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1.
Aim To explore the inhibitory effect of isobavachalcone ( IBC) on migration and invasion of tongue squamous cell carcinoma Tca8113 cells and its possible mechanism. Methods Tca8113 cells were treated in different concentrations of IBC in vitro. Cell proliferation was detected by MTT; Wound healing assay and Transwell chamber assay were used to detect the ability of cell migration and invasion; Western blot was applied to detect the expression of Akt, p-Akt, MMP-2 and MMP-9 proteins. Results IBC could inhibit the proliferation of Tca8113 cells in a concentra-tion-and time-dependent manner. IBC can reduce cell migration and invasion. Western blot showed that IBC could an decrease the expression of p-Akt, MMP-2 and MMP-9 proteins in a concentration- dependent manner. However, the level of Akt was not affected by the concentration of IBC treatment. Conclusion IBC could inhibit the proliferation, migration and invasion in Tca8113 cells and its mechanism may be associated with the down-regulation of MMP-2 and MMP-9 proteins and the inhibition of phosphorylation of upstream Akt. 相似文献
2.
目的通过建立和应用斑马鱼Ⅱ型糖尿病合并血栓模型,对益母草碱、黄精多糖、脱氧野尻霉素的联合用药在降血糖和抗血栓方面进行疗效评价。方法在链脲佐菌素建立斑马鱼Ⅱ型糖尿病模型的基础上,分别采用苯肼、花生四烯酸和普纳替尼建立血栓模型,设置对照组、模型组、二甲双胍+阿司匹林组、联合药高中低浓度组,进行药物干预后,观察尾静脉血栓形成情况;采用试剂盒测定各组幼鱼的组织糖含量;采用邻联茴香胺染色法对心脏红细胞进行定量分析,计算抑制血栓率;使用实时荧光定量聚合酶链反应检测相关血栓基因mRNA的表达。结果与模型组相比,联合用药能显著增加斑马鱼心脏红细胞染色强度、抑制血栓形成、下调血栓相关基因表达和降低组织糖含量。结论3种药物的联合使用可有效降低组织糖含量并具有抗血栓效果,在治疗Ⅱ型糖尿病和血栓药物开发方面具有巨大潜力。 相似文献
3.
Aim To investigate the effects of cimifugin on mouse atopic dermatitis (AD) induced by fluorescein isothiocyanate (FITC) and further explore the mechanism of its action. Methods ICR mice were randomly divided into blank group, model group, positive group (dexamethasone),low dose group,high dose group and administration group of cimifugin. FITC solution was applied to the shaved abdomen of mice in the sensitization stage, and 0.6 % FITC solution was applied to attack the ears of mice in the stimulation stage. The administration groups were given medicine for seven consecutive days. The effects of cimifugin on body weight, thymus index and spleen index of mice were detected. Ear inflammatory cell infiltration was observed by HE staining. The ear swelling of mice was measured, and Th2 cytokines IL-5,IL-13 and the key promoter of allergy IL-33 were detected by ELISA. The epithelial barrier structural proteins, filaggrin, claudinl,occludin and E-cadherin,were detected by immunohistochemistry and Western blot. Results Compared with the blank group, the model group showed significant AD symptoms. Compared with the model group, cimifugin transdermal administration group significantly reduced ear inflammatory cell infiltration,ear swelling, IL-5,IL-13 and IL-33, and significantly increased the expression of filaggrin and occludin. Conclusions Transdermal administration of cimifugin could significantly inhibit AD in mice, and its mechanism involves repairing epithelial barrier function, restoring filaggrin and occludin, inhibiting allergy promoting factor IL-33, and finally inhibiting AD inflammation. © 2023 Publication Centre of Anhui Medical University. All rights reserved. 相似文献
4.
