A Network Pharmacology Study on Active Components and Targets of Citri Reticulatae Pericarpium for Treating Keloids

[Objectives]To investigate the mechanisms and pharmacologic effects of Citri Reticulatae Pericarpium against keloids by network pharmacology systematically.[Methods]TCMSP,Uniprot and BATMAN-TCM databases were used to obtain the active constituents and targets of Citri Reticulatae Pericarpium."Keloid"was used as key word to search for related therapeutic targets from Drug Bank,OMIM,TTD,and GEO databases.The Chinese medicine compound-target network was constructed by Cytoscape software.Besides,gene ontology(GO)and Kyoto Encyclopedia of genes and genome enrichment analysis were also performed.Afterward,Discovery Studio software was used to assess the interaction of key components and genes.[Results]Five active components of Citri Reticulatae Pericarpium,773 compound targets and 676 keloid treatment targets were obtained in the databases.After the intersection,there are 47 targets of Citri Reticulatae Pericarpium for treating keloids.Hub genes were identified such as MMP9,IL6,TNF,TP53,and VEGFA,which were enriched in tumor necrosis factor-α,nuclear factor kappa-B,and other signaling pathways.The molecular docking stimulation confirmed the interaction between the MMP9 and three components of Citri Reticulatae Pericarpium.[Conclusions]Citri Reticulatae Pericarpium may play an important role in treating keloids through modulating genes and signaling pathways.The present study sheds light on the mechanisms of active compounds of Citri Reticulatae Pericarpium for the treatment of keloids.

Establishment of HPLC Fingerprint, Cluster Analysis and Principle Component Analysis of Citri Reticulatae Pericarpium Viride

[Objectives] This study aimed to establish HPLC fingerprint and conduct cluster analysis and principle component analysis for Citri Reticulatae Pericarpium Viride. [Methods] Using the HPLC method, the determination was performed on XSelect~® HSS T3-C_(18) column with mobile phase of acetonitrile-0.5% acetic acid solution(gradient elution) at the flow rate of 1.0 mL/min. The detection wavelength was 360 nm. The column temperature was 25℃. The sample size was 10 μL. With peak of hesperidin as the reference, HPLC fingerprints of 10 batches of Citri Reticulatae Pericarpium Viride were determined. The similarity of the 10 batches of samples was evaluated by Similarity Evaluation System for Chromatographic Fingerprint of TCM(2012 edition) to determine the common peaks. Cluster analysis and principal component analysis were performed by using SPSS 17.0 statistical software. [Results] The HPLC fingerprints of the 10 batches of medicinal materials had total 11 common peaks, and the similarity was 0.919-1.000, indicating that the chemical composition of the 10 batches of medicinal materials was consistent. There were 11 common components in the 10 batches of medicinal materials, but their contents were different. When the Euclidean distance was 20, the 10 batches of samples were divided into two categories, S4 in the first category, and the others in the second one. When the Euclidean distance was 5, the second category could be further divided into two sub-categories, S1 and S10 in one sub-category, and S2, S3, S5, S6, S7, S8 and S9 in the other one. The principle component analysis showed that cumulative contribution rate of the two main component factors was 92.797%, and the comprehensive score of S7 was the highest with the best quality. [Conclusions] The results of HPLC fingerprinting, cluster analysis and principle component analysis can provide reference for the quality control of Citri Reticulatae Pericarpium Viride.

Evaluation of bioactive flavonoids in Citri Reticulatae Pericarpium from different regions and its association with antioxidant andα-glucosidase inhibitory activities

