation of blood" （Treatise on Febrile Diseases· Pulse Differentiation Method）， "pathogen transferring through blood vessels， obstructed by blocking" （Jinkui Yaolue·Zangfu Jingluo Xianhou Bingmaizheng First）， and "damage of the heart， adjust its Yingwei". Based on the consistency of vessel-collateral as the channel of blood circulation in TCM with the blood vessels in western medicine， and guided by the Yingwei theory of vessel-collateral theory， the diagnostic criteria of syndrome differentiation of disease of vessel-collateral and vascular system represented by coronary heart disease， arrhythmia， heart failure and others was established to guide the prevention and treatment of vascular diseases. Based on the above analysis， guided by the Yingwei theory of vessel-collateral theory， and on the basis of related researches of vessel-collateral and vascular system， this paper discussed the etiology and pathogenesis of chronic coronary syndrome （CCS） in TCM. Taking useful collateral with unblocking as the treatment principle， the representative Tongluo prescription （Tongxinluo） was constructed， the research progress of Tongxinluo from various aspects such as animal experiment research， pharmacological research and clinical evidence-based research was summarized， a comprehensive system from etiology， pathogenesis， syndrome differentiation to treatment was formed， in order to provide new ideas for the clinical treatment of CCS.

Research Progress on G2/M Arrest in Breast Cancer Cells by Active Compounds of Traditional Chinese Medicine / 中国实验方剂学杂志

The global incidence of breast cancer has increased year by year. Breast cancer has the highest mortality rate in female patients with malignant tumors. Traditional Chinese medicine（TCM） has made great contribution to health of human being， improving the overall curative effect， reducing the patients' pain， improving the quality of life and alleviating adverse reactions in patients. TCM and its active compounds can inhibit the proliferation of breast cancer cells by inducing cell cycle arrest， invasion， metastasis and reversing multidrug resistance. The effect of the compounds in TCM is obvious on inducing the arrest of the breast cancer cells cycle. It′s a novel method to fight against breast cancer by influencing the progress of the breast cancer cell cycle and inducing the cell cycle arrest in breast cancer cells. Lots of studies have shown that the G2/M phase checkpoint which transition from gap-phase （G2 phase） to mitotic phase （M phase） in the cell cycle is the key point for cell survival or death. Many antitumor drugs can inhibit the proliferation of tumor cells through the cell cycle arrest. We summarized the domestic and foreign literatures in recent years， and comprehensively explained the research progress on the related regulatory molecules in G2/M arrest. In addition， we summarized and sorted out the researches on the methods and ways of alkaloids， polysaccharides， terpenes， flavonoids， saponins and other active compounds of TCM in inducing the G2/M arrest of human breast cancer cells. By summarizing the active compounds of various Chinese medicines in inducing G2/M arrest of breast cancer cells， and reviewing the research progress on mechanism of active TCM compounds for inhibiting the proliferation of breast cancer cells， we will， in this paper， investigate the mechanism of active TCM compounds for inhibiting the proliferation of breast cancer cells through inducing G2/M arrest of human breast cancer cells， so as to provide a scientific basis for in-depth research on the anti-breast cancer mechanism of the active compounds in TCM.

Scientific Connotation and Clinical Value of Traditional Chinese Medicine Lianhua Qingke Improving Ventilation Function Through "Reducing Phlegm" / 中国实验方剂学杂志

Airway mucus is an important part of the defense barrier function of the airway. Abnormal secretion of airway mucus is closely related to recurrent attacks， delay or aggravation of respiratory infectious or infectious diseases such as chronic obstructive pulmonary disease （COPD）， community-acquired pneumonia， and coronavirus disease 2019 （COVID-19）. Lianhua Qingke tablets， an innovative traditional Chinese medicine （TCM） developed under the guidance of the theory of collateral disease of TCM， has the function of reducing phlegm and relieving cough， which can reduce the generation and viscosity of sputum and promote sputum excretion. Clinical studies have shown that it can significantly improve the symptoms of expectoration and cough in patients with acute bronchitis or COVID-19， confirming its scientific connotation and clinical value of reducing phlegm and relieving cough to improve ventilation and exchanging function.

