P6A及其类似物的构象研究

纤维蛋白β链的降解产物Ｐ６Ａ及相关的类似物，具有明确的血管效应。生物检测表明，当Ｐ６Ａ的Ｎ端用不同的氨基酸替代时，可以导致不同的结果。就舒血管作用而言，或增强Ｐ６Ａ的效应，或减弱Ｐ６Ａ的效应，或与Ｐ６Ａ相当，或无活性，因而是结构依赖的。本文采用Ｂｉｏｓｙ公司设计的Ｄｉｓｃｏｖｅｒ程序，计算了８种化合物可能的优势构象。结果表明，在α－右手螺旋、α－左手螺旋和β－伸展三种可能的构象状态中，８个化合物的β－伸展构象的总能量都比α－螺旋低，β－伸展可能就是它们在溶液中的构象。本文计算了分子中有重要影响的某些原子间距离以及二面角，发现舒血管活性最强的Ｇｌｎ－Ｐ６Ａ的有关二面角具有特殊性，这是一项有意义的发现。

药物的光学异构体与药效

药物的光学异构体与药效李全，谢毓元（中国科学院上海药物研究所，上海２０００３１）对称性是生物界中极常见的一种现象，若从分子水平上讲，几乎所有的生物分子都有手性，因为构成机体的物质如氨基酸、糖类以及机体的代谢和调控过程中所涉及的物质（如酶、受体和载体等...

3，4─二酰氧基苯骈吡喃类化合物的生物活性及定量构效关系研究

根据苯骈吡喃钾通道启开剂的构效关系，结合前胡丙素的结构特征，设计合成了１８个３，４－二酰氧基苯骈吡喃类化合物，测试体内外生物活性。

钾通道开放剂的构效关系研究进展

钾通道开放剂的构效关系研究进展庞素华１）周家驹（中国科学院化工冶金研究所计算机室，北京１０００８０）李仁利（北京医科大学药学院，北京１０００８３）目前，已鉴别了十几种类型的钾通道，每种类型又有不同亚型．由于钾通道类型多，常共存于同一细胞的膜上，且缺少...

用于肿瘤光动力治疗的光敏剂的构效分析

用于肿瘤光动力治疗的光敏剂的构效分析吴谊群１）（福州大学化学系，福州３５０００２）肿瘤光动力治疗是８０年代初兴起并在近年发展起来的一种新的治疗肿瘤的方法〔１〕，即利用肿瘤组织对特定化学物质的选择性摄入，这些特定的化学物质在一定波长的光作用下产生光动力...

毒扁豆碱类似物抑制胆碱酯酶构效关系的研究

测定了２９个毒扁豆碱类似物的抑制胆碱酯酶活性，对其结构与抑酶活性强度、抑制时间及毒性之间的关系进行了探讨，结果表明：（１）去掉毒扁豆碱的第二个并吡咯环可保持抑酶活性并降低毒性和延长作用时间．（２）胺甲酰氧侧链氮原子上选用较长碳链烷基亦可保持抑酶活性并降低毒性和延长作用时间．（３）二氢吲哚环１位和３位选择较小的烷基取代基时活性较高．

Chemical Constituents of Angelica sinensis

Aim To investigate the active constituents responsible for thepharmacological activities of Angelica sinensis (Oliv) Diels. Methods Chromatography was used toisolate chemical components, and spectroscopy was used to identify their structures. Results Sevencompounds were isolated and their structures were identified as ferulic acid (1), conife-rylferukte(2) , bis (2-ethylhexyl) phthalate (3), dibutyl phthalate (4), lignoceric acid (5), palmitic acid(6), and Z-6, 7-cis-dihydroxyligustilide (7) Conclusion Bis (2-ethylhexyl) phthalate and dibutylphthalate were obtained from Angelica sinensis for the first time.

