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}
Pub Date : 2025-09-25DOI: 10.1016/j.phytochem.2025.114685
Yebi Qin , Xinyan Shao , Yinzheng Xie , Hailin Lu , Kaien Chen , Xi Zheng , Guodong Chen , Lishe Gan , Song Ang , Dongli Li
The phytochemical assessment of Pogostemon esquirolii resulted in the isolation and identification of sixteen sesquiterpenoids, including eudesmane-type (1–6, 9, and 11), bisabolane-type (8 and 10), caryolane-type (13–14), guaiacane-type (15–16), and other types (7 and 12). Of them, compounds 1–10, namely pogostesquines A–J, are ten previously undescribed ones. Compound 7 possessed an unusual backbone with the isopropyl group substituted at C-8 instead of C-7. Their structures were confirmed by extensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and ECD calculations. All the compounds were reported from this plant for the first time. Biological evaluation revealed that compound 4 exhibited the most anti-neuroinflammatory activity by inhibiting NO production in LPS-induced BV2 mouse microglial cells. Subsequently, network pharmacology analyses indicated that compound 4 primarily alleviated neuroinflammation-induced cognitive dysfunction through the TNF signaling pathway. Molecular docking studies, molecular dynamics simulations techniques, and western blotting analysis further clarified that compound 4 could downregulate the expression of TNF-α and IL-6, and inhibit the activity of inflammation-associated inducible enzymes iNOS and COX-2. Concurrently, it was further demonstrated that compound 4 could inhibit the activation of NF-κB and MAPK signaling pathways via the TNF pathway.
{"title":"Isolation, characterization, and anti-neuroinflammatory activity of sesquiterpenoids from Pogostemon esquirolii","authors":"Yebi Qin , Xinyan Shao , Yinzheng Xie , Hailin Lu , Kaien Chen , Xi Zheng , Guodong Chen , Lishe Gan , Song Ang , Dongli Li","doi":"10.1016/j.phytochem.2025.114685","DOIUrl":"10.1016/j.phytochem.2025.114685","url":null,"abstract":"<div><div>The phytochemical assessment of <em>Pogostemon esquirolii</em> resulted in the isolation and identification of sixteen sesquiterpenoids, including eudesmane-type (<strong>1</strong>–<strong>6</strong>, <strong>9</strong>, and <strong>11</strong>), bisabolane-type (<strong>8</strong> and <strong>10</strong>), caryolane-type (<strong>13</strong>–<strong>14</strong>), guaiacane-type (<strong>15</strong>–<strong>16</strong>), and other types (<strong>7</strong> and <strong>12</strong>). Of them, compounds <strong>1</strong>–<strong>10</strong>, namely pogostesquines A–J, are ten previously undescribed ones. Compound <strong>7</strong> possessed an unusual backbone with the isopropyl group substituted at C-8 instead of C-7. Their structures were confirmed by extensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and ECD calculations. All the compounds were reported from this plant for the first time. Biological evaluation revealed that compound <strong>4</strong> exhibited the most anti-neuroinflammatory activity by inhibiting NO production in LPS-induced BV2 mouse microglial cells. Subsequently, network pharmacology analyses indicated that compound <strong>4</strong> primarily alleviated neuroinflammation-induced cognitive dysfunction through the TNF signaling pathway. Molecular docking studies, molecular dynamics simulations techniques, and western blotting analysis further clarified that compound <strong>4</strong> could downregulate the expression of TNF-α and IL-6, and inhibit the activity of inflammation-associated inducible enzymes iNOS and COX-2. Concurrently, it was further demonstrated that compound <strong>4</strong> could inhibit the activation of NF-κB and MAPK signaling pathways via the TNF pathway.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"241 ","pages":"Article 114685"},"PeriodicalIF":3.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182111","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 : 2025-09-25DOI: 10.1016/j.phytochem.2025.114687
Jiang Wan , Xin Chen , Can Wang , Ying-Peng Tong , Yeun-Mun Choo , Xiao-Fei Shen , Yu-Feng Wang , Chun-Xiao Jiang , Jin-Feng Hu
