Pub Date : 2025-10-14DOI: 10.1016/j.phytochem.2025.114706
Shu-Xi Jing , Chun-Huan Li , Yan-Chun Liu , Ting-Ting Zhou , Ran Fu , Shi-Hong Luo , Yu Zheng , Xiao-Nian Li , Yan Liu , Sheng-Hong Li
Ten previously undescribed sesterterpenoids (1–10), characterized by α,β-unsaturated-γ-lactam and γ-lactone motifs, were isolated from Colquhounia coccinea var. mollis and their structures were elucidated via spectroscopic analyses (1D/2D NMR, HRMS, ECD) and X-ray crystallography. Biological evaluation identified colquhoulactam A (1) as an inhibitor of IFN-γ secretion in T cells, exhibiting an IC50 value of 12.83 μM and superior activity compared to its γ-lactone analogues. Furthermore, plausible biogenetic pathways were proposed to link lactam-bearing colquhoulactams to colquhounoids, underscoring divergent oxidative modifications in terpenoid biosynthesis.
{"title":"γ-lactam and γ-lactone-containing sesterterpenoids from Colquhounia coccinea var. mollis with immunosuppressive activity","authors":"Shu-Xi Jing , Chun-Huan Li , Yan-Chun Liu , Ting-Ting Zhou , Ran Fu , Shi-Hong Luo , Yu Zheng , Xiao-Nian Li , Yan Liu , Sheng-Hong Li","doi":"10.1016/j.phytochem.2025.114706","DOIUrl":"10.1016/j.phytochem.2025.114706","url":null,"abstract":"<div><div>Ten previously undescribed sesterterpenoids (<strong>1</strong>–<strong>10</strong>), characterized by <em>α,β-</em>unsaturated-<em>γ-</em>lactam and <em>γ-</em>lactone motifs, were isolated from <em>Colquhounia coccinea</em> var. <em>mollis</em> and their structures were elucidated via spectroscopic analyses (1D/2D NMR, HRMS, ECD) and X-ray crystallography. Biological evaluation identified colquhoulactam A (<strong>1</strong>) as an inhibitor of IFN-γ secretion in T cells, exhibiting an IC<sub>50</sub> value of 12.83 μM and superior activity compared to its <em>γ</em>-lactone analogues. Furthermore, plausible biogenetic pathways were proposed to link lactam-bearing colquhoulactams to colquhounoids, underscoring divergent oxidative modifications in terpenoid biosynthesis.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"242 ","pages":"Article 114706"},"PeriodicalIF":3.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-14DOI: 10.1016/j.phytochem.2025.114707
Qianqian Zhang , Ping Zhang , Yijin Wu , Huimin Li , Jingya Ruan , Jiaming Cheng , Yi Zhang , Tao Wang
Ohwia caudata, a significant traditional Chinese medicine, exhibits anti-inflammatory properties and is clinically used to treat dysentery, gastroenteritis, and other inflammatory conditions. However, the bioactive constituents responsible for its anti-inflammatory activity remain poorly understood. In the study, a phytochemical investigation of O. caudata leaves led to the isolation and structural elucidation of twenty-one previously undescribed compounds, including ohcanosides A–T (1–20) and (1R)-1,2,3,4-tetrahydro-7,8-dihydroxy-1-isoquinolinecarboxylic acid (21), along with three known isolates (22–24). All the known compounds were reported from the Ohwia genus for the first time. To assess the anti-inflammatory potential of these isolates, a LPS-stimulated RAW264.7 macrophage model was employed. The results demonstrated that compounds 3, 7–10, 14, 15, 17, 19, 20, and 22–24 significantly inhibited nitric oxide (NO) production in a concentration-dependent manner (3, 10, and 30 μM). Molecular docking studies further revealed strong binding affinities between compounds 9, 10, 14, and 17 and phosphatidylinositol 3-kinase (PI3K), with binding energy values below −5 kcal/mol, suggesting stable receptor-ligand interactions. Additionally, Western blot analysis confirmed that these compounds exert their anti-inflammatory effects by downregulating key proteins (PI3K, Akt, and p-Akt) in the PI3K/Akt signaling pathway. These findings provide valuable insights into the anti-inflammatory mechanisms of O. caudata and highlight its potential as a source of novel anti-inflammatory agents.
