Experimental Study of Emilia Sonchifolia Combined with Coptidis Rhizoma for the Prevention and Treatment of Oral Ulcer

Objective: This paper aims to investigate the therapeutic effect of the combination of Emilia Sonchifolia and Coptidis Rhizoma on oral ulcer rats. Methods: 36 SD rats of half male and half female were kept for 7 days, and 6 rats among them were selected as normal group by random sampling method, and the rest rats were randomly divided into model group, positive control group, Emilia Sonchifolia group, Coptidis Rhizoma group and combined group after the establishment of oral ulcer model. The normal group and model group were given blank film, the positive control group was given Guilin Watermelon Frost, and the Emilia Sonchifolia group, Coptidis Rhizoma group and combined group were given the corresponding oral film, which was administered to the ulcer for 7 days continuously, 2 times per day. The healing of oral ulcer was assessed at the end of the last day of administration, and the ulcer area was calculated on the 1st, 3rd, 5th and 7th days after successful modeling, and the serum levels of IL-2 and TNF-α in rats were detected by Emilia Sonchifolia. Results: The grading of ulcer healing in the positive control group and the combined group was better than the other groups, and the difference was statistically significant when compared with the model group (p Coptidis Rhizoma group, Emilia Sonchifolia group, combined group and positive control group was smaller than that in the model group, and the difference was statistically significant (p Emilia Sonchifolia group, Coptidis Rhizoma group and combined group were all effective in reducing the area of oral ulcer, among which the combined group was more effective. The level of pro-inflammatory factor TNF-α was reduced and the level of anti-inflammatory factor IL-2 was increased in the Emilia Sonchifolia group, Coptidis Rhizoma group and combined group, and the difference was statistically significant (p Conclusion: The combination of Coptidis Rhizoma and Emilia Sonchifolia is effective in the treatment of oral ulcer in rats, and the effect of the combination is better than that of the drug alone.

Effects of Cinnamon Granules on Pharmacokinetics of Berberine in Rhizoma Coptidis Granules in Healthy Male Volunteers

The effects of Cinnamon granules on pharmacokinetics of berberine in Rhizoma Coptidis granules in healthy male volunteers,and the compatibility mechanism of Jiao-Tai-Wan（JTW） composed of Rhizoma Coptidis granules and Cinnamon granules were investigated.The concentration of berberine in plasma of healthy male volunteers was determined directly by high performance liquid chromatogra-phy（HPLC） after an oral administration of Rhizoma Coptidis granules alone or combined with Cinnamon granules（JTW）.The plasma concentration-time curves of berberine were plotted.The data were analyzed with Drug and Statistics（DAS） 2.0 pharmacokinetic program（Chinese Pharmacology Society） to obtain the main pharmacokinetic parameters.The results showed that the plasma concentration-time curve of berberine was described by a two-compartment model.The Cmax,Tmax,t1/2 and CLz/F of berberine in Rhizoma Coptidis granules were 360.883 μg/L,2.0 h,3.882 h,119.320 L.h-1.kg-1 respectively,and those of berberine in JTW were 396.124 μg/L,1.5 h,4.727 h,57.709 L.h-1.kg-1 respectively.It was suggested that Rhizoma Coptidis granules combined with Cinnamon granules could increase the plasma concentration of berberine,promote berberine absorption and lengthen the detention time of berberine in healthy male volunteers.

Active Ingredients and Mechanism of Action of Rhizoma Coptidis against Type 2 Diabetes Based on Network-Pharmacology and Bioinformatics

A pharmacological network of"component/target/pathway"for Rhizoma coptidis against type 2 diabetes(T2D)was established by network-pharmacology,and the active components of Rhizoma coptidis and its mechanism were explored.A literature-based and database study of the components of Rhizoma coptidis was carried out and screened by ADME paramcters.The targets of Rhizoma coptidis were predicted by the ligand similarity method.Related pathways were analyzed with databases,and software was used to construct a "component/target path" network.The mechanism was further confirmed by GEO database with R software.A total of 12 active components were screened from Rhizoma coptidis,involving 57 targets including MAPKI,STAT3,INSR,and 38 signaling pathways were associated with T2D.Related signaling pathways included essential pathways for T2D such as insulin resistance,and pathways that had indirect effect on T2D.It was suggested that Rhizoma coptidis may exert its effects against T2D through multi-component,multi-target,and multi-pathway forms.