Six previously undescribed mono-acetylated sesquiterpene lactones (named opiparolides A‒F, 1–6, resp.), along with five structurally related known compounds, were isolated and characterized from the renewable leaves of the endangered Chinese endemic plant Michelia opipara (family Magnoliaceae) using an LC-MS/MS-based Ion Identity Molecular Networking (IIMN) strategy in combination with conventional chromatographic techniques. The chemical structures and absolute configurations of the compounds were unambiguously determined through comprehensive analyses, including NMR spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), GIAO-based NMR calculations with DP4+ analysis, and electronic circular dichroism (ECD) spectroscopy. Opiparolides A (1) and B (2) were identified as germacrane-type sesquiterpene lactones characterized by a typical α-methylene-γ-lactone moiety, while opiparolides C–F (3–6) are classified as C-15-functionalized eudesmane-type sesquiterpene lactones containing an α,β-unsaturated pentatomic lactone ring. Compounds 1–6 were evaluated for their inhibitory activity against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages, exhibiting IC50 values ranging from 8.6 to 16.8 μM. The interactions of sesquiterpene lactones 1 and 6 with the NO signaling pathway were examined through molecular docking studies. Moreover, molecular dynamics simulations further explored the structure and molecular properties of compound 6-iNOS complex. The findings highlight the critical importance of preserving plant species diversity as a reservoir for chemically diverse natural products with potential therapeutic applications in inflammation treatment.
{"title":"Phytochemical and biological studies on rare and endangered plants endemic to China. Part XLVII. Sesquiterpene lactones from the leaves of Michelia opipara and their anti-inflammation effects","authors":"Jiang Wan , Xin Chen , Can Wang , Ying-Peng Tong , Yeun-Mun Choo , Xiao-Fei Shen , Yu-Feng Wang , Chun-Xiao Jiang , Jin-Feng Hu","doi":"10.1016/j.phytochem.2025.114687","DOIUrl":"10.1016/j.phytochem.2025.114687","url":null,"abstract":"<div><div>Six previously undescribed mono-acetylated sesquiterpene lactones (named opiparolides A‒F, <strong>1</strong>–<strong>6</strong>, resp.), along with five structurally related known compounds, were isolated and characterized from the renewable leaves of the endangered Chinese endemic plant <em>Michelia opipara</em> (family Magnoliaceae) using an LC-MS/MS-based Ion Identity Molecular Networking (IIMN) strategy in combination with conventional chromatographic techniques. The chemical structures and absolute configurations of the compounds were unambiguously determined through comprehensive analyses, including NMR spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), GIAO-based NMR calculations with DP4+ analysis, and electronic circular dichroism (ECD) spectroscopy. Opiparolides A (<strong>1</strong>) and B (<strong>2</strong>) were identified as germacrane-type sesquiterpene lactones characterized by a typical <em>α</em>-methylene-<em>γ</em>-lactone moiety, while opiparolides C–F (<strong>3</strong>–<strong>6</strong>) are classified as C-15-functionalized eudesmane-type sesquiterpene lactones containing an <em>α</em>,<em>β</em>-unsaturated pentatomic lactone ring. Compounds <strong>1</strong>–<strong>6</strong> were evaluated for their inhibitory activity against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages, exhibiting IC<sub>50</sub> values ranging from 8.6 to 16.8 μM. The interactions of sesquiterpene lactones <strong>1</strong> and <strong>6</strong> with the NO signaling pathway were examined through molecular docking studies. Moreover, molecular dynamics simulations further explored the structure and molecular properties of compound <strong>6</strong>-iNOS complex. The findings highlight the critical importance of preserving plant species diversity as a reservoir for chemically diverse natural products with potential therapeutic applications in inflammation treatment.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"241 ","pages":"Article 114687"},"PeriodicalIF":3.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182152","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 : 2025-09-25DOI: 10.1016/j.phytochem.2025.114689