尾藤是一种重要的中药，具有抗炎特性，临床用于治疗痢疾、肠胃炎和其他炎症。然而，其抗炎活性的生物活性成分仍然知之甚少。在这项研究中，对尾叶O. caudata叶子的植物化学研究导致了21个先前未描述的化合物的分离和结构解析，包括ohcanosides a -t（1-20）和(1R)-1,2,3,4-四氢-7,8-二羟基-1-异喹啉羧酸（21），以及三个已知的分离物（22-24）。所有已知化合物均为首次从该属植物中分离得到。为了评估这些分离株的抗炎潜力，采用lps刺激的RAW264.7巨噬细胞模型。结果表明，化合物3、7-10、14、15、17、19、20和22-24在浓度依赖性（3、10和30 μM）下显著抑制NO的生成。分子对接研究进一步发现，化合物9、10、14和17与磷脂酰肌醇3-激酶（PI3K）具有很强的结合亲和性，结合能值低于-5 kcal/mol，表明受体-配体相互作用稳定。此外，Western blot分析证实，这些化合物通过下调PI3K/Akt信号通路中的关键蛋白（PI3K、Akt和p-Akt）来发挥抗炎作用。这些发现为蛇尾草的抗炎机制提供了有价值的见解，并突出了其作为新型抗炎药来源的潜力。
{"title":"Anti-inflammatory metabolites from the leaves of Ohwia caudata","authors":"Qianqian Zhang , Ping Zhang , Yijin Wu , Huimin Li , Jingya Ruan , Jiaming Cheng , Yi Zhang , Tao Wang","doi":"10.1016/j.phytochem.2025.114707","DOIUrl":"10.1016/j.phytochem.2025.114707","url":null,"abstract":"<div><div><em>Ohwia caudata</em>, a significant traditional Chinese medicine, exhibits anti-inflammatory properties and is clinically used to treat dysentery, gastroenteritis, and other inflammatory conditions. However, the bioactive constituents responsible for its anti-inflammatory activity remain poorly understood. In the study, a phytochemical investigation of <em>O</em>. <em>caudata</em> leaves led to the isolation and structural elucidation of twenty-one previously undescribed compounds, including ohcanosides A–T (<strong>1</strong>–<strong>20</strong>) and (1<em>R</em>)-1,2,3,4-tetrahydro-7,8-dihydroxy-1-isoquinolinecarboxylic acid (<strong>21</strong>), along with three known isolates (<strong>22</strong>–<strong>24</strong>). All the known compounds were reported from the <em>Ohwia</em> genus for the first time. To assess the anti-inflammatory potential of these isolates, a LPS-stimulated RAW264.7 macrophage model was employed. The results demonstrated that compounds <strong>3</strong>, <strong>7</strong>–<strong>10</strong>, <strong>14</strong>, <strong>15</strong>, <strong>17</strong>, <strong>19</strong>, <strong>20</strong>, and <strong>22</strong>–<strong>24</strong> significantly inhibited nitric oxide (NO) production in a concentration-dependent manner (3, 10, and 30 μM). Molecular docking studies further revealed strong binding affinities between compounds <strong>9</strong>, <strong>10</strong>, <strong>14</strong>, and <strong>17</strong> and phosphatidylinositol 3-kinase (PI3K), with binding energy values below −5 kcal/mol, suggesting stable receptor-ligand interactions. Additionally, Western blot analysis confirmed that these compounds exert their anti-inflammatory effects by downregulating key proteins (PI3K, Akt, and <em>p</em>-Akt) in the PI3K/Akt signaling pathway. These findings provide valuable insights into the anti-inflammatory mechanisms of <em>O. caudata</em> and highlight its potential as a source of novel anti-inflammatory agents.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"242 ","pages":"Article 114707"},"PeriodicalIF":3.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-14DOI: 10.1016/j.phytochem.2025.114705
Tianyu Dong , Yajie Du , Tingting Huang , Jiuchang Su , Qingxiang Yang , Jie Guo , Peilei Chen , Jingjing Xing , Hongying Duan
Rehmannia glutinosa roots produce a group of lipophilic bioactive components known as iridoid glycosides. However, the molecular mechanisms by which DNA methylation regulates the biosynthesis of iridoid glycosides in R. glutinosa remain unknown. Herein, the development of R. glutinosa roots and the content of iridoid glycosides in the Wenxian region were significantly higher than those in Xinxiang. Low methylation level contributed to the accumulation of iridoid glycosides and the expression of related enzyme genes. Demethylation promoted both roots growth and development, as well as the accumulation of iridoid glycosides. Up-regulated genes including aldehyde dehydrogenase (RgALDH13), 1-hydroxy-2-methyl-2-butenyl 4-diphosphate reductase (RgHDR1), geraniol 10-hydroxylases (RgG10H3 and RgG10H4), 1-deoxy-d-xylulose 5-phosphate reductoisomerase (RgDXR1), uroporphyrinogen decarboxylase (RgUPD1), and various transcription factors, collectively form the regulatory network for iridoid glycoside biosynthesis. Furthermore, the primary active region of the RgG10H4 promoter is located in the −164 bp region, where the RgMYB2 protein specifically binds to the TAACCA motif in the RgG10H4 promoter. Collectively, low DNA methylation enhances core gene expression, promoting iridoid glycoside accumulation, with RgMYB2-RgG10H4 positively regulating this process. The study provides new insights into the regulation of iridoid glycosides biosynthesis in plants by DNA methylation.
