蓝萼甲素抗凝血作用研究

目的:研究蓝萼甲素抗凝血作用.方法:测定蓝萼甲素对小鼠毛细管凝血时间和尾尖出血时间的作用;测定蓝萼甲素对小鼠凝血酶时间(TT)、凝血酶原时间(PT)、活化部分凝血激酶时间(APTT)、血浆复钙时间(PRT)的影响.测定蓝萼甲素对家兔体外TT、PT、APTT和PRT的影响.结果:蓝萼甲素能显著延长小鼠毛细管凝血时间和尾尖出血时间;显著延长小鼠TT、PT、APTT和PRT.蓝萼甲素在体外显著延长家兔TT、APTT和PRT.结论:蓝萼甲素具有抗凝血活性.     

枳术颗粒对功能性消化不良大鼠胃动力的改善作用

目的 研究枳术颗粒对功能性消化不良（functional dyspepsia,FD）大鼠的药效及作用机制。方法 复合因素造模法诱导大鼠FD模型,造模成功后给予枳术颗粒治疗2周,观察枳术颗粒对FD大鼠胃残留率、小肠推进率、血清中胃泌素（gastrin,GAS）、胃饥饿素（growth hormone releasing peptide,Ghrelin）、降钙素基因相关肽（calcitonin gene related peptide,CGRP）及生长抑素（somatostatin,SS）含量的影响;苏木素-伊红（hematoxylin-eosin,HE）染色法观察胃窦组织、十二指肠组织病理变化;利用qRT-PCR检测下丘脑及胃组织中GAS、Ghrelin、CGRP、SS mRNA表达和胃及十二指肠组织中肾上腺素能受体β1(β1-adrenergic receptor,ADRB1)、生长抑素受体（somatostatin receptor,SSTR）、胃饥饿素-O-乙酰转移酶（ghrelinO-acyltransferase,GOAT）、胃饥饿素受体（growth hormone secr...     

基于糖基化修饰的靶向药物传递系统研究概况

近年来,基于药物受体及转运体介导的靶向药物传递系统已被广泛研究,靶向药物传递系统增强药物在病变部位的浓度和疗效,最大限度地降低了药物毒副作用。人体不同细胞表面高表达的特异性凝集素受体及脑毛细血管内皮细胞、肿瘤细胞高表达的葡萄糖转运体亚型Ⅰ,可与其相应的糖基配体产生特异性识别。将糖基配体分子如甘露糖、半乳糖、葡萄糖等,键接在药物传递系统上,可赋予其靶向性。这些糖基配体具有无毒、无免疫原性、生物相容性和生物可降解性良好等诸多优点,可广泛用于对药物传递系统的糖基化修饰。本文综述了近5年来糖基化修饰药物传递系统的靶向机制、合成方法及靶向特性,并对其发展前景作了展望。     

Antibiotic resistance differentiates Echinacea purpurea endophytic bacterial communities with respect to plant organs

Recent findings have shown that antibiotic resistance is widespread in multiple environments and multicellular organisms, as plants, harboring rich and complex bacterial communities, could be hot spot for emergence of antibiotic resistances as a response to bioactive molecules production by members of the same community. Here, we investigated a panel of 137 bacterial isolates present in different organs of the medicinal plant Echinacea purpurea, aiming to evaluate if different plant organs harbor strains with different antibiotic resistance profiles, implying then the presence of different biological interactions in the communities inhabiting different plant organs.Data obtained showed a large antibiotic resistance variability among strains, which was strongly related to the different plant organs (26% of total variance, P < 0.0001). Interestingly this uneven antibiotic resistance pattern was present also when a single genus (Pseudomonas), ubiquitous in all organs, was analyzed and no correlation of antibiotic resistance pattern with genomic relatedness among strains was found.In conclusion, we speculate that antibiotic resistance patterns are tightly linked to the type of plant organ under investigation, suggesting the presence of differential forms of biological interaction in stem/leaves, roots and rhizosphere.     

儿童中成药在呼吸和消化系统疾病中的用药特点与成分特征

目的 探索分析儿童中成药治疗呼吸和消化系统疾病的用药规律和成分特征,为小儿呼吸系统、消化系统疾病的治疗及新药研发提供参考。方法 搜集《中国药典》2020年版一部中治疗小儿呼吸系统和消化系统疾病的中成药处方,对其中的中成药饮片进行频次和关联规则分析,利用TCMSP、ETCM、TCMD数据库对高频饮片进行成分检索,通过RDkit化学信息分析平台计算获得相应的分子描述符,最后提取环结构获得Murcko骨架。结果 共搜集得到小儿呼吸系统中成药处方106种、消化系统61种,剂型共涉及12种。其中治疗呼吸系统中成药主要包含清热、发散类中药,药性以寒为主,以苦寒居多,主要归肺、心经;而治疗消化系统中成药主要包含消食、理气类中药,药性以甘温居多,主要归脾、胃经。对成分骨架结构进行统计,发现两系统重叠骨架占比大,多为黄酮类、苯环类等,对特有成分的理化性质进行分析,发现二者有显著性差异。结论 儿童中成药治疗呼吸系统疾病常用入肺经的清热药,治疗消化系统疾病常用归脾、胃经的消食药,且用药偏温和,与儿童脾胃虚弱、五脏娇嫩相适应。通过化学信息学研究发现治疗呼吸系统和消化系统疾病共有成分骨架在两系统中占比均较高,多...     

