Network pharmacology-based analysis of heat clearing and detoxifying drug JC724 on the treatment of colorectal cancer

BACKGROUND Heat-clearing and detoxifying drugs has protective effect on colorectal cancer(CRC).Given the complicated features of Traditional Chinese medicine formulas,network pharmacology is an effective approach for studying the multiple interactions between drugs and diseases.AIM To systematically explore the anticancer mechanism of heat-clearing and detoxifying drug JC724.METHODS This study obtained the active compounds and their targets in JC724 from Traditional Chinese Medicine System Pharmacology Database.In addition,the CRC targets were obtained from Drugbank,TTD,DisGeNET and GeneCards databases.We performed transcriptome analysis of differentially expressed genes in CRC treated with JC724.Venn diagram was used to screen the JC724-CRC intersection targets as candidate targets.Core targets were selected by proteinprotein interaction network and herb ingredient-target-disease network analysis.The functional and pathway of core targets were analysed by enrichment analysis.RESULTS We found 174 active ingredients and 283 compound targets from JC724.940 CRC-related targets were reserved from the four databases and 304 CRC differentially expressed genes were obtained by transcriptome analysis.We constructed the network and found that the five core ingredients were quercetin,βBeta sitosterol,wogonin,kaempferol and baicalein.The core JC724-CRC targets were CYP1A1,HMOX1,CXCL8,NQO1 and FOSL1.JC724 acts on multiple signaling pathways associated with CRC,including the Nrf2 signaling pathway,oxidative stress,and the IL-17 signaling pathway.CONCLUSION In this study,we systematically analyzed the active ingredients,core targets and main mechanisms of JC724 in the treatment of CRC.This study could bring a new perspective to the heat-clearing and detoxifying therapy of CRC.

丹参的多种临床应用

丹参的多种临床应用曹元成，马英玲丹参，苦能降泄，微寒清热，入心、肝二经血分，而有活血祛瘀、凉血消肿、清心除烦等作用。前人认为丹参能“补血”，而有“一味丹参，功同四物”的说法，其实为祛瘀通经之品，所谓能够“补血”，实为“瘀血法则新血生”之义。在临床上有...

Responses of Detoxifying, Antioxidant and Digestive Enzyme Activities to Host Shift of Bemisia tabaci (Hemiptera: Aleyrodidae)

The polyphagous B-biotype of Bemisia tabaci （Gennadius） has demonstrated a high capacity to adapt to numerous hosts from diverse plant families. To illustrate induced responses by the host plant, biochemical research on eight plant-insect interaction correlative enzymes, representing detoxifying, antioxidant and digestive pathways, were investigated. Transferring whitefly adults to Zhongmian 23 from the pre-adapted host Zhongmian 41 induced activities of carboxylesterase （by 1.80-fold）, glutathione S-transferase （by 3.79-fold）, proteinase （by 1.62-fold） and amylase （by 2.41-fold） activities, hut decreased polyphenol oxidase （by 1.89-fold） and peroxidase （by 1.88-fold）. However, transferring whitefly adults to the favorite host abutilon from Zhongmian 41 was associated with increased activities of cytochrome P450 monooxygenase （by 1.61-fold） and amylase （by 1.42-fold）, and decreased activities of polyphenol oxidase （by 2.96-fold） and peroxidase （by 2.07-fold）. Our results, together with previous studies, proved that multiple pathways are involved in coping with host shifts by polyphagous herbivores, and the taxonomic status and preference of the host transferred would affect which pathway would be induced. These results would represent a key challenge in developing long-term sustainable insect control strategies.

Earthworms: Charles Darwin’s ‘Unheralded Soldiers of Mankind’: Protective &Productive for Man &Environment

