Pub Date : 2026-01-13DOI: 10.1016/j.fitote.2025.107081
Adrian Wilmers , Olivier Potterat , Roman Huber , Stefanie Kowarschik
Urtica dioica L. (U. dioica) has shown anti-inflammatory effects and is regarded as a potential natural agent for treating chronic inflammatory conditions. The differential effects of U. dioica preparations have not yet been investigated. The influence of nine different U. dioica preparations (teas, extracts, juice and tincture) on proliferation, apoptosis/necrosis and viability of primary human T cells were analyzed with standard methods. The effect on T lymphocytes was evaluated via cluster of differentiation (CD)25/CD69 marker expression, degranulation assays and the production of pro-inflammatory cytokines. Using Jurkat reporter cell lines, an influence on transcription factors was analyzed. U. dioica preparations selectively modulate T cell activation by downregulating the key activation markers CD25 and CD69. In addition, they reduce the production of the pro-inflammatory cytokine interleukin-2, inhibit T cell degranulation and suppress nuclear factor of activated T-cells (NFAT)-dependent transcription. The results highlight the potential of U. dioica as a natural agent, capable to modulate T cell-mediated immune responses. The immunomodulating effect differs between the extracts and preparations due to extraction methods and used plant material.
{"title":"Comparative study of different stinging nettle preparations regarding to their immunomodulating effect on primary human T-lymphocytes","authors":"Adrian Wilmers , Olivier Potterat , Roman Huber , Stefanie Kowarschik","doi":"10.1016/j.fitote.2025.107081","DOIUrl":"10.1016/j.fitote.2025.107081","url":null,"abstract":"<div><div><em>Urtica dioica</em> L. (<em>U. dioica</em>) has shown anti-inflammatory effects and is regarded as a potential natural agent for treating chronic inflammatory conditions. The differential effects of <em>U. dioica</em> preparations have not yet been investigated. The influence of nine different <em>U. dioica</em> preparations (teas, extracts, juice and tincture) on proliferation, apoptosis/necrosis and viability of primary human T cells were analyzed with standard methods. The effect on T lymphocytes was evaluated via cluster of differentiation (CD)25/CD69 marker expression, degranulation assays and the production of pro-inflammatory cytokines. Using Jurkat reporter cell lines, an influence on transcription factors was analyzed. <em>U. dioica</em> preparations selectively modulate T cell activation by downregulating the key activation markers CD25 and CD69. In addition, they reduce the production of the pro-inflammatory cytokine interleukin-2, inhibit T cell degranulation and suppress nuclear factor of activated T-cells (NFAT)-dependent transcription. The results highlight the potential of <em>U. dioica</em> as a natural agent, capable to modulate T cell-mediated immune responses. The immunomodulating effect differs between the extracts and preparations due to extraction methods and used plant material.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107081"},"PeriodicalIF":2.6,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973642","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 : 2026-01-12DOI: 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":"2026-01-12","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}
Plant-derived bioactive compounds play a crucial role in managing metabolic syndrome (MetS) components such as hyperglycemia, insulin resistance, and atherogenic dyslipidemia. The present study investigates the glucose and lipid lowering potential of a novel compound mixture composed of garcinol, piperine, butyl oleate, pipnoohine, and bismurrayanimbine (molar ratio of 9:33:1:4:1) and its effects on insulin resistance and atherogenic indices in streptozotocin induced (60 mgkg−1, ip) diabetic rats. The oral administration of the compound mixture at low (10 mgkg−1), therapeutic (25 mgkg−1), and high (50 mgkg−1) doses resulted in dose-dependent improvement in oral glucose tolerance with an increase of 6%, 9%, and 12%, respectively. There was a corresponding elevation in serum insulin (4%, 66%, 66%) and C-peptide (18%, 152%, 153%), along with reduction in serum fasting glucose (8%, 29%, 30%) and percentage of HbA1C (18%, 27%, 31%) compared to diabetic untreated rats (p < 0.05). Histopathological assessment of H and E-stained sections of the pancreatic tissue confirmed islet cell restoration. At the therapeutic dose, the mixture reduced homeostatic model assessment of insulin resistance (HOMA-IR) and increased homeostatic model assessment of β-cell functions (HOMA-β), aligning with pancreatic functions. Furthermore, all doses improved the antioxidant status and reversed atherogenic dyslipidemia in diabetic rats. Biochemical analysis revealed significant improvement in hepatic hexokinase activity at 25 and 50 mgkg−1 doses (p < 0.05). Overall, the compound mixture showed promising results as an adjunct therapy for managing hyperglycemia and atherogenic dyslipidemia associated with MetS, highlighting its potential to be developed as a therapeutic agent.
