Berberine reverses LPS-induced repression of CYP7A1 through an anti-inflammatory effect

Objective: To evaluate the anti-inflammatory effect of berberine(BBR) on the lipopolysaccharide(LPS)-induced acute phase response and its modulation of the altered bile acid metabolism induced by LPS treatment.Methods: An acute phase response was induced by intraperitoneal injection of LPS(5 mg/kg, ip) in C57 BL/6 J mice, and the BBR treatment group was orally administered with BBR(200 mg/ky, ig). The levels of TNFα, IL-1β and IL-6 in the serum were measured using an ELISA kit, and their expression levels in the liver were measured using q RT-PCR. The bile acid pool was measured using a commercial bile acid kit, and the expression levels of enzymes involved in bile acid metabolism were measured by q RTPCR. The expression levels of CYP7 A1, p65 NF-κ B and the MAPK signaling pathway was measured using Western blotting.Results: LPS treatment suppressed the expression of CYP7 A1 and CYP8 B1, and the total bile acid pool was also reduced. Pretreatment with BBR inhibited the pro-inflammatory biomarkers TNFα and IL-1β in the serum, as well as the expression of TNFα, IL-1β and i NOS mRNA in the liver. BBR treatment did not affect the reduction in the bile acid pool size induced by LPS, but significantly increased the concentration of bile acids in the liver, which was consistent with the upregulated expression of CYP7 A1 and CYP8 B1. The MAPK signaling pathway was activated by BBR treatment, while the p65 NF-κ B signaling pathway was inhibited.Conclusion: BBR can offer an anti-inflammatory effect and reverse the inhibition of CYP7 A1 and CYP8 B1 expression caused by LPS treatment, as well as induce the production of bile acids in liver, probably via MAPK signaling; However, treatment with BBR had no effect on the size of total bile acid pool.     

Regulation of Moxibustion on the Expression of NF-κBp65 and PPARγ mRNA in Colon of Rats with Ulcerative Colitis

Objective: To explore the mechanism of herb-partitioned moxibustion for ulcerative colitis(UC) through observing the colonic mucosal histopathological changes and the expression of nuclear factor kappaB(NF-kB) and peroxisome proliferators-activated receptor γ(PPARγ) mRNA of UC rats. Methods: Male SD rats were randomly divided into a normal group and a model group. UC model was established by general immunological plus local irritation method. After model identification, rats in the model group were randomly divided into a model group, a herb-partitioned moxibustion(HPM) group and a Western medicine(Salicylazosulfapyridine, SASP) group. Rats in the HPM group received treatment at bilateral Tianshu(ST 25) and Dachangshu(BL 25), two cones for each point, once a day for 7 d. SASP group rats were gavaged with SASP. The pathological scores were evaluated according to hematoxylin-eosin(HE) staining of colonic tissues. We used light microscopy to observe degree of colonic mucosal damage and the quantitative polymerase chain reaction(QPCR) to detect the expression of NF-κBp65 and PPARγ in colorectal mucosa. Results: Compared with the normal group, histopathological scores were significantly higher in the model group(P0.05); compared with the model group, the scores were decreased significantly in the HPM group and the SASP group. Compared with the normal group, NF-κBp65 mRNA expression was increased with statistical significance in the model group(P0.05); compared with the model group, NF-κBp65 mRNA expressions were decreased significantly in the HPM group and the SASP group. Compared with the normal group, PPARγ mRNA expression was increased significantly in the model group(P0.05); compared with the model group, PPARγ mRNA expressions were decreased significantly in the HPM group and the SASP group. Conclusion: HPM could improve the mucosa damage of UC rats, which is possibly through down-regulating NF-κBp65 to achieve anti-inflammatory effect. Whether decreasing the PPARγ mRNA is possibly involved in preventing precancerosis will need further study.     

