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Profiling the chemical differences of diterpenoid alkaloids in different processed products of Aconiti Lateralis Radix Praeparata by UHPLC-LTQ-Orbitrap mass spectrometry combined with untargeted metabolomics and mass spectrometry imaging UHPLC-LTQ-Orbitrap质谱联用非靶向代谢组学和质谱成像分析附子不同炮制品中二萜类生物碱的化学差异
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-08-01 DOI: 10.1016/S1875-5364(25)60936-8
Yang Yu , Changliang Yao , Jianqing Zhang , Yong Huang , Shuai Yao , Hua Qu , Tong Zhang , Dean Guo
Aconiti Lateralis Radix Praeparata (Fuzi) represents a significant traditional Chinese medicine (TCM) that exhibits both notable pharmacological effects and toxicity. Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components, primarily diterpenoid alkaloids. To comprehensively analyze the chemical variations between different Fuzi products, ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) was employed to systematically characterize Shengfuzi, Heishunpian and Baifupian. A total of 249 diterpenoid alkaloids present in Shengfuzi were identified, while only 111 and 61 in Heishunpian and Baifupian were detected respectively, indicating substantial differences among these products. An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers. Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples, 8 robust markers distinguishing these products were identified, including AC1-propanoic acid-3OH, HE-glucoside, HE-hydroxyvaleric acid-2OH, dihydrosphingosine, N-dodecoxycarbonylvaline and three unknown compounds. Additionally, the MS imaging (MSI) technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi, revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian. The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products. This research provides valuable insights into the material basis for future investigations of different Fuzi products.
附子是一种重要的中药,具有显著的药理作用和毒性。通过对附子的有毒有效成分(主要是二萜类生物碱)进行改性,采用多种加工方法降低附子的毒性。为了全面分析不同附子产品之间的化学差异,采用超高效液相色谱-线性离子阱四极杆轨道阱质谱法(UHPLC-LTQ-Orbitrap MS)对生附子、黑顺片和白附片进行了系统表征。生附子中共检出249种二萜类生物碱,黑顺片和白附片中分别检出111种和61种,差异较大。非靶向代谢组学方法结合多元统计分析发现了42种潜在的化学标记。通过对52批黑顺片和白附片的商品样品进行验证,鉴定出8个区分产品的稳健标记,包括ac1 -丙酸- 3oh、he -葡萄糖苷、he -羟戊酸- 2oh、二氢鞘氨醇、n -十二脱氧羰基缬氨酸和3个未知化合物。此外,利用MS成像(MSI)技术可视化了生附子中化学成分的空间分布,揭示了不同加工工艺对黑顺片和白附片化学成分变化的影响。不同二萜生物碱亚型的分布格局部分解释了不同产品间的化学差异。本研究为今后对扶子产品的研究提供了有价值的物质基础。
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引用次数: 0
Design and synthesis of novel saponin-triazole derivatives in the regulation of adipogenesis 新型皂苷-三唑衍生物在脂肪形成调控中的设计与合成
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-08-01 DOI: 10.1016/S1875-5364(25)60830-2
Yongsheng Fang , Zhiyun Zhu , Chun Xie, Dazhen Xia, Huimin Zhao, Zihui Wang, Qian Lu, Caimei Zhang, Wenyong Xiong, Xiaodong Yang
Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