{"title":"A novel compound mixture mitigates hyperglycemia, insulin resistance, dyslipidemia, and oxidative stress in streptozotocin induced diabetic rats: A therapeutic drug lead for metabolic syndrome","authors":"Thushara Indika Sampath , Susanthi Jayasinghe , Anoja Priyadarshani Attanayake , Veranja Karunaratne","doi":"10.1016/j.fitote.2026.107091","DOIUrl":"10.1016/j.fitote.2026.107091","url":null,"abstract":"<div><div>Plant-derived bioactive compounds play a crucial role in managing metabolic syndrome (MetS) components such as hyperglycemia, insulin resistance, and atherogenic dyslipidemia. The present study investigates the glucose and lipid lowering potential of a novel compound mixture composed of garcinol, piperine, butyl oleate, pipnoohine, and bismurrayanimbine (molar ratio of 9:33:1:4:1) and its effects on insulin resistance and atherogenic indices in streptozotocin induced (60 mgkg<sup>−1</sup>, ip) diabetic rats. The oral administration of the compound mixture at low (10 mgkg<sup>−1</sup>), therapeutic (25 mgkg<sup>−1</sup>), and high (50 mgkg<sup>−1</sup>) doses resulted in dose-dependent improvement in oral glucose tolerance with an increase of 6%, 9%, and 12%, respectively. There was a corresponding elevation in serum insulin (4%, 66%, 66%) and C-peptide (18%, 152%, 153%), along with reduction in serum fasting glucose (8%, 29%, 30%) and percentage of HbA<sub>1C</sub> (18%, 27%, 31%) compared to diabetic untreated rats (<em>p</em> < 0.05). Histopathological assessment of H and <em>E</em>-stained sections of the pancreatic tissue confirmed islet cell restoration. At the therapeutic dose, the mixture reduced homeostatic model assessment of insulin resistance (HOMA-IR) and increased homeostatic model assessment of β-cell functions (HOMA-β), aligning with pancreatic functions. Furthermore, all doses improved the antioxidant status and reversed atherogenic dyslipidemia in diabetic rats. Biochemical analysis revealed significant improvement in hepatic hexokinase activity at 25 and 50 mgkg<sup>−1</sup> doses (<em>p</em> < 0.05). Overall, the compound mixture showed promising results as an adjunct therapy for managing hyperglycemia and atherogenic dyslipidemia associated with MetS, highlighting its potential to be developed as a therapeutic agent.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107091"},"PeriodicalIF":2.6,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965010","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 : 2026-01-11DOI: 10.1016/j.fitote.2026.107092
Hana Slimi , Hayet Edziri , Fatma Nouira , Lamjed Bouslama , Maha Mastouri , Adele Cutignano
Herniaria hirsuta L. (Caryophyllaceae) is an annual herb known as hairy rupturewort. It is used in traditional medicine, particularly in North Africa, to prevent and cure kidney stones and as a diuretic. Rich in saponins, it possesses many other bioactive secondary metabolites including flavonoids and their glycosides. Plant specimens harvested in Tunisia were chemically investigated and their extracts tested for antiviral activity. Ethyl acetate and butanol extracts showed significant activity against Herpes Simplex type-2 (HSV-2) virus (IC50 = 31.15 μg/mL, SI =10.97 and IC50 = 46.04 μg/mL, SI = 6.44, respectively). Ultra-High Performance Liquid Chromatography-High Resolution ElectroSpray Ionization Mass Spectrometry (UHPLC-HRESIMS) analyses combined with Nuclear Magnetic Resonance (NMR) spectroscopy revealed the occurrence of a family of isorhamnetin glycosides, containing 1 to 3 sugar units. By using a bioassay guided fractionation approach, we identified a new flavonoid glycoside: its chemical structure was resolved by extensive use of NMR spectroscopy and HRESIMS/MS as isorhamnetin-3-O-(2-O-(4-acetyl)-α-L-rhamnopyranosyl, 6-O-α-L-rhamnopyranosyl)-β-D-galactopyranoside, which exhibited an IC50 = 20.34 μM (SI >15). Notably, its co-occurring deacetyl derivative resulted inactive. In vitro assays suggested that the antiviral action is exerted during the early stages of the viral cycle, preventing HSV-2 from infecting target cells.