Rapid and simultaneous determination of moisture and berberine content in Coptidis Rhizoma and Phellodendri Chinensis Cortex by near-infrared spectroscopy and chemometrics

Coptidis Rhizoma(Chinese:Huanglian)and Phellodendri Chinensis Cortex(Chinese:Huangbo)are widely used Traditional Chinese Medicine,and often used in combination because of their similar pharmacological effects in clinical practice.However,the quality control methods of the two drugs are different and complicated,which is time consuming and laborious in practical application.In this paper,rapid and simultaneous determination of moisture and berberine in Coptidis Rhizoma(CR)and Phellodendri Chinensis Cortex(PC)was realized by near-infrared spectroscopy(NIRs)combined with global models.Competitive adaptive reweighted sampling(CARS)and successive projection algorithm(SPA)method were applied for variable selection.Principal component analysis(PCA)and partial least squares regression method(PLSR)were applied for qualitative and quantitative analysis,respectively.The characteristic variables of berberine showed similarity and consistency in distribution,providing basis for the global models.For moisture content,the global model had relative standard error of prediction set(RSEP)value of 3.04%and 2.53%for CR and PC,respectively.For berberine content,the global model had RSEP value of 5.41%and 3.97%for CR and PC,respectively.These results indicated the global models based on CARS-PLS method achieved satisfactory prediction for moisture and berberine content,improving the determination e±ciency.Furthermore,the greater range and larger number of samples enhanced the reliance of the global model.The NIRs combined with global models could be a powerful tool for quality control of CR and PC.

Qualitative and Quantitative Analysis for the Quality Control of Rhizoma Coptidis by HPLC-DAD and HPLC-ESI-MS

For quality control purpose, an approach of fingerprinting and simultaneous quantification of five major bioactive constituents of Rhizoma Coptidis was established via a high-performance liquid chromatograph coupled with a photodiode array UV detector（HPLC-DAD） and an electrospray ionization mass spectrometer（HPLC-ESI/MS） The compounds were identified on the basis of the comparison of their mass spectra with literature data and those of standard samples and quantified by the HPLC-DAD method. Baseline separation was achieved on an XTerra C18 column（5 μm, 250 mm×4.6 mm i. d.） with linear gradient elution of formate buffer（consisting of 0.5% formic acid, adjusted to pH=4.5 with ammonia） and acetonitrile（consisting of 0.2% formic acid and 0.2% triethylamine）. The me- thod was validated for linearity（r^2〉0.9995）, repeatability（RSD〈3.1%）, intra- and inter-day precision（RSD〈1.8%） with recovery（99.9%-105.1%）, limits of detection（0.15-0.35 μg/mL）, and limits of quantification（0.53-0.82 μg/mL）. The similarities of 32 batches of Rhizoma Coptidis and their classification according to their manufacturers were based on the retention time and peak areas of the characteristic compounds. The five compounds were selected for quality assessment ofRhizoma coptidis via partial least squares analysis（PLS）.

Network pharmacology-based analysis of effective components and mechanism of Rhizoma coptidis in treating diabetes