{"title":"Integrated multi-omics demonstrates DNA demethylation-driven activation of the RgMYB2-RgG10H4 axis enhancing iridoid glycoside biosynthesis in Rehmannia glutinosa","authors":"Tianyu Dong , Yajie Du , Tingting Huang , Jiuchang Su , Qingxiang Yang , Jie Guo , Peilei Chen , Jingjing Xing , Hongying Duan","doi":"10.1016/j.phytochem.2025.114705","DOIUrl":"10.1016/j.phytochem.2025.114705","url":null,"abstract":"<div><div><em>Rehmannia glutinosa</em> roots produce a group of lipophilic bioactive components known as iridoid glycosides. However, the molecular mechanisms by which DNA methylation regulates the biosynthesis of iridoid glycosides in <em>R</em>. <em>glutinosa</em> remain unknown. Herein, the development of <em>R</em>. <em>glutinosa</em> roots and the content of iridoid glycosides in the Wenxian region were significantly higher than those in Xinxiang. Low methylation level contributed to the accumulation of iridoid glycosides and the expression of related enzyme genes. Demethylation promoted both roots growth and development, as well as the accumulation of iridoid glycosides. Up-regulated genes including aldehyde dehydrogenase (<em>RgALDH13</em>), 1-hydroxy-2-methyl-2-butenyl 4-diphosphate reductase (<em>RgHDR1</em>), geraniol 10-hydroxylases (<em>RgG10H3</em> and <em>RgG10H4</em>), 1-deoxy-<span>d</span>-xylulose 5-phosphate reductoisomerase (<em>RgDXR1</em>), uroporphyrinogen decarboxylase (<em>RgUPD1</em>), and various transcription factors, collectively form the regulatory network for iridoid glycoside biosynthesis. Furthermore, the primary active region of the <em>RgG10H4</em> promoter is located in the −164 bp region, where the RgMYB2 protein specifically binds to the TAACCA motif in the <em>RgG10H4</em> promoter. Collectively, low DNA methylation enhances core gene expression, promoting iridoid glycoside accumulation, with <em>RgMYB2</em>-<em>RgG10H4</em> positively regulating this process. The study provides new insights into the regulation of iridoid glycosides biosynthesis in plants by DNA methylation.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"242 ","pages":"Article 114705"},"PeriodicalIF":3.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13DOI: 10.1016/j.phytochem.2025.114704
Yufeng Liu , Tao Chen , Ge Zou , Guang Shao , Guangying Chen , Zhigang She
Seven previously undescribed metabolites, including four cladosporols, named cytosporols A−C (1−3), cladosporol L (4), and three polyketides, photinide G (5), cytorhizophin K (7), pestalotiotone C (9), were isolated from the cultures of the mangrove-derived fungus Cytospora heveae NSHSJ-2. The planar structures of the undescribed compounds were determined by analyzing their detailed spectroscopic data. The absolute configurations were further determined through electronic circular dichroism calculations, the modified Mosher's method, NMR calculations and DP4+ analysis. In the bioassay, cytosporol C (3) displayed cytotoxic activities against MDA-MB-435, MDA-MB-231, A549, HepG2 and HCT-116 cell lines with IC50 values ranging from 7.7 to 31.4 μM. Meanwhile, cytosporol C (3) revealed DPPH· scavenging activity with the EC50 value of 47.6 μM.
