Protective mechanism of Paeoniae Radix Alba against chemical liver injury based on network pharmacology,molecular docking,and in vitro experiments

Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell experiments.Methods:Network pharmacology was used to identify the common potential targets of P.Radix and chemical liver injury.Molecular docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1.The cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of P.Radix,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western blot.Results:Analysis through network pharmacology revealed 13 key compounds of P.Radix,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and CASP3.Gene Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation.Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and CASP3.Different concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 cells.Conclusion:P.Radix primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,CASP3.TGP,the main active compound of P.Radix,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.

凤丹(Paeonia ostii T.)自毒物质的检测及其作用机制

药用牡丹的种植中存在明显的连作障碍现象,为探讨其机制,利用已萌发长根的凤丹(Paeonia ostii)种子对凤丹根际土壤和根的水浸提液进行了自毒化感检测;采用高效液相色谱法(HPLC)对种植4a的凤丹根际土壤及其根皮中的化感自毒物质进行了定性和定量分析;在此基础上,利用外源法研究了盆栽凤丹幼苗对5种检出物质(阿魏酸、肉桂酸、香草醛、香豆素和丹皮酚)及其混合物在3种不同浓度下对植株生长的影响和生理响应。结果表明:(1)连续种植4a的凤丹根际土壤和根浸提液对已萌发种子根的生长有显著的抑制作用(p<0.05),显示凤丹根分泌物具有自毒化感的潜势;(2)HPLC分析表明在凤丹根际土壤中存在5种以上的酚酸类物质(阿魏酸、肉桂酸、香草醛、香豆素和丹皮酚),其中阿魏酸、肉桂酸、香草醛、香豆素为前人已报道的化感物质;(3)在实验室条件下,所设浓度范围内,5种物质及其混合物对凤丹幼苗的高度、根长及地下和地上生物量均有明显影响,尤其对根长和地下生物量的影响最为明显(p<0.05),此结果与连作移栽幼苗时,根部首先发黑死亡的现象相一致;(4)凤丹幼苗的根系活力和叶绿素含量在各处理中表现出相似性,即低浓度时根系活力和叶绿素含量高,高浓度时根系活力和叶绿素含量低,低浓度的阿魏酸和香草醛对幼苗根系活力和叶绿素合成有促进作用。此结果显示自毒物质可能是通过影响根系酶活性和叶绿素合成来影响群体中其它个体的生长。本实验的结果显示栽培4a的凤丹土壤水提液具有抑制自身种子根系生长的活性,此提示栽培凤丹连作障碍可能主要与自身分泌到土壤中的酚酸类物质的自毒作用有关。

几种化感物质对凤丹(Paeonia ostii)生长的影响

通过盆栽实验研究了5种化感物质阿魏酸、肉桂酸、香草醛、香豆素和丹皮酚及其混合物在不同浓度下对凤丹生长的影响。结果表明:5种化感物质及其混合物对凤丹茎高和地下部生物量有明显影响,对茎径生长没有明显影响,高浓度的混合物和香豆素抑制效果最明显;低浓度的阿魏酸和香草醛对凤丹生长有促进作用,表现出"低促高抑"的现象。

Fatty acid analysis in the seeds of 50 Paeonia ostii individuals from the same population

