Pub Date : 2026-03-01Epub Date: 2026-01-22DOI: 10.1016/j.fitote.2026.107110
Yuan-Yuan Zhu , Xin Meng , Qing-Shan Chen , Li-Li Zhang , Hai-Xue Kuang , Yang Liu , Juan Pan , Yan Liu
Six new dihydroisoflavones (1–6) along with eight congeners (7–9, 11–15) as well as a known chalcone derivative (10) were isolated from Polygonatum sibiricum. To enhance the specificity and efficiency of the separation process, a combination of MSDIAL and MassQL techniques was used alongside column chromatography with silica gel, ODS, and preparative HPLC. The structural elucidation of the compounds was accomplished via thorough spectral characterisation, encompassing techniques such as 1D and 2D NMR, HR-ESI-MS, IR, UV and ECD. These findings were further validated by comparing them with data from existing literature. Furthermore, the neuroprotective activity of all purified compounds was assessed using a PC12 cell model subjected to H₂O₂ induction. The results of our study indicated that compounds 2, 3, 5, 11, and 12 significantly alleviated H₂O₂-induced damage in PC12 cells, increasing cell viability to approximately 74%, 76%, 79%, 76%, and 72%, respectively, at 50 μM without exhibiting cytotoxicity.
{"title":"New dihydrohomoisoflavones from Polygonatum sibiricum with neuroprotective activity","authors":"Yuan-Yuan Zhu , Xin Meng , Qing-Shan Chen , Li-Li Zhang , Hai-Xue Kuang , Yang Liu , Juan Pan , Yan Liu","doi":"10.1016/j.fitote.2026.107110","DOIUrl":"10.1016/j.fitote.2026.107110","url":null,"abstract":"<div><div>Six new dihydroisoflavones (<strong>1–6</strong>) along with eight congeners (<strong>7–9</strong>, <strong>11–15</strong>) as well as a known chalcone derivative (<strong>10</strong>) were isolated from <em>Polygonatum sibiricum</em>. To enhance the specificity and efficiency of the separation process, a combination of MSDIAL and MassQL techniques was used alongside column chromatography with silica gel, ODS, and preparative HPLC. The structural elucidation of the compounds was accomplished via thorough spectral characterisation, encompassing techniques such as 1D and 2D NMR, HR-ESI-MS, IR, UV and ECD. These findings were further validated by comparing them with data from existing literature. Furthermore, the neuroprotective activity of all purified compounds was assessed using a PC12 cell model subjected to H₂O₂ induction. The results of our study indicated that compounds <strong>2</strong>, <strong>3</strong>, <strong>5</strong>, <strong>11</strong>, and <strong>12</strong> significantly alleviated H₂O₂-induced damage in PC12 cells, increasing cell viability to approximately 74%, 76%, 79%, 76%, and 72%, respectively, at 50 μM without exhibiting cytotoxicity.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107110"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-03DOI: 10.1016/j.fitote.2026.107116
Yabo Chen , Kun Li , Yanting Gong , Xunkang Wang , Ruiqing Zhu , Mengyao Guan , Liyong Lai , Yiping Jiang , Tianshuang Xia , Xiaoqiang Yue , Hailiang Xin
Rhododendron molle (Blume) G. Don is a plant of great significance in traditional Chinese medicine, particularly valued for its analgesic properties. This review systematically consolidates contemporary research on its phytochemistry, pharmacology, and structure-activity relationships. Over 200 compounds have been identified, with diterpenoids—notably those featuring 12 novel carbon skeletons—recognized as the principal bioactive and toxic constituents. These compounds underpin the plant's broad pharmacological profile, including marked anti-inflammatory, immunomodulatory, and potent antinociceptive activities. A central contribution of this review is a critical structure-activity relationships analysis that systematically identifies key functional groups (e.g., the C-2 and C-3 hydroxyls) as pivotal for the antinociceptive efficacy of grayanane diterpenoids. Promising lead compounds, such as Rhodojaponin III, are highlighted for their potential in developing new therapeutics for rheumatoid arthritis and neuropathic pain, as well as natural insecticides. By integrating traditional knowledge with modern science, this review not only validates the traditional uses of R. molle but also provides a foundational framework for future research, explicitly pointing to the need for in-depth mechanistic studies, comprehensive toxicity profiling, and rational drug development.
