The preventive effect and mechanism of Dayuanyin in hypoxic pulmonary hypertension through NF-κB signaling pathway / 药学学报

Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg·kg-1), and positive control sildenafil group (100 mg·kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% ± 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF-κB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF-κB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-κB and signal transducer and activator of transcription 3 (STAT3) by DYY.

Identification of multi-target anti-cancer agents from TCM formula by in silico prediction and in vitro validation / 中国天然药物

Cancer is a complex disease associated with multiple gene mutations and malignant phenotypes, and multi-target drugs provide a promising therapy idea for the treatment of cancer. Natural products with abundant chemical structure types and rich pharmacological characteristics could be ideal sources for screening multi-target antineoplastic drugs. In this paper, 50 tumor-related targets were collected by searching the Therapeutic Target Database and Thomson Reuters Integrity database, and a multi-target anti-cancer prediction system based on mt-QSAR models was constructed by using naïve Bayesian and recursive partitioning algorithm for the first time. Through the multi-target anti-cancer prediction system, some dominant fragments that act on multiple tumor-related targets were analyzed, which could be helpful in designing multi-target anti-cancer drugs. Anti-cancer traditional Chinese medicine (TCM) and its natural products were collected to form a TCM formula-based natural products library, and the potential targets of the natural products in the library were predicted by multi-target anti-cancer prediction system. As a result, alkaloids, flavonoids and terpenoids were predicted to act on multiple tumor-related targets. The predicted targets of some representative compounds were verified according to literature review and most of the selected natural compounds were found to exert certain anti-cancer activity in vitro biological experiments. In conclusion, the multi-target anti-cancer prediction system is very effective and reliable, and it could be further used for elucidating the functional mechanism of anti-cancer TCM formula and screening for multi-target anti-cancer drugs. The anti-cancer natural compounds found in this paper will lay important information for further study.

Evaluation of the preventive effect of DL0805-2 against monocrotaline induced rat pulmonary arterial hypertension / 药学学报

In the treatment of hypertensive crisis, the novel Rho kinase inhibitor DL0805-2 can rapidly lower systematic blood pressure, reduce pulmonary artery pressure, and has a significant protective effect on lung injury. This experiment intends to evaluate the efficacy of DL0805-2 against pulmonary arterial hypertension (PAH) and preliminarily reveals its underlying mechanism. Animal welfare and experimental procedures are in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Sprague Dawley (SD) rats were randomly divided into DL0805-2 low, medium, and high dose groups (1, 3, and 10 mg·kg-1), bosentan positive control group, model group, and blank control group. The drug was administered daily on the 7th day after model establishment by monocrotaline injection. On the 25th day of the experiment, relevant indicators were examined to observe the therapeutic effect of DL0805-2 on pulmonary hypertension. DL0805-2 significantly relieved the abnormal changes in the physiological parameters related to PAH induced by monocrotaline, including reducing right ventricular systolic pressure, alleviating cardiac damage caused by pressure overload, and reducing the levels of endothelin-1 and inflammatory factors in lung tissues. DL0805-2 also attenuated pulmonary arteries remodeling. It was preliminarily discovered that DL0805-2 exerts preventive and therapeutic effect on PAH through Rho-kinase pathway. Our results suggested that DL0805-2 had good therapeutic effects on monocrotaline-induced PAH rat model. It intervened early in the disease process, effectively prevented the development of the disease, and reduced the mortality of the diseased animals. The mechanism is related to Rho-kinase pathway.

Puerarin protects against myocardial ischemia/reperfusion injury by suppressing NLRP3 inflammasome activation via TLR4/Myd88/NF-κB pathway in rats / 药学学报

This study was to investigate the protective effects of puerarin on myocardial ischemia/reperfusion (MI/R) injury and the underlying mechanism. The MI/R-model was established by ligating the left anterior descending artery (LAD) for 60 min followed by 24 h reperfusion, puerarin (10, 30, and 100 mg·kg-1) was orally administered 20 min before reperfusion. Cardiac function, myocardial infarct index, cardiac damage markers, inflammatory cytokines, and apoptosis index were measured to evaluate the protective effects of puerarin on MI/R injury. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome and Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor kappa B (NF-κB) pathway were determined by Western blot. All animal experimental procedures were approved by the ethics committee of the Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences. The results showed that puerarin could significantly improve cardiac function, reduce myocardial infarct size, decease the levels of lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase-MB (CK-MB), and cardiac troponin T (cTnT) and suppress cardiomyocyte apoptosis. Meanwhile, puerarin could notably decrease the levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed that puerarin could downregulate the expression of TLR4, Myd88, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-caspase 1, cleaved-gasdermin-D (GSDMD), IL-1β, and IL-18, as well as the phosphorylation levels of inhibitor of NF-κB α (IκBα), IκB kinase β (IKKβ), and NF-κB. These findings demonstrated that puerarin could alleviate MI/R injury by suppressing NLRP3 inflammasome activation, possibly via TLR4/Myd88/NF-κB pathway.