{"title":"Cytotoxic tetralone homology dimers from mangrove-associated fungus Cytospora heveae NSHSJ-2","authors":"Yufeng Liu , Tao Chen , Ge Zou , Guang Shao , Guangying Chen , Zhigang She","doi":"10.1016/j.phytochem.2025.114704","DOIUrl":"10.1016/j.phytochem.2025.114704","url":null,"abstract":"<div><div>Seven previously undescribed metabolites, including four cladosporols, named cytosporols A−C (<strong>1</strong>−<strong>3</strong>), cladosporol L (<strong>4</strong>), and three polyketides, photinide G (<strong>5</strong>), cytorhizophin K (<strong>7</strong>), pestalotiotone C (<strong>9</strong>), were isolated from the cultures of the mangrove-derived fungus <em>Cytospora heveae</em> NSHSJ-2. The planar structures of the undescribed compounds were determined by analyzing their detailed spectroscopic data. The absolute configurations were further determined through electronic circular dichroism calculations, the modified Mosher's method, NMR calculations and DP4+ analysis. In the bioassay, cytosporol C (<strong>3</strong>) displayed cytotoxic activities against MDA-MB-435, MDA-MB-231, A549, HepG2 and HCT-116 cell lines with IC<sub>50</sub> values ranging from 7.7 to 31.4 μM. Meanwhile, cytosporol C (<strong>3</strong>) revealed DPPH· scavenging activity with the EC<sub>50</sub> value of 47.6 μM.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"242 ","pages":"Article 114704"},"PeriodicalIF":3.4,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13DOI: 10.1016/j.phytochem.2025.114703
Zong-Yi Zhang , Jia-Nan Wang , Peng Sun , Xiao-Cui Shi , Yi-Dian Xiao , Kai-Long Ji , Chun-Fen Xiao , Xiao-Nian Li , You-Kai Xu , Dong-Hua Cao
Nine previously unreported phragmalin-type limonoid orthoesters, named ivorenoids G–O (1–9), together with seventeen known analogues (10–26) were isolated from the twigs and leaves of Khaya ivorensis. Their structures, including absolute configurations, were determined by extensive spectroscopic analyses, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Selected compounds were evaluated for cytotoxicity against five human cancer cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480), and their structure–activity relationships were systematically analyzed. Notably, compound 15 exhibited cytotoxicity against A549 and SMMC-7721 cell lines, with IC50 values of 14.0 ± 0.4 μM and 14.9 ± 0.6 μM, respectively. Compound 22 showed cytotoxicity against SW480 cells, with an IC50 value of 7.5 ± 0.2 μM, while compound 25 displayed cytotoxicity against A549 cells, with an IC50 of 14.6 ± 1.9 μM. These findings highlight the potential of limonoid orthesters derived from K. ivorensis as promising lead compounds for further anticancer drug development.
{"title":"Phragmalin-type limonoid orthoesters from the twigs and leaves of Khaya ivorensis and their cytotoxic activities","authors":"Zong-Yi Zhang , Jia-Nan Wang , Peng Sun , Xiao-Cui Shi , Yi-Dian Xiao , Kai-Long Ji , Chun-Fen Xiao , Xiao-Nian Li , You-Kai Xu , Dong-Hua Cao","doi":"10.1016/j.phytochem.2025.114703","DOIUrl":"10.1016/j.phytochem.2025.114703","url":null,"abstract":"<div><div>Nine previously unreported phragmalin-type limonoid orthoesters, named ivorenoids G–O (<strong>1</strong>–<strong>9</strong>), together with seventeen known analogues (<strong>10</strong>–<strong>26</strong>) were isolated from the twigs and leaves of <em>Khaya ivorensis</em>. Their structures, including absolute configurations, were determined by extensive spectroscopic analyses, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Selected compounds were evaluated for cytotoxicity against five human cancer cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480), and their structure–activity relationships were systematically analyzed. Notably, compound <strong>15</strong> exhibited cytotoxicity against A549 and SMMC-7721 cell lines, with IC<sub>50</sub> values of 14.0 ± 0.4 μM and 14.9 ± 0.6 μM, respectively. Compound <strong>22</strong> showed cytotoxicity against SW480 cells, with an IC<sub>50</sub> value of 7.5 ± 0.2 μM, while compound <strong>25</strong> displayed cytotoxicity against A549 cells, with an IC<sub>50</sub> of 14.6 ± 1.9 μM. These findings highlight the potential of limonoid orthesters derived from <em>K. ivorensis</em> as promising lead compounds for further anticancer drug development.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"242 ","pages":"Article 114703"},"PeriodicalIF":3.4,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-08DOI: 10.1016/j.phytochem.2025.114693
