scholarly journals Effects of Radix Scrophulariae on Hyperthyroidism Assessed by Metabonomics and Network Pharmacology

2021 ◽  
Vol 12 ◽  
Author(s):  
Ning Zhang ◽  
Fang Lu ◽  
Zihui Li ◽  
Hongwei Zhao ◽  
Mu Pang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Unsaturated Fatty Acids ◽  
Chinese Herb ◽  
Enrichment Score ◽  
Sphingolipid Metabolism ◽  
Network Pharmacology ◽  
Control Group ◽  
Disease Genes ◽  
Model Group ◽  
System Pharmacology

Radix Scrophulariae (Chinese name: Xuanshen), a traditional Chinese herb, is used for the treatment of hyperthyroidism, and in this study, its mechanisms were evaluated by metabonomics and system pharmacology. To study the anti-hyperthyroidism effects of R. Scrophulariae, a male SD rat (180–220 g) model of hyperthyroidism induced by Euthyrox was used. Thirty rats were randomly distributed into three groups: the Model group, the R. Scrophulariae treatment group (RS group) and the healthy Control group. Using the UHPLC/Q-TOF-MS metabolomics approach, 44 metabolites were found to be profoundly altered in the model group, and the levels of these biomarkers were significantly decreased after treatment with R. Scrophulariae. Forty-four metabolites and 13 signaling pathways related to R. Scrophulariae, including the biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis and sphingolipid metabolism, were explored, and linoleic acid metabolism and sphingolipid metabolism were identified as the most relevant metabolic pathways. In addition, the system pharmacology paradigm revealed that R. Scrophulariae contains 83 active ingredients and is related to 795 genes, and 804 disease genes are related to hyperthyroidism. The construction of the R. Scrophulariaceae-chemical composition-target-hyperthyroidism network identified a total of 112 intersection genes. The enriched gene targets were analyzed, and five pathways were found to be enriched. Among them pathways, the HIF signaling pathway had the highest enrichment score, which indicated that this pathway might be the main signaling pathway related to the treatment of hyperthyroidism by R. Scrophulariae.The integrated approach involving metabolomics and network pharmacology revealed that R. Scrophulariae might play a role in the treatment of hyperthyroidism by regulating the “IL6-APOA1-cholesterol” pathway and disturbing the HIF signaling pathway. The results demonstrate that the combination of metabolomics and network pharmacology could be used to reflect the effects of R. Scrophulariae on the biological network and metabolic state of hyperthyroidism and to evaluate the drug efficacy of R. Scrophulariaceae and its related mechanisms.

scholarly journals Utilizing Network Pharmacology to Explore the Possible Mechanism of Coptidis Rhizoma in Kawasaki Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Xue Fan ◽  
Xin Guo ◽  
Ying Li ◽  
Mingguo Xu
Keyword(s):  
Kawasaki Disease ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Receptor Protein ◽  
Network Pharmacology ◽  
Control Group ◽  
Coptidis Rhizoma

Background: The purpose of the research is to identify the main active ingredients in Coptidis Rhizoma (CR) and explore the possible molecular mechanisms in the treatment of Kawasaki disease (KD).Materials and Methods: A total of 58 children with KD were randomly divided into a control group and a Berberine treatment group. The therapeutic indicators of the two groups before and after treatment were compared. Then, compounds and drug targets of CR from the TCMSP, SWISS, SEA, and the STITCH were collected, and targeted KD genes were retrieved from the DisGeNET, DrugBank, and GeneCards databases. The network pharmacology approach involved network construction, target prediction, and module analysis. GO and KEGG enrichment analysis were performed to investigate the possible pathways related to CR for KD treatments. Finally, protein expression was determined to verify the core targets using Western blotting in the cell experiment.Results: In total, nine compounds, 369 relative drug targets, and 624 KD target genes were collected in the above database. The network analysis revealed that 41 targets might be the therapeutic targets of CR on KD. GO and KEGG enrichment analysis revealed that the biological processes, namely, response to hormone, response to inorganic substance, and enzyme-linked receptor protein signaling pathway, and Pathways in cancer, Toll-like receptor signaling pathway, and Pancreatic cancer are the most significant. Protein expression of CASP3, PTGS2, and SRC was upregulated and AKT1 and ERK were downregulated.Conclusion: We provided useful resources to understand the molecular mechanism and the potential targets for novel therapy of KD.