与三七(P. notoginseng)相关的皂苷在多种疾病中显示出显着的治疗功效。然而,由于某些高产皂苷的药理作用降低,其临床应用受到限制。本研究合成了36种人参皂苷Rg1/Rb1和三七皂苷R1的皂苷-1,2,3-三唑衍生物,并对其体外抗脂肪生成活性进行了评价。研究发现人参皂苷rg1 -1,2,3-三唑衍生物a17具有良好的脂肪生成抑制作用。结构-活性关系分析表明,通过Click反应在皂苷侧链中加入氨基取代的1,2,3-三唑可增强抗脂肪生成活性。此外,其他几种衍生物表现出普遍的脂肪生成抑制作用。与母体人参皂苷Rg1相比,化合物a17的效力增强。机制研究表明,a17在体外表现出剂量依赖性的脂肪形成抑制,并伴有前脂肪细胞表达降低。过氧化物酶体增殖物激活受体γ (PPARγ),脂肪酸合成酶(FAS)和脂肪酸结合蛋白4 (FABP4)脂肪形成调节剂。这些发现证实了人参皂苷rg1 -1,2,3-三唑衍生物a17是一种有前景的脂肪细胞分化抑制剂和潜在的治疗肥胖和相关代谢紊乱的药物。本研究为开发各种代谢综合征的有效治疗方法提供了基础。
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引用次数: 0
(±)-Talapyrones A−F: six pairs of dimeric polyketide enantiomers with unusual 6/6/6 and 6/6/6/5 ring systems from Talaromycesadpressus (±)-Talapyrones A−F:来自Talaromycesadpressus的六对具有特殊6/6/6和6/6/6/5环体系的二聚体聚酮对映体
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-08-01 DOI: 10.1016/S1875-5364(25)60928-9
Meijia Zheng , Xinyi Zhao , Chenxi Zhou , Hong Liao , Qin Li , Yuling Lu , Bingbing Dai , Weiguang Sun , Ying Ye , Chunmei Chen , Yonghui Zhang , Hucheng Zhu
(±)-Talapyrones A−F (16), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher’s method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A−F (16) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C8 poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 16 were discussed.
(±)-Talapyrones A−F(1−6)是从真菌Talaromyces adpressus中分离得到的六对二聚聚酮对映体,具有独特的6/6/6和6/6/6/5环体系。通过光谱分析和HR-ESI-MS数据确定了它们的结构,并利用改进的Mosher法和电子圆二色性(ECD)计算确定了它们的绝对构型。(±)-Talapyrones A−F(1−6)具有6/6/6三环骨架,可能是由1个α-吡酮衍生物分子与1个C8聚β-酮链分子的Michael加成反应形成的。另外,化合物2/3和4/5分别是两对C-18外映体。讨论了1 - 6可能的生物合成途径。
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引用次数: 0
Ten new lignans with anti-inflammatory activities from the leaves of Illicium dunnianum 山八仙叶中10种新的具有抗炎活性的木脂素
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-08-01 DOI: 10.1016/S1875-5364(25)60934-4
Ting Li , Xiaoqing He , Dabo Pan , Xiaochun Zeng , Siying Zeng , Zhenzhong Wang , Xinsheng Yao , Wei Xiao , Haibo Li , Yang Yu
The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum (I. dunnianum) resulted in the isolation of five pairs of new lignans (15), and 7 known analogs (612). The separation of enantiomer mixtures 15 to 1a/1b5a/5b was achieved using a chiral column with acetonitrile−water mixtures as eluents. The planar structures of 12 were previously undescribed, and the chiral separation and absolute configurations of 35 were reported for the first time. Their structures were determined through comprehensive spectroscopic data analysis [nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass (HR-ESI-MS), infrared (IR), and ultraviolet (UV)] and quantum chemistry calculations (ECD). The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide (LPS)-stimulated BV-2 cells. Compounds 1a, 3a, 3b, and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner. Western blot and real-time polymerase chain reaction (PCR) assays revealed that 1a down-regulated the messenger ribonucleic acid (mRNA) levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), COX-2, and iNOS and the protein expressions of COX-2 and iNOS. This research provides guidance and evidence for the further development and utilization of I. dunnianum.