Tree peony seeds are rich in α-linolenic acid(ALA), and the peony seed oil is now being produced in China. Paeonia ostii is the most widely used tree peony species for oil extraction, which is commercially called Fengdan and treated as a single cultivar. Here, 50 P. ostii individuals from the same population in northern China were randomly selected for fatty acids(FAs) analysis. Thirteen FAs were isolated, and the most abundant five were palmitic acid(5.31–6.99%), stearic acid(1.22–2.76%), oleic acid(18.78–28.15%), linoleic acid(11.86–26.10%), and ALA(41.11–57.51%). There were significant individual differences of plants in FA quality and quantity and the linoleic acid content in Plant No. 48 even exceeded the scope of 1–99%. Further statistical analysis indicated that most of the individual FAs, saturated FAs, unsaturated FAs, and total FAs levels showed significant positive correlations to each other, whereas the seed yield per plant was independent and not correlated to the factors mentioned above. Ward’s hierarchical clustering results grouped the 50 plants into four clusters based on FA contents and seed yield, and the seven plants in Cluster IV were identified as good candidates for oil production. Our results confirmed that the individual differences did occur in P. ostii and Fengdan cannot be simply treated as one uniform cultivar. Also, these results may help simplify the selection of plants for oil peony breeding and accelerate the development of the oil peony industry.

Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase

Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-kB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RBinduced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to saikogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NFkB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.

RAD-sequencing improves the genetic characterization of a threatened tree peony(Paeonia ludlowii)endemic to China:Implications for conservation

Compared with traditional genetic markers,genomic approaches have proved valuable to the conservation of endangered species.Paeonia ludlowii having rarely and pure yellow flowers,is one of the world’s most famous tree peonies.However,only several wild populations remain in the Yarlung Zangbo Valley(Nyingchi and Shannan regions,Xizang)in China due to increasing anthropogenic impact on the natural habitats.We used genome-wide single nucleotide polymorphisms to elucidate the spatial pattern of genetic variation,population structure and demographic history of P.ludlowii from the fragmented region comprising the entire range of this species,aiming to provide a basis for conserving the genetic resources of this species.Unlike genetic uniformity among populations revealed in previous studies,we found low but varied levels of intra-population genetic diversity,in which lower genetic diversity was detected in the population in Shannan region compared to those in Nyingzhi region.These spatial patterns may be likely associated with different population sizes caused by micro-environment differences in these two regions.Additionally,low genetic differentiation among populations(Fst=0.0037)were detected at the species level.This line of evidence,combined with the result of significant genetic differentiation between the two closest populations and lack of isolation by distance,suggested that shared ancestry among now remnant populations rather than contemporary genetic connectivity resulted in subtle population structure.Demographic inference suggested that P.ludlowii probably experienced a temporal history of sharp population decline during the period of Last Glacial Maximum,and a subsequent bottleneck event resulting from prehistoric human activities on the Qinghai-Tibet Plateau.All these events,together with current habitat fragment and excavation might contribute to the endangered status of P.ludlowii.Our study improved the genetic characterization of the endangered tree peony(P.ludlowii)in China,and these genetic inferences should be considered when making different in situ and ex situ conservation actions for P.ludlowii in this evolutionary hotspot region.

Selection of Stable Reference Genes for Quantitative Real-Time PCR on Paeonia ostii T.Hong et J.X.Zhang Leaves Exposed to Different Drought Stress Conditions

The definition of relatively stable expressed internal reference genes is essential in both traditional blotting quantification and as a modern data quantitative strategy.Appropriate internal reference genes can accurately standardize the expression abundance of target genes to avoid serious experimental errors.In this study,the expression profiles of ten candidate genes,ACT1,ACT2,GAPDH,eIF1,eIF2,α-TUB,β-TUB,TBP,RNA Pol II and RP II,were calculated for a suitable reference gene selection in Paeonia ostii T.Hong et J.X.Zhang leaves under various drought stress conditions.Data were processed by the four regularly used evaluation software.A comprehensive analysis revealed that RNA Pol II was the most stable gene and eIF2 was the least stable one.In addition,the geNorm program provided the optimal choice of two reference gene combination,RNA Pol II andβ-TUB,for qRT-PCR normalization in P.ostii subjected to different drought stress levels.Our research provided convenience for gene expression analysis in P.ostii under drought stress and promoted research of effective methods to alleviate P.ostii drought stress in the future.

