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Jia Li,1,&ast; Xiao Wang,1,&ast; Shining Xun,2,&ast; Qiuting Guo,3 Yao Wang,1 Yanzuo Jia,1 Wenfei Wang,1 Yujiao Wang,1 Taotao Li,1 Tiantian Tang,1 Junbo Zou,1 Mei Wang,1 Ming Yang,4 Fang Wang,4 Xiaofei Zhang,1,4 Changli Wang1 1Department of Pharmaceutics, The Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China; 2Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China; 3Xianyang Vocational Technical College, Xianyang, People’s Republic of China; 4Department of Pharmaceutics, Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaofei Zhang, Department of Pharmaceutics, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China, Tel +86 177 7003 7322, Fax +86 29-38185333, Email 2051028@sntcm.edu.cn Changli Wang, Department of Pharmaceutics, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China, Tel +86 132 3910 3433, Email wcl3433@163.comPurpose: To investigate the effective components and possible mechanism of action of Lavandula angustifolia Mill. essential oil (LEO) in preventing vomiting through the olfactory pathway.Materials and Methods: A new network pharmacology–based method was established to analyze main components and pathways of LEO involved in antiemetic effects by introducing component content; biological activities of key proteins of the olfactory pathway and their corresponding compounds were verified by molecular docking technique; and finally pica in a rat model was established to verify the molecular mechanism of antiemetic effects of LEO by enzyme-linked immunosorbent assay (ELISA) to determine the serum 5-HT, substance P, and DA levels in each group and by immunohistochemistry to determine the contents of 5-HT3R, CaMKII and ERK1/2 proteins in the medulla oblongata tissue.Results: Network pharmacology combined with molecular docking analysis showed that the mechanism of the antiemetic effect of LEO may be related to (2Z)-3,7-dimethyl-2,6-octadienyl acetate, linalyl acetate, butanoic acid, hexyl ester, 4-hexen-1-ol, 5-methyl-2-(1-methylethenyl)-, acetate, .tau.-cadinol and other active ingredients, which regulate the cyclic adenosine monophosphate (cAMP) signaling pathway and the expression of BRAF, PDE and other targets on the pathway. An ELISA revealed that LEO reduced the levels of 5-hydroxytryptamine (5-HT), substance P, and dopamine in serum compared with the model group (P < 0.05). Immunohistochemical analysis showed that LEO decreased the expression of 5-HT3R, CaMKII, and ERK1/2 proteins in the medulla oblongata of rats compared with the model group (P < 0.01).Conclusion: LEO may achieve the antiemetic effect by reducing the content of 5-HT and inhibiting its related receptors, thereby regulating downstream Ca2+/CaMKII/ERK1/2 pathway of the cAMP signaling pathway.Keywords: Lavandula angustifolia Mill, vomiting, weight coefficient, molecular docking, mechanism validation

Context The coriander plant Centipeda minima (L.) A. Braun et Aschers (Compositae) is used for the treatment of allergic rhinitis. Objective Analyze the difference of the C. minima volatile oil from 7 geographic areas and its therapeutic effect on allergic rhinitis. Materials and methods The volatile oils from different geographic areas were extracted and analyzed, the protein and biological pathway for the treatment of allergic rhinitis were predicted by network pharmacology. Established three groups of Sprague-Dawley rat allergic rhinitis models (n = 10). The treatment group was given 100 μL/nostril of 0.1% C. minima volatile oil, the blank and model groups were given the same amount of normal saline. After 15 days, serum inflammatory factors were detected by ELISA. Nasal mucosa tissues were examined by hematoxylineosin staining and immunuhistrochemistry. Results There are differences in the content of volatile oil in the seven geographic areas. Experiments showed that the concentration of TNF-α in the serum of the administration group decreased from 63.66 ± 2.06 to 51.01 ± 4.10 (pg/mL), IL-4 decreased from 41.90 ± 3.90 to 28.68 ± 3.39 (pg/mL), IgE decreased from 22.18 ± 1.40 to 17.59 ± 1.60 (pg/mL), IL-2 increased from 314.14 ± 10.32 to 355.90 ± 10.01(pg/mL). Immunohistochemistry showed that compared with the model group, the PTGS2 and MAPK3 proteins in the administration group were significantly reduced. Discussion and conclusions C. minima volatile oil is a multi-target and multi-pathway in the treatment of allergic rhinitis, which provides a new research basis and reference for the treatment of allergic rhinitis.

Laminaria japonica, one of the most widespread seafood consumed in China and many other nations, has been traditionally utilized as an effective therapeutically active substance for treating weight loss, phlegm elimination, and detumescence for more than 2000 years. Numerous studies have found that the polysaccharides play an indispensable role in the nutritional and medicinal value of L. japonica. Water extraction and alcohol precipitation method is the most used method. Approximately 56 LJPs were successfully isolated and purified from L. japonica, whereas only few of them were well characterized. Modern pharmacological studies have shown that L. japonica polysaccharides (LJPs) have high-order structural features and multiple biological activities, including anti-tumor, anti-thrombotic, anti-atherosclerosis, hypolipidemic, hypoglycemic, antioxidant, anti-inflammatory, renoprotective, and immunomodulatory. In addition, the structural characteristics of LJPs are closely related to their biological activity. In this review, the extraction and purification methods, structural characteristics, biological activities, clinical settings, toxicities, and structure-activity relationships of LJPs are comprehensively summarized. The structural characteristics and biological activities as well as the underlying molecular mechanisms of LJPs were also outlined. Furthermore, the clinical settings and structure-activity functions of LJPs were highlighted. Some research perspectives and challenges in the study of LJPs were also proposed.