Objective:To identify the active ingredients,potential targets,and mechanism of Rhizoma coptidis by bioinformatics method,and to explore the hypoglycemic effect of Rhizoma coptidis by in vitro experiments.Methods:The chemical components of Rhizoma coptidis were collected through database search,and oral bioavailability and drug-likeness were used for preliminary screening.The targets of Rhizoma coptidis and diabetes-related targets were collected by database retrieval and reverse docking techniques,and the biological process of cross-set proteins was analyzed.The inhibitory effects of Rhizoma coptidis onα-glucosidase,α-amylase activity,and advanced glycation end products(AGEs)were determined via in vitro experiments.In addition,the effects of Rhizoma coptidis on preadipocyte differentiation,absorption of glucose by adipocytes,and the level of intracellular triglyceride were investigated using the adipocyte differentiation model.Results:There were 11 potentially active ingredients in Rhizoma coptidis.IL-6,caspase-3,epidermal growth factor receptor(EGFR),MYC,and estrogen receptor 1 were considered as the key genes.The bioinformatics analysis showed that Rhizoma coptidis played an antidiabetic role mainly via biological processes and signaling pathways including hormone receptor activity,glutathione binding,steroid binding,etc.In vitro experiments showed that the extract of Rhizoma coptidis inhibited the activities ofα-glucosidase andα-amylase,and the generation of AGEs;meanwhile,the extract promoted the absorption of glucose by adipocytes.In addition,the extract of Rhizoma coptidis decreased triglyceride level.Conclusions:Our network pharmacology and in vitro experiments demonstrate the anti-diabetic effects and possible underlying mechanisms of Rhizoma coptidis extract.

Associated Bacteriostasis Research of Coptidis Rhizoma-Folium Isatidis and Coptidis Rhizoma-Flos Poprli against Escherichia coli O2

[Objective] The paper was to explore the combined inhibitory effect of rhizoma coptidis-folium isatidis and rhizoma coptidis-flos poprli against Escherichia coli O2.[Method] Contrast test of single and associated bacteriostasis against known serotype E. coli O2 was conducted using microcheckerboard method.[Result] The MIC of rhizoma coptidis, folium isatidis and flos poprli were 1/8 extracting liquid, 1/8 extracting liquid and 1/2 extracting liquid, respectively. When combined with folium isatidis or flos poprli, the MIC of rhizoma coptidis was 1/8 extracting liq-uid or 1/16 extracting liquid compared with single use. When combined with rhizoma coptidis, the MIC of folium isatidis and flos poprli were 1/8 extracting liquid and 1/16 extracting liquid.[Conclusion] When rhizoma coptidis was combined with folium isatidis or flos poprli, the FIC values were 2 and 0.625, performing independent action and additive effect, respectively.

Main alkaloids of Rhizoma Coptidis improved palmitic acidinduced insulin resistance in HepG2 cells via AMPK and MAPK signaling pathway

Rhizoma Coptidis,a traditional Chinese herbal medicine,has been used for treating diabetes for thousands of years.However,the molecular basis for this action has not been elucidated.In the present study,the effects of seven main alkaloids of Rhizoma Coptidis on glycometabolism were investigated and the related molecular mechanism of five active compounds on insulin resistant(IR)cell model was explored for the first time.Results showed that berberine,palmatine,epiberberine,columbamine and groenlandicine enhanced glucose consumption in the palmitic acid(PA)-induced IR-HepG2 cells,indicating that these compounds could improve IR.In addition,we found that among these active alkaloids,berberine,columbamine,epiberberine and groenlandicine could inhibit the activation of ERK and p38 pathway,while berberine,columbamine,palmatine and epiberberine could activate AMPK pathway.Moreover,palmatine and columbamine regulated the mRNA expression of GLUT2 to ameliorate IR via activating AMPK and inactivating p38 MAPK signal pathway.To sum up,berberine,columbamine,palmatine,epiberberine and groenlandicine might be the active reagents,which contribute to the glucose lowering effects of Rhizoma Coptidis.

Summary of Professor Tong Xiaolin's clinical experience of applying Rhizoma Coptidis(Huang Lian)

With the advantages of less toxicity and side effects, traditional Chinese medicine(TCM) is showing a bright future with a good clinical practice. Chinese herbal medicine, which usually contains various active ingredients, could provide multiple therapeutic effects. Professor Tong Xiaolin has accumulated abundant experience during many years of clinical practice and applies Rhizoma Coptidis(RC) well with the treatment of diabetes and its complications. Rhizoma coptidis is a classical natural herb which is used frequently by professor Tong Xiaolin. In this review, we summarize Tong Xiaolin's clinical experience of applying Rhizoma Coptidis(Huang Lian) in the treatment of disease from two aspects as well as introducing some traditional Chinese medical theory and clinical experience, with a prospect of guiding clinician to use RC more suitably and reasonably.

