Abstract：ObjectiveA new prescription containing Portulacae Herba was created and the molecular mechanism of the new prescription for treating diabetes was clarified based on big data of traditional Chinese medicine （TCM）.MethodTaking Portulacae Herba as the key word， the TCM Inheritance Support System and Encyclopedia of TCM （ETCM） were used to excavate the most frequently used medicines combined with Portulacae Herba， and form a new prescription. Based on the basic theory of TCM， this paper analyzed the rationality of the new prescription in treating diabetes， and used the Integrative Pharmacology-based Research Platform of TCM （TCMIP） to predict the target of the new prescription， and constructed the interaction network between drugs and targets of diabetes-related diseases， the key targets of drug intervention were enriched and analyzed， and the network graph of TCM-chemical composition-key target-pathway was drawn.ResultThere were 89 prescriptions containing Portulacae Herba in ETCM. The most frequently used medicines in combination with Portulacae Herba were Phellodendri Chinensis Cortex， Rehmanniae Radix and Saposhnikoviae Radix， the four medicines were combined into a new prescription. According to the new prescription to treat diabetes， 89 key core target information was obtained， among which there were 10 targets of drug and disease， including phosphoinositide-3 kinase regulatory subunit 1 （PIK3R1）， insulin （INS）， glucokinase （GCK）， etc. The new prescription treated diabetes by regulating growth hormone receptor signaling， protein kinase A （PKA） activation， adrenoceptors and other pathways.ConclusionThe therapeutic effect of new prescription containing Portulacae Herba created by big data analysis of TCM on diabetes reflects multi-component， multi-target， multi-pathway characteristics of TCM， which can provide scientific basis for explaining the mechanism and material basis of this new prescription in the treatment of diabetes.
Keywords：Portulacae Herba;Traditional Chinese Medicine Inheritance Support System （TCMISS）;Encyclopedia of TCM （ETCM）;integrative pharmacology;formula;protein kinase;molecular mechanism
Abstract：ObjectiveTo explore the anti-liver cancer potential of Fufang Biejia Ruangan Pian （FBRP） and its compatibility characteristics from a network perspective， so as to provide a theoretical basis for the clinical repositioning of FBRP.MethodThree self-pairs of cancer and para-cancerous tissue samples were collected from three patients with primary liver cancer， and the whole genome expression profiling chip was used to detect the differential genes related to the development and progression of liver cancer. After collecting the phenotype-related genes and the candidate targets of the corresponding prescriptions of FBRP from The Encyclopedia of Traditional Chinese Medicine （ETCM） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） V2.0， the "differentially expressed genes related to liver cancer development-candidate targets of FBRP efficacy substance group" interaction network was constructed according to the interaction information between the above-mentioned differentially expressed genes related to liver cancer and the candidate targets of the FBRP efficacy group， and then the major network nodes were screened. After that， the enrichment analysis of the pathway was performed in order to explore the biological basis of various pharmacological efficacy groups of FBRP， including Xiaozheng Sanjie group （Trionycis Carapax and Curcumae Rhizoma）， Buxue Huoxue group （Paeoniae Radix Rubra， Angelicae Sinensis Radix and Notoginseng Radix et Rhizoma）， Yiqi Jianpi group （Codonopsis Radix and Astragali Radix）， Yuyin Yanggan group （Placenta Hominis and Cordyceps） and Qingre Jiedu group （Isatidis Radix and Forsythiae Fructus）.ResultThe major network targets of the five efficacy groups may be involved into several common pathways but also associated with some special pathological processes. Those common pathways mainly contained the regulation of nervous system， the balance of immune-inflammatory system， the regulation of energy metabolism of various substances and cancer-related pathways， while the point was also reflected by the follows：①The regulating effects of Xiaozheng Sanjie group and Yiqi Jianpi group were summarized as promoting Qi circulation and relieving depression and replenishing Qi-blood， benefiting spirit. Buxue Huoxue group may also participate in the regulation of promoting Qi circulation and relieving depression and Yuyin Yanggan group may participate in the regulation of replenishing Qi-blood and benefiting spirit. ②The regulatory effects of the Xiaozheng Sanjie group and the Yuyin Yanggan group were summarized as essence， Qi and blood supplement. Buxue Huoxue group focused on the improvement of the immune-circulatory system. Qingre Jiedu group mainly regulated the balance of immune-inflammatory system by acting on T cell receptor signaling pathway. ③Yiqi Jianpi group was demonstrated to show the effects on various material and energy metabolisms. Yuyin Yanggan group exerted effects on lipid metabolism， carbohydrate metabolism， protein metabolism and hormone metabolism. Qingre Jiedu group was also involved into metabolism of nucleotide and hormone. ④In the aspect of alleviating the pathological changes of cancer， the regulatory effects of the five efficacy groups on cell cycle and other functions could be summarized as dispelling pathogenic factors. ⑤The whole prescription focused on the anti-liver cancer potential of FBRP as a whole， while each efficacy group emphasized that each efficacy group had its own functional characteristics. The two network analysis models complemented and verified each other.ConclusionFBRP has the anti-hepatoma potential. By revealing the biological connotation of its efficacy and the rationality of the compatibility， the regulation mechanism of FBRP to correct the imbalance network of inflammation and cancer in liver is clarified， which can provide the possibility and biological basis for FBRP to increase the clinical indications for the prevention and treatment of liver cancer.
Keywords：network pharmacology;Fufang Biejia Ruangan Pian;malignant transformation of inflammatory-carcinoma;hepatocellular carcinoma;theory of composing prescriptions;clinical repositioning;compatibility
Abstract：ObjectiveTo predict the potential molecular mechanism of Yangxue Antai Fang in treating prethrombolic state of recurrent spontaneous abortion （RSA-PTS）.MethodThe chemical constituents and drug targets of Yangxue Antai Fang were collected by Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP V2.0）. RSA-PTS disease target information was collected by TCMIP V2.0 and improved by Online Mendelian Inheritance in Man （OMIM） database. The interaction of these targets was analyzed and key target network was constructed. Gene ontology （GO） function and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were further performed. Finally， Cytoscape 3.5.1 was used to build up a multidimensional network of TCM-ingredient-target-pathway. The levels of absorption， distribution， metabolism， excretion and toxicity （ADMET） of the main components in the network were analyzed.ResultA total of 310 chemical constituents and 975 targets were collected from 8 TCMs in Yangxue Antai Fang. A total of 143 targets of RSA-PTS were obtained. A total of 243 core targets were obtained by the interrelationship analysis of drug and disease targets. The analysis of the top 100 core targets showed that these targets might participate in treating RSA-PTS by affecting biological processes related to thrombosis， such as blood coagulation， platelet activation， positive regulation of angiogenesis and so on. Pathway analysis showed that these targets were mainly concentrated in complement and coagulation cascades， platelet activation， estrogen signaling pathway， thyroid hormone signaling pathway， etc. Multidimensional network analysis in combination with ADMET level showed that 14 components （leonurine， paeonol， vanillin， and so on） may play a therapeutic role in RSA-PTS by affecting coagulation factors Ⅱ （F2）， plasminogen （PLG） and estrogen receptor 1 （ESR1） proteins involved in complement and coagulation cascades， platelet activation， thyroid hormone signaling pathway and others.ConclusionThe main chemical constituents in Yangxue Antai Fang may improve RSA-PTS by regulating complement and coagulation cascades， blood coagulation， platelet activation and other biological processes.
Abstract：The scientific interpretation of the connotation of traditional Chinese medicine （TCM） theory is an important part of the development of TCM. Combined ancient classic theories with modern science and technology is a new path for the innovative development of TCM theory. Based on this， taking Zhishi Xiebai Guizhitang as an example， the molecular mining technology of integrative pharmacology-based research platform of TCM V2.0 （TCMIP V2.0） was used to analyze the mechanism of Zhishi Xiebai Guizhitang in preventing and treating gastropathic stomachache. A total of 220 chemical components in Zhishi Xiebai Guizhitang were obtained， and 674 targets were involved， of which 12 core targets directly affected angina pectoris and gastroesophageal reflux disease， including insulin （INS）， glyceraldehyde-3-phosphate dehydrogenase （GAPDH）， RAC-α serine/threonine-protein kinase 1 （AKT1）， tumour protein p53 （TP53）， albumin （Alb）， mitogen-activated protein kinase 3 （MAPK3）， interleukin-6 （IL-6）， etc. And tumor necrosis factor （TNF） signaling pathway， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， IL-17 signaling pathway， hypoxia-inducible factor-1 （HIF-1） signaling pathway and other 121 pathways involved in these related diseases. All of these are the biological basis of Weiluo Tongxin theory. Combing the classical theories of TCM combined with the exploring the molecular mechanism of representative prescriptions can provide a demonstration and reference for the scientific connotation research of TCM theory.