Aim and Objective: Myocardial infarction, cerebral infarction, and other diseases caused by vascular obstruction have always jeopardized human life and health. Several reports indicate that Rhei Radix et Rhizoma has a good clinical effect in the prevention and treatment of cardiovascular diseases. Owing to the complexity of herbal medicine, the pharmacodynamic mechanism of Rhei Radix et Rhizoma is still unclear. The objectives of this study were to explore the two-way adjustment mechanism of Rhei Radix et Rhizoma and provide a new solution for the prevention and treatment of cardiovascular disease. Materials and Methods: This study used data mining, reverse pharmacophore matching, network construction, GO and KEGG Analysis, and molecular docking to investigate the two-way adjustment mechanism of Rhei Radix et Rhizoma. The methods used were based on systems pharmacology and big data analysis technology. Results: The results suggest that Rhei Radix et Rhizoma uses a two-way adjustment of activating blood circulation, as well as blood coagulation in the prevention and treatment of cardiovascular diseases. The components involved in activating blood circulation are mainly anthraquinone components. The corresponding targets are NOS2, NOS3, CALM1, and the corresponding pathways are calcium signaling pathway, VEGF signaling pathway, platelet activation, and the PI3K-Akt signaling pathway. For blood coagulation, the components are mainly tannin components; the corresponding targets are F2, F10, ELANE, and the corresponding pathways are the neuroactive ligand-receptor interaction, complement and coagulation cascades. Conclusion: This study indicated that Rhei Radix et Rhizoma exerts the two-way adjustment of activating blood circulation and blood coagulation in the prevention and treatment of cardiovascular diseases. It can make up for the side effects of the existing blood circulation drugs for cardiovascular disease, only activating blood circulation, and the uncontrollable large-area bleeding due to the long-term use of the drugs. This study provides a material basis for the development of new blood-activating drugs based on natural medicine.

In order to improve the water solubility of the volatile oils extracted from Flos magnoliae (FM) and Centipeda minima (CM), they were prepared as a microemulsion (ME), which were then used in the development of an FM and CM volatile oil ME for the treatment of allergic rhinitis (AR). ME was prepared by phase inversion emulsification, and the prescription factors such as emulsifier, co-emulsifier, oil phase, Km, which represents the ratio of the mass of emulsifier to that of the co-emulsifier, and preparation factors such as temperature affecting the formation of the ME were selected according to the formation area of ME in a pseudo-ternary phase diagram. The quality of the ME was evaluated based on its appearance, particle size, Zeta potential and stability. The content of eucalyptol in ME was determined by gas chromatography-mass spectrometry (GC-MS). The cumulative permeability of the ME within 24 h was measured with a transdermal diffusion tester. The results revealed that the best formula for preparation of the ME was as follows: Castor oil polyoxyethylene ether (EL-40) was the emulsifier; the co-emulsifier was anhydrous ethanol; the Km was 2:1; the mixed phase of volatile oil and isopropyl myristate with mass ratio of 1:1 was used as oil phase; and the preparation temperature was 25°C. The content of eucalyptol in the ME was 2.57 mg/g, and the cumulative permeability of the ME in 24 h was significantly increased compared with that of the reference oil solution. The appearance of the ME was uniform, and the solution was transparent. In conclusion, compared with traditional preparations, FM and CM volatile oil ME is a novel, improved and more effective preparation for the treatment of AR.

Objective. To analyze the potential active ingredients and related crucial targets of the ShengDiHuang Decoction (SDHD) formula in the treatment of dysfunctional uterine bleeding (DUB) by using network pharmacology and verification experiment. Methods. In this study, we determined the potential active ingredients from the traditional SDHD formula and their targets with the network pharmacology method. The network of “compound-disease-target” was constructed by the software of Cytoscape. Software of DAVID was used to enrich pathways for these 87 targets of SDHD. Further, the therapeutic effect of SDHD on DUB was verified by observing the morphological changes of the uterus and ovaries and determining the expression of ERS2 and progesterone in the plasma. Results. 52 compounds of Rheum and 5 compounds of Rehmannia were selected, and 87 potential targets were screened by network pharmacology. Furthermore, 7 main active ingredients were acquired by the ADME process. In addition, enrichment analysis of drug-target networks indicated that SDHD may play a role in overall coordination through “multicomponent and multitarget” in different organ patterns by regulating multiple pathways directly or indirectly. Finally, in the verification experiment of SDHD on DUB, it was found that SDHD can effectively repair the uterus and ovaries and also have an upregulation effect on the target ESR2 and increase the content of progesterone. Conclusion. Overall, this study revealed potential mechanisms of multitarget and multicomponent about SDHD in the treatment of DUB and provided a scientific foundation for further studying the mechanism.

Phellinus spp., an important medicinal fungus mushroom extensively cultivated and consumed in East Asia for over 2000 years, is traditionally considered a precious food supplement and medicinal ingredient. Published studies showed that the polysaccharides are major bioactive macromolecules from Phellinus spp. (PPs) with multiple health-promoting effects, including immunomodulatory, anti-cancer, anti-inflammatory, hepatoprotective, hypoglycemic, hypolipidemic, antioxidant, and other bioactivities. Although the polysaccharides extracted from the fruiting body, mycelium, and fermentation broth of Phellinus spp. have been extensively studied for the extraction and purification methods, structural characteristics, and pharmacological activities, the knowledge for their structures and bioactivity relationship, toxicologic effects, and pharmacokinetic profile is limited. This review systematically summarizes the recent progress in the isolation and purification, chemical structures, bioactivities, and the underlying mechanisms of PPs. Information from this review provides insights into the further development of polysaccharides from PPs as therapeutic agents and functional foods.