Assessing anthropogenic pressure and threats on Paeonia emodi Wall.ex Royle habitats in Garhwal Himalaya

The Garhwal Himalaya is among the major repositories of immensely valuable wild edible plants and provides food security to the local population.Among the valuable plant species that grow in this region,Paeonia emodi(family Paeoniaceae)is an important wild edible species that found in temperate regions with an altitude range between 1800 and 2800 m.The species is facing a severe threat to its sustainability due to overharvesting,habitat disturbances,and a lack of effort regarding conservation.For the first time,this study investigated anthropogenic pressure,population decline perceptions in the natural habitat,and vulnerability assessment of P.emodi under selected study sites(n=23 villages).A semi structured questionnaire was used to interview approximately 45%of the local inhabitants,including herbal practitioners(Vaidhyas or Dais)of each village.On the basis of demographic characteristics,the perceptions and responses of 464 local people were documented regarding potential causes of deterioration and feasible options for sustainable utilization.Using the weight survey method,we estimated the actual amount of collection based on personal interaction and direct observation.In order to determine the threats status,a rapid vulnerability assessment(RVA)was performed and were used based on the current exploitation and usage.The present study revealed that leaf(100%)was the most frequently harvested part,followed by stem(95.65%),seed(26.09%),root(21.74%)and flower(13.04%).The village Triyuginarayan and Pothivasa recorded the highest collection scores while the purpose of the collection was mostly edible(100%),medicinal(100%),and least commercial(8.70%).According to the literature review and the present survey,the RVA(total=21)is categorized as category II(intermediate side of the RVA index),indicating a degree of vulnerability.The study revealed that P.emodi faces extinction in the Garhwal Himalayas.Growing this species through agro-production techniques may alleviate the pressure on the existing population as a result of the availability of raw materials for commercial and household uses.These findings will provide an effective framework for conservation and management decisions and plans.

川赤芍总苷提取工艺优化、组成和抗氧化活性分析

探究超声波辅助乙醇提取川赤芍总苷,通过单因素和响应面优化提取工艺,采用高效液相色谱(HPLC)法检测总苷组成,并通过体外抗氧化试验评价总苷的抗氧化活性。结果表明:最佳提取工艺为超声功率175 W、超声时间42 min、乙醇浓度70%、液料倍数30(mL/g),此工艺条件下提取的川赤芍总苷得率为(5.86±0.32)%。HPLC分析总苷共检测到21个特征峰,其中没食子酸0.63 mg/g、氧化芍药苷11.28 mg/g、儿茶素18.64 mg/g、芍药内酯苷5.82 mg/g、芍药苷54.82 mg/g、苯甲酰芍药苷15.74 mg/g、丹皮酚原苷0.98 mg/g,共占总质量的95.35%。总苷清除DPPH·、ABTS+·和·OH-的IC50值分别为0.78、1.13、0.98 mg/mL,总苷的抗氧化活性强弱与浓度呈现较好的正相关。

叶面喷施胺鲜酯及其与油菜素内酯复配液对油用牡丹生理特性及产量的影响

为筛选出适合油用牡丹高产高效栽培中的植物生长调节剂应用技术,本试验以凤丹为材料,分别于盛花期(4月7日)、籽粒形成期(4月18日)、果荚与籽粒快速生长期(5月10日)叶面喷施不同质量浓度的胺鲜酯(D1、D2和D3)及其与油菜素内酯复配液(BD1、BD2和BD3),研究其对植株生理特性、籽粒产量指标(百粒重、单果籽粒重、单株籽粒重及籽粒产量)的影响。结果表明,与对照组相比,喷施植物生长调节剂处理的牡丹叶片生理特性和籽粒产量关键参数均有明显提高:7月3日时,BD2处理叶片SOD活性较对照显著提高5.24%;5月19日和7月3日时,所有处理叶片MDA含量均较对照显著降低;7月3日时,所有处理叶片可溶性糖含量与对照均有显著性差异,其中BD2处理最高,较对照增加33.84%;6月10日时,所有处理叶片总叶绿素含量均显著高于对照,其中BD3处理增幅最大,为98.11%;3个测定时期,除6月10日的BD3处理外其他处理叶片净光合速率均显著高于对照,且随着胺鲜酯质量浓度的提高呈现先增加后降低趋势。所有处理单株籽粒重及籽粒产量均显著高于对照,其中BD3增幅均最大,分别为10.45%与10.44%。相关性分析表明,SOD活性与Chl a、Chl b、Car、总叶绿素含量和净光合速率呈极显著正相关,与可溶性糖含量呈显著正相关,与MDA含量呈极显著负相关;总叶绿素含量与净光合速率呈极显著正相关,净光合速率与单果籽粒重、单株籽粒重和籽粒产量呈显著正相关。综之,12、16 mg/L胺鲜酯与0.05 mg/L油菜素内酯复配喷施油用牡丹植株的生理特性表现优异,并可获得较高籽粒产量。