A review on pharmacological effects of Rhizoma Coptidis(Huang lian)

Huang Lian(Rhizoma coptidis, RC), which has effects on clearing damp-heat, quenching fie, and counteracting poison, is a herb frequently used in many traditional formulas. At present, there are many researches on the pharmacological effects of RC. In this review, we summarize the research progress on pharmacological effects of RC from four main aspects, in order to guide clinical application and explore the prospects of the application of RC.

三黄膏质量标准提升研究

目的:提升三黄膏的质量标准。方法:制备三黄膏,进行性状观察和粒度检查,采用薄层色谱法对该制剂中的黄连药材进行定性鉴别,采用高效液相色谱法测定该制剂中的小檗碱、表小檗碱、黄连碱、巴马汀含量并规定其总含量限度。结果:本研究所制得的三黄膏为黄色至棕黄色的软膏;粒度检查符合相关规定;建立的薄层色谱法专属性强,可准确鉴别黄连药材;小檗碱、表小檗碱、黄连碱、巴马汀的平均总含量为4.01 mg/g,其含量限度不得少于3.21 mg/g。结论:本研究建立的三黄膏质量标准稳定、可行,可有效控制该制剂的质量。

黄连防治鸭病毒性肠炎机制的网络药理学分析及动物试验验证

旨在探讨黄连防治鸭病毒性肠炎(duck viral enteritis,DVE)的作用机制,本研究首先应用中药系统药理学分析平台(Traditional Chinese Medicine System Pharmacology Analysis Platform,TCMSP)筛选黄连活性成分及作用靶点,GeneCards数据库分析DVE相关靶点,Venny和Cytoscape3.7.2软件绘制黄连与DVE交集靶点及构建“药物-成分-疾病-靶点”网络,利用STRING数据库建立蛋白相互作用网络(protein interaction network,PPI),借助DAVID数据库进行靶点GO功能富集分析和KEGG通路富集分析,然后分正常对照组、病毒感染组和黄连防治组进行动物干预试验,采集组织样本进行病理组织学观察和相关细胞因子测定,结果表明:筛选出黄连14个活性成分和212个作用靶点,其中,与DVE交集的靶点25个,涉及RNA聚合酶Ⅱ启动子转录、序列特异性DNA结合转录因子活性、免疫应答、炎症反应和细胞凋亡等生物学过程,富集在Toll样受体信号通路、炎症性肠病、细胞因子-细胞因子受体相互作用、单纯疱疹病毒感染等信号通路,核心靶点是IL-6、IL-10和STAT1;病毒感染组鸭肝、脾和十二指肠发生不同程度的病理损伤,且这些组织中IL-6含量较正常对照组鸭显著提升(P≤0.05),IL-10和STAT1含量显著降低(P≤0.05),而黄连防治组鸭肝、脾和十二指肠组织病理损伤明显减轻,IL-6、IL-10和SYAT1含量趋于正常水平。由此可见,黄连能有效缓解鸭病毒性肠炎所致的鸭机体组织病理损伤,其作用机制涉及到多种炎症反应信号通路。

