Insight into the Efficacy and Potential Mechanism of Fructus Aurantii on Skin Based on Network Pharmacology

[Objectives]This study was conducted to explore the mechanism and pharmacological activity of Fructus Aurantii on human skin through network pharmacology.[Methods]The active components and targets of Fructus Aurantii were screened byTCMSPand SymMap data-bases,and the targets were humanized after de-duplication by UniProt database.Relevant therapeutic targets were searched in Gencards data-base with"skin"as the key word,and those with higher weights were retained.An effective component-human skin action target network of Fructus Aurantii was established by Cytoscape software.Then,the topological analysis of protein-protein interaction(PPI)network was made by using String database and Cytoscape software.Gene Ontology(GO)funetional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were carried out by david database,and the analysis results were visualized by Hiplot soft-ware.[Results]Thirteen active compounds of Fructus Aurantii were obtained by screening,and 99 gene targets of Fructus Aurantii which might have pharmacological activity on human skin were obtained by intersection analysis.PTGS2,PTGS1,HSP90AB1,HSP90AAI,NCOA2 and PIK3CG might be core action targets of Fructus Aurantii on human skin according to the topological analysis of the active component-target network.The analysis of PPI network showed that IL-1β,INS,TNF,TP53 and ESR1 might be core action proteins of Fructus Auranti.GO enrichment analysis showed that Fructus Aurantii might balance the imbalance of skin microenvironment caused by various in-vitro stimuli by participating in biological processes such as response to xenobiotic stimulus and regulation of small molecule metabolic process.KEGG pathway enrichment analysis showed that the targets of Fructus Aurantii acting on human skin were enriched in pathways in cancer,Kaposi sarcoma-associated herpesvirus infection,pathways in measles,AGE-RAGE signaling pathway in diabetic complications,IL.-17 signaling pathway,etc.[Conclusions]Fructus Aurantii may act on human skin targets through a variety of active components,and play a regulatory role in skin-related diseases.

Essential oil extracted from Quzhou Aurantii Fructus prevents acute liver failure through inhibiting lipopolysaccharide-mediated inflammatory response

Quzhou Aurantii Fructus(QAF)has a long history as a folk medicine and food for the treatment of liver diseases.While our earlier study provided evidence of hepatoprotective properties contained within the flavonoids and limonins constituents in QAF,the potential preventative effects afforded by essential oil components present within QAF remains enigmatic.In this study,we prepared Quzhou Aurantii Fructus essential oil(QAFEO)and confirmed its anti-inflammatory effects on liver inflammation through experimentation on lipopolysaccharide and D-galactosamine(LPS/D-GalN)induced acute liver failure(ALF)mouse models.Using RNA-sequence(RNA-seq)analysis,we found that QAFEO prevented ALF by systematically blunting the pathways involved in response to LPS and toll-like receptor signaling pathways.QAFEO effectively suppressed the phosphorylation of tank-binding kinase 1(TBK1),TGF-beta activated kinase 1(TAK1),interferon regulatory factor 3(IRF3),and the activation of mitogen activated kinase-like protein(MAPK)and nuclear factor-kappa B(NF-κB)pathways in vivo and in vitro.Importantly,QAFEO substantially reduced myeloid differentiation primary response gene 88(MyD88)-toll-like receptor 4(TLR4)interaction levels.Moreover,8 compounds from QAFEO could directly bind to REAL,TAK1,MyD88,TBK1,and IRF3.Taken together,the results of our study support the notion that QAFEO exerts a hepatoprotective effect through inhibiting LPS-mediated inflammatory response.