Biao Sun , Yun-Lin Ao , Xia Cao , Jia-Bing Zhang , Xia Zhang , Dong-Hao Lu , Man Lin , Jun-Shan Liu , Xiao-Qi Zhang
Nine undescribed hop bitter acids, humulupulones A–I (1–9), along with three known ones (10–12) were isolated from the pistillate flower of Humulus lupulus L. (hops). Structurally, compounds 1 and 2 possess an unprecedented nitrogen-containing skeleton in α-acids, and this is the first time that nitrogen has replaced oxygen at the same position, thereby forming a new skeleton consisting of a fused α-acid and a dimethyl-substituted pyridine. Compound 3 is a rare pyridine-2,4-dione derivative simultaneously incorporating prenyl and isopropyl moieties. Compounds 7–10 were separated into four pairs of enantiomers by chiral HPLC separation. Their structures were unambiguously established by comprehensive spectroscopic analysis, X-ray crystallography, and ECD calculations. Moreover, compounds 2, 4, and 7 exhibited significant anti-inflammatory activities in the CuSO4-induced zebrafish inflammation model. Compounds 4, 5, 7–10 and 12 possessed significant anti-dengue virus (DENV) activities at the viral adsorption and entry stages with IC50 values ranging from 0.29 μM to 70.09 μM, while compounds 7, 10, and 11 exerted anti-DENV activities at the viral replication stage with IC50 values of 71.47 ± 7.30, 19.36 ± 6.77, and 16.18 ± 3.49 μM, respectively.
{"title":"Hop bitter acids from the pistillate flower of Humulus lupulus L. and their anti-inflammatory and anti-dengue virus activities","authors":"Biao Sun , Yun-Lin Ao , Xia Cao , Jia-Bing Zhang , Xia Zhang , Dong-Hao Lu , Man Lin , Jun-Shan Liu , Xiao-Qi Zhang","doi":"10.1016/j.phytochem.2025.114689","DOIUrl":"10.1016/j.phytochem.2025.114689","url":null,"abstract":"<div><div>Nine undescribed hop bitter acids, humulupulones A–I (<strong>1</strong>–<strong>9</strong>), along with three known ones (<strong>10</strong>–<strong>12</strong>) were isolated from the pistillate flower of <em>Humulus lupulus</em> L. (hops). Structurally, compounds <strong>1</strong> and <strong>2</strong> possess an unprecedented nitrogen-containing skeleton in <em>α</em>-acids, and this is the first time that nitrogen has replaced oxygen at the same position, thereby forming a new skeleton consisting of a fused <em>α</em>-acid and a dimethyl-substituted pyridine. Compound <strong>3</strong> is a rare pyridine-2,4-dione derivative simultaneously incorporating prenyl and isopropyl moieties. Compounds <strong>7</strong>–<strong>10</strong> were separated into four pairs of enantiomers by chiral HPLC separation. Their structures were unambiguously established by comprehensive spectroscopic analysis, X-ray crystallography, and ECD calculations. Moreover, compounds <strong>2</strong>, <strong>4</strong>, and <strong>7</strong> exhibited significant anti-inflammatory activities in the CuSO<sub>4</sub>-induced zebrafish inflammation model. Compounds <strong>4</strong>, <strong>5</strong>, <strong>7</strong>–<strong>10</strong> and <strong>12</strong> possessed significant anti-dengue virus (DENV) activities at the viral adsorption and entry stages with IC<sub>50</sub> values ranging from 0.29 μM to 70.09 μM, while compounds <strong>7</strong>, <strong>10</strong>, and <strong>11</strong> exerted anti-DENV activities at the viral replication stage with IC<sub>50</sub> values of 71.47 ± 7.30, 19.36 ± 6.77, and 16.18 ± 3.49 μM, respectively.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"241 ","pages":"Article 114689"},"PeriodicalIF":3.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182144","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}