芍药花芽分化及花期调控研究进展

芍药(Paeonia lactiflora Pall.)是芍药科芍药属多年生草本花卉,具有重要的观赏和药用价值,但芍药的花期短而集中,易枯萎导致花的质量降低。适宜的温度、光照、水分、营养和植物激素有助于促进芍药花芽分化和打破休眠。在促成和抑制栽培中,选用早、晚花品种,温度调控和外源物质也可控制芍药的花期。为有效延长芍药的供花时间,通过对近年来国内外相关文献的梳理归纳,阐述了芍药花芽分化发育和休眠的生理学机制、促成和抑制栽培等方面的研究进展,以期为芍药花期调控研究提供理论依据。

油用牡丹凤丹的单株产量构成要素

【目的】为促进凤丹优良种质筛选和高产品种培育提供参考。【方法】以6龄凤丹为研究对象,在果实开裂期,检测10个生长性状(主枝基径、主枝长、2年生枝基径、2年生枝长、小枝长、小枝基径、复叶数量、叶柄长、复叶长和复叶宽)和5个繁殖性状(单果数量、单果长、种子量、败育单果荚数量和产量),分析各性状的相关性,采用逐步回归法筛选与产量相关的性状,再对所筛选的性状进行通径分析,明确其对产量的效应。【结果】凤丹的繁殖性状指标的变异系数大于生长性状。与产量显著相关的性状有种子数量、单果长、2年生枝基径、2年生枝长和小枝长;种子数量对种子产量的影响最大(相关系数R=0.811),其次为单果长(R=0.210),小枝长、2年生枝基径和2年生枝长通过影响种子数量和单果长来对种子质量产生影响。以产量(y)为因变量,以种子数量(x_(1))、单果长(x_(2))、小枝长(x_(3))、2年生枝基径(x_(4))为自变量,构建的凤丹单株产量模型为y=0.142x_(1)+1.123x_(2)+0.027x_(3)+0.014x_(1)x_(2)+0.011x_(1)x_(4)-0.043x_(2)x_(4)-3.386。【结论】单株产量构成的关键要素为种子数量(果实数量)和单果长(果实大小),说明凤丹的单株产量由“库”的大小所决定,同时受到“源”强度的影响。实际生产中在调“源”的同时,更应关注扩“库”增产措施的应用。

白芍标准煎液指纹图谱及化学成分指认

目的建立白芍饮片标准煎液的指纹图谱,对白芍有效成分进行指认,以期为白芍饮片的质量控制及临床应用提供理论依据。方法收集10批白芍饮片,分别制备白芍标准煎液;采用超高效液相色谱(ultra performance liquid chromatography,UPLC)法建立白芍标准煎液的指纹图谱,以2012版《中药色谱指纹图谱相似度评价系统》进行指纹图谱相似度分析;通过与对照品比对、与文献核对质谱数据,对共有峰进行指认。结果经检测,10批白芍标准煎液指纹图谱共标定了22个共有峰,各峰分离度较好,各样品间相似度均>0.9;共指认出5个共有峰:儿茶素,芍药内酯苷,芍药苷,除虫菊素Ⅱ,苯甲酰芍药苷。结论该研究建立的指纹图谱方法精密度、重复性、稳定性良好,可为白芍饮片的质量评价提供理论参考。

