Pub Date : 2025-08-01DOI: 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 (1−6), 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 (1−6) 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 1−6 were discussed.
{"title":"(±)-Talapyrones A−F: six pairs of dimeric polyketide enantiomers with unusual 6/6/6 and 6/6/6/5 ring systems from Talaromycesadpressus","authors":"Meijia Zheng , Xinyi Zhao , Chenxi Zhou , Hong Liao , Qin Li , Yuling Lu , Bingbing Dai , Weiguang Sun , Ying Ye , Chunmei Chen , Yonghui Zhang , Hucheng Zhu","doi":"10.1016/S1875-5364(25)60928-9","DOIUrl":"10.1016/S1875-5364(25)60928-9","url":null,"abstract":"<div><div>(±)-Talapyrones A−F (<strong>1</strong>−<strong>6</strong>), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus <em>Talaromyces adpressus</em>. 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 (<strong>1</strong>−<strong>6</strong>) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of <em>α</em>-pyrone derivative and one molecule of C<sub>8</sub> poly-<em>β</em>-keto chain. In addition, compounds <strong>2</strong>/<strong>3</strong> and <strong>4</strong>/<strong>5</strong> are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of <strong>1</strong>−<strong>6</strong> were discussed.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 8","pages":"Pages 932-937"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749692","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}
Pub Date : 2025-08-01DOI: 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 (1–5), and 7 known analogs (6–12). The separation of enantiomer mixtures 1–5 to 1a/1b–5a/5b was achieved using a chiral column with acetonitrile−water mixtures as eluents. The planar structures of 1–2 were previously undescribed, and the chiral separation and absolute configurations of 3–5 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.
{"title":"Ten new lignans with anti-inflammatory activities from the leaves of Illicium dunnianum","authors":"Ting Li , Xiaoqing He , Dabo Pan , Xiaochun Zeng , Siying Zeng , Zhenzhong Wang , Xinsheng Yao , Wei Xiao , Haibo Li , Yang Yu","doi":"10.1016/S1875-5364(25)60934-4","DOIUrl":"10.1016/S1875-5364(25)60934-4","url":null,"abstract":"<div><div>The anti-inflammatory phytochemical investigation of the leaves of <em>Illicium dunnianum</em> (<em>I. dunnianum</em>) resulted in the isolation of five pairs of new lignans (<strong>1</strong>–<strong>5</strong>), and 7 known analogs (<strong>6</strong>–<strong>12</strong>). The separation of enantiomer mixtures <strong>1</strong>–<strong>5</strong> to <strong>1a</strong>/<strong>1b</strong>–<strong>5a</strong>/<strong>5b</strong> was achieved using a chiral column with acetonitrile−water mixtures as eluents. The planar structures of <strong>1</strong>–<strong>2</strong> were previously undescribed, and the chiral separation and absolute configurations of <strong>3</strong>–<strong>5</strong> 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 <strong>1a</strong>, <strong>3a</strong>, <strong>3b</strong>, and <strong>5a</strong> demonstrated partial inhibition of NO production in a concentration-dependent manner. Western blot and real-time polymerase chain reaction (PCR) assays revealed that <strong>1a</strong> down-regulated the messenger ribonucleic acid (mRNA) levels of tumor necrosis factor α (<em>TNF-α</em>), interleukin-6 (<em>IL-6</em>), <em>COX-2</em>, and <em>iNOS</em> and the protein expressions of COX-2 and iNOS. This research provides guidance and evidence for the further development and utilization of <em>I. dunnianum</em>.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 8","pages":"Pages 990-996"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749836","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}
Pub Date : 2025-08-01DOI: 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.
{"title":"Combining label-free quantitative proteomics and 2D-DIGE to identify the potential targets of Sini Decoction acting on myocardial infarction","authors":"Fei Feng , Weiyue Zhang , Yan Cao , Diya Lv , Yifeng Chai , Dandan Guo , 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}
Pub Date : 2025-08-01DOI: 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.
{"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 , Shuying Zhang , Xuanxi Jiang , Jie Liao , Xin Shao , Xin Peng , Zheng Wang , Xiaoyan Lu , 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}
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 (1−12) and eight known compounds (13−20) 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 3−5 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 9−11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine. Compounds 1−3 and 6−11 were identified as racemates. Compounds 2, 7, 9, 10, and 12 were confirmed via X-ray crystallographic analysis. All isolated compounds (1−20) 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.