hirsuta L.（石竹科）是一种一年生草本植物，被称为毛破裂草。在传统医学中，特别是在北非，它被用来预防和治疗肾结石，并作为利尿剂。它富含皂苷，还具有许多其他生物活性次生代谢产物，包括黄酮类化合物及其苷类。对在突尼斯收获的植物标本进行了化学研究，并对其提取物进行了抗病毒活性测试。乙酸乙酯和丁醇提取物对2型单纯疱疹病毒（HSV-2）具有显著的抑制作用（IC50 = 31.15 μg/ml, SI =10.97; IC50 = 46.04 μg/ml, SI = 6.44）。超高效液相色谱-高分辨率电喷雾质谱分析（uhplc - hresms）结合核磁共振（NMR）光谱分析发现了一个异鼠李素糖苷家族，包含1至3个糖单位。采用生物测定指导分离的方法，鉴定出一种新的黄酮类苷类化合物，通过核磁共振光谱和HRESIMS/MS鉴定其化学结构为异鼠李糖素-3- o -(2-O-（4-乙酰基）-α- l -鼠李糖pyranosyl， 6-O-α- l -鼠李糖pyranosyl -β- d -半乳糖吡喃苷，IC50为 = 20.34 μM （SI bbb15）。值得注意的是，其共发生的脱乙酰衍生物导致失活性。体外实验表明，抗病毒作用在病毒周期的早期阶段发挥作用，阻止HSV-2感染靶细胞。
{"title":"A new antiviral isorhamnetin glycoside from the Tunisian plant Herniaria hirsuta L.","authors":"Hana Slimi , Hayet Edziri , Fatma Nouira , Lamjed Bouslama , Maha Mastouri , Adele Cutignano","doi":"10.1016/j.fitote.2026.107092","DOIUrl":"10.1016/j.fitote.2026.107092","url":null,"abstract":"<div><div><em>Herniaria hirsuta</em> L. (Caryophyllaceae) is an annual herb known as hairy rupturewort. It is used in traditional medicine, particularly in North Africa, to prevent and cure kidney stones and as a diuretic. Rich in saponins, it possesses many other bioactive secondary metabolites including flavonoids and their glycosides. Plant specimens harvested in Tunisia were chemically investigated and their extracts tested for antiviral activity. Ethyl acetate and butanol extracts showed significant activity against Herpes Simplex type-2 (HSV-2) virus (IC<sub>50</sub> = 31.15 μg/mL, SI =10.97 and IC<sub>50</sub> = 46.04 μg/mL, SI = 6.44, respectively). Ultra-High Performance Liquid Chromatography-High Resolution ElectroSpray Ionization Mass Spectrometry (UHPLC-HRESIMS) analyses combined with Nuclear Magnetic Resonance (NMR) spectroscopy revealed the occurrence of a family of isorhamnetin glycosides, containing 1 to 3 sugar units. By using a bioassay guided fractionation approach, we identified a new flavonoid glycoside: its chemical structure was resolved by extensive use of NMR spectroscopy and HRESIMS/MS as isorhamnetin-3-<em>O</em>-(2-<em>O</em>-(4-acetyl)-α-L-rhamnopyranosyl, 6-<em>O</em>-α-L-rhamnopyranosyl)-β-D-galactopyranoside, which exhibited an IC<sub>50</sub> = 20.34 μM (SI >15). Notably, its co-occurring deacetyl derivative resulted inactive. <em>In vitro</em> assays suggested that the antiviral action is exerted during the early stages of the viral cycle, preventing HSV-2 from infecting target cells.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107092"},"PeriodicalIF":2.6,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965741","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 : 2026-01-06DOI: 10.1016/j.fitote.2026.107088
Nurettin Yaylı , İshak Erik , Büşra Korkmaz , Gözde Bozdal , Can Özgür Yalçın , Kamil Coşkunçelebi , Serdar Makbul , Şengül Alpay Karaoğlu
The present study is mainly focused on the isolation and structure elucidation of four new (1–4), two known astragalin (5), and kaempferol-3,7-di-O-β-D-glucopyranoside (6) from the aerial parts of Scorzonera aucheriana DC. The structures of the isolated compounds were elucidated based on 1D and 2D NMR (1H, 13C/APT, COSY, HMBC, and HSQC), UV, FT-IR, and HRESI-MS data. The total phenol and flavonoid contents and the antioxidant activity of S. aucheriana crude methanol extract and its fractions (n-hexane, chloroform, ethyl acetate, and water) were investigated. The highest antioxidant activities against