scholarly journals Puerarin Suppress Apoptosis of Human Osteoblasts via ERK Signaling Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Ling-juan Liu ◽  
Li-qun Liu ◽  
Tao Bo ◽  
Shi-jun Li ◽  
Zhen Zhu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Chinese Herb ◽  
Inhibitory Effect ◽  
Erk Signaling ◽  
Control Group ◽  
Human Osteoblasts ◽  
Antiapoptotic Effect ◽  
Protein Levels ◽  
Bax Protein ◽  
Radix Puerariae

Puerarin, the main isoflavone glycoside extracted from Radix Puerariae, is an isoflavone traditional Chinese herb. Previous studies have demonstrated that puerarin could regulate osteoblast proliferation and differentiation to promote bone formation. However, the effect of puerarin on the process of human osteoblasts (hOBs) apoptosis is still unclear. In this study, we detected the function of puerarin on serum-free-induced cell apoptosis using ELISA and TUNEL arrays and then found that the mortality of hOBs was significantly decreased after exposure to 10−10–10−6 M puerarin and reached the maximal antiapoptotic effect at the concentration of 10−8 M. In addition, compared with the control group, puerarin notably increased the Bcl-2 protein levels while it decreased the Bax protein levels in the hOBs in a dose-dependent way. 10−7 M puerarin decreased the Bax/Bcl-2 ratio with a maximal decrease to 0.08. Moreover, puerarin activated ERK signaling pathways in hOBs, and the antiapoptotic effect induced by puerarin was abolished by incubation of ERK inhibitor PD98059. Similarly, the estrogen receptor antagonist ICI182780 also suppressed the inhibitory effect of puerarin on hOBs apoptosis. In conclusion, puerarin could prevent hOBs apoptosis via ERK signaling pathway, which might be effective in providing protection against bone loss and bone remolding associated with osteoporosis.

scholarly journals MicroRNA-34a alleviates steroid-induced avascular necrosis of femoral head by targeting Tgif2 through OPG/RANK/RANKL signaling pathway

2017 ◽  
Vol 242 (12) ◽  
pp. 1234-1243 ◽  
Author(s):  
Wu-Xun Peng ◽  
Chuan Ye ◽  
Wen-Tao Dong ◽  
Lei-Luo Yang ◽  
Chun-Qing Wang ◽  
...  
Keyword(s):  
Femoral Head ◽  
Signaling Pathway ◽  
Normal Control ◽  
Normal Control Group ◽  
Control Group ◽  
Micro Ct ◽  
Model Group ◽  
Model Control ◽  
Model Control Group ◽  
Necrosis Of Femoral Head

The study aims to investigate the effect of microRNA-34a (miR-34a) targeting Tgif2 on steroid-induced avascular necrosis of femoral head (SANFH) by regulating OPG/RANK/RANKL signaling pathway. SD rats were divided into normal control and model (RNAKL rat models) groups. The model group was further assigned into model control, negative control, miR-34a mimics and miR-34a inhibitors groups. QRT-PCR was applied to detect miR-34a, Tgif2, OPG, RANK and RNAKL mRNA expressions. Femoral head tissues were collected for Micro-CT scanning and HE staining. QRT-PCR and Western blotting were used to detect expressions of miR-34a, Tgif2, OPG, RANK, RANKL and Runx2, OPN and OC in bone tissues. Dual-luciferase reporter gene assay was used to testify the target relationship between miR-34a and Tgif2. Compared with the normal control group, the model group showed increased Tgif2, RANK and RANKL mRNA expressions, but decreased miR-34a and OPG mRNA expressions. Tgif2 mRNA expression was negatively correlated with miR-34a and OPG mRNA expressions. Micro-CT showed cystic degeneration of femoral head, with decreased bone volume/total volume (BV/TV), bone surface area/bone volume and trabecular number in the model control group compared with the normal control group. Compared with the model control group, the miR-34a mimics group showed increased BV/TV and trabecular thickness and Runx2, OPN and OC expressions, while the parameters decreased in the miR-34a inhibitors group. Compared with the normal control group, the other groups showed increased Tgif2, RANK and RANKL expressions but decreased miR-34a and OPG expressions. Compared with the model control group, Tgif2, RANK and RANKL expressions decreased and miR-34a and OPG expressions increased in the miR-34a mimics group, while the miR-34a inhibitors group had a reverse trend in contrast to the miR-34a mimics group. Tgif2 is a target gene of miR-34a. In conclusion, miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway. Impact statement miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway, which can be used as a new theoretical basis for SANFH treatment.

scholarly journals Metabolomics Study of Guizhi Fuling Capsules in Rats With Cold Coagulation Dysmenorrhea