{"title":"Structurally novel tryptamine-derived alkaloids from the seeds of Peganum harmala and their antiviral activities against respiratory syncytial virus","authors":"Zhongnan Wu , Yubo Zhang , Guocai Wang , Qing Tang , Yaolan Li , Xiaoqing Xie , Yushen Liang , 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}
Pub Date : 2025-08-01DOI: 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 (2−4, 6−12) 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 1−5 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 5−12 to analyze their anti-inflammatory structure-activity relationships.
{"title":"Diketopiperazines with anti-skin inflammation from marine-derived endophytic fungus Aspergillus sp. and configurational reassignment of aspertryptanthrins","authors":"Jin Yang , Xianmei Xiong , Lizhi Gong , Fengyu Gan , Hanling Shi , Bin Zhu , Haizhen Wu , Xiujuan Xin , Lingyi Kong , 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}
Pub Date : 2025-08-01DOI: 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.
{"title":"Advances in the study of pharmacotherapy for addiction to naturally-derived psychoactive substances","authors":"Kexin Xie , Deli Xiao , Peng Xu , Haowei Shen , 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}
Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A−G, 1−7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8−25) 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, Bingyu Liu, Qian Wei, Chen Zhang, Jiamin Shang, Xiaoxue Li, Xiuying Yang, Jinhua Wang, 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}
Pub Date : 2025-08-01DOI: 10.1016/S1875-5364(25)60931-9
Juan Zhang , Jiankun Yan , Hongjun Dong , Rui Zhang , Jing Chang , Yanli Feng , Xinrong Xu , Wei Li , Feng Qiu , Chengpeng Sun
In continuation of research aimed at identifying anti-inflammatory agents from natural sesquiterpenoids, an activity-guided fractionation approach utilizing lipopolysaccharide (LPS)-mediated RAW264.7 cells was employed to investigate chemical constituents from Inula Britannica (I. britannica). Seven novel sesquiterpenoid dimers inulabritanoids A−G (1−7) and two novel sesquiterpenoid monomers inulabritanoids H (8) and I (9) were isolated from I. britannica together with eighteen known compounds (10−27). The structural elucidation was accomplished through comprehensive analysis of 1D and 2D nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) spectra, complemented by quantum chemical calculations. Compounds 1, 2, 12, 16, 19, and 26 demonstrated inhibitory effects on NO production, with IC50 values of 3.65, 5.48, 3.29, 6.91, 3.12, and 5.67 μmol·L−1, respectively. Mechanistic studies revealed that compound 1 inhibited IκB kinase β (IKKβ) phosphorylation, thereby blocking nuclear factor κB (NF-κB) nuclear translocation, and activated the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, leading to decreased expression of NADPH oxidase 2 (NOX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1β, and IL-1α and increased expression of NAD(P)H: quinone oxidoreductase 1 (NQO-1) and heme oxygenase-1 (HO-1), thus exhibiting anti-inflammatory effects in vitro. These results indicate that dimeric sesquiterpenoids may serve as promising candidates for anti-inflammatory drug development.
为了进一步从天然倍半萜类化合物中鉴定抗炎药物，采用脂多糖（LPS）介导的RAW264.7细胞活性引导分离方法对英属植物英属（I. Britannica）的化学成分进行了研究。从britannica中分离到了7个新的倍半萜类二聚体inulabritanoids A ~ G（1 ~ 7）和2个新的倍半萜类单体inulabritanoids H(8)和I(9)，以及18个已知化合物（10 ~ 27）。通过1D和2D核磁共振（NMR）、高分辨率质谱（HR-MS）和电子圆二色（ECD）光谱的综合分析，并辅以量子化学计算，完成了结构解析。化合物1、2、12、16、19和26对NO产生有抑制作用，IC50值分别为3.65、5.48、3.29、6.91、3.12和5.67 μmol·L−1。机械的研究表明,化合物1抑制κB激酶β(IKKβ)磷酸化,从而阻断核因子κB (NF -κB)核易位,并激活kelch-like ECH-associated蛋白1 (Keap1) /核转录因子红细胞两个相关因子2 (Nrf2)信号通路,导致降低NADPH氧化酶的表达2 (NOX-2),诱导一氧化氮合酶(间接宾语),肿瘤坏死因子α(TNF -α)、白细胞介素- 6 (il - 6)、单核细胞趋化蛋白1 (MCP-1), il - 1β,提高NAD(P)H：醌氧化还原酶1 （NQO-1）和血红素氧化酶1 （HO-1）的表达，具有体外抗炎作用。这些结果表明，二聚倍半萜可能是抗炎药物开发的有希望的候选者。