Background:To explore the differences of 14 batches of Citri Reticulatae Pericarpium from different regions.Methods:The main aim of this study was to develop a high-performance liquid chromatography method-photodiode array detection for determining the contents of five flavonoids and the chromatographic fingerprints of Citri Reticulatae Pericarpium from different regions.Theα-glucosidase inhibitory activities and antioxidant properties of Citri Reticulatae Pericarpium,based on free-radical scavenging assays against 1,1-diphenyl-2-picrylhydrazyl,2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid),and hydroxyl radicals,were estimated and compared.Results:Among the tested compounds,the content of hesperidin(13.386-68.235 mg/g)was the highest and that of hesperitin(0.045-0.277 mg/g)was the lowest.In comparing different sources of Citri Reticulatae Pericarpium,the contents of narirutin in Citri Reticulatae Pericarpium from Guangdong(0.824-0.851 mg/g)and Sichuan(1.069-1.204 mg/g)provinces of China were lower than in other provinces.In contrast,nobiletin(8.429-12.237 mg/g)and tangeretin(3.947-4.613 mg/g)were most abundant in Guangdong sources of Citri Reticulatae Pericarpium,followed by samples from Sichuan Province(nobiletin:6.761-7.658 mg/g;tangeretin:3.422-3.933 mg/g).Correlation analysis showed that nobiletin and tangeretin were the main contributors to the antioxidant capacity,and narirutin was the main active component inhibiting theα-glucosidase activity of Citri Reticulatae Pericarpium.Conclusion:This work revealed that the intrinsic quality of Citri Reticulatae Pericarpium was affected by different growing regions,which provides a scientific basis for controlling the quality of Citri Reticulatae Pericarpium and rationally developing and utilizing Citri Reticulatae Pericarpium.

Clinical Study on Dark Tea with Pericarpium Citri Reticulatae Combined with Metformin for Type 2 Diabetes Mellitus

[Objectives]To observe the clinical effect of dark tea with pericarpium citri reticulateae combined with metformin for type 2 diabetes mellitus.[Methods]A total of 80 cases of patients with type 2 diabetes mellitus were randomly divided into the control group and the observation group with 40 cases in each group.The control group was given metform for treatment,and the observation group was given dark tea with pericarpium citri reticulateae combined with metformin for treatment.The two groups were continuously treated for 12 weeks.The indexes of patients were observed and recorded,such as the body mass index(BMI),abdominal circumference(AC),hemoglobin A1c(HbA1c),fasting blood glucose(FBG),postprandial 2 h blood glucose(P2hBG),uric acid(UA),total cholesterol(TC),and triglyceride(TG).The incidence of adverse reactions during the treatment period and the patient satisfaction for treatment in the two groups were counted.[Results]After treatment,the FBG,P2hBG and HbA1c in the two groups were decreased when compared with those before treatment(P<0.05)and the decrease of the above indexes in the observation group was more significant than that in the control group(P<0.05).After treatment,the BMI,AC,UA,TC and TG in the observation group were decreased more significantly when compared with those before treatment and those in the control group after treatment,differences were statistically significant(P<0.05).The above indexes in the control group did not change significantly before and after treatment(P>0.05).The incidence of adverse reactions was 2.5%in the observation group and 5.0%in the control group,the difference was not statistically significant(P>0.05).The patient satisfaction was 97.5%in the observation group and 55.0%in the control group,the difference was significant(P<0.05).[Conclusions]The curative effect of dark tea with pericarpium citri reticulateae combined with metformin for type 2 diabetes mellitus is better than that of western medicine alone and has no obvious adverse reactions,thus it is worthy of clinical promotion and application.

金水六君煎物质基准中半夏和陈皮的薄层鉴别研究

目的:建立经典名方金水六君煎物质基准中半夏和陈皮的薄层鉴别方法。方法:以半夏对照药材为对照,对金水六君煎中半夏进行薄层鉴别研究,以橙皮苷和陈皮对照药材为对照,对金水六君煎中陈皮进行薄层鉴别研究,并对其进行方法学验证。结果:建立的薄层色谱法能鉴别出半夏和陈皮,斑点对应较好,阴性无干扰,方法学考察结果显示,方法适应性良好。结论:本法简单可行、结果可靠、重复性好,可作为金水六君煎物质基准的质量控制方法。