Affecting the absorption of active ingredients in the intestine serves as one of the important compatibility mechanisms of traditional Chinese medicine. The aim of this study was to investigate the compatibility mechanism of ShengDiHuang Decoction (SDHD) by using the single-pass intestinal perfusion in situ model. The major effective ingredients, catalpol, aucubin, acteoside, rehmannioside D, rehmannioside A, rhein, aloe emodin, emodin, chrysophanol, and physcion, were determined by HPLC. By analysing the effects of different concentrations, different pH, intestinal segments, protein inhibitors, and tight junction regulators on SDHD absorption, it was found that catalpol, aucubin, rehmannioside D, rehmannioside A, acteoside, rhein, and chrysophanol may undergo active transport, while aloe-emodin and emodin may undergo passive transport. Catalpol, aucubin, and rehmannioside D may be substrates of BCRP and MRP2, while rehmannioside A and rhein may be substrates of BCRP, and acteoside and chrysophanol may be substrates of P-gp, BCRP and MRP2. By comparing the Papp values of the major effective ingredients between single herb and herb-pairs, the compatibility of rehmannia and rheum could significantly promote the absorption of components in rehmannia. It is verified that rheum has a synergistic effect on the absorption of rehmannia in SDHD.

Aim Aralia taibaiensis is a natural medicinal and food plant that is rich in triterpenoid saponins with hypoglycaemic, antioxidant, hepatoprotective, anti-gastric ulcer and anti-inflammatory effects. This study has significance in terms of the antioxidant, anti-aging and organ protective effects of Aralia taibaiensis total saponins (TSAT) in D-galactose-induced aging rats. Methods The saponin composition of TSAT was determined and quantified by high performance liquid chromatography (HPLC). We consolidated the antioxidant and enzyme inhibitory activities of TSAT in vitro and assessed the effects of TSAT on daily mobility, body weight, behaviour, organ indices, oxidation-related indices and pathological changes in aging rats. Results In vitro experiments showed that TSAT had a scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), tyrosinase, hydroxyl radicals (HO•) and superoxide radicals (•O2-) and was closely related to the dose of TSAT. In vivo experiments showed that after 8 weeks of continuous gavage administration, the rats gradually recovered their body weight, daily activity ability, learning and memory ability and organ index and effectively improved D-gal-induced organ injury. Specifically, TSAT significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) and significantly decreased malondialdehyde (MDA) levels in the serum, brain, heart, lung, spleen and kidney of aging rats compared to the model group. In addition, TSAT significantly inhibited the D-gal-induced upregulation of hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. The histopathological results showed that TSAT reversed D-gal-induced damage to the brain, heart, lung, kidney, liver and spleen to varying degrees. Conclusion TSAT is a high-quality natural product with antioxidant and anti-aging properties that can alleviate D-gal-induced aging damage in rats., Graphical Abstract

Averrhoa carambola L. (star fruit) is an edible fruit that is extensively cultivated in southern China, Southeast Asia, India, and northern South America. It has a sweet and juicy taste and is frequently used in fruit salads and fruit platters, as a garnish in cocktail drinks and beverages, or squeezed into juice and served as a beverage. Traditionally, it has been used for treating diabetes and diabetic nephropathy, arthralgia, vomiting, lithangiuria, coughing, hangovers, and chronic paroxysmal headache for thousands of years. Currently, approximately 132 compounds have been isolated from A. carambola. Among them, flavonoids, benzoquinone, and their glycosides have been considered as biologically active substances, which are responsible for various biological activities. Pharmacological studies have revealed that crude extracts or monomeric compounds from A. carambola exhibit multiple bioactivities, such as anti-oxidant, anti-hyperglycemic, anti-obesity, anti-hyperlipidemic, anti-tumor, anti-inflammatory, hepatoprotective, cardioprotective, anti-hypertensive, neuroprotective, and others. Thus, A. carambola is a valuable treatment in Chinese medicine with therapeutic potential for multiple diseases, especially diabetes and diabetes-related diseases. Even though it is a very promising candidate in the development of functional food and the pharmaceutical industry, reports on its bioactivities have only been conducted in vivo and in vitro and there is a gap in research regarding clinical settings and safety. This review therefore provides a comprehensive and systematic overview of current progress on botany, ethnopharmacology, phytochemistry, pharmacology, and toxicity of A. carambola, providing a valuable reference for further developments and applications of A. carambola in the pharmaceutical industry and functional food.

Cooperative Multi-robot observation of moving the targets (CMOMMT) represents the problem in which a group of autonomous mobile robots equipped with a limited range of sensors that can be used to keep moving targets in observation. The robots plan the movement of the target in coordination to maximize the observation time during which each target appears within the sensing range of at least one robot. We present a novel multi-objective optimization model based on UAVs for CMOMMT schemes which features fairness of observation among different targets as an additional objective. The proposed model uses a quad-tree data structure to model the movement decisions of UAVs in order to maximize duration and the variable qualities (resolutions) of observations. For any given future time, a probabilistic occupancy map for each target is estimated in a Bayesian framework. The experiment results display the effectiveness of the proposed method.

Background. To predict the active components and potential targets of traditional Chinese medicine and to determine the mechanism behind the curative effect of traditional Chinese medicine, a multitargeted method was used. Jingzhi Guanxin prescriptions expressed a high efficacy for coronary heart disease (CHD) patients of which essential oils from Chuanxiong and Jiangxiang were confirmed to be the most important effective substance. However, the interaction between the active components and the targets for the treatment of CHD has not been clearly explained in previous studies.Materials and Methods. Genes associated with the disease and the treatment strategy were searched from the electronic database and analyzed by Cytoscape (version 3.2.1). Protein-protein interaction network diagram of CHD with Jiangxiang and Chuanxiong essential oils was constructed by Cytoscape. Pathway functional enrichment analysis was executed by clusterProfiler package in R platform.Results. 121 ingredients of Chuanxiong and Jiangxiang essential oils were analyzed, and 393 target genes of the compositions and 912 CHD-related genes were retrieved. 15 coexpression genes were selected, includingUGT1A1,DPP4,RXRA,ADH1A,RXRG,UGT1A3,PPARA,TRPC3,CYP1A1,ABCC2,AHR, andADRA2A. The crucial pathways of occurrence and treatment molecular mechanism of CHD were analyzed, including retinoic acid metabolic process, flavonoid metabolic process, response to xenobiotic stimulus, cellular response to xenobiotic stimulus, cellular response to steroid hormone stimulus, retinoid binding, retinoic acid binding, and monocarboxylic acid binding. Finally, we elucidate the underlying role and mechanism behind these genes in the pathogenesis and treatment of CHD.Conclusions. Generally speaking, the nodes in subnetwork affect the pathological process of CHD, thus indicating the mechanism of Jingzhi Guanxin prescriptions containing Chuanxiong and Jiangxiang essential oils in the treatment of CHD.