Rules of Syndrome and Treatment of Unstable Angina Pectoris Guided by Vessel-collateral Theory and Mechanism Analysis Based on Network Pharmacology / 中国实验方剂学杂志

Objective:Guided by nutrient-defense stages in the vessel-collateral theory， the modern medical cases of unstable angina pectoris（UAP） were systematically collated and analyzed to explore the rules of syndrome and treatment of UAP and the molecular mechanism of core Chinese herbal combination in the treatment of UAP based on network pharmacology. Method:All medical cases with UAP treated by Chinese medicinal compounds were retrieved from PubMed，China National Knowledge Infrastructure （CNKI），Wanfang Data， VIP， and SinoMed published between database inception and November 2020. The syndromes of medical cases were determined based on the nutrient-defense stages of the vessel-collateral theory. Rules of syndrome and treatment of UAP were investigated by data mining methods， such as frequency statistics， cluster analysis， and enhanced FP-Growth algorithm. The molecular mechanism of core Chinese herbal combination in the treatment of UAP was analyzed by network pharmacology. Result:The first four syndromes of UAP with high frequencies were deficiency and stagnation of collateral Qi， blood stasis obstructing collaterals， depression and stagnation of collateral Qi， and turbid phlegm obstructing collaterals. The Chinese herbal medicines with high frequencies included Salviae Miltiorrhizae Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Chuanxiong Rhizoma， and Astragali Radix， which were effective in resolving stasis， dredging collaterals， replenishing Qi， consolidating defensive Qi， regulating Qi， relieving depression， and dispelling phlegm. The association analysis indicated that the core Chinese herbal combination in the treatment of UAP was Salviae Miltiorrhizae Radix Chuanxiong Rhizoma-Astragali Radix. Four Chinese herbal combinations were obtained by cluster analysis. As revealed by network pharmacology， the key components of Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Astragali Radix in the treatment of UAP included quercetin， luteolin， and tanshinone Ⅱ_A， and the key targets included serine/threonine-protein kinase 1 （Akt1）， mitogen-activated protein kinase 1 （MAPK1）， Jun， interleukin （IL）-6， and MAPK8. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis showed that phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathway might serve as the main pathway for its therapeutic efficacy. Conclusion:The basic pathogenesis of UAP is deficiency/depression and stagnation of collateral qi and turbid phlegm obstructing collaterals. The treatment should follow the principles of replenishing Qi， resolving stasis， and dredging collaterals， assisted with regulating Qi and resolving phlegm. The therapeutic efficacy of Salviae Miltiorrhizae Radix-Chuanxiong Rhizoma-Astragali Radix was achieved via multi-component， multi-target， and multi-pathway. This study is expected to inspire future UAP-related studies at the molecular level based on vessel-collateral theory.

Collaterals Doctrine Guided Investigation into Traditional Chinese Medicine Pathogenesis and Clinical Treatment of Myocardial Fibrosis Following Acute Myocardial Infarction / 中国实验方剂学杂志

Interventional or thrombolytic therapy for acute myocardial infarction （AMI） has the effect of opening occluded coronary arteries. However， due to no myocardial regurgitation， ischemia/reperfusion injury and microvascular structure and function destruction， leading to myocardial fibrosis following AMI， ventricular remodeling， and even cardiac failure may occur. Collaterals doctrine is used to guide the investigation into traditional Chinese medicine pathogenesis and clinical treatment of myocardial fibrosis following AMI. Consequently， it proposes the pathogenesis characteristic of "Qi deficiency and blood stasis， collaterals obstruction" and medication principle of "dispersing and dredging"， to develop the formula of Tongxinluo. Fundamental and clinical researches have demonstrated it can effectively protect the structure and function of myocardial microvascular endothelial cells， improve no reflow and reperfusion injury， and inhibit myocardial fibrosis after AMI， which further supports scientific value of the collaterals doctrine.

