Modulation of gut microbiota by berberine and decocted Coptis chinensis Franch.in a high-fat diet-induced metabolic syndrome rat model

Objective:To investigate the effect of decocted Coptis chinensis Franch.(Huanglian Jianji,黄连煎剂,HLJJ) and berbenne on the gut microbiota of the rats with metabolic syndrome (MS) induced by high-fat diet (HFD).Methods:Sixty Sprague Dawley rats were randomly divided into normal diet (ND) group (n =15)and HFD group (n =45).After 8 weeks of feeding,the HFD group was further divided into three groups:a group provided with a combination of HLJJ and HFD for 4 weeks,a group provided with a combination of berberine and HFD for 4 weeks,and a group supplied only with HFD for 4 consecutive weeks.Epididymal fat weight,serum high-density lipoproteincholesterohC (HDL-C),lowdensity lipoproteincholesterol-C (LDL-C) and irisin levels were measured.In addition,the V3-V4 region of the cecum microbiota 16S rRNA gene amplicon was sequenced on the Illumina MiSeq platform.Results:MS was successfully induced in the rats with HFD for 8 weeks.After 12 weeks,serum irisin levels in the HFD + berberine group were significantly increased compared with those in the HFD group (P <.05).The high-quality tags were delineated into 1149 operational taxonomic units at a 97% similarity level.Furthermore,at the genus level,Akkermansia muciniphila (A.muciniphila),Bacteroides,and Ruminococcus were markedly increased,whereas Candidatus arthromitus,Prevotella,Phascolarctobacterium were in great decrease in the HLJJ group and the berberine group,compared with the HFD group.The abundance of A.muciniphila,Ruminococcus gnavus and Bacteroides was significantly higher in the berberine group,whereas,the abundance of Oscillospira was lower in the berberine group,compared with the HLJJ group.Conclusion:HLJJ and berberine changed the gut microbiota in rats with MS.The mechanism underlying the treatments of berberine and HLJJ on HFD-induced MS is partly different.

Structural and Histochemical Features of the Slow-Growing Perennial Coptis chinensis Franch.(Ranunculaceae)

Huanglian(Coptis chinensis Franch.)is a slow-growing perennial medicinal herb with considerable economic value.This study aimed to determine the structural characteristics and the levels of berberine deposits in the organs and tissues of Huanglian using light and epifluorescence microscopy.The adventitious roots are composed of primary and secondary structures with endodermis,exodermis,and phellem.The rhizome structures are composed of primary and secondary structures with cuticle and phellem.The leaves are composed of sclerenchymatous rings,isolateral mesophyll,and thin cuticles.We detected berberine in the xylem walls of the roots and rhizomes as well as in the sclerenchymatous rings of the petioles.We postulate that as the exodermis is developed,the deposition of berberine in the xylem closest to the root tips may affect water and nutrient absorption and transfer.Leaf blades had a thin cuticle and isolateral mesophyll,suggesting shade tolerance.These structural and histochemical features suggest that Huanglian is adapted to the slow growing nature of a shady environment.

Determination of coptis chinensis’ quality by FT-NIR spectroscopy

As a kind of traditional Chinese medicinal materials coptis chinensis has a lot of medicinal value and closely related to human health, Widely used in clinical or disease prevention and treatment. So the quality of medicinal coptis chinensis rapid determination is very important. Calibration model for determination of Coptis chinensis’ quality was built by partial least squares and near infrared spectroscopy, and the method of spectral pretreatment was discussed. Berberine and moisture content were used as evaluation index of Coptis chinensis’ quality according to traditional Chinese medicine standard in this experiment. The first derivative and vector normalization were adopted for the spectral preprocessing. The performance of the final model was evaluated according to root mean squares error of cross-validation (RMSECV), root mean square error of prediction (RMSEP) and correlation coefficient (R). According to the model of calibration set, the R values were 0.9298 and 0.8898, RMSECV were 0.239% and 0.302%. The R values of prediction set were 0.9347 and 0.9146, RMSEP were 0.104% and 0.330%, and prediction results were accurate and reliable. This method could be applied in rapid analysis of Coptis chinensis. The method was suitable for production fields and research fields, and had a wide application prospect.

Advance of Studies on Anti-atherosclerosis Mechanism of Berberine

Coptis Chinensis is a traditional Chinese medicine herb that has the effect of clearing heat and drying dampness,purging fire to eliminate toxin.Berberine is the main alkaloid of Coptis Chinensis,and recent researches showed that berberine had the effect of anti-atherosclerosis.This paper reviewed the anti-atherosclerosis mechanism of berberine,which may be related to regulating lipids,anti-inflammation, decompression,reducing blood sugar,and inhibiting vascular smooth muscle cell proliferation.