DPPH and FRAP were observed in the ethyl acetate fraction of S. aucheriana. The antimicrobial activity of the methanol extract, its solvent fractions, and isolated compounds (1–6) was evaluated against 10 microorganisms. The chloroform and ethyl acetate fractions exhibited antimicrobial activity against all tested microorganisms. Compounds 1–3, 5, and 6 exhibited anti-tuberculosis activity with MICs ranging from 30.9 μg/mL to 250 μg/mL. Compounds 2, 4, and 5 have also demonstrated moderate antifungal activity, with MICs ranging from 110 μg/mL to 765 μg/mL against C. albicans, a pathogenic yeast. Compounds 1–3 showed almost no cytotoxic activity in L-929 cells.
{"title":"Phytochemical analysis and antimicrobial, antioxidant, and cytotoxic activities of Scorzonera aucheriana DC (Asteraceae)","authors":"Nurettin Yaylı , İshak Erik , Büşra Korkmaz , Gözde Bozdal , Can Özgür Yalçın , Kamil Coşkunçelebi , Serdar Makbul , Şengül Alpay Karaoğlu","doi":"10.1016/j.fitote.2026.107088","DOIUrl":"10.1016/j.fitote.2026.107088","url":null,"abstract":"<div><div>The present study is mainly focused on the isolation and structure elucidation of four new (<strong>1–4</strong>), two known astragalin (<strong>5),</strong> and kaempferol-3,7-di-O-<em>β</em>-D-glucopyranoside (<strong>6</strong>) from the aerial parts of <em>Scorzonera aucheriana</em> DC. The structures of the isolated compounds were elucidated based on 1D and 2D NMR (<sup><strong>1</strong></sup>H, <sup><strong>13</strong></sup>C/APT, COSY, HMBC, and HSQC), UV, FT-IR, and HRESI-MS data. The total phenol and flavonoid contents and the antioxidant activity of <em>S. aucheriana</em> crude methanol extract and its fractions (<em>n</em>-hexane, chloroform, ethyl acetate, and water) were investigated. The highest antioxidant activities against DPPH and FRAP were observed in the ethyl acetate fraction of <em>S. aucheriana</em>. The antimicrobial activity of the methanol extract, its solvent fractions, and isolated compounds (<strong>1–6</strong>) was evaluated against 10 microorganisms. The chloroform and ethyl acetate fractions exhibited antimicrobial activity against all tested microorganisms. Compounds <strong>1–3</strong>, <strong>5</strong>, and <strong>6</strong> exhibited anti-tuberculosis activity with MICs ranging from 30.9 μg/mL to 250 μg/mL. Compounds <strong>2</strong>, <strong>4</strong>, and <strong>5</strong> have also demonstrated moderate antifungal activity, with MICs ranging from 110 μg/mL to 765 μg/mL against <em>C. albicans</em>, a pathogenic yeast. Compounds <strong>1–3</strong> showed almost no cytotoxic activity in L-929 cells.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107088"},"PeriodicalIF":2.6,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932929","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 : 2026-01-03DOI: 10.1016/j.fitote.2026.107086
Bin Wang , Jin Cai , Guojun Zhou , Mohan Zhang , Meng Yang , Yanxuan Li , Baoyi Zhang , Youping Luo , Nasihat , Xueming Zhou , Guolei Huang , Caijuan Zheng
