HPLC法同时测定杜仲平压片中6种成分

目的建立HPLC法同时测定杜仲平压片(杜仲叶)中京尼平苷酸、新绿原酸、绿原酸、隐绿原酸、咖啡酸、芦丁的含有量。方法该药物50%甲醇提取液的分析采用Thermo Hypersil Gold C18色谱柱(250 mm×4.6 mm,5μm);流动相乙腈-0.1%磷酸,梯度洗脱;体积流量1.0 mL/min;柱温35℃;检测波长238、324、354 nm。结果 6种成分在各自范围内线性关系良好(r≥0.999 8),平均加样回收率98.07%~100.34%,RSD 1.03%~1.96%。结论该方法准确可靠,重复性好,可用于杜仲平压片的质量控制。     

Marine omega-3 fatty acid supplementation in non-alcoholic fatty liver disease: Plasma proteomics in the randomized WELCOME* trial

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The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story,yet mesmerizing

The prevalence of colorectal cancer (CRC) has markedly increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria have inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids–microbiota axis such as probiotics, metformin, ursodeoxycholic acid and fecal microbiota transplantation. Thus, by targeting the bile acids–microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment.     

Ursolic acid promotes apoptosis,autophagy, and chemosensitivity in gemcitabine‐resistant human pancreatic cancer cells

Gemcitabine (GEM) resistance in pancreatic adenocarcinoma mediated by the receptor for advanced glycation end products (RAGE) has been demonstrated. Therefore, investigating the safety and the potential of new auxiliary methods for pancreatic cancer treatment is urgent. Ursolic acid (UA), a natural pentacyclic triterpenoid found in apple peels, rosemary, and thyme, has been reported to have anticancer capacity. This study aimed to reveal the underlying mechanisms of UA in cell death and drug enhancement, especially in GEM‐resistant pancreatic cancer cells. First, GEM‐resistant cells (MIA Paca‐2^GEMR cells) were established by incrementally increasing GEM culture concentrations. UA treatment reduced cell viability through cell cycle arrest and endoplasmic reticulum (ER) stress, resulting in apoptosis and autophagy in a dose‐dependent manner in MIA Paca‐2 and MIA Paca‐2^GEMR cells. High RAGE expression in MIA Paca‐2^GEMR cells was suppressed by UA treatment. Interestingly, knocking down RAGE expression showed similar UA‐induced effects in both cell lines. Remarkably, UA had a drug‐enhancing effect by decreasing cell viability and increasing cell cytotoxicity when combined with GEM treatment. In conclusions, UA triggered ER stress, subsequently regulating apoptosis‐ and autophagy‐related pathways and increasing GEM chemosensitivity in pancreatic cancer cells by inhibiting the expression of RAGE.     

基于生物量、活性物质积累和抗氧化能力的当归高海拔种植区域选择

目的以根茎生物量、活性物质含量以及抗氧化能力为指标,选择适宜提高当归品质的高海拔种植区域。方法在严格控制种质、水分和土壤养分的条件下,以不同海拔(2 100、2 500和2 900 m)2年生当归根茎为材料,分别对干质量、活性物质含量以及抗氧化能力进行测定与分析。结果高海拔虽不能促进当归根茎生物量,却显著提高了活性物质的积累量和抗氧化能力;以单株积累量计算,2 900 m未抽薹当归根茎中阿魏酸、可溶性糖、酚和黄酮类含量分别为2 100 m植株的2.06、1.13、1.34和1.15倍;体外抗氧化能力也随海拔升高逐渐增加。综合分析表明,在2 100～2 900 m海拔内,未抽薹当归根茎中活性物质的总积累量(干质量和单株)均随海拔升高逐渐增加。结论提升当归种植海拔高度可显著提高根茎活性物质量;活性物质生物合成与积累受到低温和光照的综合调控。该研究结果将为提高当归产量和品质以及大面积种植栽培提供理论基础与依据。     

Analysis of the role of palmitoleic acid in acute anterior uveitis

PurposeTo study the role of palmitoleic acid (PA) in the pathogenesis of acute anterior uveitis (AAU).MethodsPA levels in feces from AAU patients were measured by gas chromatography coupled with a mass spectrometer (GC-MS) and compared with samples obtained from healthy individuals. Enzyme linked immunosorbent assay (ELISA) and flow cytometry (FCM) were used to assess the effect of PA on dendritic cells (DCs) and CD4⁺T cells obtained from mice, AAU patients and healthy individuals. C57BL/6 mice were fed with PA or vehicle and experimental autoimmune uveitis (EAU) was induced with a human retinal IRBP651-670 peptide. Disease severity of EAU was evaluated by clinical manifestation and histology. Differentiation of splenic Type 1 helper T cells (Th1) and Th17 cells was evaluated by FCM. Tandem mass tag (TMT)-based proteomics analysis was used to identify differentially expressed proteins following incubation of DCs with PA.ResultsThe fecal concentration of PA was increased in AAU patients as compared with healthy individuals. In vitro, PA promoted apoptosis of DCs and inhibited the secretion of TNF-α from mouse bone-marrow-derived dendritic cells (BMDCs) as well as in DCs from AAU patients and healthy individuals. It only decreased DCs surface marker expression and IL-12p70 secretion in BMDCs and healthy individuals DCs but not in AAU patient DCs. PA-treated BMDCs inhibited Th cell differentiation from mouse naïve CD4⁺T cells and IL-17 and IFN-γ secretion in co-culture supernatants. PA also inhibited the differentiation of Th cells and secretion of IFN-γ and IL-17 in CD4⁺T cells from mice, AAU patients and healthy individuals. In vivo, PA-treated EAU mice showed milder clinical and histopathological intraocular manifestations as compared with the control group. PA feeding inhibited differentiation of splenic Th17 cells, whereas Th1 cells were not affected. Up to 30 upregulated and 77 downregulated proteins were identified when comparing PA-treated DCs with controls.ConclusionAn increased expression of fecal PA was observed in AAU patients. PA was shown to have immunoregulatory effects on DCs and CD4⁺T cells and attenuated disease severity in EAU mice.     