Biological properties and clinical applications of berberine

Berberine,an isoquinoline alkaloid isolated from the Chinese herb Coptis chinens is and other Berber is plants,has a wide range of pharmacological properties.Berberine can be used to treat many diseases,such as cancer and digestive,metabolic,cardiovascular,and neurological diseases.Berberine has protective capacities in digestive diseases.It can inhibit toxins and bacteria,including Helicobac terpylo riprotect the intestinal epithelial barrier from injury,and ameliorate liver injury.Berberine also inhibits the proliferation of various types of cancer cells and impedes invasion and metastasis.Recent evidence has confirmed that berberine improves the efficacy and safety of chemoradiotherapies.In addition,berberine regulates glycometabolism and lipid metabolism,improves energy expenditure,reduces body weight,and alleviates nonalcoholic fatty liver disease.Berberine also improves cardiovascular hemodynamics,suppresses ischemic arrhythmias,attenuates the development of atherosclerosis,and reduces hypertension.Berberine shows potent neuroprotective effects,including antioxidative,antiapoptotic,and anti-ischemic.Furthermore,berberine exerts protective effects against other diseases.The mechanisms of its functions have been extensively explored,but much remains to be clarified.This article summarizes the main pharmacological actions of berberine and its mechanisms in cancer and digestive,metabolic,cardiovascular,and neurological diseases.

黄连中生物碱类成分抗溃疡性结肠炎的作用机制研究进展

黄连是一味常用中药,具有清热燥湿,泻火解毒等功效,其中的主要活性成分为小檗碱、药根碱、黄连碱、表小檗碱等生物碱。现代药理学研究表明,黄连具有抗菌、抗氧化、免疫调节等药理作用,广泛用于治疗细菌性痢疾、胃炎、溃疡性结肠炎等胃肠道疾病。近年来,含黄连的复方、黄连及其中的生物碱类成分在溃疡性结肠炎的治疗中取得一定进展。基于此,主要从抑制炎症反应、调节免疫失衡、肠道菌群-宿主互作调控以及维持肠黏膜屏障功能角度,系统分析和归纳黄连及其生物碱类成分的抗溃疡性结肠炎机制,从而为黄连及溃疡性结肠炎治疗药物的开发提供参考。

基于网络药理学探究黄连调控巨噬细胞干预动脉粥样硬化斑块稳定性的潜在机制

目的探究黄连调控巨噬细胞干预动脉粥样硬化斑块稳定性的潜在机制。方法对GEO数据库中的动脉斑块相关数据集进行差异分析得到巨噬细胞干预动脉粥样硬化斑块相关基因。从TCMSP数据库获取黄连的有效成分和潜在靶点。对两者取交集后找出发挥作用的化学成分和潜在靶点。对潜在靶点进行蛋白质-蛋白质相互作用(PPI)、基因本体(GO)、京都基因与基因组百科全书(KEGG)分析,探究黄连调控巨噬细胞干预动脉粥样硬化斑块稳定性的作用机制。结果稳定斑块组和破裂斑块组差异分析共找到892个差异基因。通过TCMSP共找出黄连中的11个化学成分,251个靶点。两者取交集后得到16个黄连调控巨噬细胞的潜在靶点。PPI结果显示,DPP4、TNFAIP6、IL6ST、POR、RUNX1T1、HMOX1、CAV1等16个交集基因之间有较强的相互作用关系,且DPP4、HMOX1、CAV1和VCAM1处于PPI网络的枢纽位置。GO结果表明,生物学过程(BP)与对脂多糖的反应、对细菌来源分子的反应、对T细胞激活的正向调节等有关。细胞组成(CC)与膜筏、膜微区、膜区等细胞器有关。分子功能(MF)参与肽酶活化剂活性、趋化因子活性等分子功能的调节。KEGG结果与流体剪切应力及动脉粥样硬化、NF-kappa B信号传导途径有关。结论黄连内槲皮素可能通过调节DPP4、HMOX1、CAV1等靶点影响斑块内巨噬细胞的信号传导途径,进而干预斑块稳定性。

氮、磷、钾对黄连植株生长、小檗碱含量的影响

氮、磷、钾缺乏都大大影响黄连植株的正常生长，叶片硝酸还原酶的活性和根茎小檗碱的含量都很低。尤其是缺氮植株生长最差，死苗也多；缺磷、缺钾植株长新叶少而小，缺钾植株新根生长少且易衰老。