Pathogenesis of Metabolic Syndrome from "Qi of five Internal Organs" / 中国实验方剂学杂志

Metabolic syndrome (MS) is a group of syndromes caused by the disorder of metabolism of various substances in the body. The main clinical manifestations are dyslipidemia, central obesity, hypertension, abnormal glucose tolerance and insulin resistance. With the changes of diet structure and habits, the incidence rate of MS is increasing, and the patients are younger. It is an important factor in many diseases, such as diabetes, atherosclerosis, coronary heart disease, hyperlipidemia, cirrhosis and some cancers. MS has seriously affected people's lives and health. Central obesity and insulin resistance are recognized as important pathogenic factors. At present, the pathogenesis of MS and its components has not been fully understood. The clinical manifestations of metabolic syndrome are complex and diverse. Traditional Chinese medicine (TCM) believes that the occurrence of metabolic syndrome is related to such factors as proper diet, emotional disorders, excessive escape and little movement, old age and physical deficiency. TCM scholars have studied the pathogenesis of MS in such pathological factors as phlegm and blood stasis, such visceral functions as liver, spleen and kidney, roles of Qi and blood, and emotional factors. As the basic substance of organism, Qi is closely related to the process of metabolism. The occurrence of MS is closely related to the rise and fall of Qi moving to and from the body as well as the abnormal gasification function of the transformation of Qi. Qi is derived from the five internal organs, which are respectively called Heart Qi, liver Qi, spleen Qi, lung Qi and kidney Qi. The "Qi of the five internal organs" is involved in the whole process of the generation, transportation and excretion of the essence of the body. Based on the "Qi of five internal organs", this paper discusses the pathogenesis of MS with phlegm, blood stasis and water drink as pathological factors.

Discussion About Guidance of Diagnosis and Treatment of COVID-19 by Luobing Theory / 中国实验方剂学杂志

This paper uses the Luobing theory to guide the diagnosis and treatment of coronavirus disease-2019 (COVID-19), and states that lung collateral includes Qi collateral and blood collateral, and is the basis for playing the function of lung of dominating Qi, controlling breathing and connecting all vessels. The concept of Qi channel is different from that of Qi collateral, but its function is closely related to lung collateral. COVID-19 belongs to "pestilence" in traditional Chinese medicine. The epidemic pathogenic factor enters from mouth and nose and then causes the disease. The early characteristics of this disease include the invasion of the lung by the epidemic pathogenic factor, the obstruction of Qi channels, the prevailing of the evil and the retreat of the good, and the deficiency and stagnation of Qi collateral. Generation of toxic heat from inside, obstruction of Qi channels and dysfunction of "breathing and blood transfer" are the key links to the development and aggravation of this disease. Qi disease involves blood, blood wound intrudes into collateral, and blood consumption and hemorrhage are the late outcome of this disease. Based on the experience of doctors of all dynasties in the treatment and medication of pestilence, the treatment principle of active intervention in the early and middle stage is proposed, including focusing on pathogenesis and expelling of toxin, drug use before syndrome onset and active intervention, and the whole regulation and multi-target treatment. Lianhua Qingwen developed under the guidance of Luobing theory can inhibit the activity of novel coronavirus in vitro, relieve clinical symptoms (such as fever, cough, weakness, shortness of breath and so on) and reduce the rate of disease progression to severity. Lianhua Qingke can diffuse the lung, clear the lung heat, relieve cough and reduce sputum. It can be used to relieve the symptoms of cough and sputum in patients with COVID-19, which proves the important scientific value of Luobing theory and collateral-dredging drugs in epidemic prevention and control.

Study on Clinical Efficacy of Lianhua Qingke Granule in Treatment of Mild and Ordinary COVID-19 / 中国实验方剂学杂志