Effect of Chaiqinchengqi decoction on inositol requiring enzyme 1α in alveolar macrophages of dogs with acute necrotising pancreatitis induced by sodium taurocholate

OBJECTIVE: To investigate the effect of Chaiqinchengqi decoction(CQCQD) on inositol requiring enzyme 1α(IRE1α) in alveolar macrophages(AMs)of the dog model of acute necrotising pancreatitis(ANP) induced by sodium taurocholate.METHODS: Fifteen beagle dogs were randomised into a control group,ANP group and CQCQD group(n = 5 per group). ANP was induced by a retrograde duct injection of 50 mg/kg of 5% sodium taurocholate. The dogs in the control group received injections of the same volume of saline as the sodium taurocholate. After the models were induced,the dogs in the CQCQD group were administered 10 m L/kg CQCQD every 2 h for 6 h. Two hours after the last administration of either CQCQD or saline,they were sacrificed by anaesthesia. AMs were collected to determine the IRE1α and Interleukin-1β(IL-1β)m RNA and protein expression,and pancreatic tissues were collected for histopathology analysis.RESULTS: Compared with the ANP group,the m RNA and protein expression of IRE1α and the protein expression of IL-1β of AMs in the CQCQD group were significantly down-regulated,and the pancreatic histopathology score of the CQCQD group also was lower. There was no significant difference in the m RNA expression of IL-1β of AMs between the two groups.CONCLUSION: The CQCQD-induced down-regulation of the IL-1β protein expression may involve the down-regulation of the m RNA and protein expression of IRE1α in AMs.     

Gene mining and efficient biosynthesis of a fungal peptidyl alkaloid

Objective: Peptidyl alkaloids, a series of important natural products can be assembled by fungal nonribosomal peptide synthetases(NRPSs). However, many of the NRPSs associated gene clusters are silent under laboratory conditions, and the traditional chemical separation yields are low. In this study, we aim to discovery and efficiently prepare fungal peptidyl alkaloids assembled by fungal NRPSs.Methods: Bioinformatics analysis of gene cluster containing NRPSs from the genome of Penicillium thymicola, and heterologous expression of the putative gene cluster in Aspergillus nidulans were performed.Isolation, structural identification, and biological evaluation of the product from heterologous expression were carried out.Results: The putative tri-modular NRPS Anc A was heterologous-expressed in A. nidulans to give anacine(1) with high yield, which showed moderate and selective cytotoxic activity against A549 cell line.Conclusion: Heterologous expression in A. nidulans is an efficient strategy for mining fungal peptidyl alkaloids.     

A Study on the Mechanism of Bruceine D in the Treatment of Non‑small Cell Lung Cancer H1299 Cells

Background: Non?small cell lung cancer (NSCLC) is considered one of the leading causes of cancer?related death. Despite the availability of drugsfor the treatment of NSCLC, the need for the development of novel agents with high efficiency and fewer adverse effectsremains unmet. The natural compound bruceine D (BD) is widely recognized for its notable anti?inflammatory, antiparasitic, and hypoglycemic activities. However, it is unclear whether BD can be used as a novel agent for NSCLC treatment. Materials and Methods: MTT and colony formation assays were used to assess the antiproliferative effect of BD on NSCLC cells. Wound healing and transwell assays were performed to determine the effect of BD on the migration and invasion of H1299 cells, respectively. Western blotting assay was used to detect the expression levels of proteins. Results:We demonstrated thatBD significantly inhibited the proliferation of H1299,A549, and H226 cells with respective IC50 values of 6.06 ± 0.52, 7.15 ± 0.90, and 7.21 ± 0.75 μM. In addition, BD suppressed colony formation of H1299 cells in a dose?dependent manner. Following treatment with BD, the migration and invasive capabilities of H1299 cells were significantly inhibited in a dose? and time?dependent manner. Moreover, the results of Western blotting demonstrated that BD treatment resulted in the upregulation of the protein expression of E?cadherin and downregulation of the expression of N?cadherin, twist, snail, integrin αv, integrin β4, matrix metalloproteinase-7, and β-catenin proteins. Conclusion: BD inhibits proliferation, migration, and invasion of NSCLC cells; therefore, BD may be considered for its potential in adjuvant therapy for NSCLC.     