杜鹃花（Rhododendron molle (Blume) G. Don）是一种具有重要药用价值的植物，其镇痛作用尤为重要。本文系统地综述了其植物化学、药理学和构效关系的当代研究。已经鉴定出200多种化合物，其中二萜类化合物——特别是那些具有12个新碳骨架的化合物——被认为是主要的生物活性和有毒成分。这些化合物支撑着植物广泛的药理学特征，包括显著的抗炎、免疫调节和有效的抗伤活性。这篇综述的核心贡献是一个关键的构效关系分析，该分析系统地确定了关键官能团（例如，C-2和C-3羟基），这些官能团对grayanane二萜的抗伤害性功效至关重要。有前景的先导化合物，如Rhodojaponin III，因其在开发类风湿关节炎和神经性疼痛的新疗法以及天然杀虫剂方面的潜力而受到强调。通过传统知识与现代科学的结合，本文不仅验证了霉霉的传统用途，而且为未来的研究提供了基础框架，明确指出需要深入的机制研究，全面的毒性分析和合理的药物开发。
{"title":"Grayanane diterpenoids from Rhododendron molle: Structural diversity, mechanisms of antinociceptive action, and structure-activity relationships","authors":"Yabo Chen , Kun Li , Yanting Gong , Xunkang Wang , Ruiqing Zhu , Mengyao Guan , Liyong Lai , Yiping Jiang , Tianshuang Xia , Xiaoqiang Yue , Hailiang Xin","doi":"10.1016/j.fitote.2026.107116","DOIUrl":"10.1016/j.fitote.2026.107116","url":null,"abstract":"<div><div><em>Rhododendron molle</em> (Blume) G. Don is a plant of great significance in traditional Chinese medicine, particularly valued for its analgesic properties. This review systematically consolidates contemporary research on its phytochemistry, pharmacology, and structure-activity relationships. Over 200 compounds have been identified, with diterpenoids—notably those featuring 12 novel carbon skeletons—recognized as the principal bioactive and toxic constituents. These compounds underpin the plant's broad pharmacological profile, including marked anti-inflammatory, immunomodulatory, and potent antinociceptive activities. A central contribution of this review is a critical structure-activity relationships analysis that systematically identifies key functional groups (e.g., the C-2 and C-3 hydroxyls) as pivotal for the antinociceptive efficacy of grayanane diterpenoids. Promising lead compounds, such as Rhodojaponin III, are highlighted for their potential in developing new therapeutics for rheumatoid arthritis and neuropathic pain, as well as natural insecticides. By integrating traditional knowledge with modern science, this review not only validates the traditional uses of <em>R. molle</em> but also provides a foundational framework for future research, explicitly pointing to the need for in-depth mechanistic studies, comprehensive toxicity profiling, and rational drug development.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107116"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A comprehensive 13C NMR-based dereplication and LC-MS/MS based-molecular networking analyses were performed on the bark extract of Xylopia ferruginea (Hook.f. Thomson) and led to the discovery of fifteen isoquinoline alkaloids; lysicamine (1), liriodenine (2), O-methylmoschatoline (3), anonaine (4), norlirioferine (5), isoboldine (6), columbamine (7), jatrorrhizine (8), palmatine (9), nuciferine (10), roemerine (11), N-methylasimilobine (12), N-methylasimilobine N-oxide (13), stephanine (14) and isocorydine (15). Further purification led to the isolation of one new compound, 4,5-dihydro-2-hydroxy-1-methoxy-7H-dibenzo[de,g]quinolin-7-one (16), and four known compounds; lysicamine (1), liriodenine (2), nuciferine (10) and roemerine (11). Selected alkaloid isolates were evaluated for neuroprotective activity in a transgenic Caenorhabditis elegans model expressing human amyloid-beta (A). Lysicamine (1) and liriodenine (2), exhibited moderate neuroprotective activity with paralysis delayed by 1.1 h and 0.5 h, respectively. This study highlights the chemical profile and neuroprotective activity of isoquinoline alkaloids from X. ferruginea and underscores the utility of integrative dereplication and molecular networking approaches in natural product discovery.