Tuernisan Tudi , Ruxianguli Rouzimaimaiti , Deng Zang , Jiangyu Zhao , Haji Akber Aisa
NMR-guided investigation of Nigella glandulifera Freyn et Sint seeds led to the isolation and characterization of 11 previously undescribed alkaloids, designated nigelladine D–N (1–11). These include three skeletons: (+)/(−)-nigelladine D (1a/1b), and nigelladine E–F (2–3); three piperidines: nigelladine G (4), (+)/(−)-nigelladine H (5a/5b), and nigelladine I (6); three indole alkaloids: (+)/(−)-nigelladine J (7a/7b) and nigelladine K–L (8–9); as well as two pyrrole alkaloids: nigelladine M–N (10–11). In addition, three known 1,4-diazaindane-type pyrrole alkaloids were obtained: agrocybenine (12), the enantiomeric pairs (±)-flavascensine (13a/13b), and (±)-howlumine (14a/14b). Their structures were elucidated using 1D and 2D NMR (Nuclear Magnetic Resonance) spectroscopic analyses, electronic circular dichroism (ECD), quantum chemical calculations, and single-crystal X-ray diffraction (Cu Kα) analysis. Nigelladine D (1) skeleton arises from a piperidine ring and a pyrrole ring fusion through a shared nitrogen atom. Nigelladine E (2) exhibits an unprecedented 6/6/6/6 dipiperidine-condensed cyclopentane framework, likely formed through dimerization of two piperidine derivatives, whereas nigelladine F (3) consists of two piperidine units linked by a pyrrole ring. Furthermore, all compounds exhibited weak inhibitory activity against phosphodiesterase 5 (PDE5) and menin–mixed lineage leukemia 1 (menin–MLL1) protein–protein interaction. Compound 2 significantly increased the melanin content, comparable to that of the positive control 8-methoxypsoralen (8-MOP) (134.50 ± 3.91 % and 134.80 ± 10.24 %, respectively).
{"title":"NMR-guided isolation of alkaloids from Nigella glandulifera seeds and their bioactivities","authors":"Tuernisan Tudi , Ruxianguli Rouzimaimaiti , Deng Zang , Jiangyu Zhao , Haji Akber Aisa","doi":"10.1016/j.phytochem.2025.114693","DOIUrl":"10.1016/j.phytochem.2025.114693","url":null,"abstract":"<div><div>NMR-guided investigation of <em>Nigella glandulifera</em> Freyn et Sint seeds led to the isolation and characterization of 11 previously undescribed alkaloids, designated nigelladine D–N (<strong>1</strong>–<strong>11</strong>). These include three skeletons: (+)/(−)-nigelladine D (<strong>1a/1b</strong>), and nigelladine E–F (<strong>2</strong>–<strong>3</strong>); three piperidines: nigelladine G (<strong>4</strong>), (+)/(−)-nigelladine H (<strong>5a/5b</strong>), and nigelladine I (<strong>6</strong>); three indole alkaloids: (+)/(−)-nigelladine J (<strong>7a/7b</strong>) and nigelladine K–L (<strong>8</strong>–<strong>9</strong>); as well as two pyrrole alkaloids: nigelladine M–N (<strong>10</strong>–<strong>11</strong>). In addition, three known 1,4-diazaindane-type pyrrole alkaloids were obtained: agrocybenine (<strong>12</strong>), the enantiomeric pairs (±)-flavascensine (<strong>13a/13b</strong>), and (±)-howlumine (<strong>14a/14b</strong>). Their structures were elucidated using 1D and 2D NMR (Nuclear Magnetic Resonance) spectroscopic analyses, electronic circular dichroism (ECD), quantum chemical calculations, and single-crystal X-ray diffraction (Cu Kα) analysis. Nigelladine D (<strong>1</strong>) skeleton arises from a piperidine ring and a pyrrole ring fusion through a shared nitrogen atom. Nigelladine E (<strong>2</strong>) exhibits an unprecedented 6/6/6/6 dipiperidine-condensed cyclopentane framework, likely formed through dimerization of two piperidine derivatives, whereas nigelladine F (<strong>3</strong>) consists of two piperidine units linked by a pyrrole ring. Furthermore, all compounds exhibited weak inhibitory activity against phosphodiesterase 5 (PDE5) and menin–mixed lineage leukemia 1 (menin–MLL1) protein–protein interaction. Compound <strong>2</strong> significantly increased the melanin content, comparable to that of the positive control 8-methoxypsoralen (8-MOP) (134.50 ± 3.91 % and 134.80 ± 10.24 %, respectively).</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"242 ","pages":"Article 114693"},"PeriodicalIF":3.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-27DOI: 10.1016/j.phytochem.2025.114692
Anni Kontouri , Nikolaos Georgakis , Anastassios C. Papageorgiou , Nikolaos Ε. Labrou