Keywords：Weiluo Tongxin;Zhishi Xiebai Guizhitang;molecular mechanism;integrative pharmacology;inflammation;cardiovascular disease;traditional Chinese medicine theory
Abstract：ObjectiveTo explore the effect of Anmeidan （AMD） on the learning and memory levels of sleep deprived rats through mitochondrial mediated hippocampal neuronal apoptosis pathway.MethodForty-eight SD rats were randomly divided into blank group， model group， low， medium， high-dose AMD groups （4.86， 9.72， 19.44 g·kg-1·d-1） and estazolam group （0.1 mg·kg-1·d-1）. Insomnia model was prepared by self-made sleep deprivation box for 14 days. Morris water maze was used to detect learning and memory levels， enzyme-linked immunosorbent assay （ELISA） was used to detect the expressions of cytochrome C （Cyt-C）， cysteine aspartic acid protease-3 （Caspase-3） in hippocampus. Transmission electron microscopy （TEM） was used to observe the morphological structure of mitochondria in hippocampus. Protein and mRNA expressions of Cyt-C， Caspase-3， Bcl-2， Bax were detected by immunofluorescence （IF） and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） respectively.ResultIn the model group， the incubation period of the platform and the total distance of swimming and the time of first arriving platform were prolonged， the number of platform crossing and the time of target quadrant movement were reduced， protein and mRNA expressions of Bcl-2 dropped， protein and mRNA expressions of Bax increased （P<0.01）， and mitochondrial structure was abnormal with crista fracture， swelling and deformation. And protein and mRNA expressions of Cyt-C， Caspase-3 increased significantly （P<0.01）. Low， medium and high-dose AMD groups could improve levels of space exploration and navigation of SD rats （P<0.01）， increase protein and mRNA expressions of Bcl-2， decrease protein and mRNA expressions of Bax， improve the damage of mitochondria， and decrease the protein and mRNA expressions of Cyt-C， Caspase-3 （P<0.01）.ConclusionAMD can improve the learning and memory levels of SD rats， the effect is related to the mitochondrial mediated hippocampal neuronal apoptosis pathway and decrease of Cyt-C and Caspase-3 expressions.
Keywords：Anmeidan;sleep deprivation;apoptosis;learning and memory;cytochrome C （Cyt-C）;cysteine aspartic acid protease-3 （Caspase-3）
Abstract：ObjectiveTo explore the effect of Qizhu Zhenwutang on renal interstitial fibrosis in rats ligated with unilateral ureter， transforming growth factor-β1 （TGF-β1）/Smads and oxidative stress.MethodA total of 30 male SD rats were randomly divided into sham operation group， model group， high-dose group， low-dose group and irbesartan group （n=6）. The left ureter ligation was performed in the model group and the treatment group. In the sham operation group， the ureter was not ligated， only the ureter was separated， and the abdominal cavity was closed. Rats in each group were given drugs by gavage on the next day after operation. Sham operation group and model group were given aseptic distilled water 10 mL·kg-1 by gavage， high-dose Qizhizhenwu Tang group was given 22.2 g·kg-1 by gavage， low-dose group was given 11.1 g·kg-1 by gavage， and irbesartan group was given 0.02 g·kg-1 by gavage. Rats in each group were sacrificed on the 14th day after operation， 24-hour urine was collected before sampling， and the total amount of 24 hour urine protein （24 h-Upr） was detected. Blood samples were collected from the abdominal aorta to detect serum creatinine（SCr） and blood urea nitrogen （BUN）. The tissues were stained with htoxylin eosin （HE） and Masson， and the pathological changes were observed under light microscope， immunohistochemical method was used to detect α-SMA， FN and Col-Ⅰ expressions. Western blot method was used to detect the expressions of TGF-β1， Smad3， p-Smad3 and NOX4.ResultCompared with sham group， SCr， BUN and collagen volume fraction （CVF），24 h-Upr in model group were all increased （P<0.05， P<0.01）. The expressions of α-SMA， Col-Ⅰ， FN， TGF-β1， p-Smad3， NOX4 were higher （P<0.05）. Compared with the model group， SCr， BUN and CVF were lower in high-dose group and irbesartan group （P<0.05）. 24 h-Upr was lower in high-dose group （P<0.05）， the expressions of α-SMA， Col-Ⅰ， FN， TGF-β1， Smad3， p-Smad3， NOX4 in traditional Chinese medicine treatment group were less （P<0.05）.ConclusionQizhi Zhenwutang can reduce the urinary protein of UUO rats， protect the renal function， and inhibit the occurrence and development of renal interstitial fibrosis， the mechanism may be related to the inhibition of TGF-β1/Smads signaling pathway and oxidative stress response.
Abstract：ObjectiveTo observe the expression of adenosine monophosphate activated protein kinase （AMPK）/transcription factor EB （TFEB） autophagy signaling pathway protein in type 2 diabetes （T2DM） complicated with nonalcoholic fatty liver disease （NAFLD） rats after intervention with Shihu mixture （SHM）.MethodAmong 40 male SD rats， 10 rats were randomly selected as normal group according to body weight. The remaining 30 rats were fed with high-fat and high-sugar diet for 6 weeks， and then intraperitoneally injected with streptozotocin （STZ） to establish a T2DM NAFLD model. They were divided into normal control group （10 mL·kg-1·d-1）， model control group （10 mL·kg-1·d-1）， metformin group （100 mg·kg-1·d-1）， SHM group （11.3 g·kg-1·d-1）. The rats in each group were gavaged for 4 weeks. After gavage， the rats were euthanized. Abdominal aortic blood and liver tissue were collected to detect fasting blood glucose （FBS）， glycated serum protein （GSP）， insulin （INS）， triglyceride （TG）， total cholesterol （TC）， high density lipoprotein cholesterol（HDL-C）， low-density lipoprotein cholesterol（LDL-C） content. Htoxylin eosin （HE） staining was performed to observe changes in liver tissue morphology. Western blot was used to detect AMPK/TFEB signaling pathway-related protein expression.ResultCompared with the model control group， FBS and GSP of the SHM group and the DMBG group decreased （P<0.05）， while INS increased （P<0.05）. Compared with the model group， HDL increased in the SHM group and the DMBG group （P<0.05）， whereas TC， TG and LDL contents decreased （P<0.05）. Liver HE staining results showed that both SHM and Metformin could improve the liver morphology of T2DM and NAFLD rats to some extent. Western blot results showed that p-AMPK/AMPK of SHM and metformin increased （P<0.05）， while the expressions of TFEB and LC3Ⅱ increased （P<0.05）.ConclusionSHM can improve glucose and lipid metabolism by activating AMPK/TFEB autophagy signaling pathway， so as to improve liver pathological morphology.