Preparation of a co-amorphous form of bexarotene-PVP-K30 and evaluation in rats / 药学学报

Bexarotene is a synthetic analogue of retinoic acid and exerts protective effects on the nervous system. However, low bioavailability and poor solubility of the crystal type I form severely limits the application of bexarotene in the clinic. A co-amorphous sample of bexarotene-PVP-K30 was prepared and the structure was characterized by X-ray diffraction and infrared spectroscopy. To determine the pharmacokinetics and tissue distribution of bexarotene, an LC-MS method was established to profile and quantify bexarotene in plasma and tissues of SD rats. In vitro dissolution indicated that the co-amorphous form improved the dissolution of bexarotene in pure water 4.17-fold. After rats were orally administered bexarotene or bexarotene-PVP-K30 co-amorphous (equivalent to 30 mg·kg-1 bexarotene) the AUC of bexarotene was 7 034.89 and 10 174.03 μg·L-1·h respectively, the peak time was advanced from 7.33 h to 0.9 h with the amorphous form, and Cmax was enhanced from 627.76 to 3 011.88 μg·L-1. The co-amorphous form yielded higher concentrations of bexarotene in various tissues, especially brain, liver and kidney. Animal welfare and experimental procedures complied with the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. The results indicate that bexarotene-PVP-K30 co-amorphous improves the pharmacokinetic characteristics of bexarotene and provides preclinical data in support of bexarotene-PVP-K30 for the treatment of brain diseases.

The effect and mechanism of baicalein on regulating gut microbiota and improving chemotherapy-induced intestinal mucositis in mice / 药学学报

We evaluate the therapeutic effects of baicalein on chemotherapy-induced intestinal mucositis (CIM) in mice. The role of gut microflora regulation in the therapeutic effects of baicalein was investigated meanwhile. Male Balb/c mice were randomly divided into three groups including normal control group, model group and experimental group. Except for normal control group, mice were injected with 5-fluorouracil and irinotecan to induce CIM. Animal welfare and experimental procedures comply follow the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Baicalein significantly reduced disease activity index (DAI) of CIM mice and decreased the content of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in serum. There were significant differences in the composition of the gut microbiota among groups according to the analysis of α diversity, β diversity, and the species differences. Compared with the normal control group, the Ruminococcaceae_UCG_014 and unclassified_f_Lachnospiraceae in mice of model group were significantly decreased while Bacteroides, Escherichia_Shigella, Enterococcus, Parabacteroides, Clostridium_ sensu_stricto_1, and Lactococcus were significantly increased. Baicalein significantly decreased the abundance of Bacteroides, Escherichia_Shigella, Parabacteroides, Enterococcus, Clostridium_sensu_stricto_1, and Lactococcus. Meantime, norank_f_Muribaculaceae was notably increased by baicalein. The content of IL-6 and TNF-α in the serum of the three groups were positively correlated with the abundance of Clostridium_sensu_ stricto_1, Lactococcus, Bacteroides, and Enterococcus according to correlation analysis. This study suggested the potential therapeutic effect of baicalein on CIM in mice. Regulation of gut microbiota probably plays a critical role in the therapeutic effects of baicalein.

Study on the therapeutic effects and mechanism of cryptotanshinone on mice with chemotherapy-induced mucositis / 药学学报