Aim To investigate the neuroprotective effect of prophylactic administration of salidroside (Sal) on MCAO rats. Methods A total of 52 SD adult male rats were randomly divided into sham operation group (Sham), model group (MCAO) and salidroside pre-administration group (MCAO + Sal). The dose of Sal was 50 mg·kg-1. MCAO model was administered by continuous intraperitoneal injection for 7 days, followed by the wire embolization 0.5 h after the 7th day of administration, and the materials were taken 24 h after anesthesia. TTC staining was used to detect the volume of cerebral infarction in rats, TUNEL staining was used to detect the number of nerve cell apoptosis, Western blot was used to detect the expression of Bax, Bcl-2, cleaved Caspase-3 and total Caspase-3 proteins, naphthol AS-D chloroacetate was used to detect the expression of neutrophils in brain tissues, RT-qPCR was used to detect the mRNA expression of IL-1β, IL-6 and TNF-α, and immunofluorescence staining was used to determine the expression of NeuN in brain tissues. Results Pre-administration of salidroside for seven days significantly reduced cerebral infarct volume and nerve cell apoptosis in MCAO rats, promoted the expression of Bcl-2 protein, inhibited the expression of Bax and cleaved Caspase-3 proteins, but it had no significant effect on total Caspase-3 protein, and it reduced the recruitment of neutrophils in ischemic brain tissues, decreased the mRNA expression of inflammatory factors IL-1β, IL-6, TNF-α, and up-regulated the expression of NeuN. Conclusions Pre-administration of salidroside for seven days can significantly reduce the volume of cerebral infarction in MCAO rats, inhibit nerve cell apoptosis, reduce inflammation and promote the expression of NeuN, then playing a neuroprotective role. © 2023 Publication Centre of Anhui Medical University. All rights reserved. 相似文献
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OBJECTIVE: To investigate the effect of Turkish galls extract (TGE) on the expression of IgA in serum, urine and renal tissue of IgA nephropathy (IgAN) model rats. METHODS: Fifty healthy male Sprague Dawley rats were randomly divided into normal control group, IgAN model group, and TGE 75,150 and 300 mg · kg-1 groups, 10 rats per group. The model of IgAN rats was established with bovine serum albumin (BSA) + lipopolysaccharide (LPS)+carbon tetrachlorid (CCI4)for 12 weeks. From the 13th week, TGE was ig administrated once a day for 4 weeks. At the end of the 12th and 16th weeks, 24 h urine protein was measured by BCA method. At the end of the 16th week, serum and urinary IgA levels were measured by enzyme linked immunosorbent assay(ELISA), serum creatinine(SCR) and blood urea nitrogen (BUN) were detected by an automatic biochemical analyzer, and the renal pathological changes were evaluated with an Oxford classification scoring system. The deposition of IgA immune complex in the kidney was observed by immunofluorescence assay. RESULTS: At the end of 12th week, 24 h urine protein increased in all IgAN groups (P<0.05), compared with normal control group. At the end of 16th week, 24 h urine protein, IgA content in serum and urine,SCr and BUN content in serum, score in Oxford classification of renal tissue and deposition of IgA immune complex in the kidney in IgAN model group were all higher than in normal control group (P<0.05). Compared with IgAN model group, 24 h urine protein, IgA content in serum and urine and SCr content in serum were decreased in all TGE groups (P<0.05), and BUN content in serum and deposition of IgA immune complex in the kidney decreased in TGE 150 and 300 mg · kg-1 groups (P<0.05). The score in Oxford classification of renal tissue was decreased in TGE 300 mg.kg-1 group only. CONCLUSION: TGE has curative effect on IgAN model rats by reducing serum and urinary IgA and decreasing IgA immune complex deposition. 相似文献
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β-Sitosterol, a common sterol in herbal medicines, exhibits anti-inflammatory effects beneficial in the treatment of lung inflammation, asthma, and bronchospasm. To evaluate whether β-sitosterol also has anticolitic benefits, we tested the effect of β-sitosterol on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. β-Sitosterol inhibited colon shortening and led to lowered macroscopic scores and myeloperoxidase activity in TNBS-treated colitic mice. β-Sitosterol also inhibited the expression of proinflammatory cytokines TNF-α, IL-1β, and IL-6, and an inflammatory enzyme, cyclooxygenase (COX)-2, in the colons of TNBS-induced colitic mice, as well as the activation of NF-κB. Based on these findings, β-sitosterol may ameliorate colitis by inhibiting the NF-κB pathway. 相似文献
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Rutin is extracted from Ruta graveolens L. with many pharmacological activities such as anti-inflammation, anti-oxidation , protecting cardiovascular system and analgesia. As a natural product, rutin has the advantages of low side effects and difficult tolerance, but its instability and low bioavailability still limit its clinical application. This paper summarizes the analgesic mechnism of rutin, and looks forward to the clinical applica¬tion of rutin based on its derivative and dosage forms. It is expected to provide ideas for further analgesic research and drug development and application of rutin in the future. © 2023 Publication Centre of Anhui Medical University. All rights reserved. 相似文献
8.