Three new diphenyl ethers diorcinols P-Q (1–2), and gibellulin E (3), together with one new sesquiterpene isoversiol H (4), as well as six known diphenyl ethers (5–10) were obtained from the mangrove-derived fungus Aspergillus versicolor 21041517. Comprehensive spectroscopic techniques, ECD calculations, X-ray diffraction analyses, and modified Mosher's method were used to confirm the planner structures and absolute configurations of the new compounds. The diphenyl ethers 1, 5 and 6 exhibited inhibitory activity against three tested pathogenic bacteria. 20 diphenyl ether derivatives (5a1–5j2) were designed and semisynthesized to improve the antibacterial activity of diphenyl ethers. In particular, compound 5a1 showed potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), with the MIC value of 3.13 μg/mL. Preliminary antimicrobial mechanism investigations of 5a1 were performed. Treatment with 5a1 resulted in the leakage of the AKP, a decrease in intracellular ATP concentration, and a reduction in soluble protein content. Scanning electron microscopy demonstrated that 5a1 can damage the cell membrane of MRSA. Transcriptome assay revealed that 5a1 may target cellular energy metabolism. This study offers valuable insights that contribute to development of novel anti-MRSA agents, and providing potential strategies for addressing antibiotic.
{"title":"Antibacterial diphenyl ether derivatives from mangrove-derived fungus Aspergillus versicolor 21041517","authors":"Bin Wang , Jin Cai , Guojun Zhou , Mohan Zhang , Meng Yang , Yanxuan Li , Baoyi Zhang , Youping Luo , Nasihat , Xueming Zhou , Guolei Huang , Caijuan Zheng","doi":"10.1016/j.fitote.2026.107086","DOIUrl":"10.1016/j.fitote.2026.107086","url":null,"abstract":"<div><div>Three new diphenyl ethers diorcinols P-Q (<strong>1</strong>–<strong>2</strong>), and gibellulin E (<strong>3</strong>), together with one new sesquiterpene isoversiol H (<strong>4</strong>), as well as six known diphenyl ethers (<strong>5</strong>–<strong>10</strong>) were obtained from the mangrove-derived fungus <em>Aspergillus versicolor</em> 21041517. Comprehensive spectroscopic techniques, ECD calculations, X-ray diffraction analyses, and modified Mosher's method were used to confirm the planner structures and absolute configurations of the new compounds. The diphenyl ethers <strong>1</strong>, <strong>5</strong> and <strong>6</strong> exhibited inhibitory activity against three tested pathogenic bacteria. 20 diphenyl ether derivatives (<strong>5a1</strong>–<strong>5j2</strong>) were designed and semisynthesized to improve the antibacterial activity of diphenyl ethers. In particular, compound <strong>5a1</strong> showed potent antibacterial activity against methicillin-resistant <em>Staphylococcus aureus</em> (MRSA), with the MIC value of 3.13 μg/mL. Preliminary antimicrobial mechanism investigations of <strong>5a1</strong> were performed. Treatment with <strong>5a1</strong> resulted in the leakage of the AKP, a decrease in intracellular ATP concentration, and a reduction in soluble protein content. Scanning electron microscopy demonstrated that <strong>5a1</strong> can damage the cell membrane of MRSA. Transcriptome assay revealed that <strong>5a1</strong> may target cellular energy metabolism. This study offers valuable insights that contribute to development of novel anti-MRSA agents, and providing potential strategies for addressing antibiotic.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107086"},"PeriodicalIF":2.6,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905638","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 : 2026-01-03DOI: 10.1016/j.fitote.2026.107089