小柴胡汤对非酒精性脂肪性肝炎模型小鼠的保护作用研究

目的通过构建蛋氨酸-胆碱缺乏(MCD)饮食诱导的小鼠非酒精性脂肪性肝炎(NASH)模型,研究小柴胡汤对NASH模型小鼠的保护作用。方法选择C57BL/6小鼠为研究对象,将其随机分为对照组、模型组、小柴胡汤(高、中、低剂量)组、易善复组和强肝胶囊组。通过饲喂MCD饲料建立NASH模型,造模同时按分组给予不同药物进行干预;实验过程中记录小鼠体质量、日摄食量、日饮水量变化,实验结束对肝组织进行HE染色观察病理变化,检测血清生化指标丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、白细胞介素6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平变化,检测肝组织中TC、TG的水平变化,利用q RT-PCR技术检测肝组织脂肪酸合成酶(FAS)和固醇调节元件结合蛋白1c(SREBP-1c)的表达水平。结果小鼠体质量、日摄食量、日饮水量及肝脏系数等数据显示MCD饮食诱导的模型组小鼠会出现体质量降低、摄入量减少及肝脏湿质量下降的特点,而小柴胡汤给药组小鼠体质量、摄入量及肝脏系数较模型组小鼠显著升高;HE染色结果显示小柴胡汤可明显减轻肝组织脂肪变性和炎症程度,改善肝细胞的形态和结构;生化指标检测结果显示小柴胡汤能显著降低NASH模型小鼠血清及肝组织TG、TC水平,升高血清中HDL-C水平,降低血清中AST、ALT、IL-6、TNF-α水平;q RT-PCR结果显示模型组小鼠肝组织FAS和SREBP-1c的基因表达水平明显升高,小柴胡汤可显著降低FAS和SREBP-1c的基因表达水平。结论小柴胡汤对MCD饮食诱导的NASH模型小鼠有明显保护作用,其机制可能通过调控抑制脂肪酸合成基因(FAS、SREBP-1c)的表达,减少脂肪堆积,实现调脂作用,并通过抑制炎症因子的表达改善肝组织的损伤。     

基于网络药理学探讨黄连阿胶汤治疗失眠症的作用机制

目的采用网络药理学方法寻找黄连阿胶汤的有效成分、治疗靶标。方法根据药代动力学参数筛选药物成分,通过网络药理学方法挖掘药物和疾病靶标并构建药物-靶点网络,研究黄连阿胶汤成分的作用机制。结果发现黄连阿胶汤中的氢化小檗碱、β-谷甾醇、山姜素、山柰酚、小檗浸碱、荠苎黄酮等19个成分可能通过调控5-羟色胺、多巴胺、γ氨基丁酸、阿片受体、乙酰胆碱等25个靶点作用于失眠症治疗。结论黄连阿胶汤可能主要通过多个靶点调控多种神经递质发挥对失眠症的治疗作用。     

3,5-O-二咖啡酰基奎宁酸的制备及其对HeLa细胞的抗增殖活性研究

目的 制备高纯度3，5-O-二咖啡酰基奎宁酸，并评价其对人宫颈癌HeLa细胞的抗增殖活性。方法 采用柱色谱提取法和中压液相色谱法从奇蒿花中分离、纯化得到高纯度的3，5-O-二咖啡酰基奎宁酸。采用MTT法评价该化合物对人宫颈癌HeLa细胞的体外抗增殖活性。结果 柱色谱提取的提取率和中压液相色谱法的回收率分别为99.0%，61.2%，总回收率为54.0%。随着3，5-O-二咖啡酰基奎宁酸浓度升高，HeLa细胞存活率下降，细胞形态损伤增加，受试药物的IC₅₀值为26.5µg·mL^-1。结论 本研究提供了一种简单、高效、节能的3，5-O-二咖啡酰基奎宁酸制备方法。3，5-O-二咖啡酰基奎宁酸对HeLa细胞具有一定的体外抗增殖活性。     

Kynurenic acid and zaprinast diminished CXCL17-evoked pain-related behaviour and enhanced morphine analgesia in a mouse neuropathic pain model

Background

The G protein-coupled receptor 35 (GPR35), is considered important for nociceptive transmission, as suggested by accumulating evidence. This receptor was discovered in 1998; however, a lack of pharmacological tools prevented a complete understanding of its function and how to exploit it therapeutically. We studied the influence of CXCL17, kynurenic acid and zaprinast on nociceptive transmission in naïve and neuropathic mice. Additionally, we investigated the influence of kynurenic acid and zaprinast on morphine effectiveness in neuropathic pain.