目的探究红景天苷在高原低氧条件下改善小鼠学习记忆能力的作用。方法48只C57BL/6J♂小鼠按体重随机分成平原对照组、高原模型组和红景天苷组,每组16只,各组动物按剂量预防给药3 d后急进海拔4010 m的高原,缺氧暴露1 d后进行Morris水迷宫实验测试小鼠学习记忆能力;测定丙二醛(MDA)、过氧化氢(H_(2)O_(2))、谷胱甘肽(GSH)、谷氨酸含量及超氧化物歧化酶(SOD)、乙酰胆碱酯酶(AChE)活力;通过HE染色及尼氏染色观察海马组织病理学变化;通过Western blot法检测谷氨酸受体1(Grin1)和Bax、caspase-3的表达。研究高原低氧条件下红景天苷对小鼠记忆损伤的保护作用,并初步探讨其保护机制。结果与高原模型组比较,给予红景天苷后能明显缩短小鼠潜伏期、增加穿越平台次数,不同程度的降低小鼠脑组织MDA、H_(2)O_(2)、谷氨酸含量及AChE活力,增加GSH含量及SOD活力,改善海马体中的神经元损伤,降低海马组织中Grin1和凋亡蛋白Bax、caspase-3的表达。结论红景天苷可以减轻氧化应激损伤、调节神经递质水平、缓解海马组织损伤并减少神经元凋亡,最终改善由高原低氧造成的小鼠记忆损伤。 相似文献
9.
Luo X.-P.Yu Z.-L.Deng C.Zhang J.-J.Wang Z.-T.Dou W. 《中国药理学与毒理学杂志》2017,(6):541-546
OBJECTIVE: To explore the effect and mechanisms of baicalein on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis in mice. METHODS: BALB/c mice were randomly placed into three groups (n=10): normal control group, TNBS group, and TNBS+baicalein (20 mg.kg-1, once per day) group. Mouse colitis was induced by intrarectal injection of TNBS. Baicalein was administered by oral gavage two days prior to TNBS treatment and until the end of the study (a total of 9 d). The colon length was measured before HE staining was performed for histological damage assessment. The remaining colon pieces were collected to measure the content of tumor necrosis factor-α(TNF-α). Lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophage was used as a cell model to determine the content of nitric oxide (NO) in cell culture medium, the mRNA levels of TNF-α, interleukin-6(IL-6), IL-1β, inducible nitric oxide synthase(iNOS), cyclooxygenase 2(COX-2) and monocyte chemoattractant protein-1 (MCP-1), and the protein expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-κB (PI3K/AKT/NF-κB) pathway. RESULTS: Baicalein significantly attenuated TNBS-induced colon shortening and histological injury (P<0.05), which was correlated with the decline in the content of TNF-α in the colon. According to the in vivo results, baicalein exposure down-regulated the secretion of NO and the mRNA expression of pro-inflammatory mediators (iNOS, COX-2, MCP-1, TNF-α, IL-1β and IL-6) in LPS-stimulated RAW264.7 cells (P<0.05, P<0.01). Additionally, the phosphorylation/activation of LPS-stimulated PI3K/AKT/NF-κB pathway was inhibited by baicalein treatment. CONCLUSION: The beneficial effect of baicalein in TNBS-induced experimental colitis may be due to PI3K/AKT/NF-κB signaling inhibition. 相似文献
10.
Yun-feng SHAN Xian SHEN Yuan-kang XIE Ji-cai CHEN Hong-qi SHI Zheng-ping YU Qi-tong SONG Men-tao ZHOU Qi-yu ZHANG 《Acta pharmacologica Sinica》2009,30(11):1537-1542
Aim:
To investigate the effects and possible mechanisms of tanshinone II-A, an alcohol extract of the root of Salvia miltiorrhiza Bunge, on tumor invasion and metastasis of human colon carcinoma (CRC) cells.Methods:
The effects of tanshinone II-A on invasion and metastasis of CRC cell lines HT29 and SW480 were evaluated by in vitro and in vivo assays. Western blotting was used to investigate possible molecular mechanisms of tanshinone II-A anti-cancer actions.Results:
Tanshinone II-A inhibited migration and invasion of CRC cells in a dose-dependent manner. The inhibitory effect also depended on time, with the most significant effects observed at 72 h. Tanshinone II-A also significantly inhibited in vivo metastasis of colon carcinoma SW480 cells. It inhibited in vitro and in vivo invasion and metastasis of CRC cells by reducing levels of urokinase plasminogen activator (uPA) and matrix metalloproteinases (MMP)-2 and MMP-9, and by increasing levels of tissue inhibitor of matrix metalloproteinase protein (TIMP)-1 and TIMP-2. Tanshinone II-A was also shown to suppress the nuclear factor-kappaB (NF-κB) signal.Conclusion:
Tanshinone II-A inhibited in vitro and in vivo invasion and metastasis of CRC cells. The effect resulted from changes in the levels of uPA, MMP-2, MMP-9, TIMP-1 and TIMP-2, and apparent inhibition of the NF-κB signal transduction pathway. 相似文献11.
