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121.
溃疡性结肠炎(ulcerative colitis,UC)是多种因素导致的肠道慢性疾病,严重的肠炎会引起肝脏损伤。肠道炎症诱发菌群紊乱,导致肠道中过多的胆碱转化为三甲胺;宿主中过低的胆碱生物利用度是造成肝脏损伤的重要原因。3,3-二甲基-1-丁醇(3,3-dimethyl-1-butanol,DMB)作为胆碱的结构类似物,可有效抑制肠道中胆碱转化为三甲胺,本研究旨在探究DMB能否通过减少肠道内的胆碱的不良转化来改善UC小鼠结肠炎症及继发性肝损伤。采用葡聚糖硫酸钠诱导的结肠炎模型,造模结束后,评估结肠及肝组织病理,检测肝功能相关生化指标,使用超高效液相色谱串联质谱法检测UC所致的体内胆碱代谢变化。结果表明,DMB能够减轻UC小鼠体重下降指数,缓解结肠炎症,减少肝脏损伤,对小鼠的血清、肠道内容物与肝脏进行胆碱相关代谢物的检测,发现DMB能够有效抑制肠道中胆碱转化为三甲胺,提高宿主的胆碱利用度,有效缓解结肠炎的恶化,从而减少由于严重的肠道病变导致的肝脏受损。
相似文献122.
目的 利用多数据平台与生物信息分析技术探讨桂枝茯苓丸对乳腺癌的干预机制,并通过细胞试验对分析结果进行验证。方法 从GEO数据库下载乳腺癌相关数据集,分析乳腺癌差异基因;从TCMSP数据库中筛选出桂枝茯苓丸的主要有效成分及作用靶基因;2组靶基因映射出桂枝茯苓丸治疗乳腺癌的关键靶基因。通过TCGA数据平台分析关键靶基因在乳腺癌中的表达,并通过TIMER、CPTAC Data Portal、Kaplan-Meier plotter、TISIDB、SangerBox等数据平台分析该表达与乳腺癌免疫微环境、免疫浸润水平、基因组异质性、免疫亚型和分子亚型以及不良预后的关系。通过Metascape分析平台对关键靶基因进行KEGG通路富集,寻找可能信号通路。最后采用血清药理学方法通过CCK-8试验、细胞划痕试验、Transwell小室试验及Western blotting技术在体外对分析结果进行验证。结果 桂枝茯苓丸中有效成分42个,对应靶点185个,与GEO数据库映射得到与乳腺癌治疗相关的关键靶点14个,经与TCGA中乳腺癌差异基因比对,得到桂枝茯苓丸治疗乳腺癌的6个关键靶基因。这6个靶基因表达与乳腺癌中6种免疫细胞水平、3个免疫微环境评分、乳腺癌免疫亚型及分子亚型都有很强的相关性(P<0.05),在基因组异质性相关性上也表现出了一致性,且与不良预后有密切的关系(P<0.05)。经KEGG富集分析发现,这6个基因主要富集在PI3K/Akt等信号通路上。细胞试验发现桂枝茯苓丸含药血清可以显著抑制乳腺癌HCC1937细胞的增殖、迁移与侵袭,还可降低HCC1937细胞中p-Akt/Akt、p-PI3K/PI3K蛋白相对表达,且作用呈剂量依赖性。结论 桂枝茯苓丸可能通过阻断PI3K/Akt信号通路,调节肿瘤免疫微环境实现对乳腺癌的干预作用。 相似文献
123.