Analysis of volatile components in herbal pair herba schizonepetae-ramulus cinnamomi

Analysis of volatile components in herbal pair (HP) herba schizonepetae-ramulus cinnamomi (HS-RC), single herb HS and RC was carried out by gas chromatography-mass spectrometry (GC-MS) data and chemometric resolution method (CRM). The two-dimensional data obtained from GC-MS instruments were resolved into a pure chromatogram and a mass spectrum of each chemical compound by CRM. In total, 47, 61 and 51 chemical components in volatile oil of HS, RC, and HP HS-RC were respectively determined qualitatively and quantitatively, accounting for 90.52%, 88.37%, and 88.72% total contents of volatile oil of HS, RC, and HP HS-RC, respectively. The number of the volatile components of HP HS-RC is almost the addition of that of two single herbs, but their relative contents are changed.

Rhizoma polygonati from Mount Tai:nutritional value and usefulness as a traditional Chinese medicine,source of herbzyme,and potential remediating agent for COVID-19 and chronic and hidden hunger

Recently,traditional Chinese medicine-based treatment has succeeded in fighting coronavirus disease 2019(COVID-19),and Rhizoma polygonati(Huangjing)has been one of the recommended components.Its processed products play antidiabetic,antiviral,antitumor,antioxidation,antifatigue,antiaging,and immune enhancement roles.The climate in Mount Tai is mild,and the dense forest is suitable for the growth of Rhizome polygonati,which has gradually evolved into a unique specie.Considering the important medicinal value and pleasant taste of Mount Tai-Rhizoma polygonati,various healthy and functional food products,controlled by quality markers with anti-COVID-19 potential,as well as emergency foods can be developed.The study aimed to review current evidence on the nutritional value of Rhizoma polygonati from Mount Tai and its usefulness as a traditional Chinese medicine,source of herbzyme,and potential remediating agent for COVID-19 and food shortage.Most recent findings regarding herbal nanomedicine have revealed that nanoscale chemical compounds are potentially efficient in drug delivery or nanozyme catalysis upon bioprocessing.Nanoflower structure is found in processed Rhizoma polygonati by self-assembly and has wide application in enzymatic events,particularly nanoscale herbzyme.The novel findings regarding Mount Tai-Rhizoma polygonati could enhance its novel applications in chronic and hidden hunger,clinical nanomedicine,and as an anti-COVID-19 agent.

Ethnobotany, Pharmacology and Chemistry of Medicinal Orchids from Veracruz

Orchidaceae is a large family of 1,260 species in Mexico, of which 433 grow in the state of Veracruz, Mexico. Although economically important in horticulture because of the beauty of their flowers, researches have done little work regarding their medicinal properties. This paper aimed to present the results of ethnobotanical, pharmacological and active compounds research on Veracruz medicinal orchids. The ethnobotanical information was obtained by consulting the Atlas of the Mexican Traditional Medicine Plants, Veracruz Medicinal Flora Database （CITRO-UV project） and through field work in the Nahuatl community of Cuautlajapa, Veracruz. To obtain pharmacological and active compounds information of registered species, a search was carded out through MEDLINE （USA National Library of Medicine Journal Citation database）. Twelve medicinal orchids were recorded for Veracruz, i.e., Epidendrum chlorocorymbos Schltr., Habenaria floribunda Lindl., Isochillus latibracteatus A. Rich. ＆ Galeotti, lsochillus major Schltdl. ＆ Cham., Mormodes maculata var. unicolor （Hook.） L. O. Williams, Oestlundia luteorosea （A. Rich. ＆ Galeotti） W. E. Higgins, Oncidium ascendens Lindl., Scaphyglottis fasciculata Hook., Sobralia macrantha Lindl., Spiranthes eriophora （Rob. ＆ Greenm.）, Stanhopea oculata （G. Lodd.） Lindl. and Vanilla planifolia Andrews. Only two species have been investigated in terms of their pharmacology and active compounds. Also, information for another five species closely related to already identified ones was obtained. Given the relative poverty of current information on the topic, this paper demonstrates the need to further study the ethnobotanical, pharmacological and chemical aspects of the region＇s medicinal orchids.