不同栽培条件黄连的质量分析与评价

目的建立黄连药材HPLC指纹图谱分析方法及含量测定方法,比较分析不同栽培条件、不同产地和不同炮制方法制备的黄连药材的质量。方法采用HPLC-UV方法建立了黄连药材指纹图谱,应用HPLC-MS联用技术指认了主要色谱峰;并对黄连药材中的小檗碱、巴马汀和药根碱进行含量测定。结果指认了黄连药材指纹图谱中7个主要的色谱峰,含量测定结果表明不同的栽培条件中,遮荫条件、生长年限对黄连中小檗碱、巴马汀和药根碱的含量影响较大,而种植密度的影响不是很明显;现代生态技术栽培的黄连中这3种生物碱的含量均高于对照药材或与之基本相当。不同产地的黄连中这3种生物碱的含量差别较大。应用不同炮制方法制备的黄连中这3种生物碱的含量差别不明显。结论现代生态栽培技术替代传统人工搭棚方式栽培黄连是可行的,同时为科学炮制黄连提供依据。

利川黄连小檗碱含量

目的分析利川黄连中小檗碱含量,以确定利川黄连的最佳栽培方案。方法利用高效液相色谱(HPLC)方法测定不同海拔高度,不同株龄及不同叶片形态的利川黄连小檗碱含量。结果黄连根茎中的小檗碱含量不受株龄的影响;低海拔地区比较适宜黄连小檗碱的合成;冷杉林遮光不影响小檗碱的合成;大花叶和小花叶品种相对较有光叶和无光叶植株根茎中小檗碱含量高,但无统计学差异。结论小檗碱的合成与遮荫条件密切相关,如果在第2～3年降低遮荫率或拆除遮荫棚以促进黄连根茎快速肥大,在采收前1年再通过遮光处理促进小檗碱的合成,可能会获得小檗碱含量更高的优质黄连。

黄连生物碱的HPLC-MS分析

目的:利用高效液相色谱-质谱法,对黄连药材中的化学成分进行定性研究并对主要成分进行定量研究。方法:采用Waters Symmetry C18(3.9 mm×150 mm,5μm)色谱柱;流动相为乙腈和0.05%甲酸水梯度洗脱;检测波长345 nm;流速为0.8 mL/min;柱温35℃;正离子检测模式;电喷雾离子化(ESI)。结果:鉴定了8个成分分别为木兰花碱、格陵兰黄连碱、黄连碱、表小檗碱、非洲防己碱、药根碱、小檗碱和巴马汀;同时对小檗碱、药根碱、黄连碱和巴马汀进行了含量测定。结论:该方法简便、准确,可用于黄连药材的质量评价。

黄连药材不同部位、不同生长年限和不同海拔高度红外光谱法整体分析与评价

目的研究不同部位、不同生长年限和不同海拔高度黄连药材红外光谱的“指纹特征”以及盐酸小檗碱在黄连样品中含量的整体变化规律。方法借助于傅里叶变换红外光谱技术快速、非分离检测黄连样品不同部位、不同生长年限和不同海拔高度的红外光谱。结果黄连根茎、叶柄和须根的红外光谱图均具有明显的“指纹特征”,盐酸小檗碱的含量趋势为根茎>叶柄>须根;随着生长年限的增加黄连叶柄中盐酸小檗碱的含量随之增加,在海拔1200m种植时,黄连叶柄中盐酸小檗碱的含量低于海拔为1300、1400、1500m高度的含量;海拔高度、生长年限对黄连根茎中盐酸小檗碱的含量无影响。结论红外光谱技术能够较准确的把握黄连药材的整体质量,为规范种植黄连药材提供了一种检测方法。

黄连提取工艺的研究

根据黄连中主要有效成分生物碱易溶于热水的性质，采用正交设计筛选出黄连水提取的最佳工艺条件，并分别以回流提取、连续回流提取方式，比较水和50％乙醇作溶剂的提取效果，结果显示二者基本相同。表明黄连水提取是完全可行的。

加速溶剂萃取法快速提取黄连中的生物碱

探讨了快速溶剂萃取法(ASE)提取黄连中生物碱的可行性,并比较了该方法与回流提取法和超声提取法的优越性。以黄连中盐酸小檗碱的提取率为指标,以高效液相色谱法(HPLC)为检测方法,用正交实验对快速溶剂萃取法从黄连中提取盐酸小檗碱的工作条件进行优化。最佳仪器参数:提取溶剂为80%乙醇+0.5%HCl,提取温度为130℃,静态提取时间为10 min,提取次数为1次。快速溶剂萃取法可作为黄连中生物碱分析测定的前处理方法。