Mechanism of aqueous fructus aurantii immaturus extracts in neuroplexus of cathartic colons

AIM: To examine the effect of aqueous fructus aurantii immaturus(FAI) extracts on the intestinal plexus of cathartic colons.METHODS: Cathartic colons were induced in rats with dahuang,a laxative used in traditional Chinese medicine. Once the model was established(after approximately 12 wk),rats were administered mosapride(1.54 mg/kg) or various doses of aqueous FAI extracts(1-4 g/kg) for 14 d. Transit function was assessed using an ink propulsion test. Rats were then sacrificed,and the ultramicrostructure of colonic tissue was examined using transmission electron microscopy. The expression of the 5-hydroxytryptamine receptor 4(5-HTR4) and neurofilament-H was assessed in colon tissues using real-time PCR,Western blot,and immunohistochemistry.RESULTS: Mosapride and high dose(4 g/kg) of aqueous FAI extracts significantly improved the bowel movement in cathartic colons compared to untreated model colons as measured by the intestinal transit rate(70.06 ± 7.25 and 72.02 ± 8.74,respectively,vs 64.12 ± 5.19; P < 0.05 for both). Compared to controls,the ultramicrostructure of cathartic colons showed signsof neural degeneration. Treatment with mosapride and aqueous FAI extracts resulted in recovery of ultrastructural pathology. Treatment with mosapride alone upregulated the gene and protein expression of 5-HTR4 compared to untreated controls(P < 0.05 for both). Treatment with aqueous FAI extracts(≥ 2 g/kg) increased 5-HTR4 m RNA levels(P < 0.05),but no change in protein level was observed by Western blot or immunohistochemistry. The m RNA and protein levels of neurofilament-H were significantly increased with mosapride and ≥ 2 g/kg aqueous FAI extracts compared to controls(P < 0.05 for all).CONCLUSION: Aqueous FAI extracts and mosapride strengthen bowel movement in cathartic colons via increasing the expression of 5-HTR4 and neurofilament-H.

Chromatographic fingerprint analysis of Fructus Aurantii Immaturus by HPLC-DAD and chemometric methods

An efficient method for quality control of Fructus Aurantii Immaturus (FAI),a famous traditional Chinese medicine (TCM) was established. A simple and reliable high-performance liquid chromatography-photodiode array detector (HPLC-DAD) procedure coupled with chemometric methods was developed for fingerprint analysis,qualitative analysis and quantitative determination of this herb. In qualitative and quantitative analyses,heuristic evolving latent projection (HELP) method was employed to resolve the overlapping peaks of the tested samples. Two bioactive components,namely hesperidin and naringin,are confirmed and determined,together with four flavonoids compounds tentatively identified including two new ones. From fingerprint analysis,the fingerprint data were processed with correlation coefficients for quantitative expression of their similarity and dissimilarity. The developed method based on an integration of chromatographic fingerprint and quantitative analysis is scientific,and the obtained results can be applied to the quality control of herb medicine.

GC-MS Analysis and Antibacterial Activity Study of Volatile Oil from 11 Kinds of Aurantii Fructus Immaturus Processed Products

[Objectives]To study the volatile components and antibacterial effects of 11 kinds of Aurantii Fructus Immaturus processed products.[Methods]11 kinds of Aurantii Fructus Immaturus processed products were obtained according to the traditional processing method,the volatile oil was extracted by steam distillation,and the composition of volatile oil in the 11 kinds of processed products was analyzed by gas chromatography-mass spectrometry(GC-MS).the relative percentage content of each component in these 11 kinds of processed products was determined using the peak area normalization.The drug sensitivity activity of the volatile oil of these 11 kinds of processed products was tested using the K-B paper diffusion method and the minimum inhibition volume fraction of volatile oil of these 11 kinds of processed products was tested using the microdilution method.[Results]The highest yield of volatile oil of 11 kinds of these processed products was baking(5.193%),and the lowest was stir-bake to scorch(1.998%).A total of 36 chemical components were identified from the volatile oils of these 11 kinds of processed products.The components with the most volatile oil were stir-bake to scorch(24 kinds),and the components with the least volatile oil were the method of processing with rice-washed water(15 kinds).They contain 8 kinds of common chemical components,such as limonene,linalool,myrcene,α-pinene.The highest content of limonene came from processing with honey(60.93%),the lowest came from processing with rice-washed water(55.25%);the highest content of linalool came from processing with rice-washed water(7.139%),the lowest came from processing with honey(5.436%);the highest content of myrcene came from processing with honey(1.899%),the lowest came from stir-bake to scorch(1.632%);the highest content ofα-pinene came from raw Aurantii Fructus Immaturus(2.355%),and the lowest came from stir-bake to scorch(1.618%).The volatile oil of these 11 kinds of Aurantii Fructus Immaturus processed products has good antibacterial effect on Escherichia coli and Staphylococcus aureus.[Conclusions]The oil yields of volatile oils of 11 kinds of Aurantii Fructus Immaturus processed products are different,the content of limonene is significantly different,and the changes of other chemical components and their contents are not significantly different.The volatile oil of 11 kinds of Aurantii Fructus Immaturus processed products has certain antibacterial effect.