对山扁豆(Illicium dunnianum, I. dunnianum)叶片进行抗炎植物化学研究,分离出5对新的木脂素(1-5)和7对已知的类似物(6-12)。对映体混合物1-5至1a/ 1b-5a /5b的分离采用手性色谱柱,乙腈-水混合物为洗脱剂。其中1-2的平面结构已有报道,3-5的手性分离和绝对构型为首次报道。通过综合光谱数据分析[核磁共振(NMR)、高分辨率电喷雾电离质量(HR-ESI-MS)、红外(IR)和紫外(UV)]和量子化学计算(ECD)确定了它们的结构。通过测定新分离物对脂多糖(LPS)刺激的BV-2细胞中NO的抑制作用来评价新分离物。化合物1a、3a、3b和5a以浓度依赖的方式部分抑制NO的产生。Western blot和实时聚合酶链反应(real-time polymerase chain reaction, PCR)结果显示,1a下调肿瘤坏死因子α (TNF-α)、白细胞介素6 (IL-6)、COX-2、iNOS mRNA水平及COX-2、iNOS蛋白表达。该研究结果为进一步开发利用杜鹃属植物提供了指导和依据。
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引用次数: 0
Combining label-free quantitative proteomics and 2D-DIGE to identify the potential targets of Sini Decoction acting on myocardial infarction 结合无标记定量蛋白质组学和2D-DIGE鉴定四逆汤对心肌梗死的潜在作用靶点
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-08-01 DOI: 10.1016/S1875-5364(25)60937-X
Fei Feng , Weiyue Zhang , Yan Cao , Diya Lv , Yifeng Chai , Dandan Guo , Xiaofei Chen
Sini Decoction (SNT) is a traditional formula recognized for its efficacy in warming the spleen and stomach and dispersing cold. However, elucidating the mechanism of action of SNT remains challenging due to its complex multiple components. This study utilized a synergistic approach combining two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE)-based drug affinity responsive target stability (DARTS) with label-free quantitative proteomics techniques to identify the direct and indirect protein targets of SNT in myocardial infarction. The analysis identified 590 proteins, with 30 proteins showing significant upregulation and 51 proteins showing downregulation when comparing the SNT group with the model group. Through the integration of 2D-DIGE DARTS with proteomics data and pharmacological assessments, the findings indicate that protein disulfide-isomerase A3 (PDIA3) may serve as a potential protein target through which SNT provides protective effects on myocardial cells during myocardial infarction.
四逆汤(SNT)是公认的温脾胃散寒的传统方剂。然而,由于SNT的成分复杂,阐明其作用机制仍然具有挑战性。本研究采用基于二维荧光凝胶电泳差异(2D-DIGE)的药物亲和反应靶稳定性(DARTS)与无标记定量蛋白质组学技术相结合的协同方法,鉴定了SNT在心肌梗死中的直接和间接蛋白靶点。分析发现590个蛋白,与模型组相比,SNT组有30个蛋白显著上调,51个蛋白下调。通过将2D-DIGE DARTS与蛋白质组学数据和药理学评估相结合,研究结果表明,蛋白二硫异构酶A3 (PDIA3)可能是心肌梗死期间SNT对心肌细胞提供保护作用的潜在蛋白靶点。
{"title":"Combining label-free quantitative proteomics and 2D-DIGE to identify the potential targets of Sini Decoction acting on myocardial infarction","authors":"Fei Feng ,&nbsp;Weiyue Zhang ,&nbsp;Yan Cao ,&nbsp;Diya Lv ,&nbsp;Yifeng Chai ,&nbsp;Dandan Guo ,&nbsp;Xiaofei Chen","doi":"10.1016/S1875-5364(25)60937-X","DOIUrl":"10.1016/S1875-5364(25)60937-X","url":null,"abstract":"<div><div>Sini Decoction (SNT) is a traditional formula recognized for its efficacy in warming the spleen and stomach and dispersing cold. However, elucidating the mechanism of action of SNT remains challenging due to its complex multiple components. This study utilized a synergistic approach combining two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE)-based drug affinity responsive target stability (DARTS) with label-free quantitative proteomics techniques to identify the direct and indirect protein targets of SNT in myocardial infarction. The analysis identified 590 proteins, with 30 proteins showing significant upregulation and 51 proteins showing downregulation when comparing the SNT group with the model group. Through the integration of 2D-DIGE DARTS with proteomics data and pharmacological assessments, the findings indicate that protein disulfide-isomerase A3 (PDIA3) may serve as a potential protein target through which SNT provides protective effects on myocardial cells during myocardial infarction.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 8","pages":"Pages 1016-1024"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The transcriptomic-based disease network reveals synergistic therapeutic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus 基于转录组学的疾病网络揭示了黄连总生物碱和人参总皂苷对2型糖尿病的协同治疗作用