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Zhang ◽  
Na Su ◽  
Weiyi Liu ◽  
Qingqing Wang ◽  
Jianguo Sun ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Unsaturated Fatty Acids ◽  
Ovarian Function ◽  
Estradiol Benzoate ◽  
Control Group ◽  
Primary Dysmenorrhea ◽  
Model Group ◽  
Rat Serum ◽  
Cox 2 ◽  
Cold Coagulation

Dysmenorrhea refers to a kind of uterine cramping pain that occurs in women during the period of menstrual. Guizhi Fuling Capsules are mainly used for the treatment of various pain syndromes and especially effective in treating primary dysmenorrhea. However, the research on its modern pharmacology and mechanism of action have not been thoroughly carried out. It is not clear about the main active ingredients, potential targets and metabolic pathways involved in its efficacy. Therefore, this research project employed estradiol benzoate sensitization combined with oxytocin pain to construct the cold coagulation syndrome dysmenorrhea model, observed the anti-dysmenorrhea effect of Guizhi Fuling Capsules, and used the metabolomics to explore its mechanism. The results showed that Guizhi Fuling Capsules could considerably reduce the number of writhing times in dysmenorrhea rats, increasing the level of PGE2 and β-EP and reducing the contents of PGF2α in rat serum. Pathological sections of uterus and ovaries also showed that Guizhi Fuling Capsules could significantly relieve endometrial hyperplasia and improve ovarian function. The LC/MS-based metabolomics of rat uterine indicated that the model group has a great deviation from the control group. Compared with the model group, the Guizhi Fuling Capsules group had a tendency to shift to the control group, and the main metabolic changes was mainly concentrated on saturated and unsaturated fatty acids. Among them, arachidonic acid is in a pivotal position, and the expression of its rate-limiting enzyme (COX-2) involved in its cyclooxygenase metabolic pathway was significantly up-regulated in the model group, but significantly decreased after the intervention of Guizhi Fuling Capsules. In conclusion, Guizhi Fuling Capsules can effectively relieve primary dysmenorrhea, and this effect may be attributed to the regulation effects of Guizhi Fuling Capsules on endogenous metabolism, such as inhibiting arachidonic acid converted to prostaglandins through downregulate the expression of COX-2, which plays an anti-inflammatory effect.

scholarly journals Exogenous Hydrogen Sulfide Alleviated Left Ventricular Fibrosis Via Enhancing Cardiac Autophagy and Decreasing Cardiomyocyte Apoptosis in StreptozotocinInduced Diabetic Rats: From Network Pharmacology to Experimental Pharmacology

2020 ◽  
pp. 1-8
Author(s):  
Shumin Liu ◽  
Cheng Fang ◽  
Feixue Dong ◽  
Liangyou Zhao ◽  
Yongwu Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Expression Level ◽  
Network Pharmacology ◽  
Control Group ◽  
Associated Proteins

Streptozotocin (STZ)-induced diabetes mellitus (DM) model shows the signal of cardiac dysfunction, which is manifested as myocardial fibrosis and hypertrophy. This study was designed to predict targets of sodium hydrosulfide (NaHS) for diabetic cardiomyopathy and its corresponding triggered pathways by network pharmacology analysis and test the effects of NaHS as well as its mechanism as possible modulators of left ventricular remodeling in diabetic rats. The drug-target networks were constructed via approaches of network pharmacology, and the predicted targets and pathways were validated by in vivo experiments. Rats were randomly divided into 3 groups (n=6/group): STZ-induced DM group (STZDM); STZ-induced DM treated with H2S group (STZ-NaHS); control group. The control group was treated with daily saline (i.p.); the diabetic model was induced by intraperitoneal (i.p.) injections of 40 mg/kg/day STZ. After 12 weeks, the rat cardiac function was determined, and the pathological morphology of the heart was analysed by Masson trichrome staining in each group. The expression level of matrix metalloproteinase 9 (AGEs), CSE, CBS and several autophagy associated proteins were detected by the ELISA analysis. Results from the PPI network implied that 27 targets were key regulators. The AGE-RAGE signaling pathway in diabetic complications and the apoptotic signaling pathway was discovered to be the key to anti-diabetic cardiomyopathy of NaHS upon the GO enrichment analyses and KEGG pathway. In the in vivo experiment, compared with the control group, cardiac fibrosis and attenuated left ventricular function were observed. Furthermore, compared with the control group, the expression level of CSE, CBS and autophagy associated proteins Atg5 was significantly decreased, while that of AGEs, autophagy associated proteins p62 and p-ERK1/2 was significantly increased in the STZDM group (P<0.05). In the STZ-NaHS group, cardiac fibrosis and ventricular dysfunction were ameliorated, the expression level of CSE, CBS and autophagy associated proteins Atg5 was increased, and the expression level of AGEs, autophagy associated proteins p62 and p-ERK1/2 was significantly decreased (P<0.05). In conclusion, H2S may alleviate cardiac fibrosis of the STZ-induced DM rat model by enhancing cardiac autophagy, inhibiting cardiomyocyte apoptosis and downregulating p-ERK1/2.