The Malus hupehensis (Pamp.) Rehd. is a traditional medicine and edible plant. The previous study found that the extracts of M. hupehensis (Pamp.) Rehd. had a good antioxidant activity in vivo and ...

Chinese herbs such as Flos magnoliae (FM) and Centipeda minima (CM) can be effective in treating allergic rhinitis (AR). However, there is little research on the therapeutic mechanism of these two drugs acting on AR at the same time. In order to systematically understand the mechanism of action of two drugs acting on AR at the same time, we searched various databases to obtain 31 components and 289 target proteins of FM, 25 components and 465 target proteins of CM. The interaction networks of FM, CM, and AR proteins were constructed by Cytoscape-v3.2.1 software. The core protein of two network intersections was obtained by using Venny 2.1.0. The R platform was used for the core target protein gene ontology (GO) comment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. Thirteen common targets and seven acting pathways were obtained. The results of animal experiments showed that FM and CM volatile oil could effectively improve the symptoms of AR by regulating the common targets. In summary, this study successfully explained the potential therapeutic mechanism of FM and CM in the treatment of AR. At the same time, it indicates that the two drugs can be compatible as a new application.

This study aimed to introduce a new weight coefficient combined with network pharmacology to predict the potential active components, action targets, and signal pathways of lavender essential oil and to investigate the therapeutic effect of lavender essential oil on colitis through animal experiments. The component targets of lavender essential oil were mined from the Pubchem and SwissTargetPrediction databases, and the relative content of lavender essential oil was compared with OB (oral bioavailability) to establish a “quantity–effect” weight coefficient. Online databases such as GeneCards and String were used to construct a “lavender essential oil compound target disease target” network to extract the key targets of core compounds acting on diseases. The clusterProfiler package in R language programming of Rstudio software was used to analyze the enrichment of the related targets by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the enriched pathways were reordered according to the “quantity–effect” weight coefficient of the targets they participated in. Following up on the findings, the pharmacodynamic test showed that, after injecting lavender essential oil into mice, the levels of inflammatory cytokines including EGFR, TNF-α, and IFN-γ in serum and colon tissue decreased, and lavender essential oil could mediate Th17 cell differentiation by reducing dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) colonic mucosal damage. The results indicated that lavender essential oil can alleviate DSS-induced colonic mucosal injury in ulcerative Colitis mice. Based on the network pharmacology of the “quantity–effect” weight coefficient, this study indicated that lavender essential oil can regulate the level of inflammatory factors, inhibit inflammatory reactions through a multicomponent and multitarget strategy, and ultimately alleviate the colonic mucosal injury of UC mice. Through the weight coefficient network pharmacology mining, it was concluded that the Th17 cell differentiation, PI3K-Akt signaling pathway, and Th1 and Th2 cell differentiation of lavender essential oil in the treatment of UC may be the key pathway for the treatment of the disease. Through the establishment of a weight coefficient combined with network pharmacology and the combination of dose and effect, it shows that network pharmacology may provide a better basis for the treatment of disease mechanism.

Background: Myocardial Infarction (MI) is a cardiovascular disease with a high morbidity and mortality rate. While MI is currently treated with pharmaceuticals, there is a need for new treatment options: compound Chinese medicines may have unique advantages for the treatment of MI. Methods: A combination of network pharmacology and experimental verification is used to identify the ingredients and mechanism of Compound Longmaining (CLMN) for treating MI. Network pharmacology combined with the gene expression omnibus (GEO) chip method is used to analyze the primary pathway of CLMN for treating MI, and then molecular docking is used to verify the affinity of key target proteins in the primary pathway that bind to active molecules. The major active compounds of CLMN are screened using the docking score results. The CIBERSORT algorithm is used to evaluate immune cell infiltration in MI, and high performance liquid chromatography (HPLC) is used to control the quality of the components. Finally, a mouse model is established to verify the molecular mechanism of CLMN for treating MI using hematoxlyn eosin (HE) staining and immunohistochemistry. Results: By utilizing network pharmacology combined with molecular docking, the mechanism of action of CLMN for the treatment of MI was found to possibly be related to the ingredients of puerarin, daidzein, ferulic acid, chrysin, and galangin. These molecules regulate the NF-Kappa B signaling pathway and the expression of RELA, IKBKB, NKBIA, and other targets. The CIBERSORT algorithm and ggplot2 package analysis were used to distinguish the immune cells, such as neutrophils, macrophages, and T cells, that play a key role in the development of MI. HPLC controlled the quality of the screened medicinal ingredients. An immunohistochemical analysis showed that the TNF-α and TRAF-2 expression levels in MI of the CLMN-treated mice were decreased, while IkBα was increased. HE staining showed CLMN reduced inflammation in mouse cardiomyocytes and decreased fibrosis. Conclusions: This study showed that CLMN treatment of MI is a process that involves multi-components, multi-targets and multi-pathways, and the established multi-index component content measurement of the CLMN decoction can be used for quality control of CLMN.