Abstract：ObjectiveTo observe the changes of myocardial microvessel density， microvascular endothelial cell morphology and hemorheology in ovariectomized rats and explore the interventional effects of Erxian decoction.MethodThirty-two healthy 10 week-old female SPF SD rats were randomly divided into sham operation group， model group， estrogen group （estradiol valerate， 0.18 mg·kg-1） and Erxian decoction group （9 g·kg-1）. The rats were intragastrically administered 2 weeks after ovariectomy， once a day for 16 weeks. Sham operation groups and model groups were given equal volumes of purified water. After 16 weeks of administration， the cardiac function was measured by noninvasive ultrasound cardiogram （UCG）， CD34 in the myocardial tissue was tested by immunofluorescence staining to measure the microvessel density， the morphological structure of microvessels of myocardial tissue were detected by transmission electron microscope， the levels of estrogen （E2） in rat plasma were detected by radioimmunoassay， the levels of endothelin-1 （ET-1）， prostacyclin I2 （PGI2）， thromboxane A2 （TXA2）， endothelial growth factor （VEGF）， and von Willebrand Factor （vWF） in rat plasma were detected by enzyme-linked immuno sorbent assay （ELISA）， four items of coagulation was detected by blood coagulation analyzer， whole blood viscosity and plasma viscosity were detected by hemorheology.ResultCompared with sham operation group， the ejection fraction （EF） decreased （P<0.01）， the left ventricular short axis shortening rate （FS） decreased （P<0.01）， and the left ventricular end systolic volume （LVVols） increased （P<0.01）， myocardial microvessel density significantly reduced （P<0.01）， the endothelial cells were swollen and the cytoplasm was cavitation， E2 in rat plasma decreased （P<0.01）， ET-1， VEGF， vWF increased （P<0.01）， prostacyclin I2 /thromboxane A2 （PGI2/TXA2） decreased （P<0.01）， plasma activated partial prothrombin time （APTT） decreased （P<0.01）， fibrinogen （FIB） increased （P<0.01）， whole blood viscosity， plasma viscosity， and cassone viscosity increased （P<0.01）， whole blood high-cut， low-cut index， and red blood cell （RBC） aggregation index increased （P<0.05） in model group. Compared with model group， EF and FS increased （P<0.05）， LVVols decreased （P<0.05）， myocardial microvessel density significantly increased （P<0.01）， the endothelial cell edema was improved， and transport vesicles were clearly visible， E2 in rat plasma increased （P<0.01）， ET-1， VEGF， decreased （P<0.01）， PGI2/TXA2 increased （P<0.01）， APTT increased （P<0.01）， whole blood viscosity， whole blood high shear relative index， RBC aggregation index decreased （P<0.05）， Kasson viscosity and plasma viscosity decreased （P<0.01） in Erxian decoction group.ConclusionErxian decoction increases myocardial microvessel density， protects the structural integrity of microvascular endothelial cells， improves its endothelial secretion function and hemorheology in ovariectomized rats， and protects heart function.
Abstract：ObjectiveTo study the effects of licochalcone A （LCA） on the proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes （MH7A） as well as the related inflammatory factors， also to reveal the relevance between mitogen activated protein kinase （MAPK） signaling pathway and LCA regulation of MH7A cell proliferation and apoptosis.MethodMH7A cells were cultured and divided into blank group， LCA groups （10，20，40 μmol·L-1）. The proliferation of MH7A cells was detected by methylthiazolyldiphenyl-tetrazolium bromide（MTT）and immunofluorescence staining. The cell cycle of MH7A cells was determined by flow cytometry after PI staining and apoptosis was detected by flow cytometry after Annexin V/PI staining. The effect of LCA on interleukin-1β（IL-1β） mRNA was detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. Western blot was used to detect the effect of LCA on the key proteins of MAPK signaling pathway， meanwhile， PD98059， a specific ERK inhibitor， was used to observe the expression levels of p-ERK and IL-1β.ResultCompared with blank group， LCA could inhibit the proliferation of MH7A cells in a dose-dependent manner， and the number of living cells decreased significantly（P<0.01）， while the number of early apoptotic cells increased significantly（P<0.01）. Compared with the tumor necrosis factor-α （TNF-α，10 μg·L-1）group， LCA could reverse the expression of IL-1β mRNA induced by TNF-α（P<0.01）. and compared with the blank group， LCA also promoted the phosphorylation of ERK， JNK and p38 in a dose-dependent manner（P<0.01）. After ERK inhibitor PD98059 inhibited ERK phosphorylation， the inhibitory effect of LCA 10， 20 μmol·L-1 on IL-1β disappeared.ConclusionLCA can inhibit the proliferation and induce apoptosis of MH7A cells， which may be related to the phosphorylation of MAPK pathway related proteins， and then inhibit the expression of inflammatory factors.
Keywords：licochalcone A;fibroblast-like synoviocytes（MH7A）cells;mitogen activated protein kinase （MAPK） signaling pathway;apoptosis;interleukin-1β（IL-1β）
Abstract：ObjectiveTo explore the potential mechanisms of Panax Notoginseng Saponins （PNS） on growth inhibition of breast cancer cell line 4T1 in tumor-bearing mice by investigating the mitogen-activated protein kinase kinase kinase 1 （MEKK1）/stress activated protein kinase （SAPK）/extracellular regulated protein kinases （Erk） Kinase （SEK1）/c-Jun N-terminal kinase 1 （JNK1）/activator protein-1 （AP-1） signaling pathways.MethodThe 4T1 breast cancer mice model was established. Forty-eight mice with successful modeled and randomly divided into the low， medium and high-dose PNS groups （10， 20， 40 mg·kg-1） and the model control group （12 mice in each group）. The PNS groups received intraperitoneal injection with dosage of 10 mL·kg-1， while the controlled group was given the same dosage of saline. After administration with PNS for 28 days， tumor tissues were isolated， weighed， sliced and homogenized. Tumor cell apoptosis was detected by TdT mediated-dUTP nick end labeling （TUNEL） staining. The mRNA expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissue were detected by Real-time polymerase chain reaction（Real-time PCR）. The protein expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissue were detected by immunofluorescence staining and Western blot.ResultCompared with model group， the tumor weights of medium-dose and high-dose PNS groups were decreased significantly （P<0.05）. TUNEL staining showed that the number of apoptotic tumor cells increased with the rise of dosage of PNS （P<0.05）. The medium-dose and high-dose PNS groups showed a significant increase in the mRNA expressions of MEKK1， SEK1， JNK1 and AP-1 as well as the protein expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissues （P<0.05）， with statistically significant differences （P<0.05）.ConclusionPNS could inhibit the tumor growth of breast cancer cell line 4T1 in tumor-bearing mice， which may be related to the activation of MEKK1/SEK1/JNK1/AP-1 signaling pathways.
Keywords：Panax Notoginseng Saponins （PNS）;4T1 breast cancer cells;mitogen-activated protein kinase kinase kinase 1 （MEKK1）/stress activated protein kinase （SAPK）/extracellular regulated protein kinases （Erk） Kinase （SEK1）/c-Jun N-terminal kinase 1 （JNK1）/activator protein-1 （AP-1） signaling pathways;apoptosis
Abstract：ObjectiveTo investigate the intervening effect of velvet antler peptide （VAP） on rotenone-induced neuroblastoma （SH-SY5Y） cell damage and explore its related mechanism.Method0.5 μmol·L-1 rotenone was used to SH-SY5Y cells to establish an in vitro model of Parkinson's disease （PD）. A blank control group， a model group， high， medium and low dose VAP groups （150，100，50 mg·L-1， respectively） and a rapamycin group were established. The number of lewy bodies， changes in mitochondrial membrane potential， content of reactive oxygen species （ROS） and α-synuclein （α-syn）， protein kinase B （Akt）， and mammalian target of rapamycin （mTOR） were observed by hematoxylin-eosin（HE） staining， rhodamine 123 staining， DCFH-DA staining and immunohistochemical staining expression respectively.ResultThe results of HE staining showed that as compared with the blank group， the number of cells in model group was reduced， the tentacle structure became dull， the shape became round， and eosinophilic Lewy bodies were visible in cytoplasm. As compared with model group， there was no significant difference in cell morphology from rapamycin group and VAP high， medium and low dose groups， but there were fewer Lewy bodies in cytoplasm in these four groups. Rhodamine 123 staining showed that as compared with blank group， the mitochondrial membrane potential was increased significantly in model group （P<0.05）. As compared with the model group， the mitochondrial membrane potential was decreased in rapamycin group and VAP high， medium and low dose groups （P<0.05）. DCFH-DA staining results showed that as compared with blank group， the content of ROS was increased significantly in cells of model group （P<0.05）. As compared with model group， the content of ROS was decreased in rapamycin group and VAP high， medium and low dose groups （P<0.05）. Immunohistochemical staining showed that as compared with blank group， the protein expression levels of α-syn，Akt，and mTOR were increased significantly in model group （P<0.05）. As compared with model group， the protein expression levels of α-syn and mTOR were significantly reduced in rapamycin group and VAP high and medium dose groups （P<0.05）， and the expression levels of Akt were significantly reduced in rapamycin group and VAP high-dose group （P<0.05）.ConclusionVelvet antler peptides may play a neuroprotective role by regulating the Akt/mTOR signaling pathway and promoting the degradation of α-syn in SH-SY5Y cells.