陈皮提取物对APP/PS-1双转基因阿尔茨海默病小鼠学习记忆功能的影响

目的探讨陈皮提取物对APP/PS-1双转基因阿尔茨海默病(AD)小鼠学习记忆功能的影响.方法选用APP/PS-1双转基因AD小鼠16只,随机分为模型对照组和供试品组,8只/组,另取8只C57小鼠为正常对照组,正常对照组和模型对照组分别灌胃等量的生理盐水,供试品组灌胃陈皮提取物的生理盐水溶解液,灌胃体积为10mL/kg,1次/d,连续18d.第11天到第16天,进行Morris水迷宫的定位航行实验及空间探索实验.第17天到第18天,进行5min避暗实验.结果在Morris水迷宫实验中,与正常对照组比较,模型对照组定位航行第2天、第3天、第5天的潜伏期增加(P<0.05);与模型对照组比较,供试品组第5天的潜伏期降低(P<0.05).空间探索阶段,各组的目标象限路程百分比、时间百分比及站台穿越次数差异无统计学意义(P>0.05).在避暗实验中各组的错误潜伏期、错误次数及错误率差异均无统计学意义(P>0.05).结论陈皮提取物对APP/PS-1双转基因AD小鼠的空间学习、记忆能力有一定的改善作用.

连翘与陈皮混合挥发油提取与包合工艺优化

目的优选保和颗粒组方中连翘、陈皮混合挥发油提取工艺及β-环糊精(β-CD)包合工艺。方法以饮片粉碎粒度、提取时间、加水倍数为考察因素,挥发油收率为评价指标,采用L_(9)(3^(4))正交试验法优选。以β-CD与挥发油比例(g∶m L)、包合时间、包合温度为考察因素,挥发油包合率、包合物收率、包合物含油量的综合评分为评价指标,同上法优选包合工艺并验证。结果最佳提取工艺,将饮片粉碎至20目,加10倍水提取3 h。最佳包合工艺,β-CD∶挥发油为7∶1(g∶m L),45℃下包合反应3 h;紫外光谱扫描、X射线衍射、扫描电镜、薄层色谱等结果均证明形成了稳定的包合物。制成的包合物中连翘及陈皮混合挥发油的包合率为95.13%,包合物收率为87.84%,包合物含油量为10.29%,综合评分为76.70分。结论优化后的连翘及陈皮混合挥发油提取、包合工艺稳定可行。

基于近红外光谱技术有监督模式识别的青皮产地溯源分析

利用便携式近红外光谱仪采集不同产地(安徽、广东、四川)青皮外壁和内囊光谱数据,采用单一预处理和组合预处理方法消除光谱中的多种干扰,结合主成分分析(PCA)、簇类独立软模式分类法(SIMCA)及Fisher线性判别分析(FLDA)等模式识别方法建立青皮产地溯源模型。结果表明,光谱预处理可以在一定程度上消除基线漂移、背景噪声和谱峰重叠干扰,但无法实现产地溯源。3种模式识别方法中,PCA无法实现青皮产地溯源;青皮外壁和内囊原始光谱的SIMCA模型获得的青皮产地溯源整体鉴别率分别为99.14%和98.28%;FLDA模型获得的整体鉴别率均为99.57%,优于SIMCA模型;经光谱预处理优化后的SIMCA和FLDA模型对青皮产地溯源的鉴别率均可达100%,即便携式近红外光谱技术结合有监督模式识别方法可实现青皮产地溯源的无损分析,可为食药同源物质产地溯源拓展新途径。

基于中药特色技术传承概述广东芸香科道地药材

基于中药传统特色技术,文章通过现场观摩调研与文献检索,概述在十大广药中占有1/3的芸香科药物的药用历史、产地采收加工、性状鉴别特点。芸香科药物多含挥发油,具有芳香气,大部分具有宽中理气的功效,临床应用广泛。据考证,柚类橘红始自清代,此前使用橘类橘红;广陈皮主产区在新会地区,也称新会陈皮,药用时间至今约有600年;广佛手以肇庆高要地区产量多且质优,“佛手柑”的记载最早见于元朝。化橘红的传统加工方法是将化州柚的外层果皮切成角状,加工成7角的毛橘红药材,称为“毛七爪”;新会陈皮需在新会地区内陈化三年,方可称为“新会陈皮”。化橘红鉴别特点为表面密被柔软毡状细绒毛,有油点,气清香;新会陈皮“鬃眼”明显,对光照视呈半透明状,香气浓郁。广佛手切面的外皮呈黄色,肉呈白色,俗称“金边白肉”。文章基于中药传统理论、技术对广东地区芸香科道地药材进行概述,以期守正创新,使中药的传统特色技术得到传承发展。