Effect of Sini decoction on angiotensin Ⅱ, transforming growth factor β_1 and connective tissue growth factor in rats with myocardial fibrosis-induced banding of the abdominal aorta

OBJECTIVE: To investigate the effect of Sini decoction on rats with myocardial fibrosis induced by banding the abdominal aorta, and explore the mechanism underlying its actions on angiotensin Ⅱ(Ang Ⅱ), transforming growth factor-β_1(TGF-β_1)and connective tissue growth factor(CTGF).METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into sham operation, model, Captopril, and Sini decoction groups. The models were established by the partial banding of the abdominal aorta according to Doering's method.Eight weeks later, heart weight indexes were calculated; hemodynamic changes of the hearts were tested; changes in myocardial tissue morphology were observed by Masson staining; and myocardial collagen volume fraction was calculated. Enzyme-linked immunosorbent assay was used to measure the concentration of Ang Ⅱ in serum. The expression of TGF-β_1 and CTGF were determined by immunohistochemistry and Western blotting.RESULTS: Compared with the sham operation group, the heart weight index, collagen volume fraction of the myocardium, serum levels of Ang Ⅱ,and the expression of myocardial TGF-β_1 and CTGF in the model group were significantly increased(P 0.05). Compared with the model group, the heart weight index, collagen volume fraction of the myocardium, serum levels of Ang Ⅱ, and the expression of myocardial TGF-β_1 and CTGF in all treatment groups were significantly reduced(P 0.05).CONCLUSION: Sini decoction reduced AngⅡ level and inhibited the expression of myocardial TGF-β_1 and CTGF, which may explain the mechanism of its protective effect on myocardium with fibrosis.     

Effect of Qingxinkaiqiao compound on cortical mRNA expression of the apoptosis-related genes Bcl-2, BAX,caspase-3, and Aβ in an Alzheimer's disease rat model

OBJECTIVE: To investigate the effects of Qingxinkaiqiao(QK) compound in a rat model of Alzheimer's disease induced with β-amyloid(Aβ) 1-40.METHODS: Fifty-six three months, male,Sprague-Dawley rats were randomly divided into seven groups: blank control group, surgery group,model group, low-dose QK group, middle-dose QK group, high-dose QK group, and Aricept(donepezil hydrochloride) group, with eight rats in each group. Apart from the control and surgery groups,an Alzheimer's disease model was established in all groups by bilateral hippocampal injection of Aβ1-40. The surgery group received an injection of the same volume of physiological saline. Two days after model establishment, rats from the drug groups were administered the corresponding drugs; the control group and model group were administered an equal volume of physiological saline for 14 days. After treatment, real-time quantitative polymerase chain reaction, immunohistochemistry,and western blot assay were employed to confirm mRNA and protein expressions of Bcl-2, Bax, caspase-3, and Aβ, respectively.RESULTS: Compared with the model group, Bcl-2expression increased and Bax, caspase-3, and Aβexpression decreased in each drug treatment group(P 0.05, P 0.01). The expressions of middle-dose QK group were more significant than the high- and low-dose QK groups(P 0.01, P 0.05).CONCLUSION: QK treatment resulted in significantly up-regulated Bcl-2 expression, down-regulated Bax, caspase-3, and Aβ expression, and reduced numbers of apoptotic cells in the cortex.     