发酵枳实残渣对仔猪生长性能、抗氧化能力和肠道健康的影响

本试验旨在探究发酵枳实残渣对仔猪生长性能、抗氧化能力和肠道健康的影响。选取32头体重为(7.65±0.18)kg杜×长×大三元杂交仔猪,随机分为4组,每组8个重复,每个重复1头猪。各组分别饲喂发酵枳实残渣添加水平为0(对照组)、4%(4%FF组)、8%(8%FF组)、12%(12%FF组)的试验饲粮。试验期30 d。结果表明:1)与对照组相比,8%FF组的平均日增重和平均日采食量显著提高(P<0.05)。2)与对照组相比,8%FF组的血清总蛋白(TP)、免疫球蛋白A(IgA)、免疫球蛋白G(IgG)、免疫球蛋白M(IgM)含量和超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)活性显著提高(P<0.05),4%FF、8%FF、12%FF组的血清总抗氧化能力(T-AOC)显著提高(P<0.05),4%FF和8%FF组的血清丙二醛(MDA)含量显著降低(P<0.05)。3)与对照组相比,8%FF组的空肠绒毛高度、杯状细胞数量和绒毛高度/隐窝深度显著提高(P<0.05),空肠隐窝深度显著降低(P<0.05)。4)与对照组相比,8%FF和12%FF组的空肠闭锁小带蛋白-1(ZO-1)、超氧化物歧化酶1(SOD1)和核因子E2相关因子2(Nrf2)的mRNA相对表达水平显著提高(P<0.05),8%FF组的空肠封闭蛋白(Occludin)的mRNA相对表达水平显著提高(P<0.05)。5)与对照组相比,8%FF和12%FF组的结肠拟杆菌门(Bacteroidetes)相对丰度显著提高(P<0.05),结肠厚壁菌门(Firmicutes)相对丰度显著降低(P<0.05);4%FF和8%FF组的结肠乳杆菌属(Lactobacillus)相对丰度显著提高(P<0.05),12%FF组的结肠普氏菌属(Prevotella)相对丰度显著提高(P<0.05),4%FF、8%FF和12%FF组的结肠链球菌属(Streptococcus)相对丰度显著降低(P<0.05)。综上所述,饲粮中添加发酵枳实残渣对仔猪生长性能无负面影响,并且能提高机体抗氧化能力,改善肠道形态,增加肠道微生物多样性,最终改善仔猪的生长性能。本试验条件下,仔猪饲粮中发酵枳实残渣添加水平以8%为宜。

基于UPLC-MS/MS探讨枳实中黄酮类化合物与辛弗林药动学的相互影响

目的:基于超高效液相色谱-三重四级杆串联质谱(UPLC-MS/MS),探讨枳实中黄酮类化合物与辛弗林药动学的相互影响,为引入黄酮类化合物作为枳实的质量定量控制指标提供科学依据。方法:取24只SD大鼠,随机分为6组(n=4),A组为辛弗林+6种黄酮类化合物(新橙皮苷、柚皮苷、芸香柚皮苷、橙皮苷、川陈皮素和野漆树苷),B组为辛弗林单独给药,C组为辛弗林+柚皮苷,D组为辛弗林+新橙皮苷,E组为6种黄酮类化合物单独给药,F组采用等体积的0.9%氯化钠溶液处理,均灌胃给药。取给药后不同时间点的血浆,测定血浆中柚皮苷、新橙皮苷和辛弗林含量,应用DAS 2.0软件计算药动学参数。利用UPLC-MS/MS方法测定血药浓度。结果:A组大鼠新橙皮苷清除率为(9337.88±8373.94)L/h·kg,显著高于E组的(2558.22±610.87)L/h·kg,差异有统计学意义(P<0.05)。A组、D组大鼠新橙皮苷的分布体积分别为(2549.72±1381.42)、(1668.41±394.73)L/kg,均明显低于E组的(23388.87±6089.53)L/kg,差异均有统计学意义(P<0.05)。A组大鼠辛弗林的平均停留时间为(2.50±0.63)h,较B组、C组和D组[(1.62±0.11)、(1.70±0.17)和(1.57±0.08)h]更长,差异均有统计学意义(P<0.05)。结论:辛弗林对新橙皮苷的消除率和分布影响较大,枳实中的黄酮类化合物可延长辛弗林的平均停留时间。