Objective:To evaluate the clinical efficacy and safety of traditional Chinese medicine Lianhua Qingke granule （LH granule）in the treatment of coronavirus disease 2019（COVID-19）. Method:A randomized controlled method was used in this clinical study. The subjects were confirmed COVID-19 patients over 18 years old with cough symptoms，and the diagnosis is based on Diagnosis and Treatment Protocol for COVID-19 （Trial Version 6）. The subjects were randomized to usual treatment （control group） or in combination with LH granule （1 bag，thrice daily） for 14 days. The primary endpoint was the rate of cough recovery. Result:57 subjects were included in this study， including 25 in the control group and 32 in the observation group. The recovery rate of cough in observation group was 90.6%（29/32）， which was significantly higher than 64.0%（16/25）in the control group （P<0.05）. The effective time of cough treatment was significantly earlier than that of the control group （P<0.05）， the median time to cough recovery was markedly shorter in treatment group （P<0.05）. The recovery rate of expectoration in observation group was 94.7% （18/19）， which was significantly higher than 57.1%（8/14）in the control group （P<0.05）. The effective time of expectoration treatment was significantly earlier than that of the control group （P<0.05）， and the median time to expectoration recovery was markedly shorter in treatment group （P<0.05）. The improvement rate of CT in the observation group was 96.9% （31/32）， which was significantly higher than 72% （18/25） in the control group （P<0.05）. After treatment， the oxygenation index of the two groups increased in varying degrees， and the increase rate of the observation group was significantly higher than that of the control group （P<0.05）. There was no significant difference in the recovery rate of fever， fatigue， dry pharynx and sore throat between the observation group and the control group， and it showed that LH had a better improvement trend on the basis of usual treatment. Conclusion:On the basis of routine treatment，LH can significantly improve the symptoms of cough and expectoration of COVID-19 patients， shorten the duration of cough and expectoration symptoms， reduce lung pathological damage， improve respiratory function， and improve the symptoms of fever， fatigue， dry pharynx and sore throat.

Historical Review and Reflection About Application of Traditional Chinese Medicine in Epidemic Diseases / 中国实验方剂学杂志

Related records about discipline of diagnosis and treatment of exogenous febrile diseases by traditional Chinese medicine (TCM) were reviewed to summarize TCM knowledge about etiology, pathogenesis, progress and treatment of infectious epidemic diseases among exogenous febrile diseases. In consideration of onset time and major clinical manifestations of novel coronavirus pneumonia (NCP), this disease is considered as within the scope of pestilence in TCM, it is located in the lung, with etiology being poison of winter-warm syndrome, the viruses enter body via mouth and nose, and invade pulmonary collaterals. Based on the syndrome characteristics proposed in diagnosis and treatment schemes of various regions as well as the researches on medication rules, the present study points out the core pathogenesis of NCP is epidemic toxin invading the lung, pathogenic heat obstructing the lung and toxic heat blocking the lung. It also analyzes theoretical formula features of TCM Lianhua Qingwen and related clinical and experimental research results, in order to prove the clinical value of this drug in the outbreak of NCP.

Research on Guidance of Prevention and Treatment of Vascular Diseases by Yingwei Theory of Vessel-collateral Theory / 中国实验方剂学杂志

The blood-vein theory is inherited and developed. Combined with the related theory features of Qi and blood of traditional Chinese medicine(TCM), the progress results in two national 973 plan projects undertaken are learned from, the vessel-collateral theory guiding the prevention and treatment of vascular lesions is systematically built, the academic development of TCM collateral disease discipline is pushed from "treatment of symptoms of collateral disease" to study on "vessel-collateral theory", a new stage in the history. The pathogenesis, basic pathogenesis, clinical syndrome and syndrome differentiation therapy of vessel-collateral lesions are systematically studied, Yingwei theory, the core content of vessel-collateral theory, is proposed, the syndrome differential diagnosis standard of "vessel-collateral-vascular system disease" is established, and the blood-vessel theory of TCM is improved. The development of Yingwei theory of vessel-collateral theory is deepened. The theory of Yingwei sympathia and Yingwei's "opening by collaterals, intersecting and generating" are proposed to guide the study on prevention and control of vascular lesions. With tertiary collaterals-microvessel as a breakthrough point of research, four types of microscopic pathological features of microvessels are proposed. It is confirmed that dredging collaterals and protecting tertiary collaterals-microvessel is the common key mechanism for the treatment of major diseases of heart, brain and kidney(sugar). It protects microvessels, improves blood flow perfusion, protects tissue cells, and improves the viscera function. Dredging collaterals and protecting microvascular endothelial cells is the core mechanism of treating tertiary collaterals-microvessel lesions. It is proposed that protection of microvascular endothelial cells is a new strategy to solve the problem of microvascular lesions. After more than ten years, four studies of evidence-based medicine have been completed to solve the clinical problem of acute myocardial infarction without reflow. New drugs are provided to the international medical problem of cardiac insufficiency with premature ventricular contraction. The gap of fast and slow treatment, integration and rhythm adjustment of sinus bradycardia with premature ventricular contraction is filled. The clinical treatment effect of chronic heart failure is significantly improved, a major breakthrough in the treatment of microvascular lesions by TCM is achieved, and it is fully recognized and highly evaluated by the medical profession at home and abroad. It promotes the specialized subject platform construction and society development under the guidance of Yingwei theory of vessel-collateral theory, as well as the clinical application of syndrome differentiation diagnosis and treatment method and drugs of vessel-collateral lesions, and has significant social and economic benefits.