Potential Mechanisms of Yanghe Decoction in the Treatment of Soft Tissue Sarcoma and Arteriosclerosis Obliterans Based on Network Pharmacology

Objective The objective of this study was to investigate potential mechanisms of Yanghe Decoction(YHD)in treating soft tissue sarcoma(STS)and arteriosclerosis obliterans(ASO)based on the use of network pharmacology.Methods Candidate compounds and potential targets were identifed through the TCM Systems Pharmacology database and a comprehensive literature search.Related targets of STS and ASO were collected in the GeneCards database,DisGeNET database,and Drugbank database.Furthermore,The STRING 11.0 database was used to determine protein-protein interaction(PPI)networks;common targets were obtained and imported into Cytoscape 3.7.2.Then,a PPI network comprising common targets was drawn,and network topology analysis was performed to screen for key shared targets.Gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of key shared targets were performed by using Metascape software.Subsequently.a compound-target-pathway network was constructed via Cytoscape 3.7.2.Results The following signaling pathways were found to be associated with the mechanisms of YHD in treating STS and ASO:AGE-RAGE signaling pathway,IL-17 signaling pathway;HIF-1 signaling pathway,TNF signaling pathway,interactions between cytokines and cytokine receptors,Th17 cell differentiation,and NOD-like receptor signaling pathway.Among the compounds and targets involved in these pathways,quercetin,luteolin,and kaempferol were found to be core compounds,and TNF,IL-6,and MAPK1 were found to be core targets.Conclusion Taken together,our findings elucidated that potential mechanisms of YHD in treating STS and ASO involved cellular proliferation/differentiation,angiogen-esis,inflammation,immune responses,oxidative stress,and other related signaling pathways.

Integrated approach of network pharmacology and chemometrics for quality control of Chinese patent medicine:A case study on Huo-Luo-San

Traditional Chinese medicine(TCM)has garnered significant global interest owing to its multi-component and multi-target theoretical framework and extensive therapeutic efficacy.However,the identification of quality markers(Q-markers)remains a formidable challenge in TCM.Hence,this study aimed to integrate network pharmacology and chemometrics to identify Q-markers in Chinese patent medicine,with a focus on Huo-Luo-San(HLS)as a case study.HLS,a widely used powdered Chinese patent medicine in China,comprises a complex formula of 10 herbs,initially formulated during the Qing dynasty for treating fractures.Initially,13 components,chlorogenic acid,typhaneoside,isorhamnetin-3-O-neohesperidoside,cynaroside,notoginsenoside R_1,ginsenoside Rg_1,baicalin,berberine hydrochloride,ginsenoside Rb_1,dehydrocostus lactone,dioscin,imperatorin,and costunolide,were selected as phytochemical markers for each herb based on the Chinese Pharmacopoeia(2020 version),forming the“Herbs-Compounds-targets”network of HLS using network pharmacology.Subsequently,employing network pharmacology,the 13 HLS components were quantified using UPLC-QqQ-MS.Chromatographic conditions were optimized on a Waters Cortecs C_(18)column(2.1 mm×100 mm,1.6μm)with a gradient elution comprising 0.1%formic acid in water and acetonitrile.Analyte detection was performed in the multiple-reaction monitoring mode,and the method underwent validation for linearity,detection limit,precision,repeatability,stability,and accuracy.The validated method was then utilized to analyze the 13 components in 15 batches of HLS samples.Chemometric techniques,including hierarchical cluster analysis,principal component analysis,orthogonal partial least squares projection discriminant analysis,and box map analyses,were subsequently employed to identify the Q-markers.Ultimately,six components,baicalin,notoginsenoside R_1,berberine hydrochloride,dioscin,imperatorin,and chlorogenic acid,were selected as Q-markers for HLS.The integration of network pharmacology with chemometrics represented a novel approach for selecting Q-markers in Chinese patent medicine.