枳实化学成分和药理作用研究进展及其质量标志物预测分析

枳实作为临床常用理气中药,其化学成分主要包括黄酮类、生物碱类、香豆素类和挥发油类,药理作用主要为调节胃肠运动、抗氧化、抗炎、保肝等。本文在综述了枳实化学成分和药理作用的基础上,从植物亲缘、传统药性、药理作用和成分可测性方面对枳实的质量标志物进行预测分析,建议将柚皮苷、橙皮苷、新橙皮苷、川陈皮素、野漆树苷、柠檬烯、芳樟醇等化学成分纳入枳实质量标志物的考虑范畴,以期为完善枳实质量评价体系和提高质量标准提供科学依据。

不同基原枳实水煎液黄酮类成分及抗氧化活性差异研究

目的 比较不同基原枳实水煎液黄酮类成分和抗氧化活性差异,为枳实的质量评价和临床用药提供参考。方法 建立HPLC法同时测定枳实水煎液中8种黄酮类成分(芸香柚皮苷、柚皮苷、橙皮苷、新橙皮苷、柚皮素、橙皮素、川陈皮素、桔皮素)的含量,结合多元统计分析化学成分差异;采用DPPH法和ABTS法测定不同基原枳实水煎液的抗氧化活性,以灰色关联度分析和双变量相关性分析评价枳实水煎液中8种成分含量与抗氧化活性的相关性。结果 含量测定及统计分析结果表明不同基原枳实水煎液主要差异成分为柚皮苷和新橙皮苷,其中甜橙枳实水煎液中几乎不含柚皮苷和新橙皮苷,而酸橙枳实水煎液中这两种成分含量较高;抗氧化活性结果表明酸橙枳实水煎液抗氧化活性显著优于甜橙枳实水煎液(P <0.05);灰色关联度分析和双变量相关性分析显示,酸橙枳实水煎液中抗氧化作用的核心药效组分是橙皮苷、新橙皮苷、川陈皮素;甜橙枳实水煎液抗氧化作用的核心药效组分是芸香柚皮苷、橙皮素、川陈皮素。结论 本研究建立了HPLC法同时测定枳实水煎液中8种黄酮类成分的含量;不同基原枳实水煎液黄酮类成分含量与抗氧化能力均存在差异。

高效液相色谱法同时检测枳实及枳壳药材中12种黄酮苷类成分

目的建立同时检测枳实、枳壳药材中12种黄酮苷类成分的高效液相色谱法。方法色谱柱为Agilent Zorbax SB-C18柱(250 mm×4.6 mm,5μm),流动相为0.1%甲酸水溶液-乙腈(梯度洗脱),流速为1.0 mL/min,检测波长为284 nm(圣草次苷、新北美圣草苷、芸香柚皮苷、柚皮苷、橙皮苷、新橙皮苷、枸橘苷、柚皮素、橙皮素)、330 nm(橙皮内酯、川陈皮素、橘红素),柱温为35℃,进样量为10μL。结果上述成分质量浓度分别在0.19~46.61μg/mL、0.17~43.27μg/mL、0.20~51.07μg/mL、11.34~756.01μg/mL、0.41~101.28μg/mL、20.58~1028.79μg/mL、0.20~50.49μg/mL、0.10~25.25μg/mL、0.10~26.63μg/mL、0.24~11.96μg/mL、0.21~52.64μg/mL、0.55~27.51μg/mL范围内与峰面积线性关系良好;检测限均不大于0.10μg/mL,定量限均不大于0.41μg/mL;精密度、稳定性、重复性试验结果的RSD均小于2.0%;平均加样回收率为92.90%~114.33%,RSD为0.30%~1.98%(n=9)。结论所建立的方法简便、可靠,可用于同时检测枳实、枳壳药材中12种黄酮苷类成分。