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-08-01 DOI: 10.1016/S1875-5364(25)60935-6
Qian Chen , Shuying Zhang , Xuanxi Jiang , Jie Liao , Xin Shao , Xin Peng , Zheng Wang , Xiaoyan Lu , Xiaohui Fan
Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5’-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
黄连(Coptis chinensis)和人参c.a.m y。是传统的草药,有几千年的使用记录和广泛的治疗应用,包括抗糖尿病的特性。然而,黄连总生物碱和人参总皂苷对2型糖尿病(T2DM)的协同作用及其机制尚不清楚。研究表明,黄连总生物碱与人参总皂苷的最佳配比为4∶1,对改善小鼠原代肝细胞胰岛素抵抗和糖异生的效果最佳。该组合在改善糖耐量、降低空腹血糖(FBG)、附睾白色脂肪组织(eWAT)的重量比以及瘦素受体缺陷(db/db)小鼠胰岛素抵抗(HOMA-IR)的稳态模型评估方面显示出显著的协同作用。随后,基于RNA测序(RNA-seq)实验和公共数据库,通过整合疾病相关蛋白和蛋白-蛋白相互作用(PPIs)的转录特性,构建了T2DM肝脏特异性网络。以4∶1的比例联合治疗组的网络恢复指数(NRI)评分高于单独治疗组。本研究通过db/db小鼠的western blot实验证实,肝脏活化的腺苷5′-单磷酸活化蛋白激酶(AMPK)/乙酰辅酶a羧化酶(ACC)信号通路在T2DM的协同治疗中发挥了至关重要的作用。结果表明,黄连总生物碱与人参总皂苷4∶1联合用药可显著改善db/db小鼠的胰岛素抵抗和糖脂代谢紊乱,效果优于单独用药。协同机制与AMPK/ACC信号通路活性增强有关。
{"title":"The transcriptomic-based disease network reveals synergistic therapeutic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus","authors":"Qian Chen ,&nbsp;Shuying Zhang ,&nbsp;Xuanxi Jiang ,&nbsp;Jie Liao ,&nbsp;Xin Shao ,&nbsp;Xin Peng ,&nbsp;Zheng Wang ,&nbsp;Xiaoyan Lu ,&nbsp;Xiaohui Fan","doi":"10.1016/S1875-5364(25)60935-6","DOIUrl":"10.1016/S1875-5364(25)60935-6","url":null,"abstract":"<div><div><em>Coptis chinensis</em> Franch. and <em>Panax ginseng</em> C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from <em>Coptis chinensis</em> and total ginsenosides from <em>Panax ginseng</em> on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from <em>Coptis chinensis</em> and total ginsenosides from <em>Panax ginseng</em> was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5’-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from <em>Coptis chinensis</em> and total ginsenosides from <em>Panax ginseng</em> significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 8","pages":"Pages 997-1008"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structurally novel tryptamine-derived alkaloids from the seeds of Peganum harmala and their antiviral activities against respiratory syncytial virus 荆芥种子中结构新颖的色胺衍生生物碱及其对呼吸道合胞病毒的抗病毒活性
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-08-01 DOI: 10.1016/S1875-5364(25)60932-0
Zhongnan Wu , Yubo Zhang , Guocai Wang , Qing Tang , Yaolan Li , Xiaoqing Xie , Yushen Liang , Wen Cheng
Peganum harmala L. (P. harmala) is a significant economic and medicinal plant. The seeds of P. harmala have been extensively utilized in traditional Chinese medicine, Uighur medicine, and Mongolian medicine, as documented in the Drug Standard of the Ministry of Health of China. Twelve novel tryptamine-derived alkaloids (112) and eight known compounds (1320) were isolated from P. harmala seeds. Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers, comprising tryptamine and aniline fragments with previously undocumented C-3−N-1′ linkage and C-3−C-4′ connection, respectively. Compounds 35 were identified as indole-quinazoline heteromers, exhibiting a novel C-3 and NH-1′ linkage between indole and quinazoline-derived fragments. Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer. Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton, featuring an unusual spiro-tricyclic ring (7) and conventional bicyclic tryptamine. Compounds 911 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine. Compounds 13 and 611 were identified as racemates. Compounds 2, 7, 9, 10, and 12 were confirmed via X-ray crystallographic analysis. All isolated compounds (120) exhibited varying degrees of antiviral efficacy against respiratory syncytial virus (RSV). Notably, the anti-RSV activity of compound 12 (IC50 5.01 ± 0.14 μmol·L−1) surpassed that of the positive control (ribavirin, IC50 6.23 ± 0.95 μmol·L−1), as validated through plaque reduction and immunofluorescence assays. The identification of anti-RSV compounds from P. harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.