基于卵巢细胞外基质探索黄连对PCOS小鼠的治疗作用

目的:基于卵巢细胞外基质研究黄连对多囊卵巢综合征(PCOS)小鼠的治疗作用。方法:选取6只C57BL/6小鼠作为对照组(Control组)。选取24只C57BL/6小鼠皮下注射21 d脱氢表雄酮(DHEA)构建PCOS模型,其中6只作为模型组(PCOS组),其余18只分别使用NaCl(PCOS+NaCl组)、200 g·kg^(-1)·d^(-1)黄连活性成分(PCOS+RC200组)以及400 g·kg^(-1)·d^(-1)黄连活性成分(PCOS+RC400组)进行灌胃处理28 d。Western blot法检测各组小鼠卵巢细胞外基质重塑相关蛋白MMP-2、COL-I及LOX-1表达水平。使用KGN细胞过表达和敲低YTHDF2,分为PC3.1组、PC3.1-YTHDF2组、NC组和SiYTHDF2组。Western blot法检测MMP-2蛋白表达水平。结果:与Control组相比,PCOS组卵巢中MMP-2、COL-I及LOX-1蛋白表达水平均显著升高(P<0.05)。与PCOS+NaCl组相比,PCOS+RC200组和PCOS+RC400组卵巢中MMP-2、COL-I及LOX-1蛋白表达水平均显著降低(P<0.05)。与PC3.1组相比,PC3.1-YTHDF2组MMP-2、COL-I及LOX-1的表达水平显著升高(P<0.05)。与NC组相比,siYTHDF2组MMP-2和COL-I的表达水平显著下降(P<0.05)。结论:黄连可能通过调节MMP-2、COL-I及LOX-1改善PCOS卵巢细胞外基质重塑状态,从而影响排卵。YTHDF2可影响KGN细胞中MMP-2、COL-I及LOX-1的表达水平,可能为黄连治疗PCOS的靶点之一。

小檗碱调节糖脂代谢作用机制研究进展

随着生活质量的提高,糖脂代谢紊乱导致的疾病如糖尿病、高脂血症、肥胖症、胰岛素抵抗、脂肪肝等的发生率逐年上升。中药黄连在治疗糖脂代谢紊乱相关疾病方面有着显著疗效。小檗碱为黄连中含量最高、代表性最强的活性成分,属异喹啉类生物碱,能通过保护胰岛β细胞,改善胰岛素抵抗、调节胰岛素分泌、促进胰高血糖素样肽1(GLP-1)分泌、调节肠道菌群调节糖代谢,通过减少脂质沉积、促进脂质清除等调节脂代谢,还可通过AMPK通路、肠道菌群等共同调节糖脂代谢。其来源广泛、作用安全,在防治糖脂代谢紊乱导致的相关疾病中有着多通路、多效应的优势。该文归纳总结国内外相关文献,对小檗碱调节糖脂代谢作用机制进行综述,以期为中医药改善糖脂代谢紊乱提供一定的思路和理论依据。

基于基于“心合小肠”理论的黄连治疗高脂血症理论依据研究

目的 探讨黄连治疗高脂血症的理论依据。方法 通过梳理“心合小肠”理论与高脂血症病因病机的联系,结合黄连对胃肠道微生态影响的研究进展,探讨黄连治疗高脂血症的理论依据。结果 高脂血症的中医病因病机主要为饮食不节,久坐少动,致使脾失健运,肝失疏泄,水聚痰饮,痰浊不化,痰瘀结聚,变生脂膏。心合小肠功能相互匹配的失常,会导致身体内的“清浊”物质无法正常运转,导致清者不得上升,生飧泄之症,而浊者不能肃降,产生痰饮、水湿、浊毒等病理性物质,稽留不去,久之则产生脂质膏浊。黄连可清心燥湿,升清降浊,是从“心合小肠”理论治疗高脂血症的经典药物。黄连素降脂疗效显著,可改善脂质代谢,且无明显副作用,而肠道菌群是介导黄连素降脂作用的重要条件。结论 基于“心合小肠”理论,靶标小肠生理病理特征和肠道菌群代谢特点,可能是继续探究黄连治疗高脂血症具体机制的重要方向。

基于网络药理学探讨清肾颗粒主要药物治疗慢性肾脏病作用机制

目的基于网络药理学探讨清肾颗粒主要药物大黄、黄连、白花蛇舌草、丹参治疗慢性肾脏病(CKD)的作用机制。方法利用TCMSP及SwissTargetPrediction数据库分别检索4味中药活性成分及其靶点,运用OMIM、GeneCards、TTD数据库获取疾病靶点,通过STRING数据库筛选核心靶点,并进行GO功能与KEGG通路富集分析,利用Cytoscape3.7.2软件构建蛋白相互作用网络。结果共筛选出中药活性成分99种,药物靶点873个,活性成分治疗CKD交集靶点102个,主要活性成分包括槲皮素、木犀草素、丹参醇A等。核心靶点涉及VEGFA、EGFR、AKT1等。GO功能分析结果显示,VEGFA、EGFR、SRC等靶点参与CKD的治疗,KEGG通路富集分析结果显示,大黄、黄连、白花蛇舌草、丹参治疗CKD主要涉及HIF-1、PI3K-Akt、Rap1、MAPK等信号通路。结论大黄、黄连、白花蛇舌草、丹参可能通过HIF-1、PI3K-Akt等信号通路,调控VEGFA、EGFR、SRC等靶点治疗CKD。