衢枳壳主要化学成分及药效学作用和机制研究进展

衢枳壳作为浙江地区道地中药材,在2018年入选新“浙八味”中药材培育品种后,其药理作用得到愈来愈多的关注。研究发现,衢枳壳及其活性成分具有抗炎、平喘、降血糖、保肝、抗氧化、降血脂、调节肠道菌群、抑菌和免疫调节等多种药理作用,具有良好的药用开发前景。本研究归纳总结了衢枳壳及其主要化学成分的药理作用和机制研究进展,为衢枳壳的进一步药用开发利用提供参考。

基于倾向性评分匹配法评价调畅气机法治疗心肌桥回顾性队列研究

目的基于倾向性评分匹配法(PSM)探讨“调畅气机法”(柴胡-桔梗-枳壳-牛膝)治疗心肌桥的临床疗效。方法采用回顾性队列研究方法,选取158例心肌桥医案,将其分为暴露组与非暴露组,暴露组为接受中药汤剂中含有调畅气机法(包含柴胡-桔梗-枳壳-牛膝)的医案,非暴露组为基础类中药临症加减的医案。运用PSM进行匹配后得到样本35对。观察治疗前后中医证候积分和心电图。结果匹配后暴露组与非暴露组治疗后中医证候积分较治疗前有显著的改善(P<0.01),以暴露组改善更明显(P<0.01);匹配后暴露组的总有效率(94.29%,33/35)高于非暴露组(77.14%,27/35);暴露组的显效率(42.86,15/35%)高于非暴露组(20.00%,7/35),均差异具有统计学意义(P<0.05);匹配后暴露组的心电图总有效率(37.14%,13/35)高于非暴露组(14.29%,5/35),差异具有统计学意义(P<0.05)。结论“调畅气机法”治疗心肌桥疗效良好,缓解临床症状,且一定程度上减轻心电图心肌缺血改变。

枳壳提取物的生物学功能及其在畜禽生产中的应用

枳壳为我国常用的中草药,其提取物的活性成分有黄酮类、挥发油类、生物碱类、香豆素类等化合物,具有抗氧化、抗炎、促进胃肠动力、调节免疫、调节脂质代谢等功效。本文综述了枳壳提取物的生物学功能及其在畜禽生产中的应用,旨在为其在畜禽养殖中的应用提供参考依据。

超声辅助深共晶溶剂高效提取枳实辛弗林的工艺优化及提取动力学分析

为了研究超声辅助深共晶溶剂提取枳实辛弗林的最佳工艺条件及该提取过程的传质动力学模型,本研究采用Plackett-Burman试验、最陡爬坡试验结合Box-Behnken响应面法对超声辅助深共晶溶剂提取枳实辛弗林的关键工艺参数进行优化,基于Fick第二定律建立超声辅助深共晶溶剂提取枳实辛弗林的提取动力学模型,通过测定在不同功率、不同提取时间下提取液中的辛弗林的质量浓度,对模型进行拟合验证,求解相应的动力学参数。结果表明,最优提取溶媒为一水甜菜碱-乳酸组成的深共晶溶剂(摩尔比1∶3,含水量50%),最佳工艺为:液料比39 mL/g,超声功率220 W,超声时间20 min,在此条件下,辛弗林得率为0.4284%,与模型预测值接近,且优于传统水回流提取法、85%乙醇回流提取法、超声辅助14%乙醇提取法、超声辅助70%甲醇提取法和超声辅助水提法。对动力学实验数据拟合得到的动力学一般方程和指数方程与动力学模型相关性良好,推算出了相应的速率常数、相对萃余率等动力学相关参数,拟合得到了半衰期和有效扩散系数回归方程,为枳实辛弗林的提取工艺优化和深入理论研究提供数据参考。