阳和汤对三阴性乳腺癌细胞MDA-MB-231凋亡Egr1/p21信号通路的影响

目的:以早期生长反应基因1(Egr1)/细胞周期蛋白依赖性抑制剂(p21)信号通路为基础,探讨古方阳和汤含药血清对人三阴性乳腺癌细胞MDA-MB-231凋亡的影响。方法:制备阳和汤大鼠含药血清,体外培养三阴性乳腺癌MDA-MB-231细胞。设空白组,阳和汤高、中、低剂量组(23. 4,11. 7,5. 85 g·kg~(-1)),分别干预MDA-MB-231细胞24,48,72 h,细胞增殖检测(CCK-8)法检测各组细胞增殖情况。设空白组,阳和汤高、中、低剂量组(23. 4,11. 7,5. 85 g·kg~(-1)),干预MDA-MB-231细胞48 h,采用流式细胞仪检测各组细胞凋亡情况以及细胞周期分布情况;实时荧光定量聚合酶链式反应(Real-time PCR)检测各组细胞Egr1,p21 mRNA的表达情况;蛋白免疫印迹法(Western blot)检测各组细胞Egr1,p21蛋白的表达情况。结果:阳和汤干预MDA-MB-231细胞24,48,72 h,与空白组相比,阳和汤高、中剂量组能显著抑制MDA-MB-231细胞增殖(P 0. 01)。阳和汤干预MDA-MB-231细胞48 h,与空白组相比,阳和汤高、中剂量组细胞的凋亡率明显增加(P 0. 05,P 0. 01);阳和汤高、中剂量组细胞周期G_0/G_1期所占比例降低,G_2/M期所占比例升高(P 0. 05,P 0. 01);阳和汤高、中剂量组细胞Egr1,p21mRNA和蛋白表达均增加(P 0. 05,P 0. 01)。结论:阳和汤可激活MDA-MB-231细胞中Egr1/p21信号通路,增加Egr1,p21的表达,引起G_2/M细胞周期阻滞,从而诱导MDA-MB-231细胞凋亡。     

茯苓酸通过激活多聚腺苷二磷酸核糖聚合酶诱导人乳腺癌细胞MDA-MB-231凋亡

目的观察茯苓酸对人乳腺癌MDA-MB-231细胞增殖及凋亡的影响,并初步探讨作用机制。方法乳腺癌MDA-MB-231细胞与不同浓度(1、2、5μmol/L)的茯苓酸共孵育,采用CCK-8细胞增殖与活性检测试剂盒检测细胞存活率;流式细胞术Annexin V/PI双染色检测细胞凋亡;Western blotting法检测多聚腺苷二磷酸核糖聚合酶(PARP)及与细胞凋亡相关蛋白的表达。结果茯苓酸能够剂量和时间依赖性地抑制MDA-MB-231细胞的增殖,并可诱导MDA-MB-231细胞凋亡。浓度为1、2、5μmol/L的茯苓酸作用MDA-MB-231细胞48 h后,细胞凋亡率显著增加至25.6%、59.4%、87.2%,明显高于对照组凋亡率(5.4%);经过1、2、5μmol/L茯苓酸分别处理48 h后,实验组MDA-MB-231细胞中凋亡蛋白标志物PARP裂解量升高,且呈剂量依赖性。结论茯苓酸能抑制MDA-MB-231细胞的增殖并诱导其凋亡,其作用机制与激活PARP有关。     

参芪扶正注射液对人乳腺癌MDA-MB-231细胞增殖和凋亡的影响

目的:研究参芪扶正注射液对基底细胞样(basal-like型)乳腺癌MDA-MB~(-2)31细胞增殖和凋亡的影响,探讨参芪扶正注射液对三阴性乳腺癌的治疗作用机制。方法:体外培养人乳腺癌MDA-MB~(-2)31细胞,将其分为参芪扶正注射液组和空白组。采用噻唑蓝(MTT)比色法分别于24,48,72 h检测参芪扶正注射液对人乳腺癌MDA-MB~(-2)31细胞增殖的影响。采用流式细胞术(FCM)测定细胞周期分布和凋亡情况。实时荧光定量PCR(Real-time PCR)和免疫印迹(Western blot)检测参芪扶正注射液对MDA-MB~(-2)31细胞p53正向细胞凋亡调控因子(PUMA)表达的影响。结果:参芪扶正注射液可抑制MDA-MB~(-2)31细胞增殖,高浓度者抑制作用强,即呈现浓度依赖性,体外培养48 h时抑制作用最显著。参芪扶正注射液将MDA-MB~(-2)31细胞阻滞于细胞周期的S期,进而诱导MDA-MB~(-2)31细胞凋亡。Real-time PCR和Western blot发现参芪扶正注射液可上调MDA-MB~(-2)31细胞PUMA蛋白和基因表达。结论:参芪扶正注射液可显著抑制人乳腺癌MDA-MB~(-2)31细胞增殖,导致细胞周期阻滞,诱导细胞凋亡,其机制可能与上调PUMA基因有关。     