黄连及其配伍在消渴病中的应用

黄连味苦性寒,善泄善燥,是消渴病治疗中应用颇广的传统中药之一。现代研究表明黄连的主要成分小檗碱可通过多条细胞信号通路发挥作用,提高糖尿病患者胰岛β细胞抗氧化应激能力,改善胰岛功能,提高胰岛素敏感性,降低患者血糖及糖化血红蛋白水平,并且可减少血管内皮损伤,降低糖尿病血管并发症的风险。黄连单药使用即可对消渴病起到良好的治疗效果,与木香、葛根、人参、天花粉、黄芩、知母等相伍成药对,既可增强临床效果,又可防其苦寒败胃。黄连复方葛根芩连汤、大黄黄连泻心汤、黄连解毒汤、半夏泻心汤、黄连温胆汤、小陷胸汤则可通过多靶点、多途径、多环节发挥作用,达到降糖减脂、改善患者临床症状的效果。总之黄连及其配伍可通过抑制糖异生、调节肠道菌群结构、改善胰岛功能、降低胰岛素抵抗等多重途径,标本兼治,实现降糖降脂、延缓糖尿病进展之功效。对黄连单药及其药对、复方在消渴病治疗中的应用作以叙述,以期为消渴病的临床治疗提供思路。

黄连的化学成分及药理作用研究进展

黄连是毛茛科植物黄连、三叶黄连及云连的干燥根茎,临床广泛使用。近年来国内外研究者对黄连的化学成分及药理作用不断深入探索,黄连的临床应用更加丰富。黄连的化学成分包括生物碱、黄酮、木脂素、有机酸、挥发油等,具有抗动脉粥样硬化、抗心肌缺血、抗脑缺血、抗心律失常、降血压、抗焦虑抗抑郁、降血糖、抗炎、抗肿瘤、抑菌等药理作用。本文对黄连的化学成分及其药理作用研究进展进行综述,以期为未来黄连的研究提供依据。

黄连生物碱超声辅助低共熔溶剂提取工艺优化

目的优化黄连生物碱超声辅助低共熔溶剂提取工艺。方法以葡萄糖-乳酸(1∶5)为低共熔溶剂。在单因素试验基础上,以提取时间、含水量、液料比为影响因素,生物碱得率为评价指标,Box-Behnken响应面法优化提取工艺。结果最佳条件为提取时间35 min,含水量26%,液料比33∶1,生物碱得率为7.22%。结论该方法稳定可靠,切实可行,可为黄连开发利用提供参考。

基于“阴阳交感”及临床药理探讨“黄连-肉桂”对失眠的治疗

药物配伍是中医的魂之所在,用药如用兵,善用方者,必善药之配伍,执简驭繁。失眠皆因阳盛阴衰,阴阳失交所致,而临床上心肾不交型失眠尤为多见。黄连,味苦性寒,有泻火之功,当属阴药;肉桂,味辛甘、性大热,有补火助阳、引火归元之功,当属阳药。“黄连-肉桂”配伍,交通心肾阴阳二气,可治阴阳失调、心肾不交所致失眠之症。“黄连-肉桂”联用效果更显著,一种可能是由于两药联用后会使有效成分的溶出率更高,还有一种可能是会增多或抑制相关蛋白的表达。通过探讨“黄连-肉桂”所体现的阴阳交感的中医思想,不仅可以为治疗阴阳失调提供新的思路,也可以通过现代药理研究预测出治疗失眠的新机制,并通过实验进行药效验证,为中西医结合治疗失眠打开新思路。