Butyrate inhibit collagen-induced arthritis via Treg/IL-10/Th17 axis

Rheumatoid arthritis (RA) is a chronic autoimmune disorder demanding the development of novel therapeutic strategy. Butyrate is a functional short-chain fatty acid produced by the anaerobic intestinal microbiota. This study aimed to investigate the attenuation of butyrate on RA. The collagen-induced arthritis (CIA) mouse model was established and butyrate was administered in drinking water along with the collagen immunization. The histopathological features, clinical score, paw swelling, as well as the production of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6 and IL-17A were measured to determine the amelioration of butyrate on arthritis. The differentiation of Treg cells and Th17 cells in the splenic cells was assessed by flow cytometry. The expression of Foxp3, IL-10, Rorγt and IL-17A were detected by RT-PCR and FACS immunostaining. Anti-IL10R antibody was used in the CIA and CD4⁺ cell cultures to mediate the effects of butyrate. Butyrate significantly inhibited expressions of IL-1β, IL-6 and IL-17A, but promoted the expression of IL-10. Butyrate also increased systematical Treg cells and reduced Th17 cells. Mechanism study revealed that butyrate directly enhanced the polarization of Treg cells but not Th17 cells. All effects of butyrate on RA were inversed by the co-administered anti-IL10R antibody. This study showed that butyrate administration inhibited arthritis in CIA mice model, suppressed the expression of inflammatory cytokines. The modulation may be mediated the differentiation of CD4 T cells towards Treg cells, which produce anti-inflammatory cytokine IL-10, and thus influenced the function of Th17 cells.     

共无定形技术改善葛根素水溶性及增溶机制研究

葛根素(PUE)为异黄酮类成分,具有广泛的药理活性,但其低水溶性限制了其口服固体制剂的开发。本研究以烟酰胺(NIC)为配体通过减压旋蒸法制备了PUE-NIC共无定形体系,同时联合粉末X-射线衍射(PXRD)、差示扫描量热法(DSC)和红外光谱(FT-IR)等多种手段对其进行表征,并对其溶出行为及增溶机制进行了系统的研究。结果表明,PUE-NIC共无定形仅存在单一的玻璃化转变温度(35.1℃),为单一均相二元体系。与PUE晶体相比,在溶出过程中,共无定形不仅发生"液-液相分离"(LLPS)现象,PUE与NIC还可形成摩尔比为1∶1与1∶2的Ap型络合物,这有利于显著增加PUE的溶解度,并能维持长时间的药物过饱和态优势,有利于药物吸收。     

BmK NSPK,a Potent Potassium Channel Inhibitor from Scorpion Buthus martensii Karsch,Promotes Neurite Outgrowth via NGF/TrkA Signaling Pathway

Scorpion toxins represent a variety of tools to explore molecular mechanisms and cellular signaling pathways of many biological functions. These toxins are also promising lead compounds for developing treatments for many neurological diseases. In the current study, we purified a new scorpion toxin designated as BmK NSPK (Buthus martensii Karsch neurite-stimulating peptide targeting K_v channels) from the BmK venom. The primary structure was determined using Edman degradation. BmK NSPK directly inhibited outward K⁺ current without affecting sodium channel activities, depolarized membrane, and increased spontaneous calcium oscillation in spinal cord neurons (SCNs) at low nanomolar concentrations. BmK NSPK produced a nonmonotonic increase on the neurite extension that peaked at ~10 nM. Mechanistic studies demonstrated that BmK NSPK increased the release of nerve growth factor (NGF). The tyrosine kinases A (TrkA) receptor inhibitor, GW 441756, eliminated the BmK NSPK-induced neurite outgrowth. BmK NSPK also increased phosphorylation levels of protein kinase B (Akt) that is the downstream regulator of TrkA receptors. These data demonstrate that BmK NSPK is a new voltage-gated potassium (K_v) channel inhibitor that augments neurite extension via NGF/TrkA signaling pathway. K_v channels may represent molecular targets to modulate SCN development and regeneration and to develop the treatments for spinal cord injury.