{"title":"Targeted isolation and identification of isoquinoline alkaloids from Xylopia ferruginea bark with anti Aβ-induced paralysis activity","authors":"Nurul Azirah Mohd Nawi , Hazrina Hazni , Khalijah Awang , Sook Yee Liew , Syazreen Nadia Sulaiman , Fatimah Salim , Nur Vicky Bihud , Sheila Nathan , Sylvia Chieng , Marc Litaudon , Séverine Derbré , Muhamad Aqmal Othman , Azeana Zahari","doi":"10.1016/j.fitote.2025.107040","DOIUrl":"10.1016/j.fitote.2025.107040","url":null,"abstract":"<div><div>A comprehensive <sup>13</sup>C NMR-based dereplication and LC-MS/MS based-molecular networking analyses were performed on the bark extract of <em>Xylopia ferruginea</em> (Hook.f. Thomson) and led to the discovery of fifteen isoquinoline alkaloids; lysicamine (<strong>1</strong>), liriodenine (<strong>2</strong>), <em>O</em>-methylmoschatoline (<strong>3</strong>), anonaine (<strong>4</strong>), norlirioferine (<strong>5</strong>), isoboldine (<strong>6</strong>), columbamine (<strong>7</strong>), jatrorrhizine (<strong>8</strong>), palmatine (<strong>9</strong>), nuciferine (<strong>10</strong>), roemerine (<strong>11</strong>), <em>N</em>-methylasimilobine (<strong>12</strong>), <em>N</em>-methylasimilobine <em>N</em>-oxide (<strong>13</strong>), stephanine (<strong>14</strong>) and isocorydine (<strong>15</strong>). Further purification led to the isolation of one new compound, 4,5-dihydro-2-hydroxy-1-methoxy-7H-dibenzo[<em>de</em>,<em>g</em>]quinolin-7-one (<strong>16</strong>), and four known compounds; lysicamine (<strong>1</strong>), liriodenine (<strong>2</strong>), nuciferine (<strong>10</strong>) and roemerine (<strong>11</strong>). Selected alkaloid isolates were evaluated for neuroprotective activity in a transgenic <em>Caenorhabditis elegans</em> model expressing human amyloid-beta (A<span><math><mi>β</mi></math></span>). Lysicamine (<strong>1)</strong> and liriodenine (<strong>2</strong>), exhibited moderate neuroprotective activity with paralysis delayed by 1.1 h and 0.5 h, respectively. This study highlights the chemical profile and neuroprotective activity of isoquinoline alkaloids from <em>X. ferruginea</em> and underscores the utility of integrative dereplication and molecular networking approaches in natural product discovery.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107040"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-14DOI: 10.1016/j.fitote.2026.107093
Huan Wang , Mu Zi Li , Min Zhang , Shuang E , Men Long , Shi Jun Yu , Shi Qi Xu , De Xin Dang
Conventional treatments for allergic rhinitis (AR), such as oral medications and nasal sprays, can effectively alleviate symptoms but often cause side effects, including potential organ damage and symptom relapse after discontinuation. Aromatherapy, a traditional approach used in respiratory care, offers a potentially safer and non-invasive alternative. This study aimed to investigate the therapeutic effects and molecular mechanisms of Chrysanthemum morifolium cv. Chuju essential oil-based aromatherapy (CJA) against AR using network pharmacology, in vivo experiments, molecular docking, and molecular dynamics simulations. Volatile compounds in Chuju essential oil were identified by gas chromatography–mass spectrometry. Network pharmacology analysis was employed to predict the overlapping targets between volatile constituents- and AR-related genes, followed by the construction of a protein-protein interaction network. Key hub genes were identified using the Molecular Complex Detection clustering algorithm. To validate the results of network pharmacology, an ovalbumin-induced AR mouse model was used to evaluate the therapeutic potential of CJA. Molecular biology assays were further performed to verify key targets. Molecular docking and molecular dynamics simulations were then conducted to investigate the binding affinity and stability between the major volatile compounds and their respective targets. Our results demonstrate that (−)-isolongifolol, acetate and (Z,E)-α-farnesene are the major bioactive volatile constituents of Chuju essential oil. These compounds appear to exert anti-inflammatory effects by regulating the mTOR-PPARγ signaling cascade, thereby alleviating AR symptoms in the mouse model. Collectively, these findings highlight the therapeutic potential of CJA as a promising natural intervention for managing AR.