骆驼蓬(Peganum harmala L.)是一种重要的经济药用植物。哈玛拉籽已被广泛应用于中药、维吾尔药和蒙药中,并被列入中国卫生部《药品标准》。从苦参种子中分离到12个新的色胺衍生生物碱(1 ~ 12)和8个已知化合物(13 ~ 20)。化合物1和2代表了首次报道的色胺衍生异构体,分别由色胺和苯胺片段组成,它们分别具有先前未记载的C-3−N-1 ‘连接和C-3−C-4 ’连接。化合物3 ~ 5被鉴定为吲哚-喹唑啉异构体,在吲哚和喹唑啉衍生的片段之间具有新的C-3和NH-1 '键。化合物6显示了C-C连接的色胺-喹唑啉二聚体的二聚化模式。化合物8是一种由色胺衍生的异二聚体,具有独特的碳骨架,具有不寻常的螺旋三环(7)和常规双环色胺。化合物9 ~ 11为新型的6/5/5/5螺-四环色胺衍生生物碱,呈现出独特的色胺-螺-吡咯利嗪环体系。化合物1−3和6−11被鉴定为外消旋物。化合物2、7、9、10和12通过x射线晶体学分析得到证实。所有分离的化合物(1 ~ 20)对呼吸道合胞病毒(RSV)表现出不同程度的抗病毒作用。化合物12的抗rsv活性(IC50为5.01±0.14 μmol·L−1)优于阳性对照(利巴韦林,IC50为6.23±0.95 μmol·L−1),经斑块减少和免疫荧光实验验证。从苦参种子中分离出抗rsv化合物,可促进其抗病毒药物的开发和应用。
{"title":"Structurally novel tryptamine-derived alkaloids from the seeds of Peganum harmala and their antiviral activities against respiratory syncytial virus","authors":"Zhongnan Wu ,&nbsp;Yubo Zhang ,&nbsp;Guocai Wang ,&nbsp;Qing Tang ,&nbsp;Yaolan Li ,&nbsp;Xiaoqing Xie ,&nbsp;Yushen Liang ,&nbsp;Wen Cheng","doi":"10.1016/S1875-5364(25)60932-0","DOIUrl":"10.1016/S1875-5364(25)60932-0","url":null,"abstract":"<div><div><em>Peganum harmala</em> L. (<em>P. harmala</em>) is a significant economic and medicinal plant. The seeds of <em>P. harmala</em> have been extensively utilized in traditional Chinese medicine, Uighur medicine, and Mongolian medicine, as documented in the <em>Drug Standard of the Ministry of Health of China</em>. Twelve novel tryptamine-derived alkaloids (<strong>1</strong>−<strong>12</strong>) and eight known compounds (<strong>13</strong>−<strong>20</strong>) were isolated from <em>P. harmala</em> seeds. Compounds <strong>1</strong> and <strong>2</strong> represent the first reported instances of tryptamine-derived heteromers, comprising tryptamine and aniline fragments with previously undocumented C-3−N-1′ linkage and C-3−C-4′ connection, respectively. Compounds <strong>3</strong>−<strong>5</strong> were identified as indole-quinazoline heteromers, exhibiting a novel C-3 and NH-1′ linkage between indole and quinazoline-derived fragments. Compound <strong>6</strong> demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer. Compound <strong>8</strong> represents a tryptamine-derived heterodimer with a distinctive carbon skeleton, featuring an unusual spiro-tricyclic ring (<strong>7</strong>) and conventional bicyclic tryptamine. Compounds <strong>9</strong>−<strong>11</strong> constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine. Compounds <strong>1</strong>−<strong>3</strong> and <strong>6</strong>−<strong>11</strong> were identified as racemates. Compounds <strong>2</strong>, <strong>7</strong>, <strong>9</strong>, <strong>10</strong>, and <strong>12</strong> were confirmed <em>via</em> X-ray crystallographic analysis. All isolated compounds (<strong>1</strong>−<strong>20</strong>) exhibited varying degrees of antiviral efficacy against respiratory syncytial virus (RSV). Notably, the anti-RSV activity of compound <strong>12</strong> (IC<sub>50</sub> 5.01 ± 0.14 μmol·L<sup>−1</sup>) surpassed that of the positive control (ribavirin, IC<sub>50</sub> 6.23 ± 0.95 μmol·L<sup>−1</sup>), as validated through plaque reduction and immunofluorescence assays. The identification of anti-RSV compounds from <em>P. harmala</em> seeds may enhance the development and application of this plant in antiviral therapeutic products.