不同用量的吴茱萸炮制黄连后成分的比较

目的 考察不同用量的吴茱萸炮制黄连对小檗碱的影响以及萸黄连中吸收吴茱萸成分的情况。方法 以小檗碱、吴茱萸碱、吴茱萸次碱为指标 ,采用高效液相色谱法测定黄连 ,吴茱萸 ,10 %,2 0 %,30 %,40 %,5 0 %萸黄连中的成分含量。结果 黄连用吴茱萸炮制后小檗碱的含量减少 ,2 0 %,30 %萸黄连中小檗碱的含量较高 ;萸黄连中确实吸收了吴茱萸中的成分。结论 吴茱萸炮制黄连的用量以 2 0 %为宜。

黄连多糖抑菌活性初探

目的探讨黄连多糖对大肠杆菌和金黄色葡萄球菌的抑制作用。方法用扩散法研究黄连多糖对大肠杆菌和金黄色葡萄球菌的抑制作用,并选用黄连水提液和盐酸小檗碱作为对照。结果黄连水提液和小檗碱对菌体均有抑菌效果,黄连水提液的抑菌效果尤为明显;黄连多糖没有抑菌作用。结论黄连多糖在体外条件下,不具有对大肠杆菌和金黄色葡萄球菌的抑制作用。

不同品系黄连产量和质量的研究

目的考察和比较湖北黄连GAP基地选育的3个不同品系黄连(大花叶、无光叶、小花叶)的产量和质量。方法采用田间随机区组设计,连续3年采集3个品系黄连根茎样品,分别以烘干法测定其质量,用紫外分光光度法和高压液相色谱法分别测定其总生物碱和盐酸小檗碱的量。结果在考察的3个品系药材样本中,各品系三年生黄连产量没有显著差异(P>0.05),在四年生和五年生黄连中,大花叶和无光叶品系产量均明显高于小花叶品系(P<0.05);在三年生、四年生、五年生黄连中,各品系总生物碱和盐酸小檗碱的量无明显差异(P>0.05)。结论大花叶和无光叶品系的黄连产量高、质量合格,可作为黄连规范化种植的种子基原。

不同炮制方法对黄连主成分含量及肠吸收的影响

目的:研究黄连不同炮制品水煎剂中主成分含量的变化,探讨不同炮制方法对黄连肠吸收的影响。方法:以小檗碱、巴马汀、药根碱为黄连的代表成分,运用HPLC法测定6种不同黄连炮制品水煎剂中代表成分的含量,采用外翻肠囊法,检测并计算各代表成分的吸收速率常数(Ka)、表观渗透系数(Papp)等,分析其在小肠中的吸收特征。结果:黄连不同炮制品中小檗碱、巴马汀和药根碱的含量明显不同,均以醋黄连最高,盐黄连最低,而Ka和Papp的排序与其含量排序有较大不同,以酒黄连最高,炒黄连最低。结论:不同炮制法不仅通过改变黄连药材的组分和含量,还可能通过影响其肠吸收,使其药性及功能主治发生变化。

不同氮素水平对黄连植株生长及根茎小檗碱含量的影响

目的：根据不同氮素营养水平对黄连生长的影响，寻找最佳氮素浓度。方法：采用砂培法。结果：低氮（１／５氮）能明显地减轻缺氮症状，但过高的氮浓度（２氮）也影响黄连新根的形成及地上部位叶的生长，叶片硝酸还原酶的活性及根茎中小檗碱的含量都较低，适合黄连生长，有效成分含量又高的氮浓度范围应该在１／２氮～１氮。结论：黄连根茎形成最高有效成分时所需的供氮水平较黄连植株旺盛生长所需求的氮水平低。

薄层色谱-荧光分光光度法测定黄连及香连丸中盐酸小檗碱的含量

目的建立黄连和香连丸中盐酸小檗碱的含量测定方法。方法样品经提取、薄层展开后,采用薄层色谱-荧光分光光度法对黄连和香连丸中盐酸小檗碱进行含量测定,展开剂为苯-乙酸乙酯-异丙醇-甲醇-氨水(6:3:1.5:1.5:0.5),激发波长Ex=365nm,发射波长Em=409nm。结果盐酸小檗碱在0.473～3.784μg范围内线性关系良好,r=0.9993。黄连的回收率为99.03%,RSD=1.86%。香连丸的回收率为97.10%,RSD=1.09%。结论该法操作简便,分离效果好,灵敏度高。