Tau class glutathione transferases (GSTUs) play essential roles in plant defense by facilitating the nucleophilic attack of glutathione (GSH) to a wide range of electrophilic xenobiotics. In addition to their conjugating activity, these enzymes possess hydroperoxidase function, enabling the detoxification of harmful organic hydroperoxides into less reactive alcohols. In this study, we identified three closely related GST isoenzymes (96–98 % sequence identity) from Cicer arietinum (CaGSTUs) through computational homology screening. Full-length cDNAs encoding these GSTs were cloned, recombinantly produced in E. coli, and purified for functional characterization. Enzyme kinetics were evaluated using model substrates, cumene hydroperoxide (CuOOH) and 1-chloro-2,4-dinitrobenzene (CDNB), revealing that CaGSTU1-1 displayed superior hydroperoxidase activity and thermal stability. Based on these properties, CaGSTU1-1 was selected as the parental scaffold for directed evolution via DNA shuffling, using the homologous Glycine max isoenzyme GmGSTU4-4. Screening of the generated chimeric library resulted in the identification of a new variant, CaGmGSTU, which demonstrated a fourfold enhancement in catalytic turnover and efficiency toward both substrates. Additionally, CaGmGSTU exhibited altered ligand-binding characteristics, including increased affinity for selected pesticides. Structural modeling and viscosity-dependence kinetics indicated that these enhancements were primarily driven by changes in enzyme flexibility. Given the widespread toxicity of hydroperoxides and related pollutants, CaGmGSTU represents a promising tool for detoxification applications in environmental and agricultural biotechnology.
{"title":"Functional characterization and directed evolution of Cicer arietinum glutathione transferases for enhanced hydroperoxidase activity and ligandin function","authors":"Anni Kontouri , Nikolaos Georgakis , Anastassios C. Papageorgiou , Nikolaos Ε. Labrou","doi":"10.1016/j.phytochem.2025.114692","DOIUrl":"10.1016/j.phytochem.2025.114692","url":null,"abstract":"<div><div>Tau class glutathione transferases (GSTUs) play essential roles in plant defense by facilitating the nucleophilic attack of glutathione (GSH) to a wide range of electrophilic xenobiotics. In addition to their conjugating activity, these enzymes possess hydroperoxidase function, enabling the detoxification of harmful organic hydroperoxides into less reactive alcohols. In this study, we identified three closely related GST isoenzymes (96–98 % sequence identity) from <em>Cicer arietinum</em> (<em>Ca</em>GSTUs) through computational homology screening. Full-length cDNAs encoding these GSTs were cloned, recombinantly produced in <em>E. coli</em>, and purified for functional characterization. Enzyme kinetics were evaluated using model substrates, cumene hydroperoxide (CuOOH) and 1-chloro-2,4-dinitrobenzene (CDNB), revealing that <em>Ca</em>GSTU1-1 displayed superior hydroperoxidase activity and thermal stability. Based on these properties, <em>Ca</em>GSTU1-1 was selected as the parental scaffold for directed evolution via DNA shuffling, using the homologous <em>Glycine</em> max isoenzyme <em>Gm</em>GSTU4-4. Screening of the generated chimeric library resulted in the identification of a new variant, <em>CaGm</em>GSTU, which demonstrated a fourfold enhancement in catalytic turnover and efficiency toward both substrates. Additionally, <em>CaGm</em>GSTU exhibited altered ligand-binding characteristics, including increased affinity for selected pesticides. Structural modeling and viscosity-dependence kinetics indicated that these enhancements were primarily driven by changes in enzyme flexibility. Given the widespread toxicity of hydroperoxides and related pollutants, <em>CaGm</em>GSTU represents a promising tool for detoxification applications in environmental and agricultural biotechnology.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"242 ","pages":"Article 114692"},"PeriodicalIF":3.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Three previously undescribed diterpenoids, designated amijial (1), dictyoepoxyperoxide (2), and hydroperoxyacetyldictyolal (3), were isolated from the brown alga Dictyota dichotoma along with eight known diterpenoids. Structural analysis revealed that 1 features a unique xenicane-related skeleton with a cyclic hemiacetal structure. The nematicidal activity of the isolated compounds was evaluated against the plant-parasitic nematode Aphelenchoides besseyi. Compounds bearing the α,β-unsaturated 1,4-dialdehyde structural motif exhibited higher activity.