牡丹花青素苷合成关键基因PsDFR启动子活性分析

[目的]分析牡丹花青素苷合成关键基因PsDFR启动子的顺式作用元件及活性,为进一步研究PsDFR启动子的功能及其在牡丹花色形成中的调控机制奠定基础。[方法]以‘黑花魁’牡丹花瓣中提取的基因组DNA为模板,通过染色体步移法克隆PsDFR的启动子序列。利用生物信息在线软件预测分析启动子序列的顺式作用元件。构建5个不同长度缺失启动子与GUS基因融合的表达载体,并瞬时转化烟草叶片,通过GUS组织化学染色和酶活性检测分析缺失启动子的活性,及其对脱落酸(ABA)、茉莉酸甲酯(MeJA)、光照等不同胁迫处理的响应。[结果]克隆得到PsDFR上游1687 bp的启动子序列。生物信息学分析发现PsDFR启动子含有多个光信号、激素响应、逆境响应及组织特异表达等顺式作用元件,这暗示PsDFR的表达可能受光信号、激素和胁迫等多种信号的共同调节。GUS组织化学染色和酶活性检测表明,随启动子片段的缩短,启动子活性逐渐下降,-1623至-916区段对于启动子活性具有重要作用。MeJA和黑暗处理对各启动子片段活性均有显著抑制作用,恢复光照可促使启动子活性明显回升,而参与ABA响应的核心调控区域位于-443至-76 bp。[结论]PsDFR启动子含有多个光信号、激素响应、逆境响应及组织特异表达等顺式作用元件,其活性受光的正调控以及MeJA的负调控;-1623至-916 bp间的区域对于启动子活性具有重要作用,-443至-76 bp是响应ABA处理的核心区域。该研究为进一步揭示PsDFR应答环境信号参与牡丹花色形成的分子调控机制提供参考。

不同种皮预处理对滇牡丹种子吸水特性及萌发的影响

[目的]了解不同种皮预处理滇牡丹种子的吸水特性及萌发情况。[方法]测定4种不同种皮预处理滇牡丹种子萌发过程的物理吸水曲线并拟合曲线回归方程,进一步观测该批种子在15℃温箱中的萌发情况并进行相关分析。[结果]滇牡丹种子吸水到饱和所需的时间为144~216 h,浸泡时间与吸水量之间的关系符合对数曲线;萌发情况以50℃热水处理的滇牡丹生根率最高,达93.33%,其平均根长、平均侧根数、平均芽长、侧根率、萌发率均在各处理中最高;平均根长与平均侧根数、侧根率呈极显著正相关,萌芽率与平均侧根数、平均芽长、侧根率呈显著正相关。[结论]不同种皮预处理能有效提高种子吸水率,减少种子浸泡时间;种子播前通过较长时间(144~216 h)的水浸泡可提高滇牡丹种子的生根率,宜采用50℃热水处理滇牡丹种子。