细辛挥发油抗过敏性鼻炎有效成分及靶点预测的研究

目的:采用血清药物化学-血清药理学与网络药理学方法,预测细辛挥发油抗过敏性鼻炎的有效成分及潜在靶点。方法:36只Wistar大鼠随机分为空白组、细辛挥发油0.5,1 h组(3 g·kg^(-1)生药量)、盐酸西替利嗪片1 h组(10 mg·kg^(-1))、醋酸泼尼松片1 h组(12 mg·kg^(-1))和辛芩颗粒1 h组(15 g·kg^(-1)),每组6只。灌胃后腹主动脉采血,血样3 000 r·min^(-1)离心10 min,无菌分离血清,-20℃冷冻保存。酶联免疫吸附测定法(ELISA)测定各时间点含药血清(血清容积10%)对抗原刺激1.5 h后大鼠嗜碱性细胞白血病细胞株(RBL-2H3)细胞(细胞密度2.5×105/m L)释放组胺、氨基己糖苷酶的影响(n=6);采用气相色谱-质谱联用(GC-MS)技术检测各时间点含药血清中的成分,比较细辛挥发油、灌胃0.5,1 h后含药血清和空白血清的色谱图,寻找细辛挥发油的移行成分;对移行成分进行靶点预测,构建和分析其"成分-靶点"网络。结果:与空白血清组相比,细辛挥发油0.5,1 h含药血清组均能抑制抗原诱导RBL-2H3肥大细胞释放组胺和脱颗粒(P<0.05)。含药血清中检测到12个移行成分,分别为α-蒎烯,莰烯,2-β-蒎烯,δ-3-蒈烯,柠檬油精,1,8-桉叶素,优香芹酮,龙脑,3,5-二甲氧基甲苯,黄樟脑,甲基丁香酚,2,3,5-三甲氧基甲苯,它们可能通过调控环氧合酶-2,毒蕈碱乙酰胆碱受体M3,alpha 1肾上腺素能受体,一氧化氮合酶等靶点发挥抗过敏性鼻炎的作用。结论:该方法初步揭示细辛挥发油抗过敏性鼻炎的有效成分及其潜在靶点。

雷公藤红素对APPswe/PS1dE9双转基因AD模型小鼠肝叶部分切除术后空间学习记忆能力及海马Aβ表达的影响

目的 研究雷公藤红素对APPswe/PS1 dE9双转基因阿尔茨海默病（AD）模型小鼠肝叶部分切除术后空间学习记忆能力及海马内β-淀粉样蛋白40 （Aβ40）、β-淀粉样蛋白42（Aβ42）的影响.方法 3月龄AD模型小鼠96只,按随机数字表法分为三组,手术组（S组,手术切除肝左叶）32只;雷公藤红素组[C组,手术切除肝左叶,术前3d至术后4d每天腹腔注射二甲亚枫（DMSO）＋雷公藤红素]32只;DMSO组（D组,手术切除肝左叶,术前3d至术后4d每天腹腔注射DMSO）32只.三组小鼠采用水迷宫连续训练5d并检测术后1、3、7、14 d的学习记忆能力及小鼠术后1、3、7、14 d取标本,检测海马内Aβ40、Aβ42.结果 与S组、D组比较,术后3、7、14dC组小鼠平均逃避潜伏期缩短（P＜0.05）、跨平台次数增加（P＜0.05）;术后1、3、7、14 d海马内Aβ40、Aβ42的表达减少（P＜0.05）.结论 雷公藤红素通过Aβ40和Aβ42蛋白表达下调,改善肝叶部分切除术后AD模型小鼠的空间学习记忆能力.

黄花败酱不同部位对小鼠镇静催眠效果的比较

目的 研究黄花败酱各部位的镇静催眠作用,为镇静活性部位的分离提供指导.方法 提取分离黄花败酱石油醚、乙酸乙酯、正丁醇三个部位,采用自主活动、洞板试验以及协同戊巴比妥钠催眠试验检测三个部位对小鼠的镇静效果,并与70%乙醇总提取物比较.结果 发现正丁醇部位镇静效果显著优于其它部位,且呈一定的量效关系.结论 正丁醇部位是黄花败酱镇静活性的主要部位,对此部位进行分离有望得到镇前活性好的单体物质.