Research development of Carpesii Fructus / 中国药理学与毒理学杂志

Carpesii Fructus is the fruit of Carpesium abrotanoides L. and is recorded in the Chinese Pharmacopoeia (2015 Edition). Carpesium abrotanoides broadly distribute in China. Traditionally, Carpesii Fructus was used as a parasiticide,especially for ascariasis,pinworms and tapeworm disease. In ancient times,the Carpesium plants were used as traditional Chinese,Korean and Japanese herbal medicines for the treatment of several diseases.Carpesii Fructus was first recorded in the book"Newly Revised Canon of Materia Medica"in the Tang Dynasty of China.The original plant is Compositae Arte-misia santonica (Seriphidium cinum) from middle east Persian. At present, Carpesium abrotanoides issometimes confused with the Lappula family in species classification. In the Song Dynasty of China,"KaiYang Materia Medica"recorded that the best Carpesii Fructus was from Persian.The main compo-nents of Carpesii Fructusare terpenes,phenolic compounds,flavonoids and coumarins. Including telekin, 3-epi-isotelekin, 11β-13-dihydro-1-epi-inuviscolide, carabrone, carabrol, terpene lactone, gerilin, carpesia, valeric acid, oleic acid, linolenic acid, thirty-one alkane, sterol, etc. The chemical components isolated from whole plants of carpesia are more than 143. In clinical practice, Carpesii Fructus is mainly used as antiparasitic drugs and usually combined with other drugs since the poor efficacy as single drug. Its toxic reaction is closely related to the dose of the drug.Carpesia,asa main component of Carpesii Fructus, might lead to adverse reactions also. At present, Major issuesof Carpesii Fructusare the lack of phar-macological research,as well as lack of in-depth study on the material basis.Therefore,further studies are needed on the drug development and clinical usuage.

Effect of Tongxinluo on Apoptosis of Rat Cardiac Microvascular Endothelial Cells / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the protective effects of Tongxinluo (TXL) on apoptosis of rat cardiac microvascular endothelial cells (RCMECs) resulting from homocysteine (Hcy) induced endoplasmic reticulum stress (ERS), and to determine the signaling pathway behind its protection.</p><p><b>METHODS</b>Primary cultured RCMECs were isolated from neonatal rats using tissue explant method. The morphology of RCMECs was observed using inverted microscope, identified and differentiated by CD31 immunofluorescence method. Selected were well growing 2nd-4th generations of RCMECs. The optimal action time was determined by detecting the expression of glucose regulated protein 78 (GRP78) using immunofluorescence method. In the next experiment RCMECs were divided into 5 groups, i.e., the blank control group, the Hcy induced group (Hcy 10 mmol/L, 10 h), the Hcy + TXL group (Hcy 10 mmol/L + TXL 400 µg/mL), the Hcy +LY294002 group (Hcy 10 mmol/L + LY294002 5 µmol/L, LY294002 as the inhibitor of PI3K), the Hcy + LY294002 + TXL group (Hcy 10 mmol/L + LY294002 5 µmol/L + TXL 400 µg/mL). The apoptosis rate of RCMECs was detected by flow cytometry. mRNA and protein expressions of GRP78, C/ EBP homologous protein (CHOP), and cysteinyl aspartate specific proteinase-12 (caspase12) were detected by real-time reverse transcription PCR (RT-PCR) and Western blot respectively. Expression levels of phosphorylation of phosphatidylinositol 3-kinase (P-PI3K), total phosphatidylinositol 3-kinase (T- P13K) , phosphorylation of kinase B (P-Akt) , and total kinase B (T-Akt) were detected by Western blot.</p><p><b>RESULTS</b>Ten hours Hcy action time was determined. Compared with the blank control group, the apoptosis rate was increased (22.77%), mRNA and protein expressions of GRP78, CHOP, and Caspase-12 were increased, protein expressions of P-PI3K and P-Akt,ratios of P-PI3K/T-PI3K and P-Akt/T-Akt were decreased in the Hcy induced group (P < 0.05, P < 0.01). Compared with the Hcy induced group, the apoptosis rate was decreased (10.17%), mRNA and protein expressions of GRP78, CHOP, and Caspase-12 were decreased, and expression levels of P-PI3K, P-Akt, P-PI3K/T-PI3K, and P-Akt/T-Akt were increased in the Hcy + TXL group (P < 0.05, P < 0.01). Compared with the Hcy + TXL group, the apoptosis rate was increased (17.9%), mRNA and protein expressions of GRP78, CHOP, and Caspase-12 were increased, expression levels of P-PI3K and P-Akt, ratios of P-PI3K/T-PI3K and P-Akt/T-Akt were decreased in the Hcy + TXL + LY294002 group (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>TXL could inhibit the apoptosis of RCMECs resulting from Hcy-induced ERS and its mechanism might be associated with activating PI3K/Akt signaling pathway.</p>