不同干燥方法对枳壳外观性状与内在品质的影响

目的:考察不同干燥加工方法对枳壳药材外观性状和化学成分的影响,为筛选适宜的干燥加工方法提供依据。方法:比较不同干燥方法对枳壳水分、灰分、密度、浸出物含量等理化指标的影响;采用高效液相色谱法(HPLC)分析比较不同干燥方法对枳壳柚皮苷和新橙皮苷含量的影响;采用气相色谱-质谱联用技术(GC-MS)分析比较不同干燥方法下枳壳挥发性成分的差异。结果:趁鲜切片干燥加工方法干燥速度快,枳壳中水分含量低,但浸出物、柚皮苷、新橙皮苷含量均高于其它干燥方法。烘干后切制和晒干后切制枳壳药材外观性状与内在品质相近,晒干枳壳表皮颜色呈棕褐色,烘干枳壳表皮呈绿褐色,两者化学成分相对含量差异不显著。陈放后的枳壳表皮色泽变暗,水分含量升高,浸出物减少,柚皮苷含量升高,新橙皮苷含量降低,挥发性成分减少。结论:综合考虑药材质量、干燥速度和经济性等因素,趁鲜切片干燥适用于枳壳药材的干燥加工。

基于线粒体自噬PINK1/Parkin信号通路的枳实、麸炒枳实和烫枳实对功能性消化不良大鼠治疗作用比较

目的基于线粒体自噬PINK1/Parkin信号通路对比枳实、麸炒枳实和烫枳实对功能性消化不良(FD)大鼠的治疗作用。方法将36只大鼠随机分为正常组、模型组、多潘立酮组、枳实组、麸炒枳实组、烫枳实组。除正常组外其他各组采用碘乙酰胺灌胃结合夹尾刺激法制作FD大鼠模型。造模结束后各给药组给予相应药液灌胃,模型组和正常组给予等体积生理盐水灌胃,持续14 d。造模和给药时,记录大鼠饮食量、饮水量和体质量。给药结束后,测定大鼠小肠推进率,苏木-伊红(HE)染色观察胃组织损伤情况,Western blot检测自噬相关蛋白PINK1、Parkin、Beclin-1、p62的表达。结果与模型组比较,各给药组小肠推进率提高。在造模期间,与正常组比较,各组大鼠的体质量增长减慢,平均日饮食量降低,模型组大鼠平均日饮水量降低。在给药期间,与模型组比较,多潘立酮组、麸炒枳实组和烫枳实组平均日饮食量增加;与模型组比较,麸炒枳实组PINK1、Parkin蛋白表达增加,烫枳实组p62蛋白表达提高、Beclin-1蛋白表达降低,枳实组Beclin-1蛋白表达降低。结论枳实、麸炒枳实和烫枳实治疗FD的作用机制可能与抑制PINK1/Parkin信号通路激活有关,麸炒枳实对FD大鼠的治疗效果优于枳实和烫枳实。

微性状鉴定法在医疗机构中药饮片质量验收中的应用

目的针对易混淆中药饮片采用微性状鉴定法进行鉴别,研究其在医疗机构饮片验收中的应用价值。方法采用微性状鉴定法,借助相关仪器,以花、果实、种子、全草、根与根茎、茎、其他等不同入药部位为分类对10组31种易混淆中药表面肉眼和普通放大镜无法观察到的微观特征进行分析、归纳和总结,并拍照留存。结果观察到10组31种易混淆中药谷精草、华南谷精草、毛谷精草、枳壳、常山胡柚、木瓜、毛叶木瓜、紫苏子、白苏子、野生紫苏、沙苑子、华黄芪、卷柏(卷柏)、卷柏(垫状卷柏)、江南卷柏、深绿卷柏、翠云草、金钱草、点腺过路黄、广金钱草、绵马贯众、狗脊蕨贯众、苏铁蕨贯众、猫人参、藤梨根、雷公藤、野葡萄根、五灵脂、夜明砂、望月砂和蚕砂的微性状特征,发现各类中药具有独特的鉴别特征,花类中药可研究色泽、组织构造及表面特征(如纹理、毛被等);果实类可研究果皮结构、色泽、发达程度及外层特征(如角质层、蜡被等);种子类可研究形态、大小、色泽与纹理;全草类可研究叶的长宽比、最宽处、表面特性与分裂情况,以及茎的茸毛、气孔等;根与根茎、茎类中药可研究皮部、木部构造及维管束或导管的形态与排列,其他类别可从源头入手,借助微观镜头发现其特有微性状鉴别特征。结论微性状鉴定法作为传统性状鉴别的补充,能提高中药饮片鉴定的准确性,该方法经济实用、简便易行且结果直观,可作为一项常用的中药鉴定方法在医疗机构中推广普及,是实现中药快速检验的可行方案。