Background and objective: Myocardial Infarction (MI) is a cardiovascular disease with a high morbidity and mortality rate. While MI is currently treated with pharmaceuticals, there is a need for new treatment options: compound Chinese medicines may have unique advantages for the treatment of MI. In this study, we used network pharmacology to explore the molecular mechanisms of action of Compound Longmaining (CLMN) decoction as a potential treatment approach.Methods: Chip data related to Myocardial Infarction were downloaded from the GEO database and genes from GSE48060 and GSE66360 chips were obtained by R language. The targets of active components of CLMN and myocardial infarction disease were predicted by network pharmacology. After intersection analysis, the core targets were obtained and functional enrichment analysis was carried out. CLMN biological activity was verified by molecular docking prior to establishing a mouse MI model to verify efficacy using hematoxylin-eosin (HE) staining and immunohistochemistry.Results: KEGG pathway analysis showed that TNF, IL1B, PTGS2, VCAM1, and NFKBIA which mainly act on NF-kappa B pathway contribute to the anti-inflammatory effects of CLMN. Immunohistochemical analysis showed that TNF-α and TRAF-2 expression levels in MI of CLMN-treated mice were decreased, while IkBα was increased (P < 0.05). HE staining showed CLMN reduced inflammation in mouse cardiomyocytes and decreased fibrosis.Conclusion: CLMN regulates the NF-kappa B signaling pathway and the expression of TNF, IL1B, PTGS2, VCAM1 and NFKBIA. Chemical analysis showed that CLMN active components such as Daidzein-4,7-diglucoside, rutin and puerarin may be responsible for the therapeutic effect of the decoction.

BackgroundThis study aimed to identify the key genes and KEGG pathways inCarthamus tinctoriusL. (Safflower) andSalvia miltiorrhizaBurge. (Salvia) for the treatment of cardio-cerebrovascular disease, and to explore their potential molecular mechanisms.MethodsCompounds and targets in Safflower and Salvia were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). We obtained targets of myocardial infarction (MI) and cerebral infarction (CI) data from Therapeutic Target Database (TTD), Drugbank and DisGeNET datasets. The network of Safflower, Salvia, CI and MI was established and then executing, and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses of the functional characteristics were performed. The Chinese herbal prescription and target for CI and MI were obtained by searching in the database. Finally, the main pathways of Salvia and Safflower in Chinese patent medicines were analyzed. The MCAO model was established in rats, and compatibility of salvia with safflower was experimentally verified.ResultsWe obtained a total of 247 genes targeted by 52 compounds from Safflower and 119 genes targeted by 48 compounds from Salvia. In total, we identified 299 known therapeutic targets for the treatment of CI and 960 targets for the treatment MI. There are 23 common targets for Salvia, Safflower, MI, and CI. A total of 85 KEGG pathways were also enriched and intersected with the pathway of proprietary Chinese medicine to yield 25 main pathways. Safflower and Salvia have the best therapeutic effect in MCAO.ConclusionWe identified gene lists for Safflower and Salvia in CI and MI. Bioinformatics and interaction analyses may provide new insight into the treatment of cardio-cerebrovascular diseases with Safflower and Salvia.

Nowadays, Unmanned Aerial Vehicles (UAVs) are playing increasingly important roles in agriculture, rescuing and surveillance due to their small size, low cost and strong adaptability. Coverage Path Planning (CPP) is a fundamental problem for UAV applications, which means to find a path covering all the targets or regions of interest. Researches on CPP in a single region have been studied for decades, but rare to be devoted to covering multiple scattered regions of multiple UAVs. This paper proposes an attempt to solve this problem in a short time and take the task balance of multiple UAVs into account meanwhile. This work constructs a model for multiple UAVs to cover scattered regions firstly. In view of the high computational complexity of the precise solution, we keep innovating a heuristic measure based on the model to make the solving process feasible. To settle the problem of imbalanced time consumption caused by super regions, we improve the previously built model furthermore. A series of experiments validated that the presented approaches exhibit the effectiveness and balance of time consumption in diverse scenarios.

Background: Previous studies have shown that Malus hupehensis (Pamp.) Rehd. extracts have anti-oxidant, anti-aging and other effects, its bioavailability is low, however its absorption mechanism is still unclear. To investigate the absorption properties of hyperin, quercitrin, phloridzin, quercetin, and phloretin in total flavonoids of Malus hupehensis (Pamp.) Rehd. Extracts. Methods: In situ single-pass intestinal perfusion model and in vitro Caco-2 cell model were used in this study. The effects of concentration of the extract, administration time, temperature, different intestinal segments, paracellular pathway were analyzed, and the effect of efflux inhibitors, such as the P-gp inhibitor verapamil, the multidrug resistance protein2 (MRP2) inhibitor indomethacin, the breast cancer resistance protein (BCRP) inhibitor reserpine, on the transport were evaluated. As well as EDTA, a tight junction regulator, was studied.Results: The results indicated that the jejunum was the optimal absorption intestine segment of quercitrin, phloridzin, and phloretin. And the greatest absorption intestine segment of quercetin was ileum. Furthermore, it was found that the absorption mechanisms of phloridzin in extract was involved in passive diffusion and the mediation of P-gp and MRP2 should not be neglected. The absorption mechanisms of quercetin and phloretin from extract involved active transport and were accompanied by the participation of efflux transporters, such as P-gp, MRP2 and BCRP. And also the paracellular pathway was involved in hyperin and quercitrin. Conclusion: The absorption mechanisms of five flavonoids from Malus hupehensis (Pamp.) Rehd. extract are related to the concentration of the drugs, intestinal segments, and efflux protein.

Anxiety disorder is a common psychiatric disease. Roman chamomile as medicine or tea has long been used as a mild tranquilizer to reduce anxiety, but the mechanism is unclear. This research is based on network pharmacology combined with database mining to find the ingredients, action pathways and key targets of Roman chamomile for the treatment of anxiety. About 126 common targets related to chamomile and anxiety were obtained, and these targets were involved in 56 KEGG pathways. GEO screened LRRK2 as a key protein, and molecular docking showed that the protein could stably bind to drug components. Roman chamomile has the characteristics of multi-target and multi-pathway in the treatment of anxiety disorder. Its possible mechanism is to intervene anxiety disorder in the process of disease development, such as neuroactive ligand-receptor interaction, serotonin synapse, and cAMP signaling pathway. LRRK2 may be an important gene for Roman chamomile in the treatment of anxiety disorder. PRACTICAL APPLICATIONS: Roman chamomile is well known for its use in medicine and tea making. It contains many nutrients, which can relieve people's anxiety, help sleep, antibacterial and anti-inflammatory. In this article, through network pharmacology combined with Gene Expression Omnibus data mining and molecular docking, the target and mechanism of Roman chamomile in the treatment of anxiety were discussed, and its efficacy was verified by model animals, which not only clarified its mechanism at the systematic level, but also proved to be effective at the biological level. It provides a reference for the further development and utilization of Roman chamomile.