Keywords：Parkinson's disease;rotenone;velvet antler polypeptide;protein kinase B（Akt）;mammalian target of rapamycin （mTOR）
Abstract：ObjectiveTo observe the effects of Fushengong prescription on secretory glycoprotein （Wnt）/β-serial protein （β-catenin） signaling pathway in kidney of rats with chronic renal failure （CRF），and to further explore its mechanism of releasing the aggregation of extracellular matrix（ECM），inhibiting renal tubule interstitial fibrosis （TIF） and prolonging the progression of CRF.MethodA total of 55 SD male rats were randomly divided into the normal group，the model group，and the low， medium and high dose groups of Fushengong prescription，with 11 rats in each group.The normal group was routinely reared and the other 4 groups of rats were used to establish CRF model with 0.5% adenine fodder， fed them continuously for 21 d. After successful modeling，all model rats were switched to conventional feed. Normal saline （NS） was given the normal group and the model group by 20 mL·kg-1·d-1， the low， middle and high dose groups rats of Fushengong prescription were given intragastric administration Fushengong prescription according to the body weight of 4， 8， 16 g·kg-1，once a day，continuous gavage for 30 d. After the experiment，the pathomorphism change of renal tissues of rats was measured by Masson staining， the expression of Wnt4 and β-catenin mRNA in the kidney tissues were observed by the method of Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， the expression of Wnt4，β-catenin and matrix metalloproteinase-7（MMP-7） protein of renal tissues were detected by the methods of Western blot. The expression of Wnt4， β-catenin protein of renal tissues were detected by the methods of immunohistochemistry （IHC）.ResultCompared with normal group，renal tubule interstitial fibrosis of renal tissues increased distinctly and the expression of Wnt4，β-catenin and MMP-7 protein increased significantly in the model group. Wnt4 and β-catenin mRNA also increased significantly in model group（P<0.01）. Compared with model group， the expression of Wnt4， β-catenin and MMP-7 protein in the Fushengong prescription groups decreased obviously （P<0.05）. The expression of Wnt4 and β-catenin mRNA in Fushengong prescription groups also decreased obviously.ConclusionThe mechanism of Fushengong prescription can release the aggregation of ECM，inhibit TIF and delay the progression of CRF，which may be related with the activation of Wnt/β-catenin signal pathway.
Keywords：Fushengong prescription;chronic renal failure;Wnt/β-catenin signal pathway;extracellular matrix（ECM）;renal tubule interstitial fibrosis（TIF）
Abstract：ObjectiveAnalyze the composition of Tongzhifang，regularity of modified prescriptions based on outpatient medical records of national famous Chinese medicine practitioner Professor YU Ying-ao for the treatment of epilepsy as well as data mining， and summarize the clinical experience of Professor YU in diagnosis and treatment of epilepsy， in order to provide the reference basis for the traditional Chinese medicine treatment epilepsy.MethodBased on the data of outpatient medical records of Professor YU for epilepsy diagnosis and treatment，this study conducted standard patient follow-up，clinical data collection，pretreatment and mining analysis，and was confirmed through expert interviews. Liquorice 2.3 data mining platform and SPSS 17.0 were used for data management and statistical analysis.ResultA total of 1 219 medical records of 243 cases were completely collected. As a result， Professor YU Ying-ao's Tongzhifang for epilepsy was based on ancient prescription Baijinwan，in which Shenglongchi and Ostreae Concha enhance tranquilizing and hyperactivity-subduing effects，Citri Reticulatae Pericarpium，Armeniacae Semen Amarum，Arisaema Cum Bile and Bambusae Caulis in Taenias eliminate phlegm and free channels， Salviae Miltiorrhizae Radix et Rhizoma and Persicae Semen promote blood circulation to remove blood stasis， and the 10 herbs were meticulously composed and well compatible. According to the small sample data，the total effective rate of patients with tetany type epilepsy taking this prescription for 3 months and 6 months was 80% （P<0.01）， with no adverse reactions. As for the dosage of Tongzhifang，the dosage for adult pills is generally 3-6 times that of decoction prescriptions，and the dosage for children's pills is generally 5-10 times that of decoction prescriptions. Under the guidance of the combination of disease differentiation and syndrome differentiation，epilepsy at the acute phase was treated with additionally Hupomo 1.5-3 g，the ratio of Curcumae Radix to Alumen is usually 4∶1， severe convulsion was treated with additionally Uncariae Ramulus Cum Uncis， Bombyx Batryticatus and Pheretima， epilepsy due to trauma was treated with additionally Typhae Pollen， Eupolyphaga Steleophaga， Carthami Flos and Radix Paeoniae Rubra； constipation was treated with additionally Cannabis Fructus； fatigue was treated with additionally Astragali Radix； dyspepsia was treated with additionally Galli Gigerii Endothelium Corneum； and irritability treated with additionally Gentiana scabra Bunge.ConclusionThe composition of Professor YU's Tongzhifang for treating epilepsy with Qianzhen Zhixian Huatan Tongluo method is relatively stable. Modified prescriptions are based on syndrome differentiation. Clinical experience and dosage range of decoction prescription and pill prescription for adults and children are available.
Abstract：ObjectiveTo observe the clinical efficacy of Duhuo Jishengtang combined with minimally invasive decompression of lumber spine in the treatment of degenerative lumbar spinal stenosis with kidney deficiency syndrome for more than 3 years.MethodThrough a single-center parallel randomized controlled clinical trial， 63 patients with degenerative lumbar spinal stenosis who were hospitalized in Jiangsu Hospital of Traditional Chinese Medicine from October 2015 to April 2017 were observed for more than three years. Among them， there were 31 cases in the operation combined with traditional Chinese medicine group （observation group） and 32 cases in the operation combined with Celebrex and Mecobalamin group （control group）. Both groups were given routine treatment. The observation group was treated with Duhuo Jishengtang for 3 weeks， while the control group was treated with Celebrex and Mecobalamin for 3 weeks.ResultIn the aspect of pain improvement， only 3 months after operation， the observation group was superior to the control group （P<0.05）， with no significant advantage at other time nodes during follow-up. During the 3-month follow-up and a longer period， it was confirmed that observation group had a significant advantage in improving lumbar function （P<0.01）. At the last follow-up， the good efficacy rate of observation group was 83.87% （26/31）， while the good efficacy rate of the control group was 62.5% （20/32）. There was no unstable performance in the last follow-up of the two groups. There was no statistically significant difference between two groups.ConclusionThe middle and long-term follow-up for minimally invasive decompression of lumber spine showed a satisfactory efficacy in the treatment of degenerative lumbar spinal stenosis， with no impact on the stability of the operative segments. For patients of lumbar spinal stenosis with kidney deficiency syndrome， Duhuo Jishengtang can promote the recovery of postoperative neurological function， and improve the good efficacy rate of clinical treatment， but with no obvious advantage in pain relieve after operation.