Earthworms promises to provide cheaper solutions to several social, economic and environmental problems plaguing the human society. Earthworms can safely manage all municipal and industrial organic wastes including sewage sludge and divert them from ending up in the landfills. Their body work as a ‘biofilter’ and they can ‘purify’ and also ‘disinfect’ and ‘detoxify’ municipal and several industrial wastewater. They reduce the BOD & COD loads and the TDSS of wastewater significantly. They can even remove the EDCs (endocrine disrupting chemicals) from sewage which is not removed by the conventional sewage treatments plants. Earthworms can bio-accumulate and bio-transform many chemical contaminants including heavy metals and organic pollutants in soil and clean-up the contaminated lands for re-development. Earthworms restore & improve soil fertility by their secretions (growth hormones) and excreta (vermicast with beneficial soil microbes) & boost ‘crop productivity’. They have potential to replace the environmentally destructive chemical fertilizers from farm production. The ‘protein rich’ earthworm biomass is being used for production of ‘nutritive feed materials’ for fishery, dairy & poultry industries. They are also being used as ‘raw materials’ for rubber, lubricant and detergent industries. The bioactive compounds isolated from earthworms are finding new uses in production of ‘life saving medicines’ for cardiovascular diseases and cancer cure.

Detoxifying moniliformin in grains and water

The method to determine moniliformin content was established in our laboratory. The recovery rate is 97.7% while the moniliformin content in the sample is 8.8 mg/g. In comparison with different methods of detoxifying moniliformin in water, the best antidote is chlorinated lime. 1.5 mg active chlorine in chlorinated lime was required to detoxify 1 mg moniliformin. 5% H_(2)O_(2) spray was the best way for detoxifying moniliformin in grains. These two methods are convenient, economic and with no secondary pollution. They can be used for preventing human and livestock from the toxicity of moniliformin.

Relationship Between the Development of Methamidophos Resistance and the Activities of Three Detoxifying Enzymes in Brown Planthopper, Nilaparvata lugens

Methamidophos resistance of brown planthopper(BPH), Nilaparvata lugens was selected in laboratory for 19 generations (F1 to F19). The resistance development in BPH was approximatively shaped as the letter 'S' : resistance change was small before the fifth generation and after the fifteenth generation, and the changing pattern was sharp between the fifth and the fifteenth generation. Esterase might play an important role in the resistance development, because the esterase activity and the number of individuals with high activities increased along with the resistance development. The esterase activities of insecticide-sensitive population S, field population F0, its selective generations F5, F10 and F15 were highly correlated with the resistance ratios of these generations, and the coefficient was 0.9899. Mixed-function oxidases and glutathione S-transferase also might play some roles in the resistance development, but the big change in the activities of the two detoxifying enzymes both took place before the tenth generation.

血府逐瘀汤治疗急重症举隅

血府逐瘀汤治疗急重症举隅邓泽民，胡丕秀，邓人富血府逐瘀汤是清代王清任《医林改错》方，由当归、生地、桃仁、红花、枳壳、赤芍、柴胡、桔梗、川芎、牛膝、甘草等药组成，具有活血法瘀，行气止痛之功效。作者宗王氏之法应用本方治疗急重症，疗效满意。现择例报告如下。...

Traditional Chinese medicine for activating blood circulation and detoxifying in unstable angina pectoris:A systematic review and meta-analysis

Objective:The purpose of this review was to evaluate the effectiveness of traditional Chinese medicine for activating blood circulation and detoxifying(ABCD)in patients with unstable angina pectoris.Methods:We performed an electronic literature search of six medical databases for relevant articles published up to December 2014.Randomized controlled trials that compared ABCD Chinese medicine(alone or alongside conventional drugs)with conventional drugs or other Chinese medicines alone were included.A meta-analysis was performed for the following outcome measures:reduction of angina symptoms,electrocardiogram improvement,blood lipid levels,inflammatory factor levels,and plasma fibrinogen levels.Results:In total,11 moderate-to low-quality studies involving 686 patients were included.The evidence indicated that ABCD Chinese medicine exhibited superior effectiveness in relieving angina symptoms compared with conventional drugs[relative risk,1.23;95%confidence interval,1.05e1.44];however,electrocardiogram improvement was not very significant(relative risk,1.21;95%confidence interval,0.91e1.62).Moreover,ABCD Chinese medicine exhibited superior anti-inflammatory,anticoagulant,and lipid-lowering effects compared with other medicines.Conclusions:Within the methodological limitations of the included studies,our results suggest that ABCD Chinese medicine is beneficial for the treatment of unstable angina pectoris.