This study systematically investigated the therapeutic effects of chemotherapy-induced mucositis (CIM) by cryptotanshinone (CTS) in mice. CIM mice were prepared by intraperitoneal injection of 5-fluorouracil (5-FU) and irinotecan for 4 days. A pseudo-sterile mouse model was established by intragastric administration of mixed antibiotics (metronidazole, vancomycin, and penicillin). The body weight, disease activity index (DAI), and defecation of mice were daily monitored. The animal welfare and experimental procedures followed the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. We determined the contents of inflammatory factors, total cholesterol (TC), triglyceride (TG), and lipase activity in serum or colonic mucosa of CIM mice. We also studied the composition and relative abundance of fecal flora. The correlation of the relative abundance of fecal microbiota and environmental factors was further analyzed. CTS significantly decreased DAI and reduced the content of interleukin 6 (IL-6), interleukin 11 (IL-11), myeloperoxidase (MPO), and diamine oxidase (DAO) in the serum of CIM mice. CTS effectively increased the content of TG while reduced TC and lipase activity in serum. Results showed the incidence of CIM in pseudoaseptic model group was significantly reduced. Meanwhile, there was no significant difference in the contents of inflammatory factors and TG/TC ratio between pseudoaseptic model group and normal control group. There was a significant difference in the diversity and composition of fecal microbiota among groups. In addition, CTS restored the composition of fecal microbiota close to normal and significantly increased the abundance of g_norank_f_Muribaculaceae. Especially, g_Ruminiclostridium and g_norank_f_Muribaculaceae exhibited a significant positive correlation to TG but a negative correlation to DAO, MPO, IL-6, lipase, and TC. Cryptotanshinone significantly increased the abundance of g_norank_f_Muribaculaceae and g_ruminococcaceae_UCG-014 in fecal microbiota of CIM mice. In conclusion, we reported CTS effectively alleviated intestinal mucositis in mice induced by 5-fluorouracil and irinotecan by regulating fecal microbiota, inflammatory factors, and serum lipid.

Study on difference of chemical compositions of Guilingji before and after alchemy based on mass spectrometry and multivariate statistical analysis / 中国中药杂志

UPLC-Q-Orbitrap MS/MS and ICP-MS coupled with multivariate statistical analysis was employed to explore the differences in chemical compositions of Guilingji(GLJ) before and after alchemy.The changes in organic chemical compositions and inorganic elements were observed and 39 differential organic compositions were found in GLJ after alchemy, 24 compounds of which were identified. The differential compositions of GLJ included violet ketones, chalcones, amides, and fatty acids whose contents were increased after alchemy, as well as flavones, isoflavones, dihydroflavones, flavonoid glycosides, and coumarins whose content were decreased after alchemy. This study showed 6 inorganic elements filtered out as markers for distinguishing GLJ before and after alchemy, including B, Si, Mg, K, Cr, and Ni.The contents of Mg, K, Cr and Ni were increased while the contents of B and Si were decreased after alchemy.The difference of the contents after alchemy changed the cold and hot properties of the compound, showing the decrease of dryness, and the hot property was changed to warm and neutral properties; in addition, the membrane permeability and absorption of the compound compositions were improved. In this study, we preliminarily investigated the changes of chemical compositions in GLJ before and after alchemy as well as the effects of alchemy on physical and chemical properties and cold-heat nature of GLJ, laying a foundation for further clarifying the scientific connotation of alchemy process.

Research progress about the anti-aging effect and mechanism of flavonoids from traditional Chinese medicine / 药学学报

Aging is a normal physiological process involving coaction of many factors. The anti-aging effects of natural products have been studied by many domestic and international scholars, but not far enough, which still needed to be explored. Flavonoids, as natural products, have a variety of pharmacological activities and present in many traditional Chinese medicines. In recent years, research results indicate that flavonoids can delay the aging process of the nervous, immune, and reproductive systems, and the liver, skin and other tissues. The anti-aging effects of flavonoids have attracted more and more attention. Therefore, development of anti-aging drugs from flavonoids is of great significance to improve the quality of life for the elderly and slow the process of aging. However, the mechanism of the anti-aging effect of flavonoids remains unknown at present. This review will discuss the anti-aging effect and mechanisms of flavonoids in traditional Chinese medicine from the aspects of cellular signaling pathways and metabolic pathways based on the modern theories of aging.

Research progress of traditional Chinese antidepressant herb-pair / 药学学报

@#Depression, a global disease with various pathogenic factors, is seriously affecting human physical and mental health. In Chinese traditional medical theory, the disease belongs to the category of "Yu Zheng". At present, on the one hand, adverse reactions to antidepressant western medicine are becoming more and more prominent. On the other hand, the study of their antidepressant active ingredients and compatibility mechanisms has become a difficult field in the traditional Chinese medicine compounds due to their complexity. The Chinese antidepressant herb-pairs has become a hot topic in the field of antidepressant research. Herb-pair is the core of traditional Chinese medicine compound. In addition, the compound itself is a herb-pair. The study of traditional Chinese antidepressant herb-pairs is more conducive to clarify the compatibility mechanism of herb interaction and the mechanism of antidepressants on the body.Therefore, this paper systematically expounds antidepressant herb-pairs from the study of material, pharmacokinetics and efficacy, which aims at providing theoretical support for the compatibility mechanism of antidepressant herb-pairs and the research of new antidepressant drugs.

Salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by protecting the blood brain barrier through MMP-9 inhibition and anti-inflammation / 中国天然药物

Salvianolic acid A (SAA) is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier (BBB) through matrix metallopeptidase 9 (MMP-9) inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion (MCAO) for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 mg·kg. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.

Network pharmacology-based analysis of Chinese herbal Naodesheng formula for application to Alzheimer's disease / 中国天然药物

Naodesheng (NDS) formula, which consists of Rhizoma Chuanxiong, Lobed Kudzuvine, Carthamus tinctorius, Radix Notoginseng, and Crataegus pinnatifida, is widely applied for the treatment of cardio/cerebrovascular ischemic diseases, ischemic stroke, and sequelae of cerebral hemorrhage, etc. At present, the studies on NDS formula for Alzheimer's disease (AD) only focus on single component of this prescription, and there is no report about the synergistic mechanism of the constituents in NDS formula for the potential treatment of dementia. Therefore, the present study aimed to predict the potential targets and uncover the mechanisms of NDS formula for the treatment of AD. Firstly, we collected the constituents in NDS formula and key targets toward AD. Then, drug-likeness, oral bioavailability, and blood-brain barrier permeability were evaluated to find drug-like and lead-like constituents for treatment of central nervous system diseases. By combining the advantages of machine learning, molecular docking, and pharmacophore mapping, we attempted to predict the targets of constituents and find potential multi-target compounds from NDS formula. Finally, we built constituent-target network, constituent-target-target network and target-biological pathway network to study the network pharmacology of the constituents in NDS formula. To the best of our knowledge, this represented the first to study the mechanism of NDS formula for potential efficacy for AD treatment by means of the virtual screening and network pharmacology methods.

New situation and new strategies——research and development and internationalization of new drugs and health products of traditional Chinese medicine / 中国药理学与毒理学杂志

The 2017 China (Lianyungang) International Medical Technology Conference was held in Lianyungang,Jiangsu Province during November 15-17,2017.During this conference,the Division for Traditional Chinese Medicine and Natural Products Pharmacology of Chinese Pharmacological Society (CNPHARS) and Jiangsu Kanion Pharmaceutical Co. Ltd.jointly held the Forum on R&D and Interna-tionalization of New Drugs and Health Products of Traditional Chinese Medicine.The forum was co-chaired by Professor ZHANG Yong-xiang, President of CNPHARS, Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Chair of the Natural Product Section of Inter-national Union of Basic&Clinical Pharmacology(IUPHAR), Professor DU Guan-hua,former President of CNPHARS and Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Dr.XIAO Wei,Chairman of the Board of Jiangsu Kanion Pharmaceutical Co. Ltd. And Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS. More than 70 scholars attended the forum, including four foreign experts [Michael SPEDDING, Secretary-General of IUPHAR; Professor Valérie B. SCHINI-KERTH, Vice-Chair of the Natural Product Section of IUPHAR; Professor Cherry WAINWRGHT, Director of Centre for Natural Product Drugs of Robert Gordon University; Professor InKyeom KIM, Director of the Korean Society of Pharmacology], members of the Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS and leading researchers at Jiangsu Kanion Pharmaceutical Co.,Ltd.GU Jin-hui,Director of the Division of National Science and Technology Major Project for Drug Innovation,Department of Health Science,Technology and Education,National Health and Family Planning Commission of the People's Republic of China was also invited to attend the forum. Representatives discussed the R&D and internationalization of new drugs and health products of traditional Chinese medicine.The summary of views and advice of some experts was published here for the purpose of promoting domestic and overseas academic exchange, and playing an active role in improving the level of R&D and internationalization of new drugs and health products of traditional Chinese medicine in China.

