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.

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.

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.

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。

Paeonia suffruticosa Andrews的界定,兼论栽培牡丹的分类鉴定问题

栽培牡丹一直称为PaeoniasuffruticosaAndrews。在把作丹皮用的栽培牡丹 (凤丹 )描述为新种P .ostii后 ,观赏的栽培牡丹仍然被统称为P .suffruticosa。但在P .suffruticosa复合体内 ,P .rockii,P .jis hanensis,P .qiui和P .suffruticosassp .yinpingmudan等野生类型相继被描述并得到承认。于是 ,有人提出了栽培牡丹多元发生的观点 ,同时也出现了P .suffruticosa“是牡丹组数种植物复合体”的说法。本文在详细论述P .suffruticosa复合体分类历史的基础上 ,根据我们自己对野生类型和栽培类型的考察研究 ,认为观赏栽培牡丹的形成是多元的 ,并且包含几个物种 ;P .suffruticosa有明确的概念 ,它是观赏栽培牡丹的组成部分 ,而不代表栽培牡丹的全部 ,更不是数种植物的复合体。我们认为应根据形态特征正确鉴定观赏栽培牡丹 ,不应把它们一概鉴定为P .suffruticosa。通过文献和标本引证 ,文中界定了P .suf fruticosa的范围。此外 ,把P .yinpingmudan (D .Y .Hong,K .Y .Pan&Z .W .Xie)B .A .Shen作为P .suffruticosassp.yinpingmudanD .Y .Hong,K .Y .Pan&Z .W .Xie的异名 ,并且认定P .yinpingmudan (D .Y .Hong ,K .Y .Pan&Z .W .Xie)B .A .Shenssp .henanensis(D .Y .Hong,K .Y .Pan&Z .W .Xie)B .A .Shen是不?

Monoterpene Glycosides from the Roots of Paeonia lactiflora

A new monoterpene glycoside, together with nine known ones, 3-O-methylpaeoniflorin, mudanpioside J, paeoniflorin, benzoylpaeoniflorin, oxypaeoniflorin, benzoyloxypaeoniflorin, oxybenzoylpaeoniflorin, albiflorin and lactiflorin, was isolated from the roots of Paeonia lactiflora Pall.. The structure of the new compound was elucidated as galloylalbiflorin by the spectro- scopic evidence including ESI-MS, 1D- and 2D-NMR spectra.

Paeonivayin, A New Monoterpene Glycoside from Paeonia delavayi

A new monoterpene glycoside named paeonivayin with other seven known compounds were isolated from the roots of Paeonia delavayi Franch. and their structures were determined by means of spectroscopic studies.

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。

A New 24, 30-Dinortriterpenoid from Paeonia delavayi

A new triterpenoid. 3 beta. 4 beta. 23-trihydroxy-24, 30-dinorolean-12. 20(29)-dien-28-oic acid. together with five known compounds. 2 alpha. 3 beta. 23-trihydroxy-12-oleanen-28-oic acid-beta -D-glucose glucopyranosyl ester. palbinone. 2-hydroxy-benzoic acid, vanillic acid. syringic acid. were isolated from the roots of Paeonia delavayi Franch. Their structures were characterized by spectral analysis.

A New Monoterpene Glycoside from Paeonia veitchii

A new monoterpene glycoside, acetoxypaeoniflorin, was isolated from the root cortex of Paeonia veitchii Lynch.. The structure was elucidated by spectral methods.

Mechanisms involved in antineuralgic effects of Paeonia Lactiflora: prediction based on network pharmacology

Objective: The analgesic effect of Paeonia Lactiflora has been widely accepted in traditional Chinese medicine. But little is known about the potential mechanism. This study aims to elucidate the effective components and analgesic mechanism based on network pharmacology. Methods: TCMSP was screened to collect the possible active ingredients and their CAS and SMILES was searched in Pubchem and further be used for reverse molecular docking in Swiss Target Prediction database to obtain potential targets. Pain-related molecules were obtained from GeenCards database, and the predicted targets of Paeonia Lactiflora for pain treatment were selected by Wayne diagram. For mechanism analysis, the protein-protein interactions were constructed by String, the GO analysis and KEGG analysis were conducted in DAVID. Results: Through GO analysis and KEGG analysis, we found that the pain related signaling pathways mainly involved in serotonergic synapse, calcium signaling pathway, inflammatory mediator TRP channels. Using network-based systems biology and molecular docking analyses, we predicted that 11 active ingredients in Paeonia Lactiflora has the analgesic effects with 97 potential targets. PRKCA, CASP3, ALOX15, SLC6A4, PRKCG, ALOX5, PRKCB, ALOX12, EGFR, ADRB2, RYR3, RYR1, NOS2, PTAFR, PRKCQ, and PRKCD were involved in the analgesic effects of Paeonia Lactiflora. Conclusion: Paeonia Lactiflora may alleviate pain through inflammatory mediator regulation of TRP channels, Ca2+ signaling pathway and 5-HT receptor. PRKCA, PRKCB, PRKCD,PRKCQ, and PRKCG may be new targets for pain treatment.