蓝萼甲素对三阴性乳腺癌MDA-MB-231细胞增殖及细胞周期的影响

目的研究蓝萼甲素对三阴性乳腺癌MDA-MB-231细胞增殖及细胞周期的影响及其作用机制。方法采用MTT法检测蓝萼甲素对MDA-MB-231细胞增殖的影响;流式细胞仪检测细胞周期;Western blotting法检测细胞中cyclin B1、cyclin D1、细胞周期素依赖激酶2(CDK2)、CDK4、p53、p21、p27、组蛋白赖氨酸特异性去甲基化酶1(LSD1)、组蛋白H3第4位赖氨酸二甲基化(H3K4me2)、组蛋白H3第9位赖氨酸二甲基化(H3K9me2)蛋白表达水平。结果蓝萼甲素能显著抑制MDA-MB-231细胞的增殖,呈剂量和时间依赖性;提高G2/M期细胞比例;上调p53、p21、p27、H3K4me2、H3K9me2蛋白表达水平,下调cyclin B1、cyclin D1、CDK2、CDK4、LSD1蛋白表达水平。结论蓝萼甲素抑制MDA-MB-231细胞增殖,阻滞MDA-MB-231细胞周期于G2/M期,其机制可能与激活p53的表达及调控组蛋白的甲基化作用有关。     

汉黄芩素抑制乳腺癌细胞增殖及侵袭的实验研究

目的：研究汉黄芩素对乳腺癌细胞MDA-MB-231生长和增殖的影响,同时观察汉黄芩素对MDA-MB-231细胞黏附、迁移和侵袭能力的影响,进一步探讨其分子作用机制。方法：MTT法检测汉黄芩素对MDA-MB-231细胞生长的影响;Ki-67法检测汉黄芩素对细胞增殖的影响;划痕实验、黏附试验和侵袭小室法检测对MDA-MB-231细胞迁移和侵袭能力的影响;Western blotting检测对增殖和转移相关蛋白及相关信号通路的影响。结果：汉黄芩素能明显抑制MDA-MB-231细胞生长和增殖;低浓度情况下明显抑制乳腺癌细胞的迁移、黏附和侵袭能力;汉黄芩素有效抑制MDA-MB-231细胞Survivin,Bcl-2,ICAM-1,MMP-2,MMP-9蛋白的表达。结论：汉黄芩素明显抑制乳腺癌细胞生长和增殖,并抑制MDA-MB-231细胞迁移、黏附、侵袭,其对MDA-MB-231细胞的侵袭和黏附影响可能与其降低ICAM-1,MMP-2,MMP-9表达有关。     