Phytochemistry and pharmacology of genus Ephedra

The genus Ephedra of the Ephedraceae family contains more than 60 species of nonflowering seed plants distributed throughout Asia, America, Europe, and North Africa. These Ephedra species have medicinal, ecological, and economic value. This review aims to summarize the chemical constituents and pharmacological activities of the Ephedra species to unveil opportunities for future research. Comprehensive information on the Ephedra species was collected by electronic search(e.g., GoogleScholar, Pubmed, Sci Finder, and Web of Science) and phytochemical books. The chemical compounds isolated from the Ephedra species include alkaloids, flavonoids, tannins, polysaccharides, and others. The in vitro and in vivo pharmacological studies on the crude extracts, fractions and few isolated compounds of Ephedra species showed anti-inflammatory, anticancer, antibacterial, antioxidant, hepatoprotective, anti-obesity, antiviral, and diuretic activities. After chemical and pharmacological profiling, current research is focused on the antibacterial and antifungal effects of the phenolic acid compounds, the immunosuppressive activity of the polysaccharides, and the antitumor activity of flavonoids.

Tetrandrine inhibits migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes through down-regulating the expressions of Rac1, Cdc42, and Rho A GTPases and activation of the PI3K/Akt and JNK signaling pathways

Tetrandrine （Tet）, the main active constituent of Stephania tetrandra root, has been demonstrated to alleviate adjuvant-induced arthritis in rats. The present study was designed to investigate the effects of Tet on the migration and invasion of rheumatoid arthritis fibroblast-like synovioeytes （RA-FLS） and explore the underlying mechanisms. By using cultures of primary FLS isolated from synoviums of RA patients and cell line MH7A, Tet （0.3, 1 μmol L-1） was proven to significantly impede migration and invasion of RA-FLS, but not cell proliferation. Tet also greatly reduced the activation and expressions of matrix degrading enzymes MMP-2/9, the expression of F-actin and the activation of FAK, which controlled the morphologic changes in migration process of FLS. To identify the key signaling pathways by which Tet exerts anti-migration effect, the specific inhibitors of multiple signaling pathways LY294002, Triciribine, SP600125, U0126, SB203580, and PDTC （against PI3K, Akt, JNK, ERK, p38 MAPK and NF-kB-p65, respectively） were used. Among them, LY294002, Triciribine, and SP600125 were shown to obviously inhibit the migration of MH7A cells. Consistently, Tet was able to down-regulate the activation of Akt and JNK as demonstrated by Western blotting assay. Moreover, Tet could reduce the expressions of migration-related proteins Rho GTPases Rac 1, Cdc42, and RhoA in MH7A cells. In conclusion, Tet can impede the migration and invasion of RA-FLS, which provides a plausible explanation for its protective effect on RA. The underlying mechanisms involve the reduction of the expressions of Racl, Cdc42, and RhoA, inhibition of the activation of Akt and JNK, and subsequent down-regulation of activation and/or expressions of MMP-2/9, F-actin, and FAK.

Simultaneous quantification of ten constituents of Xanthoceras sorbifolia Bunge using UHPLC-MS methods and evaluation of their radical scavenging, DNA scission protective, and α-glucosidase inhibitory activities