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 8","pages":"Pages 972-979"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diketopiperazines with anti-skin inflammation from marine-derived endophytic fungus Aspergillus sp. and configurational reassignment of aspertryptanthrins 海洋内生真菌曲霉的抗皮肤炎症的双酮哌嗪和曲霉胺类蛋白的构型重分配
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-08-01 DOI: 10.1016/S1875-5364(25)60933-2
Jin Yang , Xianmei Xiong , Lizhi Gong , Fengyu Gan , Hanling Shi , Bin Zhu , Haizhen Wu , Xiujuan Xin , Lingyi Kong , Faliang An
Two novel diketopiperazines (1 and 5), along with ten known compounds (24, 612) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 15 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey’s method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 512 to analyze their anti-inflammatory structure-activity relationships.
从海洋真菌Aspergillus sp. FAZW0001中分离出两种新型双酮哌嗪(1和5),以及10种已知化合物(2−4,6−12),显示出明显的皮肤炎症抑制作用。化合物1 ~ 5的结构解析和构型重新评价通过综合光谱分析建立,它们的绝对构型通过单晶x射线衍射用Cu Kα辐射,Marfey的方法,并比较实验和计算的电子圆二色(ECD)光谱确定。化合物1、2和8在痤疮丙酸杆菌(P. acnes)诱导的人单核细胞系中表现出显著的抗炎活性。化合物8通过抑制toll样受体2 (TLR2)表达,调节髓样分化因子88 (MyD88)、丝裂原活化蛋白激酶(MAPK)和核因子κB (NF-κB)信号通路的激活,从而降低痤疮假单胞杆菌诱导的细胞炎症反应,从而下调白细胞介素-1β (IL-1β)的表达。此外,化合物8显示出抑制线粒体活性氧(ROS)产生和核苷酸结合寡聚结构域样受体蛋白3 (NLRP3)炎性体激活的能力,从而降低IL-1β的成熟和分泌。采用三维定量构效关系(3D-QSAR)模型对化合物5 ~ 12进行抗炎构效关系分析。
{"title":"Diketopiperazines with anti-skin inflammation from marine-derived endophytic fungus Aspergillus sp. and configurational reassignment of aspertryptanthrins","authors":"Jin Yang ,&nbsp;Xianmei Xiong ,&nbsp;Lizhi Gong ,&nbsp;Fengyu Gan ,&nbsp;Hanling Shi ,&nbsp;Bin Zhu ,&nbsp;Haizhen Wu ,&nbsp;Xiujuan Xin ,&nbsp;Lingyi Kong ,&nbsp;Faliang An","doi":"10.1016/S1875-5364(25)60933-2","DOIUrl":"10.1016/S1875-5364(25)60933-2","url":null,"abstract":"<div><div>Two novel diketopiperazines (<strong>1</strong> and <strong>5</strong>), along with ten known compounds (<strong>2</strong>−<strong>4</strong>, <strong>6</strong>−<strong>12</strong>) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as <em>Aspergillus</em> sp. FAZW0001. The structural elucidation and configurational reassessments of compounds <strong>1</strong>−<strong>5</strong> were established through comprehensive spectral analyses, with their absolute configurations determined <em>via</em> single crystal X-ray diffraction using Cu K<em>α</em> radiation, Marfey’s method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds <strong>1</strong>, <strong>2</strong>, and <strong>8</strong> exhibited significant anti-inflammatory activities in <em>Propionibacterium acnes</em> (<em>P. acnes</em>)-induced human monocyte cell lines. Compound <strong>8</strong> demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor <em>κ</em>B (NF-<em>κ</em>B) signaling pathways, thus reducing the cellular inflammatory response induced by <em>P. acnes</em>. Additionally, compound <strong>8</strong> showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds <strong>5</strong>−<strong>12</strong> to analyze their anti-inflammatory structure-activity relationships.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 8","pages":"Pages 980-989"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in the study of pharmacotherapy for addiction to naturally-derived psychoactive substances 天然精神活性物质成瘾的药物治疗研究进展