基于网络药理学-分子对接探讨茵陈蒿汤治疗妊娠期肝内胆汁淤积症的作用机制＊

目的 利用网络药理学及分子对接技术，研究茵陈蒿汤治疗妊娠期肝内胆汁淤积症（ICP）的物质基础及可能的作用机制。方法 使用TCMSP数据库挖掘茵陈蒿汤有效成分和作用靶点，利用GeneCard与OMIM数据库筛选疾病靶点。将药物与疾病靶点的交集导入String构建PPI网络，使用Cytoscape3.7.2软件筛选核心靶点，借助Metascape数据库对靶点进行基因本体论（GO）功能和基因组百科全书（KEGG）通路富集分析，从筛选靶点-成分网络图中根据degree值筛选出前5个关键成分，并将该网络中的基因靶点以degree值高低进行排序，选择前5个核心靶点，然后从RCSB PDB数据库和Pub Chem数据库获取靶点与成分的三维结构和化学结构，使用Pymol软件对蛋白质分子进行去水、去磷酸根等操作，最后使用AutoDockTools进行分子对接。结果 茵陈蒿汤中共筛选出21种有效活性成分，关键成分5个，分别为槲皮素、山奈酚、芦荟大黄素、谷甾醇、大黄酸；其治疗ICP的的核心靶点14个，分别为JUN、CASP3、TNF、TP53、MYC、EGFR、AKT1、VEGFA、MMP9、MAPK1、EGF、IL6、CXCL8、MAPK8，靶点主要涉及细胞氧化应激反应、细胞运动的正向调节、受体配体活性、细胞因子受体结合、蛋白激酶活性等生物学过程，通过乙型、丙型肝炎途径、癌症途径、MAPK、 IL-17、TNF信号通路等多途径发挥治疗ICP的作用。分子对接结果显示关键成分与对应靶点具有较好的结合活性。结论 茵陈蒿汤治疗ICP是通过槲皮素、山奈酚、芦荟大黄素、谷甾醇、大黄酸等多种成分作用于JUN、CASP3、TNF、TP53、MYC、EGFR、AKT1、VEGFA、MMP9、MAPK1、EGF、IL6、CXCL8、MAPK8等多种基因靶点，从而影响MAPK、 IL-17、肿瘤坏死因子、ErbB、 Toll样受体以及乙型丙型肝炎病毒等多种相关信号通路发挥功效，该研究为进一步深入研究其作用机制奠定了基础。     

基于网络药理学和分子对接法探索人参治疗再生障碍性贫血的分子机制＊

目的 运用网络药理学与分子对接理论研究人参（Panax ginseng C. A. Meyer）治疗再生障碍性贫血（Aplastic anemia，AA）的分子作用机制，并通过体外实验进行验证。方法 通过TCMSP数据库筛选人参的主要活性成分及其靶点；采用Gene Cards数据库、GenCLiP3数据库、DisGeNET数据库以及OMIM数据库获取治疗AA有关靶点，利用venn图筛选人参治疗AA的潜在靶点；使用Cytoscape构建药物-活性成分-基因-疾病网络图，STRING数据库构建治疗靶基因的蛋白互作网络（Protein-Protein interaction network，PPI network）图；借助ClusterProfiler和Pathview对靶基因进行GO（Gene Ontology）功能注释和KEGG（Kyoto encyclopedia of genes and genomes）通路分析以及可视化；通过SystemsDOCK对其进行分子对接。最后构建AA小鼠模型，分为空白对照组，模型组，人参二醇皂苷组和环孢霉素A组，给药2周后通过免疫印迹（Western blot）法检测相关蛋白含量及表达情况。结果 从人参中筛选出22种主要活性成分以及16个人参治疗AA的主要靶点，包括半胱氨酸蛋白水解酶3（Cysteine-containing aspartate-specific protease 3，CASP3）、半胱氨酸蛋白水解酶1（Cysteine-containing aspartate-specific protease 1，CASP1）、B淋巴细胞瘤-2（B-cell lymphoma-2，BCL-2）等靶点，GO及KEGG富集分析结果主要涉及相关信号通路凋亡、AGE-RAGE、TNF、NF-KB等；分子对接研究也表明调亡通路中的CASP3对应的晶体结构2h65和CASP1对应的晶体结构1ibc与人参二醇皂苷（Ginsenoside rh2）结合性紧密，结构稳定，结合力较强。Western blot实验结果表明，与模型组相比，Ginsenoside rh2显著上调CASP3和CASP1蛋白表达水平，具有统计学意义（P<0.05）。结论 通过网络药理学分析发现人参的Ginsenoside rh2可以调控CASP3、CASP1等靶点和凋亡等信号通路，分子对接中Ginsenoside rh2和CASP3、CASP1结合紧密，体外实验证实Ginsenoside rh2调控调亡通路的关键蛋白CASP3和CASP1，从而发挥人参治疗AA的潜在疗效。     