"External main and internal auxiliary" treatment on refractory radiation proctitis

Radiotherapy is an essential method in the comprehensive treatment of malignant tumors.However,radiation proctitis(RP)is a common complication of pelvic tumors after radiotherapy.Due to RP's various etiology and complex pathogenesis,it is currently no standard for traditional Chinese medicine(TCM)treatment.Professor Yuan-hong Zhao believes that refractory RP,which is named chronic hemorrhagic radiation proctitis(CHRP),should be classified as"Intestinal Wind Bleeding"(Bleeding like a note before defecation,bright red blood,no swelling and pain in the anus)and"Intestinal Afflux"(Refers to the symptoms of pus and blood in the lower mucus,similar to ulcerative colitis,peptic ulcer and other diseases in modern medicine.)in TCM.The critical pathogenesis of CHRP lies in local stasis and collaterals injury of intestinal collaterals.In general,it is a syndrome of excess and scarcity.External treatment with TCM is the preferred treatment strategy for CHRP,and the primary way is to disperse blood stasis and detoxify and nourish the intestinal collaterals.

Influence of rice black streaked dwarf virus on the ecological fitness of non-vector planthopper Nilaparvata lugens （Hemiptera： Delphacidae）

Rice black streak dwarf virus （RBSDV） is transmitted by the small brown planthopper （SBPH）, Laodelphax striatellus （Fallen）. Non-vector rice brown planthopper （BPH）, Nilaparvata lugens （Stal）, shares the same host rice plants with SBPH in paddy fields. The changes in nutritional composition of rice plants infected by RBSDV and the ecological fitness of BPH feeding on the infected plants were studied under both artificial climate chamber and field conditions. Contents of 16 detected amino acids and soluble sugar in RBSDV infected rice plants were higher than those in the healthy ones. On the diseased plants BPH had significantly higher nymphal survival rates, nymphal duration of the males, weight of the female adults, as well as egg hatchability compared to BPH being fed on healthy plants. However, there was no obvious difference in female nymph duration, longevity and fecundity. Defense enzymes （superoxidase dismutase, SOD and catalase, CAT） and detoxifying enzymes （carboxylesterase, CAE and glutathione S-transferase, GST） in BPH adults fed on diseased plants had markedly higher activities. The results indicate rice plants infected by RBSDV improved the ecological fitness of the brown planthopper, a serious pest but not a transmitter of the RBSDV virus.

Effects of Zhizi Chuanxiong Capsule (栀子川芎胶囊) on Abnormal Methylation in Rabbits with Atherosclerosis

Objective： To investigate the effects of Zhizi Chuanxiong Capsule（ZCC, 栀子川芎胶囊） on abnormal DNA methylation in a rabbit model of atherosclerosis（AS）. Methods： After 1 week of adaptive feeding, 48 New Zealand white rabbits were randomly divided into 4 groups： a control group（n=12） fed with normal diet for 22 weeks; a model group（n=12） fed with high fat diet for 14 weeks followed by 8 weeks of normal diet feeding; a low-dose ZCC group（n=12） fed with high fat diet and low-dose ZCC for 14 weeks, followed by 8 weeks of normal diet and low-dose drug; a high-dose ZCC group（n=12） fed with high fat diet and high-dose drug for 14 weeks, followed by 8 weeks of normal diet and high-dose drug. After 22 weeks of feeding, blood samples were taken from the rabbit ear vein, and the genomic DNA was extracted for methylation immunoprecipitation sequencing（Medip-seq）. The aorta tissues were collected for hematoxylin-eosin（HE） staining. Results： Eight rabbits died during the feeding process. HE staining showed that the size of the lipid deposition on vessel wall and atherosclerotic plaque formation were reduced in both low-and high-dose group. The Medip-seq results showed that there were 146 abnormally methylated genes（including both hypermethylated gene and hypomethylated genes） in the model group, compared with the control group. Gene Ontology（GO） and Pathway analysis showed that these abnormally methylated genes were found to be involved in multiple AS-related functions and pathways, such as protein kinase C activity, cholesterol transport, mitogen-activated protein kinase（MAPK） signaling pathway, peroxisome proliferater-activated receptor signaling pathway, vascular smooth muscle contraction, inflammation and so on. The abnormal methylated genes in AS model group were altered in both low-and high-dose groups： low-dose ZCC could change 72 of the 146 abnormally methylated genes, highdose ZCC could change 71. Through GO and Pathway analysis, these altered methylated genes were involved in protein kinase C activity, inflammatory pathway, MAPK signaling pathway, vascular endothelial growth factor signaling pathway, etc. Conclusion： ZCC could treat AS through regulating the abnormal hypermethylated and hypomethylated genes in AS rabbit model.

