Objective To explore the therapeutic mechanism of berberine in atopic dermatitis(AD)rats based on PI3K/Akt/NF-kappa B signaling pathway.Methods Sixty adult male Wistar rats were randomly divided into the blank group(normal rats),the control group(AD model,50 mg/kg berberine treatment)and the experimental group(AD model,200 mg/kg berberine treatment),with 20 rats in each group.The levels of interleukin-4(IL-4),interleukin-13(IL-13)and tumor necrosis factor-α(TNF-α)were determined by enzyme-linked immunosorbent assay(ELISA)at 1 d,7 d and 14 d of intervention.The protein levels of PI3K,p-PI3K,Akt,p-Akt and NF-κB p65 were detected by Western blot assay.Pathological changes of rat skin tissue were analyzed by HE staining.Results After intervention for 1 d,7 d and 14 d,serum levels of IL-4,IL-13,TNF-α and PI3K,p-PI3K,Akt,p-Akt and NF-kappa B p65 were higher in the control group than those in the blank group(P＜0.05).After intervention for 7 d and 14 d,the levels of the above indicators were lower in the experimental group than those in the control group(P＜0.05).After 14 days of intervention,compared with the blank group,the skin tissue of rats in the control group and the experimental group showed obvious pathological changes,including thickening of epidermis layer,excessive keratinization of the stratum comeum,thickening of spinous layer and a large infiltration of inflammatory cells in dermis.The pathological damage of rat skin tissue was significantly alleviated in the experimental group.Conclusion Berberine can inhibit the activation of PI3K/Akt/NF-kappa B signaling pathway,reduce serum level of inflammatory factors and reduce pathological damage of skin tissue in AD rats.

Objective Network pharmacology and molecular docking technology were used to analyze the potential mechanism of Sinisan(SNS)in the treatment of adolescent depression,and the relevant results were verified by experiments.Methods Through the TCMSP and ETCM databases,the effective chemical components and targets of SNS(Chaihu,Zhishi,Baishao and Gancao)were screened,and the main targets of adolescent depression were screened in the GeneCards and OMIM databases,and the common targets of drugs and disease were obtained by Venn diagram.Cytoscape 3.9.1 software was used to draw the Chinese herb-active ingredient-target action network of SNS.The STRING platform was used to construct a portein-protein interaction network(PPI)of drug-disease-common targets,and the core targets were obtained after screening.The Metascape platform was used to perform enrichment analysis of core targets.Molecular docking was carried out through the software AutoDockTools 1.5.7 to evaluate the binding ability of effective active ingredients to potential core targets.Western blotting(WB)experiments were used to verify the potential targets of SNS against adolescent depression.Results The core effective active ingredients of SNS in the treatment of adolescent depression include quercetin,kaempferol,isorhamnetin,paeoniflorin,etc.,and the potential core targets including AKT1,IL-6,PPARG,PTGS2,F7,etc.,were identified through PPI network topology analysis.The molecular docking results showed that the active substance had strong binding activity to its main target.WB experiments verified that AKT1,IL-1B and IL-6 were potential targets related to anti-adolescent depression.The main biological processes of PPI network four inverse dispersion in the treatment of adolescent depression include hormone response,and the main signaling pathways regulated such as AGE-RAGE and PI3K-AKT signaling pathway.Conclusion This study preliminarily confirmed the effective active ingredients and target information of SNS treatment in adolescent depression,and revealed the potential mechanism of SNS in the treatment of adolescent depression.

Objective Network pharmacology and molecular docking technology were used to analyze the potential mechanism of Sinisan(SNS)in the treatment of adolescent depression,and the relevant results were verified by experiments.Methods Through the TCMSP and ETCM databases,the effective chemical components and targets of SNS(Chaihu,Zhishi,Baishao and Gancao)were screened,and the main targets of adolescent depression were screened in the GeneCards and OMIM databases,and the common targets of drugs and disease were obtained by Venn diagram.Cytoscape 3.9.1 software was used to draw the Chinese herb-active ingredient-target action network of SNS.The STRING platform was used to construct a portein-protein interaction network(PPI)of drug-disease-common targets,and the core targets were obtained after screening.The Metascape platform was used to perform enrichment analysis of core targets.Molecular docking was carried out through the software AutoDockTools 1.5.7 to evaluate the binding ability of effective active ingredients to potential core targets.Western blotting(WB)experiments were used to verify the potential targets of SNS against adolescent depression.Results The core effective active ingredients of SNS in the treatment of adolescent depression include quercetin,kaempferol,isorhamnetin,paeoniflorin,etc.,and the potential core targets including AKT1,IL-6,PPARG,PTGS2,F7,etc.,were identified through PPI network topology analysis.The molecular docking results showed that the active substance had strong binding activity to its main target.WB experiments verified that AKT1,IL-1B and IL-6 were potential targets related to anti-adolescent depression.The main biological processes of PPI network four inverse dispersion in the treatment of adolescent depression include hormone response,and the main signaling pathways regulated such as AGE-RAGE and PI3K-AKT signaling pathway.Conclusion This study preliminarily confirmed the effective active ingredients and target information of SNS treatment in adolescent depression,and revealed the potential mechanism of SNS in the treatment of adolescent depression.