{"title":"Aromatherapy with Chrysanthemum morifolium cv. Chuju essential oil alleviates allergic rhinitis by modulating the mTOR-PPARγ signaling cascade","authors":"Huan Wang , Mu Zi Li , Min Zhang , Shuang E , Men Long , Shi Jun Yu , Shi Qi Xu , De Xin Dang","doi":"10.1016/j.fitote.2026.107093","DOIUrl":"10.1016/j.fitote.2026.107093","url":null,"abstract":"<div><div>Conventional treatments for allergic rhinitis (AR), such as oral medications and nasal sprays, can effectively alleviate symptoms but often cause side effects, including potential organ damage and symptom relapse after discontinuation. Aromatherapy, a traditional approach used in respiratory care, offers a potentially safer and non-invasive alternative. This study aimed to investigate the therapeutic effects and molecular mechanisms of <em>Chrysanthemum morifolium</em> cv. Chuju essential oil-based aromatherapy (CJA) against AR using network pharmacology, <em>in vivo</em> experiments, molecular docking, and molecular dynamics simulations. Volatile compounds in Chuju essential oil were identified by gas chromatography–mass spectrometry. Network pharmacology analysis was employed to predict the overlapping targets between volatile constituents- and AR-related genes, followed by the construction of a protein-protein interaction network. Key hub genes were identified using the Molecular Complex Detection clustering algorithm. To validate the results of network pharmacology, an ovalbumin-induced AR mouse model was used to evaluate the therapeutic potential of CJA. Molecular biology assays were further performed to verify key targets. Molecular docking and molecular dynamics simulations were then conducted to investigate the binding affinity and stability between the major volatile compounds and their respective targets. Our results demonstrate that (−)-isolongifolol, acetate and (Z,E)-α-farnesene are the major bioactive volatile constituents of Chuju essential oil. These compounds appear to exert anti-inflammatory effects by regulating the mTOR-PPARγ signaling cascade, thereby alleviating AR symptoms in the mouse model. Collectively, these findings highlight the therapeutic potential of CJA as a promising natural intervention for managing AR.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107093"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-22DOI: 10.1016/j.fitote.2026.107106
Ren-Fen Ma , Rui Cui , Qian Wu , Hua Zhang
Seven previously undescribed polycyclic diterpenoids, comprising four tiglianes (1–4), a daphnane (5) and two ingenanes (13 and 14), together with seven known tigliane (7–12) and six known ingenane (15–20) cometabolites, were isolated from the aerial parts of Euphorbia wallichii. The chemical structures of these compounds were elucidated through spectroscopic methods, mainly including mass spectrometry, nuclear magnetic resonance and electronic circular dichroism, and diterpenoids 1–6 feature interesting epoxy rings. Compounds 1, 7, 10, 12–14 and 18 showed promising suppressing effect on TGF-β1-induced upregulation of fibronectin (a biomarker of fibrosis) in human renal proximal tubular epithelial HK-2 cells. Further investigation demonstrated that compound 1 may exert anti-renal fibrosis potential with associated inhibition on TGF-β/Smad signaling pathway.
{"title":"Diterpenoids from Euphorbia wallichii show anti-renal fibrosis potential with associated inhibition on TGF-β/Smad signaling pathway","authors":"Ren-Fen Ma , Rui Cui , Qian Wu , Hua Zhang","doi":"10.1016/j.fitote.2026.107106","DOIUrl":"10.1016/j.fitote.2026.107106","url":null,"abstract":"<div><div>Seven previously undescribed polycyclic diterpenoids, comprising four tiglianes (<strong>1</strong>–<strong>4</strong>), a daphnane (<strong>5</strong>) and two ingenanes (<strong>13</strong> and <strong>14</strong>), together with seven known tigliane (<strong>7</strong>–<strong>12</strong>) and six known ingenane (<strong>15</strong>–<strong>20</strong>) cometabolites, were isolated from the aerial parts of <em>Euphorbia wallichii</em>. The chemical structures of these compounds were elucidated through spectroscopic methods, mainly including mass spectrometry, nuclear magnetic resonance and electronic circular dichroism, and diterpenoids <strong>1</strong>–<strong>6</strong> feature interesting epoxy rings. Compounds <strong>1</strong>, <strong>7</strong>, <strong>10</strong>, <strong>12</strong>–<strong>14</strong> and <strong>18</strong> showed promising suppressing effect on TGF-β1-induced upregulation of fibronectin (a biomarker of fibrosis) in human renal proximal tubular epithelial HK-2 cells. Further investigation demonstrated that compound <strong>1</strong> may exert anti-renal fibrosis potential with associated inhibition on TGF-β/Smad signaling pathway.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107106"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-22DOI: 10.1016/j.fitote.2026.107109
Qi He , Mei-Ru Han , Huan Xia , Qing Li , Xiao-Hong Wei , Gui-Yang Xia , Sheng Lin
By employing a molecular networking analysis strategy, we successfully guided the isolation of alkaloids from the ethyl acetate extract of Paeonia lactiflora roots. This approach led to the discovery of previously undescribed indole alkaloids, (+)/(−)-paeonialkaloid A [(+)/(−)-1], paeonialkaloids B and C (2 and 3), along with one known alkaloid (4). The structures were fully established through comprehensive spectroscopic methods, including 1D/2D NMR, HRESIMS, UV, IR, and theoretical calculations of electronic circular dichroism (ECD) spectra. Indole alkaloids have been rarely reported from the Paeonia genus. In this study, the discovery of (+)/(−)-1, 2 and 3 provides only the second report of such compounds. In addition, (+)-1, (−)-1, 2 and 3 are moderate inhibitors of human carboxylesterase 2 (hCE2), with IC₅₀ values of 13.65 ± 0.64, 13.92 ± 0.72, 14.45 ± 0.43, and 14.16 ± 1.05 μM, respectively, which was revealed through the molecular docking studies.