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Aim To study the antitumor effect of cispl-atin ( DDP) chemotherapy promoted by Taohong Siwu Decoction (TSD) on mice with lung adenocarcinoma mice. Methods Lewis lung carcinoma cell line was used to make homologous lung adenocarcinoma trans¬plantation mouse model. Normal control, Model, TSD, DDP, TSD + DDP groups were set up. The change of transplanted tumor volume after administration was observed, the weight of transplanted tumor was weighed, the expression of Ki67 in transplanted tumor tissue was detected by immunohistochemistry, TUNEL was detected by fluorescence staining, Bcl-2, Bax, cleaved Caspase-3 and cleaved Caspase-9 were detected by immunoblotting, and the content of D-dirtier in plasma was measured by ELISA. Results DDP plus TSD significantly inhibited the growth of transplanted tumor. Ki67 expression in tumor tissue was lower than that in DDP group (28. 3% ±3. 1% vs 40. 3% ±2.1% ). The combined use of TSD and DDP significantly promoted the apoptosis level of transplanted tumor. The positive rate of TUNEL was significantly higher than that of DDP group (41. 0% ±3.0% vs 30.7% ± 4.5%). Bax, cleaved Caspase-3 and cleaved Caspase-9 expressions in tumor tissue were also higher than those of DDP group, while the expression of Bcl-2 was significantly lower than that of DDP group. Moreover, we found a significant interaction between TSD and DDP on the expression of four apoptotic proteins ( P < 0.05 ) . The plasma D-dimer content in TSD + DDP group was significantly lower than that in DDP group (188. 50 ± 28. 46 vs 269.80 ± 35.92) μg • L-1(P < 0.05). Conclusion TSD may promote the inhibitory effect of DDP chemotherapy on transplanted lung adenocarcinoma by alleviating carcinoma hy-percoagulale state. © 2023 Publication Centre of Anhui Medical University. All rights reserved. 相似文献
13.
Aim To prepare the sea cucumber enzy¬molysis fermentation liquid (SCEFL) by enzymatic hydrolysis of protease and fermentation of probiotics and to investigate the effect of SCEFL on the immunosup-pression induced by cyclophosphamide in mice and to explore its mechanism by metabomic method. Methods The immunosuppressive model was induced by in-traperitoneal injection of cyclophosphamide. C57BL/6J mice were randomly divided into normal group, model group, Levamisole group, SCEFL groups (at low, medium and high doses). The pathological changes of spleen were observed by HE staining. The proportion of CD4+and CD8+T lymphocyte subsets and the pro-portion of CD4 /CD8 T lymphocyte subsets in peripheral blood were detected by flow cytometry. The con¬tents of IL-2 ( interleukin-2 ), IgG ( immunoglobulin G) and IgM (immunoglobulin G) in serum were detected by ELISA. The changes of endogenous metabolites in mouse serum were analyzed by UPLC-Q/TOF-MS metabolomics, and the related metabolic pathways were explored. Results SCEFL could improve the pathological changes of immunosuppressed mice, in¬crease the proportion of CD4 T cells and the proportion of CD4+/CD8+T lymphocyte subsets,and increase the contents of IL-2, IgG and IgM in serum. The immune function of mice was regulated mainly through six related metabolic pathways, including glyc-erophospholipid metabolism, sphingolipid metabolism, linoleic acid metabolism, a-linoleic acid metabolism, glycophosphatidylinositol-anchored biosynthesis and arachidonic acid metabolism. Conclusion SCEFL may ameliorate the immunosuppression of mice by regulating endogenous metabolic disorder. © 2023 Publication Centre of Anhui Medical University. All rights reserved. 相似文献
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Aim To study the effect of human urinary kallidinogenase(HUK)on the cognitive function of SAMP8 mouse model and its mechanism. Methods SAMP8 mice were divided intofive groups:SAMP8 group,treatment group(giving 8.75×10-3,1.75×10-2,3.5×10-2,7.0×10-2 HUK),and the SAMR1 vehicle group was used as blank control. Each group was performed Morris water maze to detect spatial cognition. Afterwards the group with the most obvious cognitive improvement(HUK group)was selected for the follow-up experiments. Immunohistochemical detection of ChAT expression in CA3 area was further verified by RtPCR. Western blot was used to detect the expression of PSD95,SYN,BDNF,and pCREB protein. The activity of MPO and the content of IL-1β and IL-18 were determined. Results The passing times in the SAMP8 group was less than that of the SAMR1 group(P<0.05). The passing times of treatment group increased compared with the SAMP8 group(P<0.05 or P<0.01),and the spatial probe time of the target quadrant was shorter(P<0.05 or P<0.01). We conducted follow-up experiments with group d(HUK group). The expression of