基于网络药理学探讨白术-枳实改善胰岛素抵抗分子机制研究

目的基于网络药理学探讨白术、枳实改善胰岛素抵抗(IR)的分子机制。方法从中药数据库获取白术、枳实的主要活性成分及靶点,通过疾病数据库获取IR靶点,取交集。对二者交集靶点进行蛋白质互作(PPI)分析,构筑PPI网络;进行富集分析,构建“成分-IR靶点-通路”网络;最后进行分子对接验证。结果白术-枳实改善IR的主要活性成分为木犀草素、川陈皮素、柚皮素等,核心靶点有肿瘤坏死因子(TNF)、肿瘤蛋白P53(TP53)、蛋白激酶B(AKT1)、白细胞介素-6(IL-6)等;分子对接验证显示,大部分核心靶点与主要活性成分的结合活性较好。白术、枳实改善IR的生物学过程包括激素应答、细胞对脂质的反应、调节炎症反应等,作用于内分泌抵抗、HIF-1、AMPK等信号通路,功能主要为调节糖脂代谢等。结论白术、枳实可能通过木犀草素、川陈皮素等活性物质对AMPK、NF-κB等信号通路发挥调节作用,初步揭示了二者多成分、多靶点、多通路改善IR的作用机制。

川枳壳黄酮类成分及其对成骨细胞增殖作用的研究

目的 研究川枳壳黄酮类化学成分及其对成骨细胞增殖的影响。方法 采用聚酰胺树脂、葡聚糖凝胶、硅胶柱色谱等方法进行成分分离,通过质谱和核磁共振波谱分析与鉴定结构,采用体外细胞实验对所得化合物进行成骨细胞增殖活性检测。结果 从川枳壳中分离得到12个黄酮类及其苷类成分,分别鉴定为柚皮苷(1)、新橙皮苷(2)、柚皮素-7-O-β-D-葡萄糖苷(3)、narirutin(4)、sarotanoside(5)、圣草酚-7-O-β-D-葡萄糖苷(6)、柚皮素(7)、芫花素(8)、圣草酚(9)、angophorol(10)、南酸枣苷(11)、tetrahydroprotogenkwanone(12)。其中化合物1~4、6~9、12具有促进成骨细胞增殖作用,且化合物12的细胞增殖率达196.3%,优于阳性药雌二醇。结论 化合物5、8、10、11、12为首次从枳壳中分离得到,化合物5、10、12为首次从柑橘属中分离得到,化合物1~4、6~9、12对成骨细胞具有明显的增殖作用。

以临床用药一致性为依据的枳壳标准汤剂制备工艺及含量测定

依据临床用药一致性原则制备枳壳标准汤剂,研究枳壳标准汤剂的制备工艺及含量测定方法。选择同一批枳壳饮片,分别对煎煮的容器、饮片浸泡时间、溶剂用量、煎煮时间及次数等参数进行研究,同时制备3批标准汤剂,采用LC MS法测定枳壳标准汤剂中6种成分的含量。研究初步确定了枳壳标准汤剂制备的工艺参数:容器选择陶瓷药罐,饮片浸泡60 min;第一煎加10倍水,煎煮30 min;第二煎加8倍水,煎煮20 min。结果表明:柚皮苷、新橙皮苷、芸香柚皮苷、橙皮苷、水合橙皮内酯和川陈皮素的平均含量分别为165.98、86.03、29.64、10.74、3.73和10.67μg/g。本研究建立了枳壳标准汤剂的提取工艺,为以临床用药一致性为基础的标准汤剂研究提供了理论基础和科学依据。