Bioprospecting of a rice culture of Trochila sp. BGP15P7IS3, an undescribed endophytic fungus from Lilium carniolicum, resulted in isolation and identification of eleven specialized metabolites, of which four pyridone alkaloid derivatives (1, 2, 4, and 5) and a biphenyl derivative (8) were identified as previously undescribed natural products. Moreover, two dibenzofuran derivatives, isousnic acid and usnic acid (9 and 10) with S absolute configuration were reported for the first time from an endophytic fungus. Additionally, the absolute stereochemistry of the previously described compound 7 was determined. The structure of the compounds isolated was established by means of HR-ESI-MS, 1- and 2D NMR, and ECD calculations, as well as utilizing previously published data. All isolates available in sufficient quantities were evaluated for their antimicrobial activity against a plant pathogen, Botrytis cinerea, and four human pathogens, Aspergillus fumigatus, Aspergillus flavus, Candida albicans, and Cryptococcus neoformans, as well as a human sextually transmitted parasite, Trichomonas vaginalis. Compound 3 displayed antifungal activity only against C. neoformans with an MIC value of 12.5 μg/mL, and compound 6 exhibited promising antifungal activity with MIC values of 0.39–3.25 μg/mL against all the aforementioned fungal pathogens, and a concentration-dependent growth inhibitory property against T. vaginalis. Based on the identification of derivatives, a revised biosynthetic pathway for pyridone-type alkaloids was proposed.
{"title":"Bioactive specialized metabolites of Trochila sp., an endophytic fungus of Lilium carniolicum","authors":"Mostafa Alilou , Yun Liu , Magdalena Steixner , Isidor Happacher , Sigrid Beate Abt , Ursula Fürnkranz , Fabio Gsaller , Ursula Peintner , Hubertus Haas","doi":"10.1016/j.phytochem.2025.114684","DOIUrl":"10.1016/j.phytochem.2025.114684","url":null,"abstract":"<div><div>Bioprospecting of a rice culture of <em>Trochila</em> sp. BGP15P7IS3, an undescribed endophytic fungus from <em>Lilium carniolicum</em>, resulted in isolation and identification of eleven specialized metabolites, of which four pyridone alkaloid derivatives (<strong>1</strong>, <strong>2</strong>, <strong>4,</strong> and <strong>5</strong>) and a biphenyl derivative (<strong>8</strong>) were identified as previously undescribed natural products. Moreover, two dibenzofuran derivatives, isousnic acid and usnic acid (<strong>9</strong> and <strong>10</strong>) with <em>S</em> absolute configuration were reported for the first time from an endophytic fungus. Additionally, the absolute stereochemistry of the previously described compound <strong>7</strong> was determined. The structure of the compounds isolated was established by means of HR-ESI-MS, 1- and 2D NMR, and ECD calculations, as well as utilizing previously published data. All isolates available in sufficient quantities were evaluated for their antimicrobial activity against a plant pathogen, <em>Botrytis cinerea</em>, and four human pathogens, <em>Aspergillus fumigatus</em>, <em>Aspergillus flavus</em>, <em>Candida albicans</em>, and <em>Cryptococcus neoformans</em>, as well as a human sextually transmitted parasite, <em>Trichomonas vaginalis</em>. Compound <strong>3</strong> displayed antifungal activity only against <em>C. neoformans</em> with an MIC value of 12.5 μg/mL, and compound <strong>6</strong> exhibited promising antifungal activity with MIC values of 0.39–3.25 μg/mL against all the aforementioned fungal pathogens, and a concentration-dependent growth inhibitory property against <em>T. vaginalis</em>. Based on the identification of derivatives, a revised biosynthetic pathway for pyridone-type alkaloids was proposed.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"242 ","pages":"Article 114684"},"PeriodicalIF":3.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177481","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 : 2025-09-24DOI: 10.1016/j.phytochem.2025.114686
Zi-Hao Ge , Si-Hui Mi , Wen-Long Kou , Guo-Dong Yao , Bin Lin , Jian Wang , Ming Bai , Xiao-Xiao Huang , Shao-Jiang Song