{"title":"Dimeric sesquiterpenoids with anti-inflammatory activities from Inula britannica","authors":"Juan Zhang , Jiankun Yan , Hongjun Dong , Rui Zhang , Jing Chang , Yanli Feng , Xinrong Xu , Wei Li , Feng Qiu , Chengpeng Sun","doi":"10.1016/S1875-5364(25)60931-9","DOIUrl":"10.1016/S1875-5364(25)60931-9","url":null,"abstract":"<div><div>In continuation of research aimed at identifying anti-inflammatory agents from natural sesquiterpenoids, an activity-guided fractionation approach utilizing lipopolysaccharide (LPS)-mediated RAW264.7 cells was employed to investigate chemical constituents from <em>Inula Britannica</em> (<em>I. britannica</em>). Seven novel sesquiterpenoid dimers inulabritanoids A−G (<strong>1</strong>−<strong>7</strong>) and two novel sesquiterpenoid monomers inulabritanoids H (<strong>8</strong>) and I (<strong>9</strong>) were isolated from <em>I. britannica</em> together with eighteen known compounds (<strong>10</strong>−<strong>27</strong>). The structural elucidation was accomplished through comprehensive analysis of 1D and 2D nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) spectra, complemented by quantum chemical calculations. Compounds <strong>1</strong>, <strong>2</strong>, <strong>12</strong>, <strong>16</strong>, <strong>19</strong>, and <strong>26</strong> demonstrated inhibitory effects on NO production, with IC<sub>50</sub> values of 3.65, 5.48, 3.29, 6.91, 3.12, and 5.67 μmol·L<sup>−1</sup>, respectively. Mechanistic studies revealed that compound <strong>1</strong> inhibited I<em>κ</em>B kinase β (IKKβ) phosphorylation, thereby blocking nuclear factor <em>κ</em>B (NF-<em>κ</em>B) nuclear translocation, and activated the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, leading to decreased expression of NADPH oxidase 2 (NOX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1β, and IL-1α and increased expression of NAD(P)H: quinone oxidoreductase 1 (NQO-1) and heme oxygenase-1 (HO-1), thus exhibiting anti-inflammatory effects <em>in vitro</em>. These results indicate that dimeric sesquiterpenoids may serve as promising candidates for anti-inflammatory drug development.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 8","pages":"Pages 961-971"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749696","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}
Pub Date : 2025-07-01DOI: 10.1016/S1875-5364(25)60912-5
Qianyu Bi , Mengran Wang , Li Luo , Beiying Zhang , Siyuan Lv , Zengna Wang , Xuming Ji
Our previous research demonstrated that the Wenxia Changfu Formula (WCF), as a neoadjuvant therapy, inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis. Given tumor-associated macrophages (TAMs) in epithelial-mesenchymal transition (EMT), this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer (NSCLC) cells. Utilizing a co-culture model treated with or without WCF, we observed that WCF downregulated cluster of differentiation 163 (CD163) expression in macrophages, reduced CCL18 levels in the conditioned medium, and inhibited the growth, invasion, and EMT of NSCLC cells induced by macrophage co-culture. Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF's effects are mediated through CCL18 and Src signaling. In vivo, WCF inhibited recombinant CCL18 (rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling. These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18, providing evidence for its potential development and clinical application in NSCLC patients.
{"title":"Wenxia Changfu Formula inhibits NSCLC metastasis by halting TAMs-induced epithelial-mesenchymal transition via antagonisticallymodulating CCL18","authors":"Qianyu Bi , Mengran Wang , Li Luo , Beiying Zhang , Siyuan Lv , Zengna Wang , Xuming Ji","doi":"10.1016/S1875-5364(25)60912-5","DOIUrl":"10.1016/S1875-5364(25)60912-5","url":null,"abstract":"<div><div>Our previous research demonstrated that the Wenxia Changfu Formula (WCF), as a neoadjuvant therapy, inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis. Given tumor-associated macrophages (TAMs) in epithelial-mesenchymal transition (EMT), this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer (NSCLC) cells. Utilizing a co-culture model treated with or without WCF, we observed that WCF downregulated cluster of differentiation 163 (CD163) expression in macrophages, reduced CCL18 levels in the conditioned medium, and inhibited the growth, invasion, and EMT of NSCLC cells induced by macrophage co-culture. Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF's effects are mediated through CCL18 and Src signaling. <em>In vivo</em>, WCF inhibited recombinant CCL18 (rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling. These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT <em>via</em> antagonistic modulation of CCL18, providing evidence for its potential development and clinical application in NSCLC patients.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 7","pages":"Pages 838-847"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604779","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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