Abstract：ObjectiveTo investigate the effect of Tiluo Yangxue Mingmu prescription on the improvement of visual function，and to analyze the effect on the vessel density and the thickness of retinal nerve fiber layer（RNFL） of optic nerve in glaucoma patients.MethodThe clinical data of 234 eyes of 117 patients of primary glaucoma treated with Tiluo Yangxue Mingmu prescription from January 2017 to July 2020 were retrospectively analyzed. Fifty-seven eyes treated with the Tiluo Yangxue Mingmu prescription were reviewed as the treatment group，and 57 eyes that were not treated with the prescription matched in gender，age and course of treatment were selected as the control group. The changes of BCVA，mean sensitivity（MS） and mean deviation（MD） of visiual field before and after treatment were analyzed. Optical coherence tomography（OCTA） was used to analyze the changes of VD and thickness of RNFL of potic nerve before and after treatment.ResultAfter treatment，compared with that before treatment，BCVA was increased （P=0），MS was increased （P=0），MD was decreased（P=0.001），VD of the whole image（P=0），VD of the inside disc（P=0.004） and all subdivisions of peripapillary（P<0.05） was increased，the RNFL thickness（except inferior nasal area） was not significantly changed. After treatment，MS was increased（P=0.003） and MD was decreased（P=0.024） in treatment group compared with those before treatment. In the control group，there was no statistical difference in the changes of visual field indicators after treatment compared with that before treatment.ConclusionFor glaucoma patients whose intraocular pressure is stable within the range of target intraocular pressure，Tiluo Yangxue Mingmu prescription can improve the visual function and VD of optic nerve，but has no significant effect on RNFL thickness.
Abstract：ObjectiveTo observe the clinical efficacy Guilu Bugu prescription in treating postmenopausal osteoporosis （PMO） with deficiency of liver and kidney Yin based on syndrome differentiation and the effect on Th17/Treg cell factors.MethodOne hundred and forty patients were randomly divided into observation group （70 cases） and control group （70 cases） by random number table. Both groups' patients got basic treatment of western medicine. Patients in control group got Jintiange capsules， 3 grains/time， 3 times/day. Patients in observation group got Guilu Bugu prescription， 1 dose/day. The treatment lasted for 6 months. And the 6-month follow-up was recorded. Before treatment， at the 6th month after treatment and at the 6th month of follow-up， bone density of lumbar vertebra L2-4 were detected by DXA， and Lumbar BMD were detected by QCT. Before treatment， at the 3rd and 6th month after treatment， deficiency of liver and kidney Yin and Chinese Osteoporosis-targeted quality of life questionnaire （COQOL） were scored. Before and after treatment， Estradiol （E2）， procollagen I amino terminal pro peptide （PINP）， osteoprotegerin （OPG）， collagen I cross linked C-terminal peptide （S-CTX）， tartrate resistant acid phosphatase （TRACP）， interleukin-17 （IL-17）， IL-22， IL-10， transforming growth factor-β1 （TGF-β1） were detected， and CD4+ cells， Th17 cells and Treg cells were calculated. And the safety was evaluated.ResultAt the 6th month after treatment and the 6th month of follow-up， DXA （bone mineral density and T-value of lumbar L2-4） and QCT bone mineral density increased （P<0.01）， and the figures in observation group were all higher than those in control group （P<0.01）. At the 3rd and 6th month after treatment， scores of deficiency of liver and kidney Yin and quality of life were all lower than those in control group （P<0.01）. Levels of PINP， S-CTX， TRACP， Th17 cells， ratio of Th17 and Treg， IL-17 and IL-22 were all lower than those in control group （P<0.01）， and levels of OPG， E2， Treg， IL-10 and TGF-β1 were all higher than those in control group （P<0.01）.There was no adverse reaction related to Guilu Bugu prescription.ConclusionBased on the supplementation of calcium and vitamin D， Guilu Bugu prescription can further improve the bone mineral density， raise the estrogen level， regulate the expressions of bone metabolism markers， Th17， Treg and relevant factors， reverse the imbalance of Th17/Treg， relieve the clinical symptoms and improve the quality of life， with a better efficacy than that of Jintange capsule and a high safety.
Keywords：postmenopausal osteoporosis;deficiency of liver and kidney Yin;Guilu Bugu prescription;bone metabolism index;Zuoguiwan;cell factors
Abstract：ObjectiveTo observe the efficacy of addition and subtraction therapy of Chuanxiong Chatiaosan combined with acupuncture for acute migraine attack with syndrome of wind phlegm blocking collaterals and to investigate its effect on neurovascular active medium.MethodOne hundred and thirty-four patients were randomly divided into control group（67 cases） and observation group （67 cases）by random number table. During the treatment， 63 patients completed the study in control group （loss to follow-up in 2 cases， and elimination in 2 cases）. 64 patients completed the study in observation group （loss to follow-up in 3 cases）. Patients in both groups got ibuprofen sustained release tablets， 1 tablet/time， 2 times/day， Zolmitriptan tablets， 2.5 mg/time， 1 time/day， which were stopped when symptoms got relieved. Patients in control group got acupuncture treatment， 1 time/day， and Zhengtian pills by oral administration， 6 g/time， 2 times/day. Based on the treatment of acupuncture in control group， patients in observation group additionally received addition and subtraction therapy of Chuanxiong Chatiaosan， 1 dose/day， with a treatment course of 10 days in both groups. Before treatment， at the first day （2， 4 ， 12 ， 24 h） and second to tenth day after the treatment， scores of pain visual analoguescale （VAS） were graded； before and after treatment， scores of duration and degree of headache， concomitant symptoms， number of headache attacks， syndrome of wind phlegm blocking collaterals， migraine specific quality of life scale （MSQ） were graded. Levels of nitric oxide （NO）， endothelin-1 （ET-1）， calcitonin gene-related peptide （CGRP）， 5-hydroxytryptamine （5-HT）， and β endorphin （β -EP） were detected before and after treatment.ResultThe clinical efficacy in observation group was better than that in control group （Z=2.115， P<0.05）. At the second and fourth hour after treatment， VAS scores were decreased in both groups， but there was no statistically significant difference between two groups. At the 12th and 24th hour after treatment， VAS scores were increased as compared with those at the previous time point （P<0.01）， and VAS scores in observation group at the 12th and 24th hour were lower than those in control group （P<0.01）， but there was no statistically significant difference in onset time for pain， effective rate for pain at second hour after treatment and the disappearance rate of pain at the third day after treatment. Time to pain relief in observation group was shorter than that in control group （P<0.01）. Degree of headache， duration of headache， number of headache attacks and accompanying symptoms were all lower than those in control group， while scores of MSQ and the total score of MSQ were all higher than those in control group （P<0.01）. Recurrence rate of pain in observation group was 18.75% （12/64）， lower than 36.51% （23/63） in control group at the 24th hour （P<0.05）. Disappearance rate of pain in observation group was 70.31% （45/64） and 90.63% （58/64） at the fifth day and tenth day after treatment， higher than 52.38% （33/63） and 76.19% （48/63） in control group （P<0.05）. Levels of NO， β-EP and 5-HT were higher than those in control group （P<0.01）， while levels of CGRP and ET-1 were lower than those in control group （P<0.01）.ConclusionChuanxiong Chatiaosan combined with acupuncture in the treatment of acute migraine attack in patients， has equivalent effect in terms of rapid pain relief， but with advantages of long-lasting analgesic effect， low recurrence rate， high pain relief rate and disappearance rate. In addition， it can also regulate neurovascular active mediators， more effectively control acute migraine attack， and improve the quality of life of patients， with a better clinical efficacy.