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-08-01 DOI: 10.1016/S1875-5364(25)60831-4
Kexin Xie , Deli Xiao , Peng Xu , Haowei Shen , Bin Di
Drug addiction, a disorder characterized by chronic relapse and compulsive drug use, poses a significant threat to public safety and human health. Addictive substances can be categorized as natural, semi-synthetic, or synthetic based on their origin. Additionally, they can be classified into three groups according to their pharmacological targets: opioids, hallucinogens, and cannabinoids that act on G-protein-coupled receptors (GPCRs); alcohols, nicotine, ketamine, barbiturates, and benzodiazepines (BDZs) that affect ligand-gated ion channel-type receptors; and psychostimulants that interact with monoamine transporters. Current treatments for drug addiction primarily include substitution therapy and non-pharmacological approaches. However, these methods have limitations, particularly in addressing the underlying causes of relapse. Several drugs in clinical trials have demonstrated potential therapeutic effects for addiction to opioids, heroin, cocaine, and other substances. This review examines the origins and pharmacological mechanisms of addiction to naturally-derived psychoactive substances (NPS) and provides an overview of recent advancements in pharmacotherapy for drug addiction.
吸毒成瘾是一种以慢性复发和强迫性吸毒为特征的疾病,对公共安全和人类健康构成重大威胁。成瘾性物质根据其来源可分为天然、半合成和合成。此外,它们可以根据其药理靶点分为三组:阿片类药物、致幻剂和作用于g蛋白偶联受体(gpcr)的大麻素;影响配体门控离子通道型受体的醇类、尼古丁、氯胺酮、巴比妥类和苯二氮卓类(BDZs);以及与单胺转运蛋白相互作用的精神兴奋剂。目前对药物成瘾的治疗主要包括替代疗法和非药物疗法。然而,这些方法有局限性,特别是在解决复发的根本原因。在临床试验中,一些药物已经显示出对阿片类药物、海洛因、可卡因和其他物质成瘾的潜在治疗效果。本文综述了自然衍生精神活性物质(NPS)成瘾的起源和药理学机制,并概述了药物成瘾药物治疗的最新进展。
{"title":"Advances in the study of pharmacotherapy for addiction to naturally-derived psychoactive substances","authors":"Kexin Xie ,&nbsp;Deli Xiao ,&nbsp;Peng Xu ,&nbsp;Haowei Shen ,&nbsp;Bin Di","doi":"10.1016/S1875-5364(25)60831-4","DOIUrl":"10.1016/S1875-5364(25)60831-4","url":null,"abstract":"<div><div>Drug addiction, a disorder characterized by chronic relapse and compulsive drug use, poses a significant threat to public safety and human health. Addictive substances can be categorized as natural, semi-synthetic, or synthetic based on their origin. Additionally, they can be classified into three groups according to their pharmacological targets: opioids, hallucinogens, and cannabinoids that act on G-protein-coupled receptors (GPCRs); alcohols, nicotine, ketamine, barbiturates, and benzodiazepines (BDZs) that affect ligand-gated ion channel-type receptors; and psychostimulants that interact with monoamine transporters. Current treatments for drug addiction primarily include substitution therapy and non-pharmacological approaches. However, these methods have limitations, particularly in addressing the underlying causes of relapse. Several drugs in clinical trials have demonstrated potential therapeutic effects for addiction to opioids, heroin, cocaine, and other substances. This review examines the origins and pharmacological mechanisms of addiction to naturally-derived psychoactive substances (NPS) and provides an overview of recent advancements in pharmacotherapy for drug addiction.