Four previously undescribed highly oxidized germacrane-type sesquiterpenoid dimers were isolated from Elephantopus tomentosus. Their planar structures and absolute configurations were unequivocally elucidated through comprehensive spectroscopic analysis, combined with experimental electronic circular dichroism (ECD) and time-dependent density functional theory (TDDFT) calculations. These dimers, characterized by an O-ether linkage, represent the first reported examples of such derivatives from the genus Elephantopus. The structural validity was verified by performing Hartree-Fock energy calculations within the quantum mechanical (QM) framework. All isolated sesquiterpenoid dimers exhibited moderate inhibitory activity against human hepatocellular carcinoma cell lines (HepG2 and Hep3B). Notably, compound 4 demonstrated the most significant cytotoxicity, with IC50 values of 1.64 μM (HepG2) and 4.85 μM (Hep3B). Furthermore, compound 4 markedly reduced mitochondrial membrane potential (MMP), indicating its role in inducing apoptosis via mitochondrial dysfunction. Network pharmacology and molecular docking further indicated that compound 4 could interact with HSP90AA1 by binding to key amino acid residues, potentially explaining its pharmacological activity.
{"title":"Highly oxidized germacrane-type sesquiterpenoid dimers from Elephantopus tomentosus L.: Structural characterization, DFT calculation and anti-hepatoma potential","authors":"Zi-Hao Ge , Si-Hui Mi , Wen-Long Kou , Guo-Dong Yao , Bin Lin , Jian Wang , Ming Bai , Xiao-Xiao Huang , Shao-Jiang Song","doi":"10.1016/j.phytochem.2025.114686","DOIUrl":"10.1016/j.phytochem.2025.114686","url":null,"abstract":"<div><div>Four previously undescribed highly oxidized germacrane-type sesquiterpenoid dimers were isolated from <em>Elephantopus tomentosus</em>. Their planar structures and absolute configurations were unequivocally elucidated through comprehensive spectroscopic analysis, combined with experimental electronic circular dichroism (ECD) and time-dependent density functional theory (TDDFT) calculations. These dimers, characterized by an <em>O</em>-ether linkage, represent the first reported examples of such derivatives from the genus <em>Elephantopus</em>. The structural validity was verified by performing Hartree-Fock energy calculations within the quantum mechanical (QM) framework. All isolated sesquiterpenoid dimers exhibited moderate inhibitory activity against human hepatocellular carcinoma cell lines (HepG2 and Hep3B). Notably, compound <strong>4</strong> demonstrated the most significant cytotoxicity, with IC<sub>50</sub> values of 1.64 μM (HepG2) and 4.85 μM (Hep3B). Furthermore, compound <strong>4</strong> markedly reduced mitochondrial membrane potential (MMP), indicating its role in inducing apoptosis via mitochondrial dysfunction. Network pharmacology and molecular docking further indicated that compound <strong>4</strong> could interact with HSP90AA1 by binding to key amino acid residues, potentially explaining its pharmacological activity.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"241 ","pages":"Article 114686"},"PeriodicalIF":3.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158445","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 : 2025-09-20DOI: 10.1016/j.phytochem.2025.114683
Dhrubojyoti D. Laskar , Michaël Jourdes , Gregory L. Helms , Qingyan Meng , Nancy A. Somerville , John R. Cort , Laurence B. Davin , Norman G. Lewis
The wine-red coloration of xylem in antisense cinnamyl alcohol dehydrogenase (CAD) down-regulated tobacco (Nicotiana tabacum) has long been reported as due to wine-red colored lignin. To investigate validity of the wine-red lignin report, both wild type (WT) and anti-sense CAD down-regulated tobacco stem xylem tissues were examined, with the red pigment found to be facilely removed by treatment with an 0.5 % HCl in MeOH solution at 4 °C. The red pigment in the xylem tissues was rapidly reconstituted in both pre-treated antisense CAD and WT xylem tissues by incubation with sinapyl aldehyde in MeOH solution, and then facilely removed by subsequent 0.5 % HCl in MeOH treatment. Only sinapyl aldehyde was demonstrated as contributing to the red pigmentation, this being consistent with its anionic quinone methide canonical form. No evidence was obtained for a wine-red lignin. Additionally, lignin-derived isolates from both antisense CAD and WT lines essentially differed only in presence of small amounts (ca. 1.41 %) of 8–O–4′ linked sinapyl aldehyde end groups and a slightly smaller molecular weight distribution (MWD) of the lignin from