Effect of Chinese Drugs for Activating Blood Circulation and Detoxifying on Indices of Thrombosis,Inflammatory Reaction,and Tissue Damage in A Rabbit Model of Toxin-Heat and Blood Stasis Syndrome

Objective： To observe the regulatory effect of Chinese drugs for activating blood circulation （ABC） and for activating blood circulation and detoxifying （ABCD） on indices of thrombosis, inflammatory reaction, and tissue damage in a rabbit model of toxin-heat and blood stasis syndrome. Methods： Fifty-four rabbits were randomized into the normal control group, model group, simvastatin group （simvastatin, 0.93 mg/kg per day）, ABC group [Xiongshao Capsule （~ff_）, 0.07 g/kg per day], and ABCD group [Xiongshao Capsule, 0.07 g/kg per day, and Huanglian Capsule （-~L^t）, 0.14 g/kg per day]. All except the normal control group received a single injection of bovine serum albumin and were fed with high-fat diets for 6 weeks. At the end of week 4 of giving high- fat diets, a dose of endoxitin was given by ear vein injection, and a randomized 2-week treatment was initiated. At the end of treatment, blood lipids, circulating endothelial cells, and the pathological changes of the aortic arch were assessed. The serum levels of matrix metalloproteinases （MMP-9）, tissue inhibitors to metalloproteinase （TIMP-1）, granule membrane protein-140 （GMP-140）, plasminogen activator inhibitor-1 （PAl-l）, high-sensitivity C-reactive protein （hs-CRP）, interleukin-6 （IL-6）, and tumor necrosis factor- ~ （TNF- oL ） were determined. Results： Compared with the model group, ABCD group showed decreased serum triglycaride （TG） level, improvement in the pathological change in the aortic arch, and reduction in the number of circulating endothelial cells （4.00_＋ 1.41 per 0.9 p~ L for ABCD group vs 7.83_＋ 1.72 per 0.9 μL for the model group）. In addition, the levels of serum GMP-140, PAl-l, and IL-6 in ABCD group were also significantly reduced [0.79＋0.20 ng/mL, 5.23± 1.39 ng/mL, 40.64 ± 10.11 pg/mL for ABCD group vs 1.08 ± 0.31 ng/mL, 7.28± 2.01 ng/mL, 54.44 ± 13.56 pg/mL for the model group, respectively, P〈0.05]. A trend showing improvement in the indices of thrombosis, inflammatory reaction, and tissue damage was observed in the ABC group when compared to the model group, but the changes were not statistically significant （P〉0.05）. Conclusions： Chinese drugs for activating blood circulation and detoxifying have beneficial effects on regulating indices of thrombosis （GMP-140 and PAl-l） and inflammatory reaction （IL-6） in rabbit model with toxic-heat and blood stasis. The effect of the activating blood circulation and detoxifying drugs in regulating the levels of serum GMP-140, PAl-l, and IL-6 was superior to that of the activating blood circulation drugs.

Effect of Chinese Herbal Medicine for Activating Blood Circulation and Detoxifying on Expression of Inflammatory Reaction and Tissue Damage Related Factors in Experimental Carotid Artery Thrombosis Rats