Objective To explore the therapeutic mechanism of berberine in atopic dermatitis(AD)rats based on PI3K/Akt/NF-kappa B signaling pathway.Methods Sixty adult male Wistar rats were randomly divided into the blank group(normal rats),the control group(AD model,50 mg/kg berberine treatment)and the experimental group(AD model,200 mg/kg berberine treatment),with 20 rats in each group.The levels of interleukin-4(IL-4),interleukin-13(IL-13)and tumor necrosis factor-α(TNF-α)were determined by enzyme-linked immunosorbent assay(ELISA)at 1 d,7 d and 14 d of intervention.The protein levels of PI3K,p-PI3K,Akt,p-Akt and NF-κB p65 were detected by Western blot assay.Pathological changes of rat skin tissue were analyzed by HE staining.Results After intervention for 1 d,7 d and 14 d,serum levels of IL-4,IL-13,TNF-α and PI3K,p-PI3K,Akt,p-Akt and NF-kappa B p65 were higher in the control group than those in the blank group(P＜0.05).After intervention for 7 d and 14 d,the levels of the above indicators were lower in the experimental group than those in the control group(P＜0.05).After 14 days of intervention,compared with the blank group,the skin tissue of rats in the control group and the experimental group showed obvious pathological changes,including thickening of epidermis layer,excessive keratinization of the stratum comeum,thickening of spinous layer and a large infiltration of inflammatory cells in dermis.The pathological damage of rat skin tissue was significantly alleviated in the experimental group.Conclusion Berberine can inhibit the activation of PI3K/Akt/NF-kappa B signaling pathway,reduce serum level of inflammatory factors and reduce pathological damage of skin tissue in AD rats.

Objective To evaluate the therapeutic effect of evodiamine(Evo)on atopic dermatitis(AD)in rat models by regulating the cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/cAMP response ele-ment binding protein(CREB)signaling pathway.Methods A rat model of AD was established by administration of multiple doses of 2,4-dinitrochlorobenzene(DNCB).The animals were randomly divided into AD group,Evo-low-dose(Evo-L,5 mg/kg)group,Evo-high-dose(Evo-H,10 mg/kg)group,Evo-H+H-89(5 mg/kg)group and dexamethasone(0.1 mg/kg)group.Normal rats were used as the control group and then the degree of skin damage of rats in each group was scored.Abdominal blood was taken to detect the levels of interleukin-4(IL-4),cAMP,and tumor necrosis factor-α(TNF-α)in serum;Skin lesion tissue was collected to detect pathological change,counting of mast cells,PKA/CREB related protein expression and expression of IL-4 and TNF-α mRNA in the tissue.Results Compared with control group,the level of cAMP in serum,the expression of p-PKA/PKA,and p-CREB/CREB in skin lesions of AD group were reduced,the severity score of skin lesions,level of IL-4 and TNF-α,epidermal thickness,number of mast cells and mRNA expression of IL-4 and TNF-α in skin lesion tissues were all significantly increased(P＜0.05).Compared with AD group,the level of cAMP in serum,the expression of p-PKA/PKA,and p-CREB/CREB in skin lesions in Evo-L group,Evo-H group,and dexamethasone group were increased,the severity score of skin lesions,level of IL-4 and TNF-α,epidermal thickness,number of mast cells,and mRNA expression of IL-4 and TNF-α in skin lesion tissues all reduced(P＜0.05).Compared with the Evo-H group,the level of cAMP in serum,the expression of p-PKA/PKA,and p-CREB/CREB in skin lesions in Evo-H+H-89 group was reduced and the severity score of skin lesion,level of IL-4 and TNF-α,epidermal thickness,num-ber of mast cells,and mRNA expression of IL-4 and TNF-α in skin lesion tissues significantly increased(P＜0.05).Conclusions Evo inhibits inflammatory response and pathological damage through regulation of cAMP/PKA/CREB signaling pathway in AD rat models.