the antisense CAD line. No evidence was obtained that poly-hydroxycinnamyl aldehydes contributed to bulk lignification; the slightly lower MWD may result from hydroxycinnamyl aldehydes functioning as terminators of polymerization during lignification. More importantly, these findings are placed in context of what is now known about 1) lignin macromolecular assembly proper in planta, 2) dirigent protein functions, 3D structures, and active sites as entry points to distinct plant phenol metabolic classes, including lignins, 3) AlphaFold2 modeling of Dir-e subfamily proteins involved in lignification, and 4) what urgently remains to be done in the study of lignification.
{"title":"Wine-red lignin revisited, dirigent proteins, and native lignin macromolecular configuration","authors":"Dhrubojyoti D. Laskar , Michaël Jourdes , Gregory L. Helms , Qingyan Meng , Nancy A. Somerville , John R. Cort , Laurence B. Davin , Norman G. Lewis","doi":"10.1016/j.phytochem.2025.114683","DOIUrl":"10.1016/j.phytochem.2025.114683","url":null,"abstract":"<div><div>The wine-red coloration of xylem in antisense cinnamyl alcohol dehydrogenase (CAD) down-regulated tobacco (<em>Nicotiana tabacum</em>) has long been reported as due to wine-red colored lignin. To investigate validity of the wine-red lignin report, both wild type (WT) and anti-sense CAD down-regulated tobacco stem xylem tissues were examined, with the red pigment found to be facilely removed by treatment with an 0.5 % HCl in MeOH solution at 4 °C. The red pigment in the xylem tissues was rapidly reconstituted in both pre-treated antisense CAD and WT xylem tissues by incubation with sinapyl aldehyde in MeOH solution, and then facilely removed by subsequent 0.5 % HCl in MeOH treatment. Only sinapyl aldehyde was demonstrated as contributing to the red pigmentation, this being consistent with its anionic quinone methide canonical form. No evidence was obtained for a wine-red lignin. Additionally, lignin-derived isolates from both antisense CAD and WT lines essentially differed only in presence of small amounts (<em>ca.</em> 1.41 %) of 8–<em>O</em>–4′ linked sinapyl aldehyde end groups and a slightly smaller molecular weight distribution (MWD) of the lignin from the antisense CAD line. No evidence was obtained that poly-hydroxycinnamyl aldehydes contributed to bulk lignification; the slightly lower MWD may result from hydroxycinnamyl aldehydes functioning as terminators of polymerization during lignification. More importantly, these findings are placed in context of what is now known about 1) lignin macromolecular assembly proper <em>in planta</em>, 2) dirigent protein functions, 3D structures, and active sites as entry points to distinct plant phenol metabolic classes, including lignins, 3) AlphaFold2 modeling of Dir-e subfamily proteins involved in lignification, and 4) what urgently remains to be done in the study of lignification.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"242 ","pages":"Article 114683"},"PeriodicalIF":3.4,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113907","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 : 2025-09-16DOI: 10.1016/j.phytochem.2025.114679
Liangxiu Liao , Tao Zhu , Shan Ran , Yizhou Bian , Ming Yao , Qingpei Liu , Wenjing Wang , Xiaolong Yang
Thirteen previously undescribed clavatol derivatives (1, 2, 3a, 3b, and 4−12), along with thirteen known compounds were isolated from the endophytic fungus Penicillium commune XL-0473. Their structures were established through comprehensive spectroscopic analyses, quantum chemical electronic circular dichroism calculations, single-crystal X-ray diffraction, and chemical synthesis experiment. Notably, compounds 1 and 2 represent the first reported clavatol dimers conjugated with amino acids. Compounds 8–11 are unprecedented derivatives containing a 1,6-dioxaspiro[4.4]nonane framework. Compound 16 demonstrated potent antibacterial activity against multidrug-resistant pathogens, with MIC values ranging from 3.13 to 6.25 μg/mL. A plausible nonenzymatic self-assembly mechanism involving ortho-quinone methide intermediates was proposed to explain their biosynthesis pathway.