Keywords：migraine;acute attack;syndrome of wind phlegm blocking collaterals;Chuanxiong Chatiaosan;acupuncture;quality of life;neurovascular active medium
Abstract：ObjectiveTo discuss the clinical efficacy of Xintong oral liquid on heart failure with syndrome of Qi deficiency， phlegm and blood stasis caused by acute myocardial infarction （AMI） and the effect on inflammatory factors.MethodOne hundred patients were randomly divided into observation group （50 cases） and control group （50 cases） by random number table. Both groups got comprehensive treatment of western medicine. Patients in control group got simulated medicine of Xintong oral liquid， 20 mL/time， 3 times/day. Patients in observation group got Xintong oral liquid， 20 mL/time， 3 times/day. The treatment lasted for 4 weeks. Before the treatment， and at the second week and forth week after treatment， levels of cardiac troponin I （cTnI）， cardiac troponin T （cTnT）， heart type fatty acid binding protein （H-FABP）， left ventricular ejection fraction （LVEF）， cardiac output （CO）， cardiac output per stroke （SV） and left ventricular end diastolic diameter （LVEDd）， N-terminal B-type natriuretic peptide （NT-proBNP）， lipoprotein phospholipase A2 （Lp-PLA2）， high sensitive C-reactive protein （hs-CRP）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） were detected. The 6-minute walking test was performed to record the 6-minute walking distance and the ratio of 6 min walking distance to estimated value. Scores of traditional Chinese medicine （TCM） syndromes， minnesota Heart Failure quality of life questionnaire （MLHFQ） and Killip classification of cardiac function were recorded. During the 2 months' follow-up， adverse cardiovascular events （MACE） were recorded， and the safety was evaluated.ResultAt the second and fourth week， levels of cTnI， cTnT， H-FABP， NT-proBNP， Lp-PLA2， hs-CRP， IL-6 and TNF-α were lower than those in control group （P<0.01）， and levels of LVEF， CO and SV were higher than those in control group （P<0.05， P<0.01）. NT-proBNP was lower than control group （P<0.01）. The 6-minute walking distance and the ratio of 6-minute walking distance to estimated value were all more than those in control group （P<0.01）. Scores of TCM syndrome integral， MLHFQ， Killip heart function grading were lower than those in control group （P<0.05， P<0.01）. Cumulative incidence of MACE was 12.0% （6/50）， which was lower than 28.0% （14/50） in control group （=4.251， P<0.05）. Levels of Lp-PLA2， hs-CRP， IL-6 and TNF-α in observation group were lower those in control group （P<0.01）.And there was no adverse reactions related to Xintong oral liquid.ConclusionBased on the comprehensive treatment of Western medicine， Xintong oral liquid can reduce the degree of myocardial injury， protect myocardium， improve cardiac function， reduce inflammatory reaction， reduce the occurrence of mace， effectively control clinical symptoms， and improve exercise tolerance and quality of life.
Keywords：myocardial infarction;heart failure;syndrome of Qi deficiency， phlegm and blood stasis;Xintong oral liquid;adverse cardiovascular events;cardiac function;inflammatory factors
Abstract：ObjectiveThe TIFY gene family will be identified and characterized from the whole genome level in Cannabis sativa，which will lay the foundation for gene function study on TIFY family genes and their regulation mechanism on the biosynthesis of cannabinoids and other secondary metabolites.MethodUsing the existing genomic data of cannabis，the CsTIFY genes were identified through bioinformatics analysis tools such as NCBI，PlantTFDB，MEME and TBtools etc.，and physicochemical properties，phylogenetic trees，gene structures，chromosome locations and gene expression patterns were analyzed and visualized.ResultFourteen TIFY family genes（CsTIFY1-CsTIFY14） were identified in Cannabis sativa，which belong to four subfamilies：TIFY，JAZ，ZML，and PPD. The CsTIFYs are composed of 365-1 369 bp nucleotides encoding 118-442 amino acid residues，and their isoelectric points are 4.64-9.96. The 14 CsTIFYs are unevenly distributed on 8 chromosomes，and their proteins are all located in the nucleus. The promoter of CsTIFYs contain multiple abiotic stress responsive cis-acting elements，which indicated that CsTIFYs might involved in the regulation of different abiotic stresses. Transcriptome profiling revealed that CsTIFYs expressed differently in female flowers of 10 differently cannabis varieties，or in flowers，bracts，stems，and leaves of the same variety.ConclusionFourteen TIFY family genes were characterized from the whole genome level in C. sativa，and their phylogenetic evolutions and gene expression patterns were analyzed，indicating that CsTIFYs may play important regulatory roles in JA signal transduction，abiotic stress and cannabinoid biosynthesis. This study will provide valuable reference for gene function study of the TIFY family genes in cannabis and cannabis breeding.
Keywords：bioinformatics;Cannabis sativa;TIFY gene family;indetifine of members;functional analysis
Abstract：ObjectiveTo quickly analyze and identify the differential chemical compositions of Aurantii Fructus Immaturus before and after stir-frying with bran and chemical compositions of wheat bran after processing by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MSE） combined with UNIFI database screening method.MethodACQUITY UPLC BEH C18 column （2.1 mm×100 mm， 1.7 µm） was used for chromatographic separation with 0.1% formic acid solution （A）-acetonitrile （B） as the mobile phase for gradient elution （0-11 min， 98%-70%B； 11-15 min， 70%-55%B； 15-16 min， 55%-35%B； 16-20 min， 35%-5%B； 20-20.5 min， 5%-98%B； 20.5-22 min， 98%B） at the flow rate of 0.3 mL·min-1 and the injection volume of 2 µL. The analytes were determined in positive ion mode with electrospray ionization （ESI） and data collection range of m/z 50-1 500. Principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA） were used to find the component differences between raw and processed products of Aurantii Fructus Immaturus， and the chemical compositions of wheat bran after processing were determined.ResultThere were 64 compounds in raw products， 58 compounds in bran-fried products， and 18 compounds in wheat bran.There were 19 different components between raw and processed products of Aurantii Fructus Immaturus， mainly volatile oil， flavonoids， phenolic acid， coumarins and saponins.ConclusionBased on the analysis of these different components before and after stir-frying with bran and the chemical compositions carried by wheat bran， the stir-frying with bran can alleviate the intensity of Aurantii Fructus Immaturus， which proves the necessity of stir-frying with bran for the processing technology of this herb， and provides a comprehensive experimental basis for research on processing mechanism of Aurantii Fructus Immaturus.
Abstract：ObjectiveTo study the microbial community composition and diversity of brown-rot Gastrodia elata and its surface soil，in order to explain the relationship between brown-rot G. elata and soil microflora in G. elata planting process and provide theoretical basis for revealing the reasons of G. elata brown-rot disease.MethodUsed internal transcribed spacer region（ITS） and 16S rDNA high-throughput sequencing technologies to detect the microbial diversity，community structure composition and community structure similarity of fungi and bacteria in healthy tuber，Brown-rot tuber，healthy soil and Brown-rot soil.ResultCompared with health groups，the number of fungi and bacteria operational taxonomic units（OTUs） was increased in brown-rot G. elata and its soil， and the abundance and diversity of fungi and bacteria in brown-rot G. elata soil were significantly decreased. The diversity of fungi in the tubers of brown-rot G. elata was significantly reduced，while the diversity of bacteria was significantly decreased. At the genus level， Mortierella was dominant fungi genus in healthy tuber and healthy soil，which was reduced 7.62% and 15.75% respectively in brown-rot tuber and brown-rot soil. And the dominant bacteria genus was Bradyrhizobium and Burkholderia-Paraburkholderia respectively. Ilyonectria was dominant fungi genus in brown-rot tuber and brown-rot soil，the dominant bacteria genus was Serratia and Bradyrhizobium respectively.ConclusionThe fungal flora in the tuber of brown-rot G. elata had a very high degree of similarity to that in the surrounding soil. These results indicated that the change of soil microbial fungal community caused the occurrence of G. elata brown-rot disease to a certain extent. And the pathogenic fungal Ilyonectria was dominant genus in fungi community of brown-rot tuber and brown-rot soil. Ilyonectria may have the main G. elata brown-rot disease pathogen.
Abstract：ObjectiveTo explore the mechanism of Qizhu granules in the treatment of diabetic nephropathy by using network pharmacology.MethodThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database （TCMSP） and The Encyclopedia of Traditional Chinese Medicine（ETCM） database were used to screen out the chemical constituents and protein targets of each drug in the Qizhu granules based on oral bioavailability and drug-like properties. The protein target was standardized into the corresponding gene name through the UniProt database. Online Mendelian Inheritance in Man（OMIM）， DisGeNET， Therapeutic Target Database （TTD）， ETCM database were used to search for related targets of diabetic nephropathy， after the intersection of the two， construct a protein interaction network through protein interaction database （STRING）， use Cytoscape to analyze the core target of the network， and the relevant targets were analyzed by KOBAS 3.0 database for Gene Ontology （GO） pathway enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis.ResultA total of 93 chemical components were obtained from Qizhu granules， involving 254 targets， and 607 targets related to diabetic nephropathy. After the intersection， 76 sputum granules were determined to treat diabetic nephropathy， including protein kinase B1 （Akt1）， vascular endothelial growth factor （VEGFA）， interleukin （IL）-6， tumor necrosis factor （TNF）， mitogen-activated protein kinase 1 （MAPK1）， matrix metalloproteinase （MMP）-9 and other core targets， after GO analysis and KEGG analysis， Qizhu granules can affect cellular response to nitrogen compound， regulation of reactive oxygen species metabolic process and other biological processes， regulate advanced glycation end product （AGE）/advanced glycation end product receptor （RAGE） signaling pathway in diabetic complications， fluid shear stress and atherosclerosis， IL-17 signaling pathways， HIF-1 signaling pathways TNF signaling pathways and other pathways.ConclusionThe therapeutic effect of Qizhu granules on diabetic nephropathy may affect Akt1，VEGFA， IL-6， TNF， MAPK1， MMP-9 and other targets， and regulate AGE/RAGE signaling pathway in diabetic complications， fluid shear stress and atherosclerosis， IL-17 signaling pathways， hypoxia-inducing factor-1（HIF-1）signaling pathways TNF signaling pathways and other pathways， which can provide a theoretical reference for further basic experimental research.