scholarly journals Response of Intestinal Mucosal Microbiota in Diarrheal Mice to Ge-gen-qin-lian Decoction

2020 ◽  
Author(s):  
Xiaoya Li ◽  
Chenyang Zhang ◽  
Huaying Hui ◽  
Xinxin Peng ◽  
Nenqun Xiao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Intestinal Mucosa ◽  
Diversity Index ◽  
Animal Experiments ◽  
Intestinal Flora ◽  
Alpha Diversity ◽  
Network Pharmacology ◽  
Control Group ◽  
Active Ingredients ◽  
Neisseria Mucosa

Abstract Background: Ge-gen-qin-lian Decoction (GD) has been extensively used for the treatment of diarrhea with intestinal dampness heat syndrome(IDHS) with a satisfying therapeutic effect. However, the active ingredients and mechanism of GD against diarrhea with IDHS have not been fully elucidated. The occurrence of diarrhea is closely related to the intestinal flora, and the compound of Traditional Chinese Medicine(TCM) can exert its curative effect by regulating the intestinal flora, and exploring the relationship between the two is conducive to the clarification of pharmacology. Results: Animal experiments indicted that the OTU number and Alpha diversity index in the intestinal mucosa flora of the treatment group(cttm) recovered and higher than that of the control group(ctcm). PCoA results showed that there were differences in the community structure between the Con and GD. At the species level, the abundance of Lactobacillus crispatus and Muribaculum intestinal in the model group(ctmm) decreased, and the Neisseria mucosa increased (p<0.05). After being treated with GD, Muribaculum intestinal increased, and Lactobacillus curlyus and Neisseria mucosa decreased (p<0.05). Combined with network pharmacology analysis, we screened out 146 active ingredients in GD corresponding to 252 component targets, and 328 disease targets in diarrhea to obtain 31 drug-disease common targets. The key targets involved TNF, IL-6, EFGR etc. KEGG pathway enrichment resulted in HIF-1 signaling pathway, VEGFA signaling pathway, Adipocytokine signaling pathway and so on (p<0.05). Conclusions: GD could restore the diversity and abundance of intestinal mucosa in diarrheal mice with IDHS, promote the abundance of Muribaculum intestinal, inhibit the abundance of Neisseria mucosa. Through the characteristic of multiple targets and multiple channels, the active ingredients of GD intervened from oxidative stress and inflammatory response to adjust the balance of intestinal mucosa flora, thereby playing the role of treating diarrhea.

scholarly journals Multiomics analysis of soybean meal induced marine fish enteritis in juvenile pearl gentian grouper, Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei Zhang ◽  
Beiping Tan ◽  
Junming Deng ◽  
Zhang Haitao
Keyword(s):  
Signaling Pathway ◽  
Marine Fish ◽  
Soybean Meal ◽  
High Throughput Sequencing ◽  
Unsaturated Fatty Acids ◽  
Intestinal Inflammation ◽  
Water Volume ◽  
Control Group ◽  
Signal Pathways ◽  
Human Beings