{"title":"Clavatol derivatives from the endophytic fungus Penicillium commune XL-0473","authors":"Liangxiu Liao , Tao Zhu , Shan Ran , Yizhou Bian , Ming Yao , Qingpei Liu , Wenjing Wang , Xiaolong Yang","doi":"10.1016/j.phytochem.2025.114679","DOIUrl":"10.1016/j.phytochem.2025.114679","url":null,"abstract":"<div><div>Thirteen previously undescribed clavatol derivatives (<strong>1</strong>, <strong>2</strong>, <strong>3a</strong>, <strong>3b</strong>, and <strong>4</strong>−<strong>12)</strong>, along with thirteen known compounds were isolated from the endophytic fungus <em>Penicillium commune</em> XL-0473. Their structures were established through comprehensive spectroscopic analyses, quantum chemical electronic circular dichroism calculations, single-crystal X-ray diffraction, and chemical synthesis experiment. Notably, compounds <strong>1</strong> and <strong>2</strong> represent the first reported clavatol dimers conjugated with amino acids. Compounds <strong>8</strong>–<strong>11</strong> are unprecedented derivatives containing a 1,6-dioxaspiro[4.4]nonane framework. Compound <strong>16</strong> demonstrated potent antibacterial activity against multidrug-resistant pathogens, with MIC values ranging from 3.13 to 6.25 μg/mL. A plausible nonenzymatic self-assembly mechanism involving <em>ortho</em>-quinone methide intermediates was proposed to explain their biosynthesis pathway.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"241 ","pages":"Article 114679"},"PeriodicalIF":3.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086781","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 : 2025-09-16DOI: 10.1016/j.phytochem.2025.114678
Lan Yao , Shiyu Li , Jinxiu Zhang , Zhuang Li , Jianhua Lv
In this study, eleven undescribed sesquiterpenoids, named marasmiellolides A−K (1−11), were isolated from the rice-fermented mycelia of the basidiomycete Marasmiellus candidus. Their structures were established through extensive spectroscopic analyses including HR-ESI-MS, 1D and 2D NMR. The absolute configurations of compounds 1−3 and 5−8 were assigned based on the comparison of the experimental and calculated ECD data. In addition, compounds 1−11 were tested for anti-inflammatory activity against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages. Compounds 1−3 exhibited significant anti-inflammatory activity with IC50 values ranging from 7.2 to 13.2 μM.