ChAT positive cells in CA3 area of SAMP8 group was significantly lower than that of SAMR1 group; the expression of positive cells in HUK group significantly increased; RtPCR showed that ChAT expression in SAMP8 group was lower than that in SAMR1 group,and ChAT expression was significantly higher than that in SAMP8 group after HUK treatment. Compared with the SAMR1 group,the levels of IL-1β,IL-18 and MPO activity in the CA3 area of SAMP8 group significantly increased,and the protein expressions of PSD95,SYN,BNDF and pCREB decreased. After HUK treatment,the content of IL-1β,IL-18 and MPO activity decreased,and the expression of PSD95,SYN,BNDF and pCREB increased. Conclusions HUK can improve the spatial cognition of SAMP8 mice. The mechanism may be achieved by promoting the expression of ChAT in CA3 area,reducing the oxidative stress and increasing synapse-related proteins. © 2023 Publication Centre of Anhui Medical University. All rights reserved. 相似文献
15.
Aim To investigate the mechanism and search for potential biomarkers of ovalbumin ( OVA ) -induced asthma in mice base on lipidomics. Methods A BALB/c mouse model of asthma was prepared by OVA. TNF-α, IL-4, IL-10, IFN-γ levels in BALF and IgE level in serum were measured by ELISA. The inflammatory changes in mouse lung tissue were observed using HE staining. Lipid mediators ( LMs) in lung tissue and serum were quantified with UPLC-MS/ MS strategy. Results IgE level in serum and TNF-α, IFN-γ levels in BALF were higher (P <0.05) of asthmatic mice.Typical inflammatory manifestations were seen in lung tissue of asthmatic mice. A total of 57 lipid mediators were quantified with UPLC-MRM. LMs metabolic profiles differed significantly in serum and lung tissue between asthmatic and normal mice, 17 significantly different LMs were found in lung tissue and 6 LMs were found in serum, and the differential metabolites were produced through the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 oxidase (P450) metabolic pathways. Conclusions OVA-induced allergic asthma can cause disorder of lip-id mediators, LMs and cytokines are involved in the occurrence and development of asthma. The differential LMs have potential research value as biomarkers for the development of allergic asthma. © 2023 Publication Centre of Anhui Medical University. All rights reserved. 相似文献
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Aim To investigate the radiosensitizing effect of the PARP inhibitor Olaparib on MCF-7 breast cancer model and to monitor the radiosensitizing effect of Olaparib by F-Fluoroerythronitroimidazole (F-FETNIM) PET/CT. Methods MCF-7 breast cancer model was established and divided into control group, Olaparib group, irradiation group and Olaparib + irradiation group according to random number table method; tumor volume was measured to calculate tumor inhibition rate and survival time of tumor-bearing mice was counted. 18F-FETNIM PET imaging was performed before and after treatment, and the tumor/muscle ratio (TMR) was calculated for quantitative analysis. Immunohistochemical staining was used to analyze the changes in the expression of HIF-1α, Ki67 and p53 proteins; The correlations between TMR and the expression of HIF-1α, Ki67 and p53 were analyzed. Data were analyzed by paired t-test, two independent samples t-test, one-way ANOVA, and Pearson correlation analysis. Results Olaparib alone had little effect on the tumor, but when combined with irradiation, the tumor growth rate was significantly slower and the survival period was significantly prolonged; PET/CT results showed that the differences in tumor TMR values between the control group, Olaparib group, IR group and Olaparib + IR group before treatment were not statistically significant (F = 0. 24, P > 0. 050); after treatment, the tumor TMR values in the IR group and Olaparib + IR group were reduced to different degrees, and the decrease was more significant in the combined group, and the difference between the two groups was statistically (P < 0. 039). Immunohistochemical results showed that HIF-1α, Ki67 and p53 proteins were the least expressed in the combined group compared to the IR group (P = 0. 004; P = 0. 002; P < 0. 001). TMR was significantly and positively correlated with the expression of HIF-1α, Ki67, and p530 = 0.918; r =0.919; r =0.914). Conclusions Olaparib suppresses tumor volume, prolongs the survival cycle of tumor-bearing mice, and downregulates several biomarkers associated with poor prognosis in MCF-7 breast cancer cells. 18F-FETNIM micro PET/CT can be used to track tumor hypoxia in real time and to assess the effectiveness of radiosensitizing response. © 2023 Publication Centre of Anhui Medical University. All rights reserved. 相似文献
18.