AbstractAs an important protein source, soybean products can cause intestinal inflammation and injury in many animals including human beings, particularly infants and juvenile individuals. Research in this field has been performed for terrestrial animals and fish, but still lacks integrity and systematicness. In this study, the main biological processes in the intestinal tract of marine fish juvenile pearl gentian grouper in the state of soybean meal-induced enteritis (SBMIE) were analyzed. A total of 720 groupers with an approximate initial weight of 12.5 g were randomly divided into three groups: the fish meal (FM) control group, the 20% SBM group (SBM20), and the SBM40 group (n = 4). Three iso-nitrogenous and iso-lipidic diets were prepared and fed to fish for 10 weeks. Each barrel contained a water volume of about 1 m3 in and was exposed to natural light and temperature. Results indicated that the growth and physiology of groupers fed with SBM were significantly negatively affected, with the gene expressions of intestinal structural protein abnormal. 16SrDNA high-throughput sequencing showed that the intestinal microflora played an important role in the pathogenesis of pearl gentian grouper SBMIE, which may activate a variety of pathogen pattern recognition receptors, such as toll-like receptors (TLRs), RIG-I-like receptors, and nod-like receptors. Transcriptome analysis revealed that changes of the SBMIE signaling pathway in pearl gentian groupers were conservative to some extent than that of terrestrial animals and freshwater fish. Moreover, the TLRs-nuclear factor kappa-B signaling pathway becomes activated, which played an important role in SBMIE. Meanwhile, the signal pathways related to nutrient absorption and metabolism were generally inhibited. Metabolomics analysis showed that isoflavones and saponins accounted for a large proportion in the potential biomarkers of pearl gentian grouper SBMIE, and most of the biomarkers had significantly positive or negative correlations with each other; 56 metabolites were exchanged between intestinal tissues and contents, which may play an important role in the development of enteritis, including unsaturated fatty acids, organic acids, amino acids, vitamins, small peptides, and nucleotides, etc. These results provide a basic theoretical reference for solving the intestinal issues of fish SBMIE and research of inflammatory bowel disease in mammals.

scholarly journals Huanglian Jiedu Decoction Exerts Antipyretic Effect by Inhibiting MAPK Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xing Li ◽  
Shizhang Wei ◽  
Xiao Ma ◽  
Haotian Li ◽  
Manyi Jing ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Western Blotting ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Potential Mechanism ◽  
Model Group ◽  
Rat Serum ◽  
Antipyretic Effect ◽  
Tnf Α

Aim. The aim of this study was to explore the antipyretic effect and potential mechanism of Huanglian Jiedu Decoction (HLJDD) on LPS-induced fever in rats. Materials and Methods. The fever rat model was established by LPS. Anal temperature of rats was measured every 1 hour after modeling. TNF-α, IL-6, PGE2, and cAMP in rat serum or hypothalamus tissue were detected by ELISA kit. In order to explore the potential active ingredients and mechanism of antipyretic effect of HLJDD, we predicted the underlying antipyretic mechanism by using network pharmacology and then verified its mechanism by Western Blotting. Results. The results showed that HLJDD can alleviate LPS-induced fever in rats. The expression levels of TNF-α, IL-6, PGE2, and cAMP in the treatment group were significantly lower than those in the model group. Western Blotting results showed that the protein expression of p-ERK, p-JNK, and p-P38 was significantly inhibited. Conclusion. The findings suggest that HLJDD has a good antipyretic effect on LPS-induced fever in rats, which may be closely related to the inhibition of MAPK signaling pathway.

scholarly journals Mechanism of Mongolian Medicine Eerdun Wurile in Improving Postoperative Cognitive Dysfunction Through Activation of the PI3K Signaling Pathway

2022 ◽  
Vol 15 ◽  
Author(s):  
Zhixin Lv ◽  
Limuge Che ◽  
Yiri Du ◽  
Jianshe Yu ◽  
Enboer Su ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cognitive Dysfunction ◽  
Water Maze ◽  
Low Dose ◽  
Escape Latency ◽  
Postoperative Cognitive Dysfunction ◽  
Treated Group ◽  
Control Group ◽  
Model Group ◽  
Group D