Evaluation of Baishao(Radix Paeoniae Alba)and Chishao(Radix Paeoniae Rubra)from different origins based on characteristic spectra of amino acids

Objective To evaluate the difference between Baishao(Paeoniae Radix Alba,PRA)and Chishao(Paeoniae Radix Rubra,PRR)from different regions based on the characteristic spectra of amino acids(AAs).Methods Fingerprints of the 21 standard AAs were established using O-phthalaldehyde-9-fluorenylmethyl chloroformate(OPA-FMOC)pre-column derivation method.The AA components in PRA and PRR were characterized qualitatively and quantitatively,and different AAs were screened using pattern recognition technology.Results Twelve AAs were identified in both PRA and PRR.Meanwhile,aspartic acid,glutamic acid,arginine,alanine,and gamma-aminobutyric acid were screened as characteristic components,and their concentrations could effectively distinguish PRA from PRR.Conclusion The established characterization method,which is based on the characteristic spectra of AAs,is accurate,efficient,and sensitive and can effectively distinguish between PRA and PRR from different producing areas,thus providing a reference for the overall characterization and evaluation of Chinese medicinal materials.

Analysis of the Volatile Components in Flowers of <i>Paeonia lactiflora</i>Pall. and <i>Paeonia lactiflora</i>Pall. var. <i>Trichocarpa</i>

Paeonia lactiflora Pall. var. trichocarpa is a variety of Paeonia lactiflora Pall., and is currently the peony herb’s principal cultivar group. Here, we study the differences in aromatic components and flowers of different varieties between two groups of cultivars, providing a reference for applying natural fragrance substances of peonies, breeding fragrant flower types, and developing and using improved varieties. Headspace solid-phase microextraction (HS-SPME), gas chromatography-mass spectrometry (GC-MS), peak area normalization for each component relative to content, component library (NIST14/NIST14S) retrieval, and a literature review were used to analyze the volatile compounds in flowers of eight peony varieties, such as “Gaoganhong”, and ten comospore peony varieties, such as “Jinshanhong”. Results showed that the main volatile compound constituents in flowers of the two groups were terpenes and alcohols. Additionally, the content of eucalyptol, caryophyllene, α-Pinene, citronellol, and 3-Hexen-1-ol, acetate, (Z) was high. Peony cultivars contained linalool, (1R)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene, and 1,4-dimethoxybenzene, while comospore peony varieties contained 1,3,6-octatriene, 3,7-dimethyl-, (Z)-, phenylethyl alcohol, and geraniol. In this study, the differences between the volatile components of flowers of different peony varieties were clarified, laying a foundation for further molecular biology research into the floral fragrance of peonies and the cultivation of new varieties of aromatic peonies. At the same time, it also provides a theoretical basis for the development and application of peony flower by-products.

Paeonia anomala的核型研究(英文)

报道了Paeonia anomalaL.的核型,澄清了新疆阿尔泰地区分布的该物种的染色体数目。分布于该地区的Paeonia anomalaL.的核型组成:2n=2x=10=6m+2sm+2st。该类群核型与该属其它类群一致———2A型。在综合比较分析该属染色体参数以及核型不均一性参数,包括最长/最短染色体比(L1/Ln)和染色体不对称系数(CKOA)的基础上,我们发现该属三个组在核型上没有明显分化,仅在木本类群(Sect.MoutanDC.)和草本类群(Sect.OnaepiaLindley和Sect.Paeonia)之间存在微小差异。此外,作为二倍体类群,新疆阿尔泰地区分布的Paeonia anomalaL.很可能是二倍体杂种,这将为研究被子植物的父母本同倍化杂交式物种起源提供一个很好的研究材料。