胶冻样芽孢杆菌对革兰氏阴性菌的抑菌活性及其抗菌次级代谢产物分析

为筛选对革兰氏阴性菌抑菌活性较好的药用植物芍药的内生菌,采用表面消毒法和平板对峙法分离筛选对大肠杆菌和沙门氏菌有拮抗作用的芍药内生菌,对其进行形态学和分子生物学鉴定,并通过全基因组学分析探究其抗菌活性物质。结果表明,从芍药根、茎、叶等不同组织分离得到20株内生菌。采用平板对峙法抑菌试验,从20株内生菌中获得1株抗菌效果较好的革兰氏阴性内生菌HNYJ291,经形态学和分子方法鉴定为胶冻样芽孢杆菌(Paenibacillus kribbensis),该菌能有效抑制大肠杆菌和沙门氏菌。对该菌进行全基因组测序分析,HNYJ291的基因组大小为5609136 bp,G+C含量为45.48%,预测其编码基因个数为4805个。分别有4779、3678、4027、3941、2994、2700个基因被NR、Swiss-Prot、Pfam、COG、GO、KEGG数据库注释,通过antiSMASH预测到与次级代谢产物合成相关的10个基因簇,主要次级代谢产物有环脂肽类抗生素(Fusaricidin B)、细菌素(Paenilan)、抗菌脂肽(Tridecaptin)、多黏菌素(Polymyxin)和抗菌肽(Paenicidin A)等。从其基因组中含有的抗菌活性物质相关基因簇可以预测出,该菌株具有开发新药和作为可饲用微生物的潜力。

施肥模式对‘凤丹’牡丹光合特性及产量的影响

为解决施肥不科学影响‘凤丹’牡丹品质产量提升的问题,以5年生‘凤丹’牡丹为试验材料,采用分阶段控量施肥的方法,研究其对‘凤丹’牡丹光合特性、产量的影响。结果表明,‘凤丹’叶片的净光合速率、气孔导度、蒸腾速率、叶绿素含量均随着复合肥施入量的增加、喷施硼肥浓度的增加呈先上升后下降的趋势,在D3B4(复合肥225 kg/hm^(2),硼肥0.3%)水平时达到最大值。叶片胞间CO_(2)浓度趋势相反,呈先降后升的变化趋势,在D3B4水平达到最低值。同时,在D3B4水平时,‘凤丹’的单株果荚数、果荚直径、千粒重、单株籽粒产量均达到最大值。本研究以盛花期复合肥底肥225 kg/hm^(2)+结果初期叶喷0.3%硼肥为‘凤丹’牡丹高产的最佳施肥模式,可为‘凤丹’牡丹科学施肥提供一定参考依据。

基于GEO数据库联合网络药理学研究川芎-赤芍药对治疗动脉粥样硬化的药理过程及分子机制

目的:探讨活血化瘀中药药对川芎-赤芍拮抗动脉粥样硬化的潜在分子机制及药理过程。方法:使用R语言Limma包分析GEO数据库GSE43292数据集,对有表达差异的动脉粥样硬化基因进行筛选和提取。川芎-赤芍药对所含的化学活性组分及靶点通过中药系统药理学数据库与分析平台检索。合并差异基因和药物作用靶点以获得共同的靶点。利用在线分析工具STRING和Cytoscape构建药物和靶点的调控网络以及靶点间的蛋白质-蛋白质相互作用(PPI)网络。然后利用R语言注释靶点基因的基因本体(GO)功能,分析京都基因与基因组百科全书(KEGG)通路,再进行基因集富集分析(GSEA)以验证KEGG的通路和富集的情况,确定靶点基因的调控功能和参与基因调控功能的信号转导通道。结果:共筛选出动脉粥样硬化差异基因1244个,川芎-赤芍药对含36个生物活性成分,其中靶点为环加氧酶1、肾上腺素受体、过氧化物酶体增殖物激活受体-γ、激酶插入域受体、孕激素受体、基质金属蛋白酶9、CXC趋化因子配体8、蛋白激酶Cβ、白细胞介素6、CD14、二肽基肽酶-4、PIK3CG、肾上腺素受体α1B、微管相关蛋白2、尿激酶纤溶酶原激活剂和单胺氧化酶B。靶点在GO中主要富集在合成DNA过程的调控、DNA生物合成的过程、含胶原的细胞外基质、细胞外基质、蛋白酶结合、细胞迁移、血管形成过程、膜筏结构、转录的调节等与动脉粥样硬化炎症、脂肪代谢及血管生成相关的生物学注释。脂质与动脉粥样硬化通路和核因子κB信号通路与动脉粥样硬化关系最为密切,并且在KEGG信号通路和GSEA均显示出富集。结论:川芎-赤芍药对通过潜在的13个活性成分作用于可能的16个靶点调控相关信号转导通路,通过抗炎、调脂和保护血管等方式产生抗动脉粥样硬化的作用。