{"title":"Indole alkaloids exhibiting hCE2 inhibitory activity from the roots of Paeonia lactiflora using a feature-based molecular network strategy","authors":"Qi He , Mei-Ru Han , Huan Xia , Qing Li , Xiao-Hong Wei , Gui-Yang Xia , Sheng Lin","doi":"10.1016/j.fitote.2026.107109","DOIUrl":"10.1016/j.fitote.2026.107109","url":null,"abstract":"<div><div>By employing a molecular networking analysis strategy, we successfully guided the isolation of alkaloids from the ethyl acetate extract of <em>Paeonia lactiflora</em> roots. This approach led to the discovery of previously undescribed indole alkaloids, (+)/(−)-paeonialkaloid A [(+)/(−)-<strong>1</strong>], paeonialkaloids B and C (<strong>2</strong> and <strong>3</strong>)<strong>,</strong> along with one known alkaloid (<strong>4</strong>). The structures were fully established through comprehensive spectroscopic methods, including 1D/2D NMR, HRESIMS, UV, IR, and theoretical calculations of electronic circular dichroism (ECD) spectra. Indole alkaloids have been rarely reported from the <em>Paeonia</em> genus. In this study, the discovery of (+)/(−)-<strong>1</strong>, <strong>2</strong> and <strong>3</strong> provides only the second report of such compounds. In addition, (+)-<strong>1</strong>, (−)-<strong>1</strong>, <strong>2</strong> and <strong>3</strong> are moderate inhibitors of human carboxylesterase 2 (hCE2), with IC₅₀ values of 13.65 ± 0.64, 13.92 ± 0.72, 14.45 ± 0.43, and 14.16 ± 1.05 μM, respectively, which was revealed through the molecular docking studies.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107109"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-12DOI: 10.1016/j.fitote.2026.107090
Solomon Tesfaye , Larissa Birkel , Siva Sankar Murthy Bandaru , Diana Astrid Barrera-Adame , Malte Eichelbaum , Ermias Lulekal , Kaleab Asres , Ephrem Engidawork , Christian Schulze , Nwet Nwet Win , Carola Schulzke , Timo H.J. Niedermeyer , Patrick J. Bednarski , Sebastian Guenther , Nadin Schultze
The traditional Ethiopian medicinal plants Acokanthera schimperi (A.DC.) Schweinf. and Gnidia involucrata Steud. ex A.Rich were explored for their potential as sources of anticancer agents. Bioassay-guided fractionation yielded a previously unreported phorbol ester (5), alongside four known compounds (1–4) from G. involucrata and a pregnane-type steroid (6) from A. schimperi. Structural elucidation was accomplished through comprehensive NMR and HRMS analyses. The antiproliferative activities of these compounds were assessed against A-427, Dan-G, MCF-7, and SiSo cancer cell lines, revealing diverse levels of activity. Notably, the pregnane derivative (6) demonstrated potent activity, with GI₅₀ values ranging from 2.3 to 4.7 μM across the tested cell lines. Mechanistic investigations demonstrated that compound (6) inhibited mitotic spindle assembly and spindle-pole separation, leading to a pronounced G2/M phase cell cycle arrest in the SiSo cell line. In contrast, compound (5) exhibited potent antiproliferative activity against the Dan-G cell line (GI₅₀ = 0.3 ± 0.05 nM) and moderate to weak activity in the remaining cell lines, with GI₅₀ values ranging from 5.2 to >50 μM, inducing early apoptosis in Dan-G cells. These findings highlight compounds 5 and 6 as promising anticancer candidates and provide a scientific basis for the ethnomedicinal use of these plants in cancer therapy.