Objective: Lingzhu San (LZS) is a traditional Chinese medicine (TCM) prescription which can be effective in treating febrile seizures (FS) and has few researches on the mechanisms. In order to better guide the clinical use of LZS, we used the research ideas and methods of network pharmacology to find the potential core compounds, targets and pathways of LZS in the complex TCM system for the treatment of FS, and predict the mechanism. Materials and Methods: Databases such as BATMAN, TCMSP, TCMID, and SWISS TARGET are used to mine the active compounds and targets of LZS, and the target information of FS was obtained through GENECARDS and OMIM. Using Venny2.1.0 and Cytoscape software to locked the potential core compounds and targets of FS. The R language and ClusterProfiler software package were adopt to enrich and analyze the KEGG and GO pathways of the core targets and the biological processes and potential mechanisms of the core targets were revealed. Results: 187 active compounds and 2113 target proteins of LZS were collected. And 38 potential core compounds, 35 core targets and 775 metabolic and functional pathways were screened which involved in mediating FS. Finally, the role of the core compounds, targets and pivotal pathways of LZS regulated FS in the pathogenesis and therapeutic mechanism of FS was discussed and clarified. Conclusions: In this paper, the multi-compounds, multi-targets and multi-pathways mechanism of LZS in the treatment of FS was preliminarily revealed through the analysis of network pharmacology data, which is consistent with the principle of multi-compounds compatibility of TCM prescriptions and unified treatment of diseases from multiple angles, and it provides a new way for TCM to treat complex diseases caused by multiple factors.

Carthamus tinctorius L.(Safflower), a herbal formula from Traditional Chinese Medicine (TCM), has been widely used for the treatment of cardio-cerebrovascular diseases, particularly cerebral infarction (CI) or cerebral ischemia-reperfusion injury. However, we know very little about the specific mechanisms associated with the therapeutic effect of Safflower on CI. In this study, we used a network pharmacology-based approach, together with rat model of CI, to gain more insight into of such mechanisms. Our analysis showed that Safflower contains 52 active compounds that target 247 genes, which were also cross-referenced with 299 genes associated with CI. Consequently, we identified 52 target genes in Safflower that were associated with CI. These 52 target genes were analyzed by gene ontology (GO) enrichment analysis, leading to the identification of 1491 biological process items, 90 molecular function items and 19 cell assembly items. Eighty-nine pathways were generated by KEGG enrichment (P

Background. Hypertension is a primary risk factor for cardiovascular disease (CVD). Tianma Gouteng decoction (TGD), originating from Zabingzhengzhixinyi, has been used for thousands of years in China to treat hypertension, giddiness, and migraine. This updated meta-analysis aimed at assessing the efficacy and safety of TGD combined with nifedipine in the treatment of primary hypertension. Methods. Related research published prior to September 1, 2019, was found in electronic databases without language limitations. Fourteen studies were selected and analyzed for specified criteria, including the quality of the studies. All outcomes were recorded exhaustive. Data management and analysis were performed using RevMan 5.3 software. Results. A total of 1,537 (769 cases in the experimental group and 768 cases in the control group) patients were enrolled. The total efficacy rate was improved significantly for the combination of nifedipine with TGD compared to nifedipine treatment alone (I2 = 22%, RR = 1.17, and 95% CI: 1.12 to 1.22). Traditional Chinese medicine (TCM) symptoms of patients were obviously improved in the experimental group than in the control group (I2 = 44%, RR = 1.26, and 95% CI: 1.17 to 1.36). TGD combined with nifedipine shows a better effect than nifedipine in decreasing diastolic blood pressure (I2 = 95%, MD = −5.32, and 95% CI: −8.19 to −2.45) and systolic blood pressure (I2 = 98%, MD = −9.35, and 95% CI: −15.03 to −3.67) of patients. A sensitivity analysis was conducted for SBP and DBP by removing 2 studies and recalculated the combined estimate on remaining studies. The results of SBP showed a small heterogeneity (I2 = 17%, MD = −13.95, 95% CI: −14.86 to −13.05, and P<0.00001) when two studies (shicaihong 2017 and xiaoyugao 2017) were removed. And the results of DBP showed no heterogeneity (I2 = 0, MD = −8.36, 95% CI: −8.91 to −7.81, and P<0.00001) when two studies (panzhixiong 2019 and shicaihong 2017) were removed. Conclusion. The combination of TGD and nifedipine has a better effect in the treatment of hypertension, including blood pressure lowering and patients’ TCMs improving. However, our findings must be handled with care because of the small sample size and low quality of clinic trials cited. Other rigorous and large-scale RCTs are in need to confirm these results.

Background. We provide an updated meta-analysis with detailed information on a combination of TCM and routine treatment. Methods. Retrieve appropriate articles with no language restrictions on keywords until 8 July 2019 in an electronic database. All trajectories are screened according to certain criteria. The quality of certified research was also evaluated. We made a detailed record of the results of the measurement. Meta-analysis was carried out by using the Revman 5.3 software. Results. Sixty-seven RCTs were included, and 6594 subjects were analyzed. Compared with routine treatment, the total effective rate (TER) of TCM combined with routine treatment was improved, and the recovery of stroke was also significantly accelerated. Regulation of blood lipids by notably shrinking the contents of TC, TG, and LDL and enhancing the levels of HDL. The levels of serum hs-CRP, WHV, and WLV decreased significantly, indicating that the expression of thrombomodulin was decreased after the comprehensive treatment of traditional Chinese medicines (TCMs). The combination of TCM treatment could enhance the protection of neural function by decreasing the NIHSS scoring while increasing the BI scoring. Paeoniae Radix Rubra, Angeticae Sinensis Radix, etc., can effectively improve the clinical symptoms of stroke convalescent patients and promote the recovery of neurological function. ACU of Baihui, Renzhong, etc., can improve the clinical rehabilitation effect of patients. However, our findings must be handled with care because of the small sample size and low quality of clinic trials cited. Other rigorous and large-scale RCTs are in need to confirm these results. Conclusion. A combination of TCM and routine treatment in the treatment of stroke could improve TER, and it is beneficial to the rehabilitation of patients in the recovery period of apoplexy. These effects can be mediated by a combination of several mechanisms. Nevertheless, due to the limitations of this study, these results should be handled with caution.