预制菜及陈皮牛肉预制菜的发展现状

随着科技的发展和人们生活方式的转变,预制菜逐渐成为热门商品。陈皮牛肉预制菜是新型的预制菜品,进一步丰富了预制菜的品种,为广大消费者提供了新的选择。通过简述预制菜的定义、分类、国内外发展概况及发展预制菜的意义,介绍陈皮牛肉预制菜的营养、特点和研究现状,并对预制菜和陈皮牛肉预制菜的未来进行展望。

不同配比陈皮-蜜橘皮茶汤品质分析

为了解陈皮、蜜橘皮以及两者不同配比合煎所得茶汤的汤色、风味感官以及活性成分等品质变化规律,以10年新会陈皮、温州蜜橘皮为研究对象,采用高效液相色谱法测定茶汤中的主要黄酮类化合物,顶空固相微萃取结合气相色谱-质谱联用技术测定其挥发性成分。结果表明,陈皮茶汤的感官评价综合得分、总黄酮、川陈皮素、橘皮素、总酚含量和抗氧化能力(DPPH法、ABTS法、FRAP法)均显著高于蜜橘皮茶汤,而蜜橘皮茶汤的橙皮苷和香蜂草苷含量显著高于陈皮茶汤;陈皮茶汤的主要挥发性成分是2-(甲氨基)苯甲酸甲酯、(-)-4-萜品醇、百里醌等,蜜橘皮茶汤的主要挥发性成分是(1 R,5 R)-rel-香芹醇、4-乙烯基-2-甲氧基苯酚、芳樟醇等;陈皮-蜜橘皮的不同质量比(5∶5、3∶7、2∶8、1∶9)茶汤中,随着陈皮比例的下降,除橙皮苷和香蜂草苷含量之外,其余相应的活性成分含量和抗氧化能力均随之降低,其中5∶5能够全面地凸显两者的优点。该研究明确了新会陈皮、温州蜜橘皮以及两者不同配比茶汤的品质变化规律,为陈皮、蜜橘皮的综合利用及精深加工提供理论基础。

基于UPLC-Q-TOF-MS法分析陈皮中的化学成分

利用超高效液相色谱-四极杆-飞行时间质谱法(UPLC-Q-TOF-MS)结合数据分析平台在线分析陈皮中71种化学成分,包括黄酮类、生物碱、香豆素和脂类等9类。通过主成分分析(PCA)及正交偏最小二乘判别分析(OPLS-DA)发现不同陈化年份陈皮中的化学成分具有明显差异,并筛选出17种特征性成分,随着陈化年份的延长,异甘草苷、山奈酚-3-O-β-D-槐糖苷、百蕊草素Ⅰ含量增加,脱水红花黄色素B、补骨脂查尔酮含量减少。此方法可用于区分陈化3,5,10,15,20年的陈皮。该研究了解了陈皮中化学组成并阐明了不同陈化年份陈皮间化学成分存在的差异,对合理开发陈皮的食用和药用价值具有指导意义,为不同陈化年份陈皮的鉴别提供了科学依据。

青皮的炮制历史沿革、效应物质及古今临方配伍研究进展

青皮为我国传统中药材,炮制历史悠久,方法多样。但随着历史的演变,一些独具特色的炮制方法逐渐消失,我们对青皮不同炮制品种的认识和传承有待加强。同时,各地对不同品种的制法各异,差别较大。而其加工炮制、质量控制、临床使用都不可避免地会受到这些问题的影响和制约。因此,本文通过对青皮炮制历史沿革、现代炮制规范的详细梳理,并综合药理作用的研究进展,强化对青皮及其炮制品优势特色的认识,寻找目前研究与开发的不足之处,为今后优化青皮炮制工艺和建立质量标准控制体系提供参考。此外,从中药功效和临床应用的角度进一步挖掘青皮及其炮制品在复方配伍方面的特点与规律,促进对现代药理活性及潜在机制的阐述,也为现代配伍研究提供依据。