{"title":"Diterpenoids from the brown alga Dictyota dichotoma with nematicidal activity against the plant parasitic nematode Aphelenchoides besseyi","authors":"Manami Iida , Tatsuo Nehira , Aki Kato , Shigeru Hoshino , Hisashi Ômura , Shinji Ohta","doi":"10.1016/j.phytochem.2025.114691","DOIUrl":"10.1016/j.phytochem.2025.114691","url":null,"abstract":"<div><div>Three previously undescribed diterpenoids, designated amijial (<strong>1</strong>), dictyoepoxyperoxide (<strong>2</strong>), and hydroperoxyacetyldictyolal (<strong>3</strong>), were isolated from the brown alga <em>Dictyota dichotoma</em> along with eight known diterpenoids. Structural analysis revealed that <strong>1</strong> features a unique xenicane-related skeleton with a cyclic hemiacetal structure. The nematicidal activity of the isolated compounds was evaluated against the plant-parasitic nematode <em>Aphelenchoides besseyi</em>. Compounds bearing the α,β-unsaturated 1,4-dialdehyde structural motif exhibited higher activity.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"242 ","pages":"Article 114691"},"PeriodicalIF":3.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-27DOI: 10.1016/j.phytochem.2025.114690
Weiqi Jiang , Wen Zhang , Chenxin Jing , Han Zhou , Zhi-Jun Zhang , Rui Wang , Ying-Qian Liu
Protoberberine alkaloids are a class of organic heterocyclic compounds categorized within the isoquinoline alkaloids, exhibiting significant therapeutic potential due to their potent biological activities. With advancements natural product chemistry, synthetic organic chemistry, biochemistry, and molecular biology, novel insights into their biosynthetic pathways, chemical synthesis pathways, mechanisms of action, and clinical applications have been elucidated. A comprehensive understanding of protoberberine alkaloids is instrumental in enhancing their commercial value and utilization of medicinal plant resources. Among these alkaloids, berberine stands out as a well-studied compound with broad-spectrum bioactivities. In this review, we summarized the progress in the study of protoberberine alkaloids, focusing on the recent advances in the biosynthetic pathway, the regulatory mechanism of biosynthesis, chemical synthesis, clinical applications and structure-activity relationship analysis of berberine. It is anticipated that this review will offer valuable insights for researchers in the fields of synthesis, medicinal chemistry, and bactericidal chemistry, who are engaged in exploring the chemistry and biology of protoberberine alkaloids.