{"title":"Eleven previously undescribed sesquiterpenoids with anti-inflammatory activity isolated from the cultures of basidiomycete Marasmiellus candidus","authors":"Lan Yao , Shiyu Li , Jinxiu Zhang , Zhuang Li , Jianhua Lv","doi":"10.1016/j.phytochem.2025.114678","DOIUrl":"10.1016/j.phytochem.2025.114678","url":null,"abstract":"<div><div>In this study, eleven undescribed sesquiterpenoids, named marasmiellolides A−K (<strong>1</strong>−<strong>11</strong>), were isolated from the rice-fermented mycelia of the basidiomycete <em>Marasmiellus candidus.</em> Their structures were established through extensive spectroscopic analyses including HR-ESI-MS, 1D and 2D NMR. The absolute configurations of compounds <strong>1−3</strong> and <strong>5−8</strong> were assigned based on the comparison of the experimental and calculated ECD data. In addition, compounds <strong>1</strong>−<strong>11</strong> were tested for anti-inflammatory activity against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages. Compounds <strong>1</strong>−<strong>3</strong> exhibited significant anti-inflammatory activity with IC<sub>50</sub> values ranging from 7.2 to 13.2 μM.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"241 ","pages":"Article 114678"},"PeriodicalIF":3.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086809","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}
Eleven previously undescribed diterpenoids, cilileucapenoids A–K (1–10 and 12), comprising two halimane diterpenoids (1 and 12) and nine spiro-labdane diterpenoids (2–10), along with one known analogue (11), were isolated from the whole plant of Leucas ciliata. The structures and absolute configurations were determined through the analysis of their HR-ESI-MS, 1D/2D NMR, electronic circular dichroism (ECD) calculations, Mosher's esterification, and single-crystal X-ray diffraction. Notably, 1 represents the first reported aromatic halimane diterpenoid, while 2 features as a rare dispiro-tetrahydrofuran-labdane skeleton. Compounds 3–10 uniformly incorporate a spiro-tetrahydrofuran moiety. In bioactivity assessments, compounds 1, 3, 4, and 7 demonstrated significant anti-inflammatory effects by inhibiting nitric oxide (NO) production in LPS-stimulated RAW264.7 macrophages, with IC50 values ranging from 9.13 to 25.94 μM. Structure-activity relationship (SAR) analysis further established that the Z-configuration of these diterpenoids confers markedly enhanced anti-inflammatory efficacy relative to the E-configuration.
{"title":"Nor-halimane and spiro-labdane diterpenoids with anti-inflammatory activity from Leucas ciliata Benth","authors":"Jia-Cai Kuang , Fu-Ling Cen , Xuan Zhang , Xu-Hua Nong , Xue-Ming Zhou , Xiao-Bao Li , Zhang-Xin Yu , Guang-Ying Chen","doi":"10.1016/j.phytochem.2025.114681","DOIUrl":"10.1016/j.phytochem.2025.114681","url":null,"abstract":"<div><div>Eleven previously undescribed diterpenoids, cilileucapenoids A–K (<strong>1</strong>–<strong>10</strong> and <strong>12</strong>), comprising two halimane diterpenoids (<strong>1</strong> and <strong>12</strong>) and nine <em>spiro</em>-labdane diterpenoids (<strong>2</strong>–<strong>10</strong>), along with one known analogue (<strong>11</strong>), were isolated from the whole plant of <em>Leucas ciliata</em>. The structures and absolute configurations were determined through the analysis of their HR-ESI-MS, 1D/2D NMR, electronic circular dichroism (ECD) calculations, Mosher's esterification, and single-crystal X-ray diffraction. Notably, <strong>1</strong> represents the first reported aromatic halimane diterpenoid, while <strong>2</strong> features as a rare <em>dispiro</em>-tetrahydrofuran-labdane skeleton. Compounds <strong>3</strong>–<strong>10</strong> uniformly incorporate a <em>spiro</em>-tetrahydrofuran moiety. In bioactivity assessments, compounds <strong>1</strong>, <strong>3</strong>, <strong>4</strong>, and <strong>7</strong> demonstrated significant anti-inflammatory effects by inhibiting nitric oxide (NO) production in LPS-stimulated RAW264.7 macrophages, with IC<sub>50</sub> values ranging from 9.13 to 25.94 μM. Structure-activity relationship (SAR) analysis further established that the <em>Z</em>-configuration of these diterpenoids confers markedly enhanced anti-inflammatory efficacy relative to the <em>E</em>-configuration.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"241 ","pages":"Article 114681"},"PeriodicalIF":3.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086840","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号