层次分析-熵权法联合星点设计-响应面法优选胆汁制陈皮炮制工艺及饮片色度与成分相关性分析

目的研究胆汁制陈皮炮制的最佳工艺参数,明确饮片色度与主要成分之间的关系。方法采用星点设计-响应面法,以辅料用量、蒸制时间、干燥时间、干燥温度为考察因素,以橙皮苷、川陈皮素、橘皮素、牛磺胆酸钠含量及外观性状、醇浸出物含量为评价指标,采用层次分析-熵权法对各评价指标赋予相应权重,计算总评归一值,优选最佳炮制工艺;采用相关性分析和回归分析研究饮片色度与主要有效成分含量的相关性,构建色度-成分的回归方程。结果胆汁制陈皮最佳炮制工艺为每100g陈皮用20g蛇胆汁浸渍完全后,蒸制15min,45℃干燥162min。饮片色度值L^(*)、b^(*)值与橙皮苷、川陈皮素、橘皮素、牛磺胆酸钠4种成分含量均具有显著相关性,a^(*)值仅与牛磺胆酸钠含量具有相关性;构建了L^(*)、b^(*)值与4种成分含量及a^(*)值与牛磺胆酸钠含量的线性回归方程。结论采用星点设计-响应面法优化的胆汁制陈皮炮制工艺具有合理性、可行性,饮片色度与成分含量具有显著相关性。

陈皮酵素对小鼠酒精性肝损伤及肠道菌群的调节作用

目的探讨陈皮酵素(Pericarpium citri reticulatae fermentation liquor,PF)对小鼠酒精性肝损伤和肠道的调节作用。方法将40只C57BL/6雄性小鼠随机分为正常组、模型组、阳性药物组[100mg/(kg·d)水飞蓟宾(silibinin,Sly)]和陈皮酵素组[500 mg/(kg·d)PF],每组10只,持续给药干预2周。通过分子生物学检测生物化学和病理学指标;16S rDNA高通量测序技术检测分析粪便微生物群。结果组织切片结果显示陈皮酵素可以显著改善酒精性肝损伤小鼠的肝脏和回肠组织损伤,减少酒精诱导的肝脏脂质积累。此外,陈皮酵素显著降低肝脏组织促炎因子[白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)]的水平,缓解酒精引起的氧化应激。同时,陈皮酵素可修复酒精引起的肠道菌群紊乱,维持肠道菌群数量,修复肠道黏膜屏障损伤。结论陈皮酵素可改善酒精性肝损伤,其机制与抗氧化、抗炎和调节肠道菌群紊乱有关,值得推广应用与开发。

陈皮产地溯源及鉴伪技术研究进展

陈皮是药食同源佳品,药用价值和经济价值高。然而,市场上陈皮产地虚标、品种假冒和陈化时间造假等现象时有发生,损害了消费者权益,亟需建立有效的陈皮产地溯源及鉴伪技术以保障陈皮质量安全和品质。本文综述了代谢组学、光谱、DNA分析、元素分析、智能感官等技术在陈皮产地溯源和品种、采收期及陈化时间鉴别方面的研究进展,对比分析了各种技术的优缺点,并提出陈皮产地溯源及鉴伪研究当前存在的问题以及未来研究重点。

不同水解方式下陈皮键合态挥发性化合物的比较

为比较不同水解条件对陈皮键合态挥发性化合物释放的影响,采用Amberlite XAD-2树脂吸附洗脱分离得到陈皮中键合态挥发性化合物前体,将其在β-葡萄糖苷酶、果胶酶、混合酶(β-葡萄糖苷酶与果胶酶)和酸4种条件下进行水解释放,采用GC-MS和气相色谱-离子迁移谱(gas chromatography-ion mobility spectrometry,GC-IMS)对水解得到的键合态挥发性化合物进行分离分析。GC-MS分析显示,3种酶法水解得到的键合态挥发性化合物共有35种,其中β-葡萄糖苷酶和混合酶水解得到的化合物主要为酯类(占比分别高达93.42%和90.55%),以苯甲酸甲酯含量最高,辛酸甲酯等脂肪酸甲酯次之,这些成分在游离态挥发性成分以及果胶酶水解中未检出;酸法水解得到的键合态挥发性化合物共有50种,主要为萜烯结构的醛类、醇类。GC-IMS分析显示,酶解生成的成分以醛、醇类为主,果胶酶酶解释放的化合物组成与空白组类似,酸解生成的成分以醛、酮、酸类为主。综上所述,β-葡萄糖苷酶较果胶酶更利于陈皮键合态挥发性化合物的释放,且水解条件较酸解温和,是释放陈皮键合态挥发性化合物的较优选择。