Saikosaponins (SSs) are a class of naturally occurring oleanane-type triterpenoid saponins found in Radix bupleuri that has been widely used in traditional Chinese medicine. As the main active principals of Radix bupleuri, SSs have been shown to suppress mouse motor activity, impair learning and memory, and decrease hippocampal neurogenesis. In the present study, we investigated the effect of five SSs (SSa, SSb1, SSb2, SSc, and SSd) on neuronal viability and the underlying mechanisms in cultured murine neocortical neurons. We demonstrate that SSa, SSb1 and SSd produce concentration-dependent apoptotic neuronal death and induce robust increase in intracellular Ca2+ concentration ([Ca2+]i) at low micromolar concentrations with a rank order of SSd > SSa > SSb1, whereas SSb2 and SSc have no detectable effect on both neuronal survival and [Ca2+]i. Mechanistically, SSd-induced elevation in [Ca2+]i is the primary result of enhanced extracellular Ca2+ influx, which likely triggers Ca2+-induced Ca2+ release through ryanodine receptor activation, but not SERCA inhibition. SSd-induced Ca2+ entry occurs through a non-selective mechanism since blockers of major neuronal Ca2+ entry pathways, including L-type Ca2+ channel, NMDA receptor, AMPA receptor, Na+-Ca2+ exchanger, and TRPV1, all failed to attenuate the Ca2+ response to SSd. Further studies demonstrate that SSd increases calcein efflux and induces an inward current in neocortical neurons. Together, these data demonstrate that SSd elevates [Ca2+]i due to its ability to increase membrane permeability, likely by forming pores in the surface of membrane, which leads to massive Ca2+ influx and apoptotic neuronal death in neocortical neurons. 相似文献
124.
中药制剂质量的科学客观评价一直是中药现代化进程中普遍存在的历史性难题。既往中药制剂质量评价多采用"以点代面,以一代全"的单成分评价模式及"唯含量论"的指标选取方式,严重偏离了中药整体观的特点,难以客观准确地评价中药制剂质量。目前,基于多指标的中药制剂质量评价模式已成为众多专家学者的共识,然而中药多成分的复杂性,使其无法实现所有成分的准确辨识,更不可能将所有成分作为中药制剂质量评价的标准。结合中药自身特点,提出在现有药效物质基础研究的基础上,借助网络药理学、分子对接等先进技术手段,选取可代表中药制剂整体效应的有限个代表性成分,并在各代表性成分量比关系考察的基础上,以代表性成分的量及各代表性成分间量的关系为参数,建立基于"组分结构"特征的中药制剂质量评价策略,以期为今后中药制剂质量评价提供新的思路。 相似文献
125.
《Journal of pharmaceutical sciences》2023,112(8):2223-2229
Formulations of human papillomavirus (HPV) 16, 18, and 31 L1 capsomere protein antigens were spray dried to obtain glassy microspheres that were then coated by atomic layer deposition (ALD) with nanometer-thin protective layers of alumina. Spray-drying was used to formulate human papillomavirus (HPV) 16, 18, and 31 L1 capsomere protein antigens within glassy microspheres to which nanoscopic protective layers of alumina were applied using ALD. Suspensions of alumina-coated, capsomere-containing microparticles were administered in a single dose to mice. ALD-deposited alumina coatings provided thermostability and a delayed in vivo release of capsomere antigens, incorporating both a prime and a boost dose in one injection. Total serotype-specific antibody titers as well as neutralizing titers determined from pseudovirus infectivity assays were unaffected by incubation of the ALD-coated vaccines for at 4, 50, or 70 °C for three months prior to administration. In addition, even after incubation for three months at 70 °C, single doses of ALD-coated vaccines produced both higher total antibody responses and higher neutralizing responses than control immunizations that used two doses of conventional liquid formulations stored at 4 °C. 相似文献
126.
127.