白芍(Radix paeoniae alba)提取物对中华绒螯蟹(Eriocheir sinensis)造血组织发育及造血因子Astakine的影响

血淋巴细胞在甲壳动物免疫反应中起着非常重要的作用,其主要由造血组织(Hematopoietic tissue,HPT)生成并随着开管式循环分布到身体各处。到目前为止,还没有相关研究表明甲壳动物造血组织是否受草本植物的影响。本研究以中华绒螯蟹(Eriocheir sinensis)为对象,利用荧光定量PCR、免疫荧光和组织化学等技术,初步探索了白芍(Radix paeoniae alba)提取物对中华绒螯蟹造血组织和造血因子Astakine的影响。结果显示,在原代培养的造血组织细胞中添加终浓度为0.85 mg/mL的白芍提取物后,造血因子Astakine mRNA的表达量显著上调(P<0.05)。进一步制备含1%白芍提取物的中华绒螯蟹饲料并进行饲喂实验,结果显示饲喂含白芍提取物饲料的中华绒螯蟹造血组织的Astakine mRNA的表达量较饲喂前上调了10.5倍,要高于对照组。免疫荧光结果同样表明,饲喂含白芍提取物饲料后中华绒螯蟹造血组织的Astakine蛋白荧光信号也要强于对照组。通过造血组织的形态学观察和造血组织体重百分比的检测,我们发现白芍组中华绒螯蟹造血组织含有较多卵形小叶,且造血组织体重百分比较饲喂前增加了6.64%,而对照组仅增加1.6%。免疫保护率实验显示,在脂多糖急性刺激下,白芍添加组的中华绒螯蟹的存活率(77.5%)要高于对照组(57.5%)。综上所述,白芍提取物可以促进中华绒螯蟹造血因子的表达和造血组织的发育,从而提高中华绒螯蟹的免疫调节功能。

芍药属牡丹组(Paeonia sect.Moutan)种间关系的分子证据:GPAT基因的PCR-RFLP和序列分析

为了探讨芍药属牡丹组Paeoniasect.Moutan的种间关系 ,对采自 1 5个野生居群 ,代表牡丹组全部 8个野生种的 1 5份材料的GPAT基因片段 (外显子 5和 6之间 2kb的内含子 )进行了PCR_RFLP分析 ,并对代表牡丹组全部 8个野生种的 9份材料进行了测序。根据 1 2个限制性内切酶的PCR_RFLP数据 ,使用Network 3 .0计算机程序的RM (reduced_median)法建立了牡丹组种间亲缘关系网络树。同时根据 8个种 9份材料的GPAT基因片段序列 ,利用PAUP 4.0计算机程序建立了牡丹组GPAT基因的最大简约(MP)树和邻接 (NJ)树。结果获得了具有很高自展值支持、分辨良好的牡丹组种间关系 (GPAT基因 )树。最重要的是 ,该基因树所显示的牡丹组种间关系与根据形态学证据提出的牡丹组的种间关系基本吻合 ,并得到其他研究证据的支持。根据这一结果 ,对牡丹组的种间关系进行了详细的讨论。

濒危植物大花黄牡丹(Paeonia ludlowii)种群数量动态

运用种群静态生命表、存活曲线、生殖力表和Leslie矩阵模型,研究了西藏特有的濒危植物大花黄牡丹种群数量动态过程。静态生命表和种群存活曲线反映出大花黄牡丹在树龄10a之前和20~25a之间分别经历了强烈的环境筛和竞争自疏,20a左右为其生理寿命,35a左右为极限寿命;大花黄牡丹种群的净增长率、内禀增长率和周限增长率较低,表现为衰退型种群;Leslie矩阵模型的模拟结果表明,在20a内种群幼苗数量和总数量呈现出下降趋势,下降了大约30%;大花黄牡丹种群存活表现为Deevey-Ⅰ型,早期个体死亡极高,幼龄苗木严重不足;现行种群数量主要是靠自身的萌蘖繁殖来维持。导致大花黄牡丹濒危的可能原因是大花黄牡丹的生物学特性以及人为干扰。

药用植物凤丹(Paeonia suffruticosa)根际土壤细菌群落16S rRNA基因的ARDRA分析

凤丹(Paeonia suffruticosa Andr.)为芍药科多年生植物,是一种重要的传统中药资源。在其生长发育的周期中与土壤微生物尤其是根际土壤微生物有密切的关系。通过构建16S rRNA基因克隆文库及文库的限制性片段长度多态性分析(ARDRA),对中国药用植物凤丹5大主要分布区域的根际土壤细菌群落多样性进行了研究。采用限制性内切酶HinfI和Csp6I对克隆文库中随机挑选的1000个白色克隆子进行了酶切分型,根据酶切图谱的不同,将其分为324个OTUs,并对38个优势OTUs进行了测序和系统发育分析。16S rRNA基因序列分析结果表明,凤丹根际土壤细菌种群主要包括:变形菌门(包括alpha、beta、gamma、detla亚门)、酸杆菌门、放线菌门、拟杆菌门及厚壁菌门等11类细菌,此外还包含了3个未归类的细菌。变形菌门和酸杆菌门为文库中的主要菌群,分别占克隆总数的47.34%和14.36%,其中Pseudomonas sp.、Burkholderia sp.和Arthrobacter sp.为优势菌属。研究结果表明,我国药用植物凤丹5大主要分布区域的根际土壤细菌种群不仅具有丰富的多样性,还存在丰富的潜在新菌种。

Development Mode and Countermeasures of Paeonia suffruticosa Andr Industrialization

The research introduced Paeonia suffruticosa industry from market demand, value and adaptability and its characteristics, providing references for Paeonia suffruticosa industrialization from product aspect. Finally, its development models were proposed, as well as countermeasures, providing suggestions and countermeasures for Paeonia suffruticosa industry.