基于BP神经网络的陈皮干燥含水率预测

为探索陈皮的热泵干燥特性,并实现热泵干燥过程中陈皮的含水率预测,研究了不同干燥温度(50、55、60℃)、干燥风速(1.0、2.0、3.0m/s)、堆叠厚度(20、30、40mm)对陈皮干燥时间和干燥速率的影响。将干燥温度、干燥风速、堆叠厚度和干燥时间作为输入层,隐藏层个数为10,陈皮的干燥含水率为输出层,搭建一个BP神经网络预测模型。研究结果表明:干燥温度、干燥风速和堆叠厚度都是影响陈皮干燥含水率的重要因素,提高干燥温度、增加干燥风速和减少堆叠厚度能够提高陈皮的干燥速率,缩短干燥时间。基于陈皮热泵干燥特性构建结构为“4-10-1”的BP神经网络模型,含水率预测值与实测值之间的均方误差MSE为0.00421,决定系数R^(2)=0.997,模型运行稳定,含水率预测结果准确且快速,能够为陈皮干燥过程中的含水率在线预测提供科学依据。

广陈皮高效液相色谱陈化特征图谱研究

【目的】建立广陈皮的高效液相色谱(HPLC)陈化特征图谱。【方法】采用HPLC-二极管阵列检测器(DAD)技术分析不同年份广陈皮之间的成分差异,测定各差异色谱峰的相对峰面积,通过聚类分析对其进行陈化等级分类,并通过中药色谱指纹图谱相似度评价系统(2012A版)进行评价。【结果】不同年份广陈皮被聚为Ⅰ、Ⅱ类两个不同的陈化等级,Ⅰ类(低陈化等级)广陈皮的相似度为0.708~0.957,Ⅱ类(高陈化等级)广陈皮的相似度为0.734~0.976,且两者之间的相似度均低于0.6。建立的特征图谱中存在9个差异色谱峰;Ⅱ类广陈皮的对照特征图谱T2可视为其陈化特征图谱,其中1~4号峰、9号峰为陈化特征峰。【结论】建立的广陈皮陈化特征图谱操作简单,具有良好的重复性与可靠性,可用于不同年份广陈皮的质量评价。

郭绍举辨证治疗泄泻用药规律探讨

【目的】分析郭绍举教授门诊治疗泄泻病例的中医证型、证候要素的分布特点及用药规律,以期为泄泻的临床诊疗提供参考。【方法】采用回顾性研究方法,分析郭绍举教授于2011年10月至2019年9月期间在深圳市中医院门诊治疗泄泻病例的证型、病位证素、病性证素、中药用药频次情况。【结果】纳入分析的2632份病例中,共涉及中医证型23种,频次最高的3种证型为脾虚湿盛、肝郁脾虚、脾胃虚寒;涉及病位证素8个,居前3位的病位证素为脾、肝、胃;涉及病性证素8个,居前3位的病性证素为湿、寒、热;涉及中药212味,频次较高的依次为白术、茯苓、陈皮等。【结论】郭绍举教授辨治泄泻的思路如下:脾虚湿盛为泄泻的核心病机,贯穿疾病始终,湿邪是促进泄泻发展的重要影响因素,中后期易夹杂阴虚、阳虚、气血两虚等复杂证候表现;治疗以健脾、运脾、化湿为基本原则,常根据病情发展及寒热虚实辨证配伍涩肠药、理气药、健脾药等。郭绍举教授辨治泄泻的用药规律可为岭南地区该病的临床诊疗提供参考。