Study,application and communication of traditional medicine among the Belt and Road Countries / 中国药理学与毒理学杂志

Most medicines used in the ancient people were the natural raw products, and most of them were discovered during the life.As the differences of the geography,climate and living habits among the different regions,various medicines were used for treatment of diseases in local people.The communica-tion of medicines made a lot of benefits for people living in different regions. Communication of medicines promote the application of medicines and natural resources.As early as 2000 year ago, the ancient Chinese people had sent a lot of medicines to many countries among the Belt and Road during their visiting to these countries. The medicines were the main contents for communication besides of the silk and porcelain.These medicines has been used for treatment of diseases for local people till now.On the Belt and Road, many spices, fruits, seeds produced in different regions were spread among the countries.Most of them were planted and produced in China.But the important events were the application of these special products, such as spices, fruits and seeds used as medicines under the guidance of traditional Chinese medical theory. These drugs have played major roles in the treatment of diseases and development of traditional Chinese medicine. Communication of the medicines, including the medical theory and drugs, improved the medical standards in China.For example,ancient Persian medicine had a significant impact on the use of tradi-tional Chinese medicine in the prescription application.And also, the medicines made important contri-butions to the health of people in the countries on the Belt and Road. Now, the science and techniques have been developed. Many principles and understandings are different from the ancient people. However, the medicines developed in the countries on the Belt and Road still used for the health of human beings.To research the ancient medicines by the modern tech-niques and through co-operation will greatly contribute to human healthand promote the social prog-ress and economic development of the countries on the Belt and Road.

Salvianolic acid A attenuates vascular remodeling in pulmonary arterial hypertension rats induced by monocrotaline / 中国药理学与毒理学杂志

OBJECTIVE Salvianolic acid A (SAA) is one of the most bioactive compounds from a traditional Chinese medicine called Dan Shen(Salvia Miltiorrhiza Bunge)and exhibits many pharmaco-logical activities.Previous studies have indicated that SAA may inhibit endothelial dysfunction and vascular remodeling in spontaneously hypertensive rats. However, whether SAA improves vascular remodeling induced by pulmonary arterial hypertension (PAH) remains unknown. In this study we examined whether SAA attenuated vascular remodeling in a PAH rat induced by monocrotaline(MCT),and elucidated the underlying mechanisms.METHODS PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg·kg-1).The rats were orally treated with either SAA(0.3,1,3 mg·kg-1·d-1)or a positive con-trol Bosentan(30 mg·kg-1·d-1)for 4 weeks.Echocardiography and hemodynamic measurements were performed on d 28.Then the hearts and lungs were harvested,the organ indices and pulmonary artery wall thickness were calculated,and biochemical and histochemical analysis were conducted.The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.RESULTS Treatment with SAA effectively ameliorated MCT-induced pulmonary artery remodeling,pulmonary hemodynamic ab-normalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium,parenchymal in-jury and collagen deposition in the lungs.Moreover,the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs.The treatments partially restored MCT-induced reductions of bone morphoge-netic protein typeⅡ receptor (BMPRⅡ) and phosphorylated Smad1/5 in the lungs. CONCLUSION SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis.Thus,SAA may have therapeutic potential for the pa-tients at high risk of PAH.

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.

Research advances in antiplatelet activation of water soluble compounds in Salvia miltiorrhiza / 中国药理学与毒理学杂志

Platelets are fragments of cytoplasm that are released from the mature megakaryocyte of the bone marrow.The main function of platelets is coagulation and hemostasis.Platelets play a central role in formation of pathological thrombosis. Many ischemic diseases are caused by excessive activa-tion of platelets, which can lead to thrombosis and death. Salvia miltiorrhiza Bunge, the dry roots and rhizomes of the Salvia miltiorrhiza plants,includes some water-soluble compounds,which play positive effects on diverse diseases such as neurodegenerative diseases, diabetic complications or cardiovas-cular diseases.In this paper,the components of the water-soluble in Salvia miltiorrhiza,as well as the applications in thrombotic diseases are summarized. The results show that water-soluble compounds include salvianolic acid A,salvianolic acid B,protocatechuic aldehyde, Danshensu,etc.The water-soluble compounds are applied to ischemic stroke,myocardial infarction and other diseases caused by thrombus. We also discussed the mechanisms of water-soluble compounds on the platelets based on our research results and the data obtained from references. The results indicate that water soluble compounds in Salvia miltiorrhiza play the antiplatelet and antithrombotic effects via different mechanisms, for example, salvianolic acid A inhibits platelet aggregation without promoting bleeding by increasing cAMP, inhibiting phosphoinositide 3-kinase (PI3K) and affecting GPCRs (G protein-coupled receptors) signaling path-ways; salvianolic acid B inhibit platelets as a P2Y12 antagonist and PDE inhibitor; Danshensu inhibits platelet activity may be related to inhibition of calcium influx.In conclusion,thrombotic diseases seriously affect human life and health. The existing antiplatelet drugs have some disadvantages. For example, aspirin may cause intracranial hemorrhage, and clopidogrel may play a slower role. Salvia miltiorrhiza as a traditional Chinese medicine has positive pharmacological activity and exerts antiplatelet aggrega-tion through different mechanisms.In the future,we will develop the new drugs which prevent and treat thrombotic diseases with the further study of the pharmacological effects and mechanisms of Salvia miltiorrhiza.