{"title":"Plant protoberberine alkaloids: structural diversity, biosynthesis, synthesis, biological activity, structure-activity relationships and clinical applications of berberine","authors":"Weiqi Jiang , Wen Zhang , Chenxin Jing , Han Zhou , Zhi-Jun Zhang , Rui Wang , Ying-Qian Liu","doi":"10.1016/j.phytochem.2025.114690","DOIUrl":"10.1016/j.phytochem.2025.114690","url":null,"abstract":"<div><div>Protoberberine alkaloids are a class of organic heterocyclic compounds categorized within the isoquinoline alkaloids, exhibiting significant therapeutic potential due to their potent biological activities. With advancements natural product chemistry, synthetic organic chemistry, biochemistry, and molecular biology, novel insights into their biosynthetic pathways, chemical synthesis pathways, mechanisms of action, and clinical applications have been elucidated. A comprehensive understanding of protoberberine alkaloids is instrumental in enhancing their commercial value and utilization of medicinal plant resources. Among these alkaloids, berberine stands out as a well-studied compound with broad-spectrum bioactivities. In this review, we summarized the progress in the study of protoberberine alkaloids, focusing on the recent advances in the biosynthetic pathway, the regulatory mechanism of biosynthesis, chemical synthesis, clinical applications and structure-activity relationship analysis of berberine. It is anticipated that this review will offer valuable insights for researchers in the fields of synthesis, medicinal chemistry, and bactericidal chemistry, who are engaged in exploring the chemistry and biology of protoberberine alkaloids.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"242 ","pages":"Article 114690"},"PeriodicalIF":3.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-26DOI: 10.1016/j.phytochem.2025.114688
Hui-Ying Li , Meng-Yu Bao , Hao-Ming Xiong , Can-Can Wang , Li-Ping Bai , Wei Zhang , Cheng-Yu Chen , Zhi-Hong Jiang , Guo-Yuan Zhu
Phytochemical investigation of the seeds of Forsythia suspensa resulted in the isolation and characterization of 17 undescribed labdane and nor-labdane diterpenoids, named suspensaditerpenes A−Q (1−17), along with 13 known ones (18−30). Their structures were elucidated by a combination of NMR, HR-MS, and X-ray diffraction analyses. Structurally, 5, 10, and 13 are labdane diterpenoids featuring a lactone ring at the side chain, marking their first description in F. suspensa. Compounds 4, 14, 15, and 25 are 14,15-dinor-diterpenoids, among which 14 and 15 have a rare 6/6/5 ring skeleton. Furthermore, all known compounds were isolated from F. suspensa for the first time. The in vitro anti-inflammatory activities assay showed that 5, 8, 13, and 14 significantly inhibited the LPS-induced NO production at 20 μM in LPS-induced RAW264.7 cells, while the remaining 24 compounds demonstrated slight NO inhibitory activity. Further studies showed that 5 suppressed the LPS-induced expression of iNOS, p-p65, and NLRP3 proteins as well as NF-κB nuclear translocation in RAW264.7 cells.
{"title":"Suspensaditerpenes A–Q, anti-inflammatory labdane and nor-labdane diterpenoids from the seeds of Forsythia suspensa","authors":"Hui-Ying Li , Meng-Yu Bao , Hao-Ming Xiong , Can-Can Wang , Li-Ping Bai , Wei Zhang , Cheng-Yu Chen , Zhi-Hong Jiang , Guo-Yuan Zhu","doi":"10.1016/j.phytochem.2025.114688","DOIUrl":"10.1016/j.phytochem.2025.114688","url":null,"abstract":"<div><div>Phytochemical investigation of the seeds of <em>Forsythia suspensa</em> resulted in the isolation and characterization of 17 undescribed labdane and nor-labdane diterpenoids, named suspensaditerpenes A−Q (<strong>1</strong>−<strong>17</strong>), along with 13 known ones (<strong>18</strong>−<strong>30</strong>). Their structures were elucidated by a combination of NMR, HR-MS, and X-ray diffraction analyses. Structurally, <strong>5</strong>, <strong>10</strong>, and <strong>13</strong> are labdane diterpenoids featuring a lactone ring at the side chain, marking their first description in <em>F. suspensa</em>. Compounds <strong>4</strong>, <strong>14</strong>, <strong>15</strong>, and <strong>25</strong> are 14,15-dinor-diterpenoids, among which <strong>14</strong> and <strong>15</strong> have a rare 6/6/5 ring skeleton. Furthermore, all known compounds were isolated from <em>F. suspensa</em> for the first time. The <em>in vitro</em> anti-inflammatory activities assay showed that <strong>5</strong>, <strong>8</strong>, <strong>13</strong>, and <strong>14</strong> significantly inhibited the LPS-induced NO production at 20 μM in LPS-induced RAW264.7 cells, while the remaining 24 compounds demonstrated slight NO inhibitory activity. Further studies showed that <strong>5</strong> suppressed the LPS-induced expression of iNOS, p-p65, and NLRP3 proteins as well as NF-κB nuclear translocation in RAW264.7 cells.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"242 ","pages":"Article 114688"},"PeriodicalIF":3.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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