白芍总苷对幼年类风湿性关节炎患儿血清B细胞激活因子的影响

目的探讨白芍总苷对幼年类风湿性关节炎患儿的临床疗效及对血清B细胞激活因子的影响。方法选取中山市中医院儿科2019年8月至2021年8月收治的40例幼年类风湿性关节炎患儿为研究对象,按照随机数表法将其分为对照组(20例)与治疗组(20例)。对照组仅接受口服布洛芬缓释混悬剂,治疗组在口服布洛芬缓释混悬剂基础上同时加白芍总苷胶囊治疗。两组均进行12周持续治疗。观察两组治疗后关节发热、肿胀、晨僵等症状的消失时间,红细胞沉降率、类风湿性因子、B细胞激活因子及C反应蛋白的变化。结果治疗后,治疗组总有效率高于对照组,治疗组的关节发热、肿胀及晨僵症状消失时间均短于对照组,且红细胞沉降率、类风湿性因子、C反应蛋白水平及B细胞激活因子均低于对照组,差异有统计学意义(P<0.05);两组患儿不良反总发生率比较,差异无统计学意义(P>0.05)。结论白芍总苷用于治疗幼年类风湿性关节炎患儿,其临床疗效显著,可抑制B细胞激活因子表达,降低患儿红细胞沉降率水平及C反应蛋白水平,改善患儿类风湿关节炎的临床症状,且安全系数良好,值得临床推广使用。

基于营卫理论探讨桂枝-赤芍配伍重塑肿瘤血管微环境的网络药理学机制

目的:采用网络药理学方法预测桂枝-赤芍配伍影响肿瘤血管生成的潜在靶点和通路,从分子网络药理学水平探索该配伍重塑肿瘤血管微环境的网络药理学机制。方法:采用中药系统药理学数据库与分析平台(TCMSP)检索桂枝、赤芍的化学成分和潜在靶点,选择口服生物利用度≥30%和类药性≥0.18作为化学成分筛选条件;在GeneCards数据库中检索血管生成的靶点;利用Cytoscape 3.6.0软件绘制桂枝-赤芍配伍-化合物-靶点-血管生成网络;使用STRING 11.0在线软件构建蛋白质-蛋白质相互作用(PPI)网络并挖掘核心靶点;采用David Bioinformatics Resources数据库对该复方活性成分潜在的靶点网络中的蛋白进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果:桂枝-赤芍配伍的33种有效成分作用于血管生成过程的77个靶点,PPI网络的核心靶点包括蛋白激酶B(Akt)1、JUN、白细胞介素6、基质金属蛋白酶、血管内皮生长因子A、一氧化氮合酶2和缺氧诱导因子-1α等多个蛋白。GO功能富集分析提示,该配伍的关键蛋白主要参与了DNA结合转录激活剂活性、血红素结合、抗氧化活性、核受体活性和转录因子活性等生物过程。KEGG通路富集分析显示,该配伍参与了缺氧诱导因子-1(HIF-1)信号通路、肿瘤蛋白53信号通路、细胞凋亡信号通路、表皮生长因子受体酪氨酸激酶抑制剂耐药信号通路、血管内皮生长因子(VEGF)信号通路和磷脂酰肌醇3激酶-Akt信号通路等,提示桂枝-赤芍配伍与肿瘤血管生成的关系最为密切。结论:桂枝-赤芍配伍中的黄芩素、谷甾醇和鞣花酸等成分可能通过HIF-1信号通路、VEGF信号通路影响肿瘤血管生成,干预肿瘤的生物学行为。