健脾疏肝抗毒汤对裸鼠MDA-MB-231-pAcGFP异种移植瘤生长及转移能力的影响

目的:观察健脾疏肝抗毒汤对荷MDA-MB-231-p Ac GFP裸鼠移植瘤生长及转移能力的影响,并探讨其作用机制。方法:应用Fugene HD Transfection Reagent转染三阴性乳腺癌细胞株MDA-MB-231细胞,经G418筛选获得稳定表达绿色荧光蛋白的乳腺癌细胞(MDA-MB-231-p Ac GFP)。流式细胞仪检测荧光细胞百分率。采用皮下接种法建立MDA-MB-231-p Ac GFP细胞异种移植瘤裸鼠,观察移植瘤的生长情况,荧光成像技术观察各脏器转移瘤的数目和大小。结果:流式细胞仪检测乳腺癌细胞转染率高达96.5%,表达有绿色荧光蛋白的MDA-MB-231-p Ac GFP细胞成瘤率为100%。模型组(A组),健脾疏肝抗毒汤组(B组),趋化因子基质细胞衍生因子-1(CXCL12)特异受体(CXCR4)抑制剂组(C组)、健脾疏肝抗毒汤联合CXCR4抑制剂组(D组)瘤体质量分别为(1.30±0.11),(0.75±0.12),(0.48±0.09),(0.44±0.07)g,瘤体体积分别为(6.635±0.500),(4.017±0.466),(2.664±0.700),(2.323±0.492)cm~3,与模型组比较,3组瘤体质量及体积均明显降低(P0.05)。3组的抑瘤率分别为42.18%,62.95%,66.28%。A,C组肝脏可见散在荧光转移结节,B组及D组肝脏未见有荧光结节。结论:健脾疏肝抗毒汤具有抑制MDA-MB-231-p Ac GFP移植瘤生长及肝转移的能力,可为健脾疏肝抗毒汤防治三阴性乳腺癌的生长转移提供实验依据。     

基于网络药理学的痰热清胶囊治疗新型冠状病毒肺炎(COVID-19)机制研究

目的探索痰热清胶囊治疗新型冠状病毒肺炎(COVID-19)的网络调控机制。方法选取痰热清胶囊中19个主要成分为研究对象,利用Swiss Target Prediction服务器和TCMSP数据库预测化合物潜在作用靶点,借助Omicsbean分析系统与String 10数据库对靶点进行基因本体(gene ontology,GO)功能富集分析和信号通路分析,利用Cytoscape 3.6.1软件进行可视化处理。结果 19个化合物可通过作用于163个相关靶点干预68条关键信号通路,如白细胞介素-17(IL-17)信号通路、T细胞受体信号通路、花生四烯酸代谢、cAMP信号通路、PI3K-Akt信号通路、甲型流感等,主要涉及抗炎、免疫调节、解热、化痰、镇咳平喘、止痛、抗菌、抗病毒、镇静等方面,构建了痰热清胶囊"化合物-靶点-通路-药理作用-功效"网络。结论痰热清胶囊中主要化学成分野黄芩苷、黄芩苷、千层纸素-7-O-葡萄糖醛酸苷、白杨素-7-O-葡萄糖醛酸苷、连翘苷、连翘酯苷E、连翘酯苷D、绿原酸、咖啡酸、异绿原酸A、熊去氧胆酸、鹅去氧胆酸等可能通过作用于TNF、EGFR、NOS3、PTGS2、IL2、GABBR1、MAPK14、ADRB2、REN、VCAM1、ACHE、PTPRC等关键蛋白干预了多个与清热、化痰、解毒相关的生物过程,从而发挥对COVID-19的治疗作用。