Protein tyrosine nitration plays a key role in many inflammatory and cardiovascular diseases and diabetes. Many natural products are used to treat these diseases through their ability to potentially interfere this reaction. Here, we describe a novel method to provide active fingerprinting of inhibition of tyrosine nitration by natural products based on post-column tyrosine nitration reaction analysis using high-performance liquid chromatography coupled to a photometric diode array. Results indicated that lotus leaf extracts exhibited obvious inhibitory activity against tyrosine nitration by peroxynitrite, and that chemical and active fingerprints were simultaneously established, with the active fingerprints indicating the active compounds of the lotus leaves. Additionally, flavonoids were screened as the principal active compounds involved in inhibiting tyrosine nitration in the lotus leaf extracts, with quercetin-3-O-glucuronide and quercetin-3-O-glucoside exhibiting the greatest contributions. Moreover, our results suggested that lotus leaves from three regions (Nanjing, Suzhou, and Hangzhou) exhibited the best inhibitory activity. These findings indicated the usefulness of this method for screening active compounds involved in inhibiting protein tyrosine nitration, and that similar strategies can likely be applied to evaluate the inhibitory activity against tyrosine nitration of other natural products.A novel analytical method based on HPLC-PDA coupled post-column derivatization to evaluate the inhibitory activity of tyrosine nitration in lotus leaf extracts. 相似文献
128.
目的结合肾宝片处方22味药材组成及其制剂工艺过程,阐明肾宝片提取物(浸膏)的化学成分,为肾宝片质量控制提供依据。方法采用UPLC分别建立浸膏1与浸膏2的指纹图谱,将浸膏1、2成分与全浸膏对应,按照浸膏1、2逐步敲入的方式,验证全浸膏中的成分,并利用UPLC-Q-TOF-MS快速鉴定各浸膏中的成分。结果基于UPLC重点分析表征了全浸膏中朝藿定A、B、C及淫羊藿苷、松果菊苷、毛蕊花糖苷、补骨脂素、异补骨脂素等21个成分;利用UPLC-QTOF-MS从浸膏1中共鉴定了朝藿定A、人参皂苷Rg1、人参皂苷Ro等17个化合物,浸膏2中鉴定了松果菊苷、毛蕊花糖苷、甘草苷、大黄素等58个化合物,从全浸膏中共鉴定了宝藿苷I、人参皂苷Rb1、甘草酸、毛蕊花糖苷等82个化合物,涵盖了处方中22味药材,主要组分包括淫羊藿黄酮组分、人参皂苷组分、制何首乌蒽醌组分、黄芪皂苷组分、肉苁蓉苯乙醇苷组分与补骨脂香豆素组分。结论基于UPLC-Q-TOF-MS对肾宝片的化学成分进行了较为全面的分析,为其物质基础及制剂工艺过程的质量控制提供了实验依据。 相似文献
129.
随着新型冠状病毒肺炎(COVID-19)在国内快速爆发,国家卫生健康委员会办公厅和国家中医药管理局办公室推出不同的诊疗方案。目前根据COVID-19危重症患者的临床特征及中医辨证认为气阴两虚证为主要证型之一,生脉散为备选中成药。注射用益气复脉(冻干)是生脉散的现代制剂,对COVID-19的可能病理过程及注射用益气复脉用于心血管疾病的COVID-19治疗的药效作用及临床应用可行性进行了探讨,以期为COVID-19的中医治疗提供参考。 相似文献
130.
目的 建立注射用丹参多酚酸(SAFI)体外抗氧化活性测定方法,并对29批样品体进行测定。方法 一定浓度的SAFI溶液与等体积的DPPH溶液混合均匀并放置一定时间后,采用紫外可见分光光度法,测定其吸光度(A)值相对于DPPH控制液(由DPPH溶液与等体积溶剂混合)的变化情况(DPPH自由基清除情况),考察波长为517 nm,并进行空白吸收考察、专属性考察、反应平衡时间的确定、DPPH线性考察、YQFM线性考察、精密度试验、重复性试验等方法学验证,以VC作为阳性对照,以SAFI清除DPPH自由基的半抑制浓度(IC50)和相对抗氧化活性作为衡量其抗氧化活性指标。结果 方法学验证结果表明,建立的体外抗氧化研究方法符合要求;29批样品IC50均值为25.26 μg/mL,相对于Vc抗氧化活性为61.8%。结论 SAFI具有较强的抗氧化活性,所建方法适用于SAFI体外抗氧化活性测定,为多维度评价中药注射剂质量提出新思路。 相似文献