Research on Collateral-unblocking Medicines for Cardiovascular Diseases under the Guidance of Vessels Collateral Theory / 中国中西医结合杂志

"Vessels Collateral Theory", as the inherit and development of "blood vessels" in Huangdi Neijing, is a systematic system by integrating severe vascular diseases. In this article, by taking cardiovascular diseases (CVD) as a cut-in point, roles of "minute collateral-microvascular" lesions in the occurrence and development of CVD were further explored. The interventional effect of collateral-unblocking medicines under the guidance of Vessels Collateral Theory was also in-depth explored, hoping to leading Chinese medical prevention and treatment of CVD.

Improved mesenchymal stem cell survival in ischemic heart through electroacupuncture / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether electroacupuncture (EA) can promote cell survival and enhance heart function of mesenchymal stem cells (MSCs) therapy.</p><p><b>METHODS</b>MSCs were isolated from bone marrow and expanded in Minimum Essential Medium Alpha (α-MEM). MI was induced in 72 Sprague-Dawley (S-D) rats by ligation of the left anterior descending coronary artery (LAD) for 30 min and reperfusion. MI rats randomly received injection of 1×10(6) DiI-labeled MSCs alone (n =24, MSC group), or plus electroacupuncture (EA) at Neiguan (PC6, n=24, EA+MSC group), or saline (n =24, saline group). EA treatment was performed for 4 days. Another 24 rats were subjected to chest-open surgery without LAD occlusion and treatment (sham group). Three time points, 4, 14 and 28 days (n =8 for each group) were included in this study. The survival of transplanted MSCs and the protective gene expression were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot at day 4 and 14. Left ventricular remodeling, cardiac function, infarction area, fibrosis and capillary density were analyzed at day 28.</p><p><b>RESULTS</b>EA can enhance MSC survival (2.6-fold up) at day 4. Big capillary density was 53% higher in EA+MSC treated group than MSC alone group. Furthermore, the rats treated by EA reduced the fibrosis and had 36% smaller infarct size comparing to MSC alone. EA also attenuated left ventricular remodeling and enhanced the functional recovery of infarcted hearts at week 4.</p><p><b>CONCLUSION</b>EA at Neiguan acupoint can promote the stem cell survival and improve ischemic heart function. EA could become a useful approach in stem cell therapy for ischemia heart diseases.</p>

NMR-based metabonomic approach on the toxicological effects of a Cimicifuga triterpenoid.

Cimicifugae Rhizoma, a well-known botanical dietary supplement, has been the subject of intense interest due to its potential application for alleviating menopausal symptom. Although there are clinic data that the Cimicifuga extract should have hepatotoxicity, no evidence on the main chemical components has been reported. Cimicidol-3-O-ß -d-xyloside (CX) is one of the main triterpenoids of the rhizome. This work studies the toxicological effects of CX after oral administration (50 mg kg(-1) per day) over a 7-day period in female SD rats using metabonomic analyses of (1) H NMR spectra of urine, serum and liver tissue extracts. Histopathological studies of liver and analyses of blood biochemical parameter, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen and creatinine revealed that CX had no negative impacts on liver and kidney. However, the metabolic signature of (1) H NMR-based urinalysis of daily samples displayed an increment in the levels of taurine, trimethylamine-N-oxide (TMAO), betaine and acetate. Elevated serum levels of creatinine, glucose, alanine, TMAO and betaine and lower levels of lactate were observed. Metabolic profiling on aqueous soluble extracts of liver showed simultaneously increases in succinate, glycogen, choline, glycerophosphorylcholine, TMAO and betaine levels and reduction in valine, glucose and lactate levels. Nevertheless, no changes in any metabonomic level were found in lipid-soluble extracts of liver. These findings indicate that CX has a slight toxicity in liver and kidney via disturbance of the metabolisms of energy and amino acids. The present study provides a reasonable explanation for the clinical hepatotoxicity of Cimicifuga extract.