目的探究红景天苷对人高转移性肝癌细胞(97H细胞)增殖、迁移、侵袭和凋亡的影响。方法采用多功能细胞分析仪检测红景天苷对97H细胞增殖的影响,划痕实验检测红景天苷对97H细胞迁移能力的影响,Transwell小室实验检测红景天苷对97H细胞侵袭能力的影响,倒置显微镜观察红景天苷对97H细胞形态的影响,透射电镜观察红景天苷对97H细胞中线粒体的影响,流式细胞术检测红景天苷对97H细胞凋亡及周期分布的影响,q-PCR技术检测红景天苷对97H细胞中相关凋亡基因的影响,蛋白免疫印迹技术检测红景天苷对97H细胞相关迁移、侵袭及凋亡蛋白的影响。结果与空白组相比,红景天苷处理组对97H细胞的增殖、迁移及侵袭均具有一定的抑制作用,且诱导97H细胞凋亡。红景天苷可以上调Caspase-3基因的相对表达(P<0.05),且可以上调E-cad、Bax、Caspase-3及Caspase-9蛋白的相对表达(P<0.05),下调N-cad、Girdin及Bcl-2蛋白的相对表达(P<0.05)。结论红景天苷对97H细胞的增殖、迁移及侵袭均具有抑制作用,且通过线粒体途径诱导97H细胞凋亡。 相似文献
19.
Aims To extract, separate and identify the flavonoid constituents in Humulus Seandens and to explore the relationship of monomers and alveolar fluid clearance (AFC) in mice in vivo. Methods Humulus seandens were extracted with alcohol and then isolated by the technology of Column and the structures were identified by spectrometry. In vivo AFC was measured using bovine serum albumin protein assays affected by luteolin-7-O-β-D-glucoside (LGL) and cosmsiin (AGL). Results The main constituents of flavanones in Humulus seandens were LGL and AGL. Both of them could improve the AFC. Conclusion The AFCs of LGL and AGL, compared to the blank control group, increased which explains the effect of flavonoid constituents on removing edema and promoting water absorption. 相似文献
20.
OBJECTIVE: To observe the effect of three signal pathway inhibitors: epidermal growth factor receptor (EGFR) inhibitor erlotinib, Anexelekto(AXL) inhibitor R428 and γ-secretase inhibitor N-(N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester(DAPT), on the proliferation of pancreatic cancer cells when any two of them are used in combination in order to offer experimental evidence for clinical medication. METHODS: Panc-28 and Panc-1 cell lines were selected in this experiment. Erlotinib, R428 and DAPT were administered alone or in combination for 72 h before MTS assay was used to detect cell proliferation. Lactate dehydrogenase (LDH) activity assay was used to investigate the cytotoxicities. The flow cytometry was used to evaluate the cell cycle. RESULTS: Erlotinib 5-80 μmol · L-1 alone had no significant effect on the proliferation of Panc-28 cells, whereas DAPT 5-80 μmol·L-1 or R428 50-800 nmol·L-1 inhibited the proliferation of Panc-28 cells in a concentrationdependent manner (rDAPT=0.995, P<.01; rR428=0.833, P<0.01) after being treated for 72 h. Compared with single use, the combination of two of the three inhibitors (erlotinib 50 μmol · L-1, DAPT 50 μmol · L-1, R428 300 nmol-L-1) inhibited the Panc-28 and Panc-1 cell proliferation but didn't cause more cytotoxicity. Erlotinib and R428 in combination inhibited the proliferation rate of two pancreatic cancer cells by more than 40% compared with R428 used alone(P<0.01). In erlotinib and R428 combination group, cell cycle of Panc-28 and Panc-1 cells at S and G1 was increased (P<0.01). CONCLUSION DAPT and R428 can inhibit the proliferation of pancreatic cancer cells to some extent. The combination of erlotinib and R428 has a synergistic inhibitory effect on proliferation of pancreatic cancer cells. 相似文献