{"title":"Bioassay-guided isolation and identification of antiproliferative compounds from Acokanthera schimperi (A.DC.) Schweinf and Gnidia involucrata Steudel ex A. Rich","authors":"Solomon Tesfaye , Larissa Birkel , Siva Sankar Murthy Bandaru , Diana Astrid Barrera-Adame , Malte Eichelbaum , Ermias Lulekal , Kaleab Asres , Ephrem Engidawork , Christian Schulze , Nwet Nwet Win , Carola Schulzke , Timo H.J. Niedermeyer , Patrick J. Bednarski , Sebastian Guenther , Nadin Schultze","doi":"10.1016/j.fitote.2026.107090","DOIUrl":"10.1016/j.fitote.2026.107090","url":null,"abstract":"<div><div>The traditional Ethiopian medicinal plants <em>Acokanthera schimperi</em> (A.DC.) Schweinf. and <em>Gnidia involucrata</em> Steud. ex A.Rich were explored for their potential as sources of anticancer agents. Bioassay-guided fractionation yielded a previously unreported phorbol ester (<strong>5</strong>), alongside four known compounds (<strong>1</strong>–<strong>4</strong>) from <em>G. involucrata</em> and a pregnane-type steroid (<strong>6</strong>) from <em>A. schimperi</em>. Structural elucidation was accomplished through comprehensive NMR and HRMS analyses. The antiproliferative activities of these compounds were assessed against A-427, Dan-G, MCF-7, and SiSo cancer cell lines, revealing diverse levels of activity. Notably, the pregnane derivative (<strong>6</strong>) demonstrated potent activity, with GI₅₀ values ranging from 2.3 to 4.7 μM across the tested cell lines. Mechanistic investigations demonstrated that compound (<strong>6</strong>) inhibited mitotic spindle assembly and spindle-pole separation, leading to a pronounced G2/M phase cell cycle arrest in the SiSo cell line. In contrast, compound (<strong>5</strong>) exhibited potent antiproliferative activity against the Dan-G cell line (GI₅₀ = 0.3 ± 0.05 nM) and moderate to weak activity in the remaining cell lines, with GI₅₀ values ranging from 5.2 to >50 μM, inducing early apoptosis in Dan-G cells. These findings highlight compounds <strong>5</strong> and <strong>6</strong> as promising anticancer candidates and provide a scientific basis for the ethnomedicinal use of these plants in cancer therapy.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107090"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-12-25DOI: 10.1016/j.fitote.2025.107054
Shiyang Zhou , Wenbin Wang , Jie Zhao , Fengming Ren
This study focused on Pleurotus geesteranus stem polysaccharide (PSP), successfully established and optimized their derivatives preparation process. The structures of these derivatives were characterized using ultraviolet spectroscopy, infrared spectroscopy, and ion chromatography-techniques that enabled identification of substituent types, determination of substitution degrees, analysis of monosaccharide compositions, and quantification of molecular weight variations. For antioxidant activity assessment, in vitro chemical models and H₂O₂-induced RAW264.7 cell model confirmed that PSP derivatives exhibit significant antioxidant capacity. Specifically, phosphorylated PSP (PPSP) at a concentration of 3.2 mg/mL exhibited scavenging rates of 98.5 %, 98.4 %, and 96.7 % against DPPH, ABTS, and hydroxyl radicals, respectively, with a total reducing capacity absorbance of 0.96. Additionally, PPSP significantly increased the levels of CAT, SOD, and GSH-Px enzymes in RAW264.7 cells while decreasing MDA content. Hypoglycemic activity was evaluated via α-glucosidase inhibition, α-amylase inhibition, and glucose consumption assays using insulin-resistant HepG2 cells as a model. Results demonstrated that PSP derivatives exerted strong inhibitory effects on α-glucosidase and α-amylase, and dose-dependently enhanced glucose consumption in insulin-resistant HepG2 cells. At 5 mg/mL, PPSP inhibited α-glucosidase and α-amylase activities by 87.3 % and 90.3 %, respectively. This study was systematically investigate their biological activities, thereby providing a novel strategy for the efficient and in-depth utilization of Pleurotus geesteranus resources. The prepared derivatives hold potential applications in functional foods and the pharmaceutical industry. However, the current research was limited to in vitro experiments. Thus, subsequent animal studies and clinical trials were warranted to further explore their in vivo mechanisms of action, pharmacokinetic profiles, and safety characteristics.