Objective To evaluate the effect of berberine on the expression of cell cycle-related miRNA and its target gene in human melanoma A375 cells.Methods In vitro cultured A375 cells were classified into several groups to be treated with berberine at different concentrations of 0 (blank control group),20,40,60,80,and 100 μmol/L,respectively,for 48 hours.qRT-PCR was performed to determine the mRNA expression of miRNA-582-5p and its target gene cyclin-dependent kinase 1 (CDK1),miRNA-188-5p and its target gene CDK2,Cyclin D1 and Cyclin A.Western blot analysis was conducted to measure the protein expression of cell cycle-related proteins CDK1,CDK2,Cyclin D1 and Cyclin A.Results qRT-PCR showed that compared with the blank control group,the 20 and 40 μmol/L berberine groups had a similar expression of miRNA-582-5p (both P ＞ 0.05),but the 60 and 80 μmol/L berberine groups had a significantly up-regulated expression of miRNA-582-5p (both P ＜ 0.05).Compared with the blank control group,all the 5 berberine groups had a significantly increased expression of miRNA-188-5p (F =22.600,P =0.002).However,the mRNA expression of CDK2,CDK1,Cyclin A and Cyclin D1 gradually decreased along with the increase of berberine concentrations (F =51.976,248.510,626.671 and 312.740,respectively,all P ＜ 0.001).Western blot analysis revealed that berberine decreased the protein expression of CDK1,CDK2,Cyclin D1 and Cyclin A (F =138.124,110.966,278.772 and 140.167,all P ＜ 0.001).Conclusion Berberine can decrease the expression of cell cycle-related proteins CDK1,CDK2,Cyclin D1 and Cyclin A,likely by decreasing their mRNA expression and increasing the expression of miRNA-582-5p and miRNA-188-5p,and then block the cell cycle progression of A375 cells and inhibit the growth of tumor.

Objective:To screen the differentially expressed miRNAs in umbilical cord tissue of children with nonsyndromic cleft lip and/or cleft palate( NSCL/P) using miRNA microarray and comprehensive bioinformatics analysis for the prediction of related the bio-logical process and signaling pathways. Methods:Umbilical cord tissues of 4 cases of healthy newborns' and 4 lip or palate tissues of 4 cases with NSCL/P without other disease aged younger than 2 years were collected. The differentially expressed miRNAs were screened by miRNA microarray. Targets of dysrugulated miRNAs were predicted by TARGETSCAN-VERT, MIRDB and RNA22-HSA. All the gene sets were analyzed by gene ontology and pathway enrichment. Results: MiRNA microarray demonstrated that 254 miRNAs were dysregulated(181 miRNAs were up-regulated and 73 downregulated,P <0. 05). The dysregulated miRNAs targets contained 5029 genes. The dysregulated miRNAs targets were enriched in anatomical structure development,cell adhesion,cell proliferation,cell motili-ty and other biological processes. The dysregulated miRNAs targets were enriched in Wnt, mTOR, cGMP-PKG, TGFβ, PI3K-Akt and other signaling pathways. Conclusion:The target genes set of miRNAs are enriched in multiple biological processes and signaling path-ways related to NSCL/P, which indicate that genetic and environmental factors may influence the development process of NSCL/P.

OBJECTIVE: To optimize the formative excipients for cough remedy granules. METHODS: Effects of different excipients on the formation, moisture absorption and relative critical humidity of cough remedy granules were examined, and the optimal excipients as well as formula were selected by adoption of the comprehensive scoring method. RESULTS: The optimal excipient for preparation of cough remedy granules was lactose, and the best formula comprised of 4 doses of spraying powder and 6 doses of lactose mixture. CONCLUSIONS: The cough remedy granules thus prepared is ideal: good in granularity, easy to dissolve and not liable to moisture absorption.

Objective: To study the antixiodant activity of sweet-potato anthocyanin (SPAC) and its inhibiting effect on growth of cancer S180. Method: The scavenging capacity of ??O2 and?OH and the inhibitory effect of MDA were determined in vitro.The SOD activity of serum and skin, the effect on S180 growth, serum GSH-Px activity and MDA were tested in mice. Results: SPAC had antioxidant activity in vitro, with elimination rate of O2?? and?OH 30.63% and 20.57% higher than the same concerntration of VC respectively. Activity of SOD in the serum and skin of mice were raised 27.30% and 13.50% respectively after giving SPAC. The growth rate of cancer S180 in the mice was inhibited, and the highest inhibitory rate was 43.12%. The activity of serum GSH-Px, SOD of the mice was raised as compared to control, but MDA declined . Conclusion: SPAC is a perfect natural pigment with inhibitory effect on growth of cancer S180 probably through its antioxidant activity.