ObjectiveTo study the effect of Eerdun Wurile (EW), a traditional Mongolian medicine, on the cognitive function of rats by activating the IRS-PI3K-AKT-GLUT4 pathway in an animal model of postoperative cognitive dysfunction (POCD).MethodsFifty clean-grade adults Sprague Dawley (SD) male rats were assigned to one of five groups: (1) a control group with no anesthesia (Group C), (2) a POCD model group with anesthesia only (Group P), (3) POCD group with low-dose EW treated (Group L), (4) a POCD group with high-dose EW treated (Group H), and (5) a POCD model group with dexmedetomidine treated (Group D) for positive control. The study started 7 days after all rats had acclimated to housing. Rats were trained in the Morris Water Maze navigation 5 days before surgery. All rats underwent the same maze for navigation and spatial exploration experiments on the preoperative day 1 and postoperative days 1, 3, 5, and their learning and memory abilities were assessed. At the end of the water maze experiment, rats were sacrificed to obtain hippocampal tissue. The mRNA levels of IRS-2, PI3K, AKT, and GLUT4 were measured in the hippocampus by real-time PCR, and the expression of IRS-2, PI3K, AKT, and GLUT4 protein in the hippocampus was determined by Western blotting to investigate the potential mechanisms at the molecular level.ResultsCompared to control Group C, Group P, L, H, and D showed prolonged escape latency (P &lt; 0.05) and decreased number of times to cross the platform (P &lt; 0.05) at 1, 3 and 5 days after surgery. Compared to Group P, Group L, H, and D showed a decrease in escape latency with an increased number of crossing the platform at all-time points after surgery (P &lt; 0.05). Within individual P, L, H, and D groups, escape latencies decreased (P &lt; 0.05) and the number of times that the platform was crossed increased (P &lt; 0.05) between postoperative days 3 and 5 compared to postoperative 1 day. Compared to Group C, the mRNA expression of IRS-2, PI3K, AKT and GLUT4 in the hippocampus of P, L, H, and D groups were decreased (P &lt; 0.05). Compared to Group P, IRS-2, PI3K, AKT, and GLUT4 in the hippocampus of L, H, and D groups were increased (P &lt; 0.05). Compared with Group D, the expression levels of IRS-2 and AKT in both L and H groups were higher. The expression level of PI3K in Group L was also higher (P &lt; 0.05) vs Group D. The expression of AKT mRNA in Group H was higher than in Group L (P &lt; 0.05). Compared to Group C, the p-IRS-2/IRS-2 ratio in the hippocampus of Group P was higher than that of Group C (P &lt; 0.05). Compared to Group P, the ratios of p-IRS-2/IRS-2 in Group L, Group H, and Group D were lower, and the ratios of the p-PI3K/PI3K, p-AKT/AKT, and p-GLUT4/GLUT4 were higher (P &lt; 0.05).ConclusionAdministration of EW showed the effect on the signaling pathway in rats with POCD. The therapeutic effect was better in the low-dose group. This could be related to the insulin downstream signal molecule PI3K and the IRS-PI3K-AKT-GLUT4 signaling pathway.

scholarly journals Utilizing Network Pharmacology to Explore the Possible Mechanism of Coptidis Rhizoma in Kawasaki Disease

2020 ◽  
Author(s):  
Xue Fan ◽  
Xin Guo ◽  
Ying Li ◽  
Mingguo Xu
Keyword(s):  
Kawasaki Disease ◽  
Signaling Pathway ◽  
Drug Targets ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Control Group ◽  
Pathway Enrichment Analysis ◽  
Routine Treatment ◽  
Coptidis Rhizoma

Abstract Background: Kawasaki disease (KD) is an acute self-limiting systemic vasculitis. In study, a randomized controlled trial regarding berberine (main component of Coptidis Rhizoma) function in treating KD was carried out and possible pharmacological mechanisms of Coptidis Rhizoma (CR) on KD therapy were investigated using an integrated network pharmacology approach. Methods: A total of 58 children with KD, younger than 5 years old, were enrolled in the study from October 2018 to May 2019. The patients were randomly divided into control group and BBR treatment group. The therapeutic indicators of the 2 groups before and after treatments were compared. Then, compounds and drug targets of CR from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, the SWISS database, the SEA database and the STITCH database were collected, and targeted KD genes were retrieved from the DisGeNET databases, the DrugBank databases and the GeneCards databases. The network pharmacology approach involved network construction, target prediction, and module analysis. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to CR for KD treatments. Results: The berberine group was able to reduce the values of CRP, NLR and PLR significantly. Also, the effect of berberine improved the resistance rate of intravenous injection of gamma globulin significantly. In total, 9 compounds and 369 relative drug targets were collected from TCMSP, SWISS, SEA and STITCH database and 624 KD target genes were collected in DisGeNET, DrugBank and GeneCards database. The network analysis revealed that 41 targets might be the therapeutic targets of CR on KD, among which ATK1, RELA, SRC, CASP3 and MTOR ranked in top 5. Gene ontology enrichment analysis revealed that the reaction to bacteria-derived molecules and to lipopolysaccharide and the apoptosis process were the key biological procedures for CR treating KD. The KEGG pathway enrichment analysis pointed out that the four signaling pathways closely related to CR treating KD including age-rage signaling pathway, fluid shear stress and atherosclerosis, TNF signaling pathway and Toll-like receptor signaling pathway in diabetic complications. Conclusions: we concluded that the introduction of routine treatment combined with berberine in treating KD has advantages than routine treatment and can be considered as a preferred approach in KD. Network pharmacology showed that CR exerted the effect of prevention KD by regulating multi-targets and multi-components.

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