The present study was designed to investigate the bioactive constituents ofXanthoceras sorbifolia in terms of amounts and their antioxidant, DNA scissiou protection, and ct-glucosidase inhibitory activities. Simultaneous quantification of 10 X. sorbifolia constituents was carried out by a newly established ultra-high performance liquid chromatography-quadrupole mass spectrometry method （UHPLC-MS）, The antioxidant activities were evaluated by measuring DPPH radical scavenging and DNA scission protective activities. The a-glucosidase inhibitory activities were investigated by using an assay with a-glucosidase from Bacillus Stearothermophilus and disaccharidases from mouse intestine. We found that the wood ofX. sorbifolia was rich in phenolic compounds with the contents of catechin, epicatechin, myricetin, and dihydromyricetin being 0.12-0.19, 1.94-2.16, 0.77-0.91, and 6.76-7.89 mg.g-1, respectively. The four constituents strongly scavenged DPPH radicals （with ECs0 being 4.2, 3.8 and 5.7 μg-mL-1, respectively） and remarkably protected peroxyl radical-induced DNA strand scission （92.10%, 94.66%, 75.44% and 89.95% of protection, respectively, at a concentration of 10 μmol.L-1）. A dimeric flavan 3-ol, epigallocatechin-（4β→8, 2β→O-7）-epicatechin potently inhibited a-glucosidase with an IC50 value being as low as 1.2 μg.mL1. The established UHPLC-MS method could serve as a quality control tool for X. sorbifolia. In conclusion, the high contents of antioxidant and α-glucosidase inhibitory constituents in X. sorbifolia support its use as complementation of other therapeutic agents for metabolic disorders, such as diabetes and hypertension.

Tongqiao Huoxue Decoction ameliorates learning and memory defects in rats with vascular dementia by up-regulating the Ca^(2+)-CaMKII-CREB pathway

The present study was aimed at determining the effects of Tongqiao Huoxue Decoction （TQHXD） on the Ca2＋-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia （VD）. The rat VD model was established by using an improved bilateral carotid artery ligation method. The Morris water maze experiment was used to evaluate the ethology of the VD rats following treatments with TQHXD at 3.01, 6.02, and 12.04 g.kg-1 per day for 31 days. At the end of experiment, the hippocampus were harvested and analyzed. Western blotting and RT-PCR were used to measure the expression levels of calmodulin-binding protein kinase II（CaMKII）, protein kinase A（PKA）, cAMP-response element binding protein（CREB）, and three N-methyl-D-aspart^c acid receptor subunits （NR1, NR2A, and NR2B）. Our results revealed that TQHXD could alleviate the loss of learning abilities and increase the memory capacity （P 〈 0.05 and P 〈 0.01 vs the model group, respectively）. The treatment with 6.02 and 12.04 g.kg-1 of TQHXD significantly up-regulated the Ca2＋-CaMKII-CREB pathway in the hippocampus. In conclusion, TQHXD showed therapeutic effects on a bilateral carotid artery ligation-induced vascular dementia model, through the up-regulation of calcium signalling oathwavs.

Anti-inflammatory and anti-arthritic effects of Guge Fengtong Formula: in vitro and in vivo studies

Rheumatoid arthritis （RA） is the most common inflammatory arthritis and a major cause of disability. Presently, the clinical therapeutic medicines for inflammatory and arthritic diseases are unsatisfactory due to severe adverse effects or ineffectiveness. The Guge Fengtong formula （GGFT）, containing the standardized extracts of Dioscoreae Nipponicae Rhizoma, Spatholobi Caulis, and Zingiberis Rhizoma, has long been used for RA treatment in China. However, the detailed anti-inflammatory and anti-arthritic activity of GGFT has not been reported so far. In the present work, we aimed to evaluate the anti-inflammatory and anti-arthritic effects of GGFT using three in vivo animal models and tried to uncover the underlying mechanism of action in RAW 264.7 macrophages. The obtained results indicated that GGFT significantly attenuated ear edema, decreased carrageenan-induced paw edema, reduced the ar- thritis score, and reversed the weight loss of the complete Freund＇s adjuvant （CFA）-injected rats. Additionally, decrease in synovial inflammatory infiltration and synovial lining hyperplasia in the joints and decline of inflammatory factors （TNF-α and IL-1β） in the serum were observed in the GGFT-treated rats. In lipopolysaccharide-activated RAW264.7 macrophages, GGFT reduced the produc- tion of NO, PGE2, and IL-6 and inhibited the expression of iNOS, COX-2, and NF-kB. Our results demonstrated that GGFT possessed considerable anti-inflammatory activity and had potential therapeutic effects on adjuvant induced arthritis in rats, providing experi- mental evidences for its application in the treatment of RA and other inflammatory diseases.