Abstract：ObjectiveTo investigate the mechanism of Sinisan in treating type 2 diabetes mellitus（T2DM） based on network pharmacology.MethodBased on electronic databases， active ingredients of Sinisan and target genes of ingredients as well as type 2 diabetes were screened out. Cytoscape software was applied to construct "herb-active ingredient-target-disease" interaction network diagram，respectively. The common genes of ingredients and disease were uploaded to the STRING database， and the protein interaction network map （PPI） was constructed. CytoNCA and Cluster Marker were used to analyze PPI，respectively. Finally，ClueGO was used to analyze gene ontology （GO） enrichment and Kyoto Encyclopedia of genes and genomes （KEGG） pathway enrichment.ResultA total of 137 active components and 110 effective genes of Sinisan in the treatment of type 2 diabetes were screened out. Based on PPI analysis，these effective genes were divided into 4 different clusters， and 12 genes were considered as the most effective targets. GO enrichment analysis showed that cluster 1 mainly involved acute inflammatory response and acetylcholine receptor signaling pathway， cluster 2 mainly involved cellular response to steroid hormone stimulu and xenobiotic stimulus，and cluster 3 was mainly engaged in the metabolism process of protein，fatty and glucose and the response to hypoxia. KEGG analysis was highly correlated with advanced glycation end products-receptor for AGE （AGE-RAGE） pathway，apoptosis pathway，inflammatory pathway，cell cycles and various metabolic pathways.ConclusionSinisan has a regulatory effect in pathogenesis and prognosis of T2DM，such as inflammation，cell apoptosis and nutrition metabolism. Moreover，its potential mechanisms on diabetic angiopathies，diabetic cognitive impairment and cancers were reveal，so as to define a direction for the fundamental research of Sinisan.
Keywords：Sinisan;type 2 diabetes and complications;network pharmacology;potential mechanism
Abstract：ObjectiveTo analyze the mechanism of Astragali Radix in the treatment of Parkinson's disease by network pharmacology and PC-12 extracellular model.MethodTraditional Chinese medicines systems pharmacology platform （TCMSP） and CD-HIT databases were used to screen out active components and targets of Astragali Radix， GENECARDS and Online Mendelian Inheritance in Man （OMIM） databases were used to screen out targets relating to Parkinson's disease and draw component-target network， STRING database was used to build the protein-protein interaction network， Bioconductor Cluster Profiler was applied in Gene Ontology （GO） enrichment analysis， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. PC-12 cells were pretreated with water extract of Astragali Radix， and Western blot was used to assess the expression of phosphorylation extracellular regulatory protein kinase 1/2（p-ERK1/2）， ERK1/2， B cell lymphoma -2 （Bcl-2） associated X protein （Bax）， Bcl-2， cysteine aspartic acid protease -3 （Caspase-3） and cleaved-Caspase3 （c-Caspase-3）. The levels of interleukin-6 （IL-6）， IL-10 and tumor necrosis factor-α（TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA） interleukin-6 （IL-6）， IL-10， tumor necrosis factor-α（TNF-α）.ResultNetwork pharmacology showed that 14 compounds in Astragali Radix， including emodin and quercetin， played a role through multi-target and multi-channel synergy， involving ERK signal pathway， Bax， Bcl-2， Caspase-3， IL-6， IL-10， TNF-α and other target proteins. Western blot showed that the expressions of Bax， p-ERK1/2， c-Caspase-3 and Bcl-2 in Astragali Radix Extract group decreased， while the expressions of Bcl-2 in Astragali Radix Extract group was significantly higher than that in model group （P<0.05）. There were statistical differences between the two groups. ELISA showed that Astragali Radix water extract could reduce the expressions of IL-6， TNF-α， but increase the expression of IL-10， with statistical differences from the model group （P<0.05）.ConclusionThis study shows that Astragali Radix can affect the expressions of these proteins， and verify the results of network pharmacology， so as to provide a basis for further study of Astragali Radix in the treatment of Parkinson's disease.
Keywords：Astragali Radix;parkinson disease;network pharmacology;extracellular regulatory protein kinase 1/2 （ERK1/2）
Abstract：Liver cirrhosis caused by the repeated action of one or more causes is a pathological stage characterized by diffuse fibrosis of the liver parenchyma， formation of false lobules and regenerative nodules， portal hypertension which caused by abnormal blood vessels inside and outside the liver. The progression of cirrhosis to decompensation is characterized by severe liver damage， with ascites， gastroesophageal varices bleeding， hepatic encephalopathy and other complications， and most of the treatments are symptomatic， with high mortality and poor prognosis. At present， the traditional Chinese medicine treatment of decompensated cirrhosis can not only effectively improve liver function， but also significantly improve the 5-year survival rate of patients， which suggests that Chinese medicine has potential advantages in preventing and treating end-stage liver disease， and promoting liver cirrhosis tissue reconstruction. Modern Chinese medicine doctors believe that liver cirrhosis is mainly caused by Qi Yin deficiency （liver， spleen， kidney），internal invasion of damp-heat epidemic toxin， and collateral stasis. Deficiency of liver and kidney Yin is a common symptom of decompensated cirrhosis. Yiguanjian， one of Kidney-Nourishing and Liver-Replenishing decoction in traditional Chinese medicine ， is the representative prescription for modern clinical treatment of chronic liver disease with "deficiency of liver and kidney Yin" syndrome. Yiguanjian， created by WEI Yu-zhen （WEI Zhi-xiu）in the Qing Dynasty， Contained in "Xu Ming Yi Lei An ". Clinical studies show that Yiguanjian can effectively improve liver function in patients with liver cirrhosis， promote ascites resolution， and reduce the occurrence of hepatic encephalopathy and other related complications. Experimental research has suggested that Yiguanjian has the characteristics of multi-path， multi-level， and multi-target comprehensive regulation. The mechanism of prevention and treatment of liver cirrhosis may be mainly related to anti-oxidative stress， improving liver inflammation， improving liver cell biosynthesis， inhibiting hepatic stellate cell activation， reducing collagen deposition， improving sinusoidal vascularization and promoting liver cell regeneration. This paper reviews the progress of clinical and experimental research of Yiguanjian in the treatment of liver cirrhosis in the past 5 years， to provide some references for the clinical application and in-depth study of Yiguanjian.
Keywords：Yiguanjian;deficiency of liver and kidney Yin;cirrhosis;hepatic stellate cells
Abstract：Psychological stress （pressure） has gradually become an important factor affecting human physical and mental health， and is one of the important factors in the progression of clinical chronic refractory diseases. Psychological stress response can be attributed to the category of emotional illness in traditional Chinese medicine （TCM）. In the theory of TCM， the liver controls dispersion and regulates mental activity. Relevant scholars believe that the liver is the core of psychological stress response in the TCM theory. When being stimulated by chronic or repeated psychological stress， the body can gradually change from the initial depression and anxiety-rela behaviors to the gastrointestinal dysfunctions， which is similar to the formation process of the syndrome of liver depression and spleen deficiency with liver-spleen disharmony. The syndrome of liver depression and spleen deficiency is also the common syndrome of TCM for psychological stress-related diseases. With the effect in soothing liver and invigorating spleen， Xiaoyaosan has been regarded as the classic formula for anti-stress. Modern studies have showed that gut microbiota not only get involved in the movement， structure and function of the digestive tract， but also affect the brain function and behavior of the host through the gut-brain axis. Therefore， the microbiota-gut-brain axis has become an important part of psychological stress to trigger the body's gastrointestinal symptoms and abnormal brain behaviors. Focusing on psychological stress， the authors explored the correlation between the syndrome of liver stagnation and spleen deficiency and the microbiota-gut-brain axis， and the intervention mechanism of Xiaoyaosan， so as to enrich the scientific connotation of the syndrome of liver stagnation and spleen deficiency.