Saffron:a potential immunological adjuvant in anti-tumor therapy / 中国药理学与毒理学杂志

A large and increasing number of patients in the world use medicinal plants and herbs for health purposes.Especially,chemoprevention using readily available natural substances from vege-tables,fruits,herbs and spices is one of the significantly important approaches for cancer prevention in the present era. Saffron is native to Iran and now recorded in "Chinese Pharmacopoeia" as a widely used Chinese medicine with good safety. Other than several useful pharmacological effects such as anticonvulsant, antidepressant, anti-inflammation, saffron and its active components (crocin, crocetin and safranal)have been shown to induce apoptosis in several tumor cell lines and mouse tumors with beneficial properties including radical scavenging, anti-mutagenic and immuno-modulating effects. In addition,saffron was reported good potential to alleviate the toxicity ofcisplatin,including the nephrotox-icity.However,the application of these components in the clinic has been limited due poor clinical trials data. This review aimed to provide a brief overview on clinical evaluation for anti-tumor potential and current molecule mechanism of saffron based on recent literature data.

Xiao-Xu-Ming decoction protects against chronic cerebral ischemia injury in rats and profile of differentially expression proteins analysis in hippocampus / 中国药理学与毒理学杂志

OBJECTIVE Vascular dementia (VD) refers to a progressive decline in memory and cognitive function caused by chronic cerebral ischemia. 2-Vessels occlusion (2-VO) has been widely used as a model of VD. Xiao-Xu-Ming decoction, a well-known traditional Chinese medicine prescrip-tion,has been widely used to treat stroke and sequelae of stroke.The present study was to investigate the mechanism of Xiao-Xu-Ming decoction(XXM) against chronic cerebral ischemia injury in rats. METHODS After XXM treatment, rats were performed a memory testing with Morris water maze and motor ability testing using prehensile test and inclined screen test.Neuronal plasticity was observed by immunofluorescent staining with MAP2 antibody. Differentially expressed proteins of rat hippocampus were analyzed by Label-free quantitative proteomics. RESULTS XXM significantly alleviated 2-VO-induced learning and memory deficits, motor ability dysfunction, and neuronal plasticity injury in rats. The mechanism might be involved in up-regulation of 39 proteins and down-regulation of 13 proteins in the hippocampus of rats after XXM treatment vs 2-VO group rats.Gene ontology and pathway analysis showed that the regulated proteins are mainly involved in oxidation reduction process, intracellular signaling cascade process, and protein catabolic process, etc. The signal pathways are mainly involved in ubiquitin mediated proteolysis and phosphatidylinositol signaling system. CONCLUSION Current findings provide new insights into the molecular mechanisms of XXM on chronic cerebral ischemia.

Network mechanism of effective constituents from the compound Yizhihao against influenza / 中国药理学与毒理学杂志

Influenza caused by influenza virus,seriously threaten human life and health.Drug treatment is one of the effective measurement. However, there are only two classes of drugs, one class is M2 blockers and another is neuraminidase (NA)inhibitors. The recent antiviral surveillance studies reported a global significant increase in M2 blocker resistance among influenza viruses, and the resistant virus strains against NA inhibitor are also reported in clinical treatment.Therefore thediscovery of new medicines with low resistance has become very urgent.As all known,traditional medicines with multi-target features and network mechanism often possess low resistance. Compound Yizhihao, which consists of radix isatidis,folium isatidis,Artemisia rupestris,is one of the famous traditional medicine for influenza treatment in China, however its mechanism of action against influenza is unclear. In this study, the multiple targets related with influenza disease and the known chemical constituents from Compound Yizhihao were collected, and multi-target QSAR (mt-QSAR) classification models were developed by Na?ve Bayesian algorithm and verified by various datasets. Then the classification models were applied to predict the effective constituents and their drug targets.Finally,the constituent-target-pathway network was constructed,which revealed the effective constituents and their network mechanism in Compound Yizhihao. This study will lay important basis for the clinical uses for influenza treatment and for the further research and development of the effective constituents.