Objective：To observe the pharmaceutical effect of Chinese drugs for activating blood circulation （Xiongshao Capsule,XSC,芎芍胶囊）and for activating blood circulation and detoxification（Xiongshao Capsule and Huanglian Capsule,XSHLC,黄连胶囊）in terms of the indices of thrombosis,inflammatory reaction and tissue damage related factors in experimental carotid artery thrombosis rats.Methods：Fifty Wistar rats were randomly divided into the sham operation group,the model group,the Simvastatin group（SG）,the activating blood circulation（ABC）group,and the activating blood circulation and detoxifying（ABCD）group,with 10 rats in each group.Simvastatin（1.8 mg/kg）,XSC（0.135 g/kg）and XSHLC（0.135 g/kg）were administered to Simvastatin,ABC and ABCD group by gastrogavage,and an equal volume of normal saline was given to the sham operation group and the model group.After 2 weeks of successive medication,the rats in the model and all drug therapy groups were made into experimental carotid artery thrombosis model.The serum levels of matrix metalloproteinases（MMP-9）,tissue inhibitors to metalloproteinase（TIMP-1）,granule membrane protein-140（GMP-140）,tissue-type plasminogen activator（t-PA）,high-sensitivity C-reactive protein（hs-CRP） and interleukin-6（IL-6）were detected with enzyme-linked immunoassay 24 h later.Results：Compared with the model group,the levels of serum GMP-140,hs-CRP,IL-6 and MMP-9 were significantly decreased,and the level of t-PA was significantly increased in the ABC and ABCD group（P〈0.05）,while the level of serum hs-CRP in ABCD group decreased significantly compared with that in the ABC group（P〈0.05）.Conclusions：Chinese drugs both for activating blood circulation and for activating blood circulation and detoxifying have good effects on regulating indices of thrombosis,inflammatory reaction and tissue damage in experimental carotid artery thrombosis rats.The effect of activating blood circulation and detoxifying drugs on regulating the level of serum hs-CRP is superior to that of activating blood circulation drug alone.

Resistance and fitness costs in diamondback moths after selection using broflanilide, a novel meta-diamide insecticide

The diamondback moth (DBM) Plutella xylostella (L.) (Lepidoptera: Plutellidae) is an insect pest found around the world that feeds on cruciferous crops. The DBM has become resistant to most insecticides in current use in the field. Broflanilide is a novel meta-diamide insecticide that binds to a new site on the γ-aminobutyric acid receptor and very efficiently protects against most pests in the order Lepidoptera, including DBM. In this study, the resistance of a laboratory-bred susceptible strain of DBM to broflanilide and the fitness costs posed by broflanilide to the DBM were evaluated. The DBM had no obvious resistance to broflanilide after 10 generations of selection. The realized heritability h2 was 0.033, suggesting a low risk of resistance developing in this strain. The F10 generation had no cross-resistance to the insecticides abamectin and endosulfan (which target the γ-aminobutyric acid receptor) and chlorantraniliprole (which targets a non-γ-aminobutyric acid receptor). The specific activities of important detoxification enzymes (cytochrome P450 monooxygenase, esterase, and glutathione S-transferase) were not obviously altered. However, the larval stage was prolonged and the adult stage was shortened significantly in F11 generation than the F0 generation. The total preoviposition period TPOP significantly prolonged 1.90 d in F11 generation. The fitness value Rf (0.93) was lower for the F11 generation than the F0 generation. The results indicated that long-term exposure to broflanilide exerts clear fitness costs in the DBM. This information will be useful in identifying reasonable broflanilide application guidelines for managing broflanilide resistance in the DBM.

Novel Kdr mutations (K964R and A943V) in pyrethroid-resistant populations of Triatoma mazzottii and Triatoma longipennisUoro Mexico and detoxifying enzymes

Although having five different ways of transmission the vector-borne is the principal way of transmission of Chagas disease, which involves insects of the subfamily Triatominae (Hemiptera: Reduviidae). Nineteen of the 31 species that occur in Mexico are associated with humans, and all are capable of transmitting the disease. Pyrethroids are the insecticides recommended for the control of these vectors in Mexico. We determined the susceptibility to the pyrethroids dcltamethrin and permethrin of peridomestic populations of Triatoma mazzottii Usinger and two populations of Triatoma longipetmis Usinger in comparison with a reference strain for each species. Bioassays were performed for the determination of the LD50 for both field populations and reference strains. A maximum of 27 fold resistance to deltamethrin was observed in T. mazzottii, meanwhile, for permethrin, T. longipennis from Jalisco show the highest value of 3.19 fold. There was significantly increased activity of esterases in field populations in comparison with their corresponding reference strain. The results of the search of kdr mutations related to the resistance to deltamethrin and permethrin in the evaluated species show the presence of mutations in the field populations, as is the case with individuals of T. mazzottii, for which the mutation was found A943V, and for the two populations of T. longipennis included in this study, we report the presence of the kdr mutation K964R. Evaluation of the various mechanisms involved in resistance to pyrethroids in triatomines from Mexico could guide us to the real justification for insecticide resistance monitoring.