Keywords：liver controls dispersion;syndrome of liver depression and spleen deficiency;chronic psychological stress;microbiota-gut-brain axis
Abstract：Myocardial ischemia-reperfusion injury （MIRI） was originated from the ischemic injury to myocardial cells due to some factors， and the injury will be aggravated after the blood supply recovery. MIRI will cause reperfusion arrhythmia， myocardial stagnation， microcirculation disorders or blood loss reflow， and become a key issue to be solved in the clinical treatment. Therefore， it is of important clinical significance to explore how to improve MIRI. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway has been regarded to be an important cascade signaling pathway to prevent MIRI， which is cross-talked in such mechanisms as oxidative stress， calcium overload， autophagy， inflammation， endoplasmic reticulum stress and mitochondrial dysfunction. This pathway is at the core site and closely related to the severity of MIRI. Meanwhile， traditional Chinese medicine（TCM） has its unique advantages in the prevention and treatment of MIRI， including multiple targets， multiple pathways， fewer toxic and side effect， as well as TCM characteristics of syndrome differentiation treatment and overall concept. A great number of studies have confirmed that this pathway is a common mechanism of action for most TCM compounds， TCM monomers and extracts. In this paper， we clarify the effect of PI3K/Akt signaling pathway crosstalk on the myocardial ischemia-reperfusion injury， with the focus on the relationship between the key targets of PI3K/Akt signaling pathway and MIRI. It will give great insights to the intricate relationship between them and promote the future development of new drugs targeting the PI3K/Akt signaling pathway. Finally， we also summarized the existing findings of TCM on PI3K/Akt pathway， which provides a reference for the treatment and drug development of MIRI.
Keywords：phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway;myocardial ischemia-reperfusion injury;traditional Chinese medicine
Abstract：The long-term existence of hyperglycemia leads to the occurrence of metabolic memory effect， which is an important reason for the formation of diabetic macrovascular disease， so the early control of metabolic memory is the key to the prevention and treatment of diabetes and its complications. The excessive formation of advanced glycation end products （AGEs） is not only an important factor to cause metabolic memory， but also the core mechanism for diabetic macrovascular disease. It is believed in traditional Chinese medicine（TCM） that Fu-xie （incubative pathogen） is the key pathogenesis of the formation of diabetic vascular diseases， and it is necessary to adopt the principle of removing pathogenic factors and opening collaterals as early as possible to prevent and cure the disease. During the Spring and Autumn Period and the Warring States Period， the theory of Fu-xie was germinated， and got mature in the Ming and Qing dynasties after the continuous development. The so-called Fu-xie means that the pathogens are of a potential nature but not cause diseases immediately. The theory of Fu-xie first appeared in Huangdi Neijing， with an original meaning of epidemic febrile disease occurring after incubation， and then its meaning continues to expand， now referring to all potential pathogenic factors that would not immediately cause diseases. As the cause and pathogenesis of many diseases， the theory of Fu-xie is widely used in clinical practice to guide the treatment of diseases. In the body， the accumulation of AEGs can induce the subsequent cascade effect in the body， and finally promote the formation and development of diabetic macrovascular diseases. This is very similar to the process of inducing metabolic disorder and disease in TCM due to the accumulation of phlegm and silt. Therefore， under the guidance of Fu-xie theory， the mechanism of AEGs in blocking metabolic memory and preventing and treating diabetic macrovascular disease was analyzed in this paper. On the one hand， it will provide a scientific basis for the exploration of Fu-xie theory affecting the disease course of diabetic macrovascular disease by regulating the generation of AEGs. On the other hand， it can also provide the material change basis for the development of Fu-xie theory in the occurrence and development of diabetic macroangiopathy.
Keywords：metabolic memory;advanced glycation end products（AGEs）;Fu-xie theory;diabetic macrovascular disease
Abstract：Volatile oil of traditional Chinese medicine （VOTCM） is a plant volatile component obtained through distillation or supercritical fluid extraction. The volatile oil is rich in terpenes and phenylpropanoids， with many different effect. It is not only widely used in healthcare products， but also has a variety of pharmacological effect， such as analgesia， antioxidant， antibacterial， anti-inflammatory， anti-tumor effect. Malignant tumor is an important threat to human health. At present， the drugs commonly used in clinical treatment of tumors are expensive with certain toxic and side effect. Although new treatment technologies are also being promoted step by step， they have higher treatment costs than traditional chemotherapies， and the long-term efficacy remained to be further confirmed. The effect of volatile oil of traditional Chinese medicine（TCM） on cancer is receiving more and more attention. In particular， it has a significant inhibitory effect on lung， liver， colon， and stomach cancer. Specifically， it can not only reduce the side effect of chemotherapy drugs， but also effectively prolong or stop the tumor recurrence， with special effects in treatment and adjuvant treatment. At the same time， various anti-tumor mechanisms of volatile oils have been discovered， such as inducing tumor cell apoptosis， inhibiting tumor blood vessel formation， inhibiting tumor cell proliferation， inducing tumor cell differentiation， interfering with multidrug resistance， and regulating the body's immune function. However， there are still some problems in the basic research， achievement transformation， and product development of volatile oil of TCM， which restricts its clinical and daily application. This paper summarizes the antitumor mechanism of volatile oil of TCM by consulting relevant domestic and foreign literatures， analyzes the current situation of volatile oils， and proposes improvement directions for its problems and development， in the expectation of laying the foundation for the research of volatile oil of TCM in anti-tumor research.
Keywords：traditional Chinese medicine;volatile oil;anti-cancer;mechanism;development
Abstract：Lung cancer is the leading cause of cancer-related deaths worldwide， and about 1.6 million people die of it each year. In China， the incidence and mortality of lung cancer rank the first， as evidenced by the fact that about 780 000 people suffering from lung cancer every year， and the 5-year survival rate is less than 20%. In addition， 85% of patients with lung cancer are non-small cell lung cancer （NSCLC）， and 70% of lung cancer patients are found to have advanced cancer or tumor metastasis. The therapies of lung cancer include surgical resection， radiotherapy， chemotherapy， targeted therapy and immunotherapy. However， these therapies have certain limitations， severe toxic and side effects， and high costs. Therefore， it is urgent to find drugs with appropriate price and reliable efficacy. Traditional Chinese medicine （TCM） is the treasure of China， with more than 5 000 years of practical experience. In ancient books， there are records of therapies for lung amassment and pneumothorax， and modern studies have proved that there are many advantages， such as multiple targets， slight side effect， wide sources and reliable effects， and it is often used as an auxiliary treatment for lung cancer. The clear mechanism of TCM against lung cancer remains to be solved. The studies on the effect of TCM against NSCLC mainly start at the effective ingredients of TCM and end at the efficacy， and explore the "process"—mechanism. At present， the mechanism of TCM against NSCLC includes inducing apoptosis and autophagy of tumor cells， inhibiting the growth， proliferation， metastasis and invasion of tumor cells， which rises to molecular and genetic level. Based on the above mechanism， aiming at the effect target and pathway， this paper summarizes the literatures of the mechanism of TCM against non-small cell lung cancer in recent years， and sorted out some anti-lung cancer TCM about property， flavor and meridian-tropism on the basis of previous studies， in order to provide ideas for scholars to study the mechanism and clinical application of TCM in resisting lung cancer， and references for the studies of the correlation between the lung cancer as well as property， flavor and meridian-tropism.
Keywords：non-small cell lung cancer;traditional Chinese medicine;effective constituent;mechanism;research progress