{"title":"Preparation of polysaccharide derivatives from the stems of Pleurotus geesteranus and antioxidant and hypoglycemic activities","authors":"Shiyang Zhou , Wenbin Wang , Jie Zhao , Fengming Ren","doi":"10.1016/j.fitote.2025.107054","DOIUrl":"10.1016/j.fitote.2025.107054","url":null,"abstract":"<div><div>This study focused on <em>Pleurotus geesteranus</em> stem polysaccharide (PSP), successfully established and optimized their derivatives preparation process. The structures of these derivatives were characterized using ultraviolet spectroscopy, infrared spectroscopy, and ion chromatography-techniques that enabled identification of substituent types, determination of substitution degrees, analysis of monosaccharide compositions, and quantification of molecular weight variations. For antioxidant activity assessment, <em>in vitro</em> chemical models and H₂O₂-induced RAW264.7 cell model confirmed that PSP derivatives exhibit significant antioxidant capacity. Specifically, phosphorylated PSP (PPSP) at a concentration of 3.2 mg/mL exhibited scavenging rates of 98.5 %, 98.4 %, and 96.7 % against DPPH, ABTS, and hydroxyl radicals, respectively, with a total reducing capacity absorbance of 0.96. Additionally, PPSP significantly increased the levels of CAT, SOD, and GSH-Px enzymes in RAW264.7 cells while decreasing MDA content. Hypoglycemic activity was evaluated <em>via α</em>-glucosidase inhibition, <em>α</em>-amylase inhibition, and glucose consumption assays using insulin-resistant HepG2 cells as a model. Results demonstrated that PSP derivatives exerted strong inhibitory effects on <em>α</em>-glucosidase and <em>α</em>-amylase, and dose-dependently enhanced glucose consumption in insulin-resistant HepG2 cells. At 5 mg/mL, PPSP inhibited <em>α</em>-glucosidase and <em>α</em>-amylase activities by 87.3 % and 90.3 %, respectively. This study was systematically investigate their biological activities, thereby providing a novel strategy for the efficient and in-depth utilization of <em>Pleurotus geesteranus</em> resources. The prepared derivatives hold potential applications in functional foods and the pharmaceutical industry. However, the current research was limited to <em>in vitro</em> experiments. Thus, subsequent animal studies and clinical trials were warranted to further explore their <em>in vivo</em> mechanisms of action, pharmacokinetic profiles, and safety characteristics.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107054"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-12-24DOI: 10.1016/j.fitote.2025.107065
Huan Yan , Yong-Sheng Zhou , Long-Gao Xiao , Wei Ni , Yupeng Geng , Hai-Yang Liu
The phytochemical reinvestigation on the whole plants of Chloranthus holostegius led to the isolation of five undescribed sesquiterpenes (named chloranholosins U-Y, 1–5), including two lindenane-type sesquiterpenes, two acorane-type sesquiterpenes, and one elemane-type sesquiterpene, together with 30 known compounds. Their structures and absolute configurations were elucidated by a comprehensive method including the spectroscopic data, and electronic circular dichroism (ECD) calculations. Chloranholosin U (1) was elucidated as a rare lindenane–dinormonotepenoid hybrid with an oxa-difuranofurone moiety. Furthermore, all new isolates and 18 known compounds were evaluated for their inhibitory activity against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophage cells, while their cytotoxic activities were also assessed against five human tumor cell lines. Though these compounds did not show inhibitory activity for NO production, compounds 16, 34, and 35 displayed moderate cytotoxicity. Compound 16 showed cytotoxicity against HL-60, HepG2, MDA-MB-231, and SW480 (IC50 10.98–36.48 μM), compounds 34 and 35 were active on HL-60 (IC50 18.98 and 14.89 μM), and 34 also inhibited A549 (IC50 24.32 μM).