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 8","pages":"Pages 897-908"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New tetrahydroanthraquinones and γ-butenolides from the fungus Auxarthron umbrinum DSM3193 真菌Auxarthron umbrinum DSM3193中新的四氢蒽醌类和γ-丁烯内酯类
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-08-01 DOI: 10.1016/S1875-5364(25)60930-7
Ling Tian, Bingyu Liu, Qian Wei, Chen Zhang, Jiamin Shang, Xiaoxue Li, Xiuying Yang, Jinhua Wang, Youcai Hu
Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A−G, 17), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (825) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC50) 3.5−12.1 μmol·L−1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
采用一株多化合物(OSMAC)法,从水稻固体培养的umbrinum (A. umbrinum) DSM3193中分离到9个新化合物,包括7个四氢蒽醌(Auxarthron A−G, 1−7)、1个γ-丁烯内酯苷(malfilamentoside E, 26)和1个γ-丁烯内酯(auxarthrolide A, 27),以及18个已知化合物(8−25)。这些化合物的结构通过核磁共振(NMR)、质谱(MS)和核磁共振计算结合DP4+分析或MAEΔΔδ参数进行了解析,而新化合物的绝对构型则通过单晶x射线衍射、电子圆二色(ECD)光谱数据分析和/或化学衍生化来确定。austrocorlutein(10)和auxarthrol H(14)对U87和U251表现出中等的细胞毒性[一半最大抑制浓度(IC50) 3.5 ~ 12.1 μmol·L−1]。此外,auxarthroone A(1)、auxarthrol H(14)、eupolyhagin B(15)和7-羟基-2-(2-羟丙基)-5-甲基色素(17)对油酸诱导的成纤维细胞增殖挑战表现出扭转作用,从而显示出成纤维细胞增殖促进活性。
{"title":"New tetrahydroanthraquinones and γ-butenolides from the fungus Auxarthron umbrinum DSM3193","authors":"Ling Tian,&nbsp;Bingyu Liu,&nbsp;Qian Wei,&nbsp;Chen Zhang,&nbsp;Jiamin Shang,&nbsp;Xiaoxue Li,&nbsp;Xiuying Yang,&nbsp;Jinhua Wang,&nbsp;Youcai Hu","doi":"10.1016/S1875-5364(25)60930-7","DOIUrl":"10.1016/S1875-5364(25)60930-7","url":null,"abstract":"<div><div>Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A−G, <strong>1</strong>−<strong>7</strong>), a <em>γ</em>-butenolide glycoside (malfilamentoside E, <strong>26</strong>), and a <em>γ</em>-butenolide (auxarthrolide A, <strong>27</strong>), together with eighteen known compounds (<strong>8</strong>−<strong>25</strong>) were isolated from rice-based solid culture of <em>Auxarthron umbrinum</em> (<em>A. umbrinum</em>) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔ<em>δ</em> parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (<strong>10</strong>) and auxarthrol H (<strong>14</strong>) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC<sub>50</sub>) 3.5−12.1 μmol·L<sup>−1</sup>]. Additionally, auxarthrolone A (<strong>1</strong>), auxarthrol H (<strong>14</strong>), eupolyphagin B (<strong>15</strong>), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (<strong>17</strong>) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 8","pages":"Pages 951-960"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Chinese Journal of Natural Medicines
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