Ethnopharmacological relevance In traditional Chinese Medicine, Rehmannia glutinosa (Gaertn.) DC., as the principle herb of ShengDiHuang Decotion (SDHD), has the effect of cooling blood and hemostasis, and tonifying the yin and kidney. Rheum L., as adjuvant herbs, assist Rehmannia glutinosa (Gaertn.) DC. to promote blood circulation to remove blood stasis. Aim of study To study the mechanism of Rhein (RH) involved in the promotion of Rehmannioside D (RD) absorption by pharmacokinetic studies, single-pass intestinal perfusion, Caco-2 cell models, molecular docking technique and western blotting. Materials and methods Initially, the intestinal absorption of RD in the presence or absence of RH was conducted through pharmacokinetic studies. Thereafter, the intestinal absorption of RD and RH was studied using the single-pass intestinal perfusion and Caco-2 cell models. Finally, using molecular docking technique and western blotting. Results We found that the promotion of RD absorption by RH was mediated by breast cancer resistance and multidrug resistance-associated protein 2, thereby affecting the permeability of the intestinal epithelium. Additionally, RH and RD can competitively bind to breast cancer resistance and multidrug resistance-associated protein 2, and that RH inhibits the expression of breast cancer resistance and multidrug resistance-associated protein 2 in the ileum to promote the intestinal absorption of RD. Conclusion This study reveals the mechanisms associated with the RH-mediated promotion of RD absorption and provides a basis for further exploring the synergistic effect of Rehmannia glutinosa (Gaertn.) DC and rhubarb.

Objective. To evaluate the clinical efficacy and safety of Compound Danshen Dripping Pill (CDDP) and Isosorbide Mononitrate (ISMN) in the treatment of unstable angina pectoris (UAP) in the elderly. Materials and Methods. CNKI, Wanfang, VIP, CBM, and PubMed databases were searched for appropriate articles without language limitations on keywords. RevMan 5.3 software was used to perform the meta-analysis. Results. This analysis compared CDDP with ISMN of 21 randomized controlled trials (RCTs) that involved a total of 2356 patients with UAP. When the treatment lasted for four weeks, the clinical effective rate was OR = 3.97, 95% CI = 2.97, 5.30, and P < 0.00001, the ECG efficiency was OR = 3.43, 95% CI = 2.13, 5.53, and P < 0.00001, and incidence of adverse reactions was OR = 0.73, 95% CI = 0.52, 1.04, and P = 0.08 > 0.05. When the treatment lasted for eight weeks, clinical efficiency rate was OR = 4.22, 95% CI = 2.37, 3.79, and P < 0.00001, incidence of adverse reactions was OR = 0.58, 95% CI = 0.26, 1.27, and P = 0.17 > 0.05, whole blood low-cut blood viscosity was SMD = -0.61 and 95% CI -1.60, 0.38, whole blood high-cut blood viscosity was SMD = -0.38 and 95% CI -0.97, 0.21, and blood cells specific volume was SMD = -0.80 and 95% CI -2.61, 1.01. Conclusion. Based on this meta-analysis, the CDDP was superior to ISMN with UAP in the elderly. However, there is still a need to further verify the clinical efficacy and safety of CDDP with more strictly designed RCTs with large sample and multiple centers in the future.

Background: Stroke is ranked second among diseases that cause mortality worldwide. Owing to its complicated pathogenesis, no satisfactory treatment strategies for stroke are available. Dachengqi decoction (DCQD), a traditional Chinese herbal medicine, has been widely used in China for a long time, as it has a good effect on stroke. However, the molecular mechanism underlying this effect of DCQD is unclear. Objective: In the present study, we aimed to reveal and explore the multi-pathway and multi-gene regulatory molecular mechanism of Dachengqi decoction in the treatment of stroke. Methods: In this study, a network pharmacology method, in combination with oral bioavailability prediction and drug-likeness evaluation, was employed to predict the active ingredients of DCQD. The target genes of the active components and the traced pathways related to these target genes were predicted. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using clusterProfiler software package on the R platform and ClueGo+CluePedia plug-ins. Finally, the key DCQD targets were verified using the Gene Expression Omnibus (GEO) dataset. Results and Discussion: According to the ADME model, 52 active components were screened from 296 active components of DCQD. After prediction and screening, 215 stroke-related targets were obtained and analyzed via GO and KEGG analyses. GO analysis showed that DCQD targets were mainly involved in the regulation of oxidative stress, lipid metabolism, inflammation, and other biological processes. KEGG pathway analysis further revealed pathways involved in stroke, such as arachidonic acid metabolic, HIF-1 signaling pathway, estrogen signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, platelet activation pathway, VEGF signaling pathway, and cAMP signaling pathway. Network analysis revealed that DCQD might be involved in the regulation of lipid metabolism, blood pressure, inflammation, angiogenesis, neuroprotection, platelet aggregation, apoptosis, and oxidation in stroke treatment. GEO dataset analysis showed that DCQD’s therapeutic effects might be exerted via the bidirectional regulation principle. Conclusion: Based on the methods of network pharmacology and GEO analysis, it was found that, during stroke treatment, DCQD regulates and controls multiple genes and multiple pathways in a synergistic manner, providing a new strategy for stroke treatment.