{"title":"Terpenoids from the whole plants of Chloranthus holostegius","authors":"Huan Yan , Yong-Sheng Zhou , Long-Gao Xiao , Wei Ni , Yupeng Geng , Hai-Yang Liu","doi":"10.1016/j.fitote.2025.107065","DOIUrl":"10.1016/j.fitote.2025.107065","url":null,"abstract":"<div><div>The phytochemical reinvestigation on the whole plants of <em>Chloranthus holostegius</em> led to the isolation of five undescribed sesquiterpenes (named chloranholosins U-Y, <strong>1</strong>–<strong>5</strong>), including two lindenane-type sesquiterpenes, two acorane-type sesquiterpenes, and one elemane-type sesquiterpene, together with 30 known compounds. Their structures and absolute configurations were elucidated by a comprehensive method including the spectroscopic data, and electronic circular dichroism (ECD) calculations. Chloranholosin U (<strong>1</strong>) was elucidated as a rare lindenane–dinormonotepenoid hybrid with an oxa-difuranofurone moiety. Furthermore, all new isolates and 18 known compounds were evaluated for their inhibitory activity against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophage cells, while their cytotoxic activities were also assessed against five human tumor cell lines. Though these compounds did not show inhibitory activity for NO production, compounds <strong>16</strong>, <strong>34</strong>, and <strong>35</strong> displayed moderate cytotoxicity. Compound <strong>16</strong> showed cytotoxicity against HL-60, HepG2, MDA-MB-231, and SW480 (IC<sub>50</sub> 10.98–36.48 μM), compounds <strong>34</strong> and <strong>35</strong> were active on HL-60 (IC<sub>50</sub> 18.98 and 14.89 μM), and <strong>34</strong> also inhibited A549 (IC<sub>50</sub> 24.32 μM).</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107065"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-12-22DOI: 10.1016/j.fitote.2025.107055
Márcio B. Weiss , Jaewon Yoon , João P.B. Domingues , Fernanda R. Jacinavicius , Vitor F. Freire , Helori V. Domingos , Manoel O. de Moraes Junior , Camila M.C. Gonçalves , Sandra R. Castro , José A.L. Lindoso , Silvya S. Maria-Engler , Leticia V. Costa-Lotufo , Ricardo M. Borges , Roberto G.S. Berlinck , Camila M. Crnkovic
Natural products are a valuable source of molecules with therapeutic and biotechnological applications. However, the complexity of biological matrices and the increasing rates of rediscovery pose significant challenges in the search for new bioactive compounds. Exploring novel specimens from biodiversity and utilizing modern cheminformatics tools are essential to advancing natural product discovery. In this study, we employed metabolomics and bioassays to investigate the potential of filamentous cyanobacteria collected in Brazil as a source of new bioactive secondary metabolites. Extracts and fractions from eight freshwater cyanobacterial strains were tested for their general toxicity against Artemia salina, as well as antiparasitic and cytotoxic activities and analyzed by UHPLC-HRMS-MS/MS. Molecular networks were constructed from MS/MS data using the GNPS platform, and dereplication was guided by DAFdiscovery results for feature prioritization. Annotation and dereplication were conducted using SIRIUS combined with manual analysis of HRMS and MS/MS spectra. Our study identified three cyanobacterial strains as producers of potentially novel and bioactive metabolites for in-depth investigations.
{"title":"Uncovering chemical novelty from freshwater filamentous Cyanobacteria","authors":"Márcio B. Weiss , Jaewon Yoon , João P.B. Domingues , Fernanda R. Jacinavicius , Vitor F. Freire , Helori V. Domingos , Manoel O. de Moraes Junior , Camila M.C. Gonçalves , Sandra R. Castro , José A.L. Lindoso , Silvya S. Maria-Engler , Leticia V. Costa-Lotufo , Ricardo M. Borges , Roberto G.S. Berlinck , Camila M. Crnkovic","doi":"10.1016/j.fitote.2025.107055","DOIUrl":"10.1016/j.fitote.2025.107055","url":null,"abstract":"<div><div>Natural products are a valuable source of molecules with therapeutic and biotechnological applications. However, the complexity of biological matrices and the increasing rates of rediscovery pose significant challenges in the search for new bioactive compounds. Exploring novel specimens from biodiversity and utilizing modern cheminformatics tools are essential to advancing natural product discovery. In this study, we employed metabolomics and bioassays to investigate the potential of filamentous cyanobacteria collected in Brazil as a source of new bioactive secondary metabolites. Extracts and fractions from eight freshwater cyanobacterial strains were tested for their general toxicity against <em>Artemia salina</em>, as well as antiparasitic and cytotoxic activities and analyzed by UHPLC-HRMS-MS/MS. Molecular networks were constructed from MS/MS data using the GNPS platform, and dereplication was guided by DAFdiscovery results for feature prioritization. Annotation and dereplication were conducted using SIRIUS combined with manual analysis of HRMS and MS/MS spectra. Our study identified three cyanobacterial strains as producers of potentially novel and bioactive metabolites for in-depth investigations.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107055"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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