Effects of tongxinluo on angiogenesis and the volume of blood perfusion in ischemic stroke rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effects of Tongxinluo (TXL) on angiogenesis and the volume of blood perfusion in ischemic stroke rats.</p><p><b>METHODS</b>The model of middle cerebral artery occlusion (MCAO) was established using craniotomy ligation of the middle cerebral artery on one side. After screening, the male SD rats were randomly divided into the sham-operation group, the model group, the large dose TXL group, the middle dose TXL group, the low dose TXL group, and the Nimodipine group. The expression of microvascular density (MVD, CD31) of the MCAO rats was detected using immunohistochemical assay after 14 days of medication. The microvascular morphology and the volume of blood perfusion in the brain tissue were observed under laser scanning confocal microscope (LSCM).</p><p><b>RESULTS</b>The positive CD31 expression was intense with significant coloring in the large dose TXL group, the middle dose TXL group, and the Nimodipine group, better than that of the model group. The blood perfusion volume in the ischemic brain cortex could be promoted in the large dose TXL group, the middle dose TXL group, and the Nimodipine group (P<0.01, P<0.05). The optimal effects were shown in the large dose TXL group (P<0.01).</p><p><b>CONCLUSION</b>TXL significantly increased the MVD of the ischemic brain tissue, promoted the post-ischemic angiogenesis, and increased the volume of blood perfusion of ischemic brain tissue, playing certain blood flow compensatory roles.</p>

Dingxin recipe ( ) prevents ischemia/reperfusion-induced arrhythmias via up-regulating prohibitin and suppressing inflammatory responses / 中国结合医学杂志

<p><b>OBJECTIVE</b>To identify the underlying mechanisms of the protective effects of Dingxin Recipe (: , DXR), a Chinese compound prescription that has been used clinically in China for more than 20 years, on ischemia/reperfusion (I/R)-induced arrhythmias in rat model.</p><p><b>METHODS</b>A total of 30 rats were randomly divided into three groups: sham group, I/R group, and DXR-pretreated I/R (DXR-I/R) group. Rats in the DXR-DXRI/R group were intragastrically administrated with DXR (12.5 g/kg per day) for consecutive 7 days, while rats I/in the sham and I/R groups were administrated with normal saline. Arrhythmias were introduced by I/R and electrocardiograms (ECG) were recorded. Two-dimensional (2-D) polyacrylamide gel electrophoresis and matrix-matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify assisted differentially expressed proteins. Immunohistochemistry, real-time quantitative polymerase chain reaction (RQ-RQPCR), Western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to analyze proteins PCR), obtained in the above experiments.</p><p><b>RESULTS</b>DXR significantly reduced the incidence and mean duration of ventricular tachycardia and ventricular fibrillation and dramatically decreased the mortality, as well as arrhythmia score, compared with those of the I/R group. Among successfully identified proteins, prohibitin (PHB) and heart fatty acid binding protein (hFABP) were up-regulated in DXR-pretreated I/R rats compared with those of the I/R rats. In addition, compared with the I/R group, the level of glutathione (GSH) was elevated accompanied by reduced expressions of interleukin-6 (IL-6) and neutrophil infiltration in I/R rats with DXR pretreatment.</p><p><b>CONCLUSIONS</b>DXR could alleviate I/R-induced arrhythmias, which might be related to increased expression of PHB. The enhanced expression of PHB prevented against the depletion of GSH and consequently inhibited apoptosis of cardiomyocytes. Furthermore, up-regulation of PHB might ameliorate I/R-induced cell death and leakage of hFABP by suppressing neutrophil infiltration and IL-6 expressions.</p>