Aim and Objective: The common disease of insomnia has complex and diverse clinical manifestations. Lavender represents an effective treatment of insomnia, but the molecular mechanism underlying the effectiveness of this treatment is not clear. The purpose of this study is to investigate the active components, target proteins and molecular pathways of lavender in the treatment of insomnia, thus explaining its possible mechanism. Materials and Methods: Firstly, 54 active components of lavender were identified by gas chromatography-mass spectrometry (GC-MS). The target protein of lavender was predicted by the Traditional Chinese Medicine System Pharmacological Database and Analysis Platform and the SwissTargetPredicating tool, and the target protein of insomnia was predicted by the DisGeNET and DrugBank databases. Then, the "component-target-disease" network diagram was constructed using the Cytoscape 3.7.1 software. KEGG and GO enrichments were analyzed using the R statistical language. Finally, the key target proteins were verified by collecting and verifying the target protein GEO data using the Discovery Studio 3.5 molecular docking verification software. Results: 906 target proteins of lavender were predicted by the Traditional Chinese Medicine System Pharmacological Database and Analysis Platform and the SwissTargetPredicating tool, and 182 insomnia target proteins were predicted by the DisGeNET and DrugBank databases. The results of GO enrichment analysis showed that it included the reaction process of ammonium ion, the regulation of the membrane potential and the secretion of catecholamine, while the results of KEGG enrichment included the calcium signaling pathway, serotonin synapse, morphine addiction and many more. Finally, using the Discovery Studio3.5 molecular docking verification software, it was verified that the key target proteins are ADRB1 and HLA-DRB1. Conclusion: The components in the lavender essential oil include the Ethyl 2-(5-methyl-5-vinyltetrahydrofuran- 2-yl)propan-2-ylcarbonate (0.774); 5-Oxatricyclo[8.2.0.04,6]dodecane, 4,12,12-trimethyl- 9-methylene-, (1R,4R,6R,10S)-(0.147); P-Cymen-7-ol (0.063); .alpha-Humulenem (0.317); Acetic acid, hexyl ester (1.374); etc. The role lavender plays in the treatment of insomnia might be accomplished through the regulation of the key targets ADRB1 and HLA-DRB1.

Myocardial infarction, cerebral infarction, and other diseases caused by vascular obstruction have always jeopardized human life and health. Several reports indicate that Rhei Radix et Rhizoma has a good clinical effect in the prevention and treatment of cardiovascular diseases. Owing to the complexity of herbal medicine, the pharmacodynamic mechanism of Rhei Radix et Rhizoma is still unclear. The objectives of this study were to explore the two-way adjustment mechanism of Rhei Radix et Rhizoma and provide a new solution for the prevention and treatment of cardiovascular disease.This study used data mining, reverse pharmacophore matching, network construction, GO and KEGG Analysis, and molecular docking to investigate the two-way adjustment mechanism of Rhei Radix et Rhizoma. The methods used were based on systems pharmacology and big data analysis technology.The results suggest that Rhei Radix et Rhizoma uses a two-way adjustment of activating blood circulation, as well as blood coagulation in the prevention and treatment of cardiovascular diseases. The components involved in activating blood circulation are mainly anthraquinone components. The corresponding targets are NOS2, NOS3, CALM1, and the corresponding pathways are calcium signaling pathway, VEGF signaling pathway, platelet activation, and the PI3K-Akt signaling pathway. For blood coagulation, the components are mainly tannin components; the corresponding targets are F2, F10, ELANE, and the corresponding pathways are the neuroactive ligand-receptor interaction, complement and coagulation cascades.This study indicated that Rhei Radix et Rhizoma exerts the two-way adjustment of activating blood circulation and blood coagulation in the prevention and treatment of cardiovascular diseases. It can make up for the side effects of the existing blood circulation drugs for cardiovascular disease, only activating blood circulation, and the uncontrollable large-area bleeding due to the long-term use of the drugs. This study provides a material basis for the development of new blood-activating drugs based on natural medicine.

Objective. To evaluate the clinical efficacy and safety of Kangfuxin liquid (KFX) combined with proton pump inhibitors (PPIs) in the treatment of gastric ulcer (GU). Materials and Methods. Electronic databases including PubMed, Wanfang, CNKI, VIP, Embase, Cochrane Library, and CBM were examined for appropriate articles without language limitations on key words before March 10, 2019. RevMan 5.3 software was applied to execute outcome assessment and finish the meta-analysis. Results. 22 articles involving 2,024 patients with a gastric ulcer were selected. Total efficacy rate and efficacy rate of gastroscopy were significantly enhanced for the combination of KFX with PPIs compared to those of PPI treatment alone (OR = 6.95, 95% CI: 4.87, 9.91, P<0.00001; OR = 2.96, 95% CI: 1.98, 4.42, P<0.00001, respectively). Same results were found for different PPIs in combination on total efficacy rate, respectively. The combination also significantly reduced the adverse events (OR = 0.39, 95% CI: 0.22, 0.70, P=0.002). In addition, KFX combined with PPI could suppress the inflammation (MD = −6.11, 95% CI: −7.45, −4.77, P<0.00001), reduce the recurrence rate (OR = 0.31, 95% CI: 0.14, 0.70, P=0.005), and enhance the clearance rate of Helicobacter pylori (HP, OR = 3.76, 95% CI: 1.80, 7.87, P=0.0004). It seemed like the combination would influence immune function by increasing levels of T-lymphocyte subsets CD4 and CD8 but not CD3 (MD = 2.40, 95% CI: 1.25, 3.55, P<0.0001); MD = 25.72, 95% CI: 14.55, 36.90, P<0.00001; MD = 0.72, 95% CI: −0.66, 2.09, P=0.31, respectively). Conclusion. KFX combined with PPIs in treatment of patients with GU could improve the total efficacy rate and efficacy rate of gastroscopy and reduce adverse events and the recurrence rate. However, the results of this study should be handled with care due to the limitations. Several rigorous RCTs are in need to confirm these findings.