Mei-Zhen Ye , Yang Yang , Cheng Yuan , Yu-Qi Yang , Ning Ding , Qin He , Shuai Huang , Lin Chen , Xian-Li Zhou
A previously unreported C19-diterpenoid alkaloid with a tetrahydrofuran skeleton, nagarudine (1), was isolated from the roots of Aconitum nagarum Stapf. The structures and absolute configurations of compound 1 was established via comprehensive spectroscopic analysis, ECD calculation, and X-ray crystallography. To explain the formation of this natural skeleton, the nagarudine analogue was synthesized. 1 displayed proliferation inhibition effect on the Sf9 cell line with an IC50 value of 16.04 μg/mL, and its apoptotic induction effect was illustrated by morphological observation. Combined with flow cytometry, staining, and Western blotting conclusively showed that nagarudine effectively induced apoptosis in Sf9 cells through the mitochondrial pathway.
{"title":"Nagarudine, a new C19-diterpenoid alkaloid from Aconitum nagarum Stapf: Isolation, structure elucidation, synthesis of nagarudine analogue, and apoptotic activity","authors":"Mei-Zhen Ye , Yang Yang , Cheng Yuan , Yu-Qi Yang , Ning Ding , Qin He , Shuai Huang , Lin Chen , Xian-Li Zhou","doi":"10.1016/j.fitote.2026.107089","DOIUrl":"10.1016/j.fitote.2026.107089","url":null,"abstract":"<div><div>A previously unreported C<sub>19</sub>-diterpenoid alkaloid with a tetrahydrofuran skeleton, nagarudine (<strong>1</strong>), was isolated from the roots of <em>Aconitum nagarum</em> Stapf. The structures and absolute configurations of compound <strong>1</strong> was established via comprehensive spectroscopic analysis, ECD calculation, and X-ray crystallography. To explain the formation of this natural skeleton, the nagarudine analogue was synthesized. <strong>1</strong> displayed proliferation inhibition effect on the Sf9 cell line with an IC<sub>50</sub> value of 16.04 <em>μ</em>g/mL, and its apoptotic induction effect was illustrated by morphological observation. Combined with flow cytometry, staining, and Western blotting conclusively showed that nagarudine effectively induced apoptosis in Sf9 cells through the mitochondrial pathway.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107089"},"PeriodicalIF":2.6,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905646","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 : 2026-01-02DOI: 10.1016/j.fitote.2025.107079
Zhongyou Yang , Jiankun Hong , Wuling Liu , Kunlin Yu , Anling Hu , Yi Kuang , Eldad Zacksenhaus , Xiao Xiao , Jingrui Song , Lei Huang , Chunlin Wang , Yanmei Li , Yaacov Ben-David
Acute erythroid leukemia (AEL), a rare form of acute myeloid leukemia (AML), is defined as type M6 under the FAB classification, and characterized by inhibition of terminal differentiation and rapid expansion of erythroid progenitors. Despite its poor prognosis, AEL responds well to chemotherapy. Yet, the frequent emergence of resistant clones is a major concern, necessitating the development of alternative therapeutic strategies to treat this rare disease. Yuxingcao formula (YXCF), which consists of 5 herbs, is used in Traditional Chinese Medicine to treat various diseases including cancer, although the underlying mechanisms are not fully understood. Herein, we shown that in an animal model of erythroleukemia induced by Friend virus, YXCF treatment strongly inhibits leukemia progression accompanied by induction of erythroid differentiation, apoptosis and cell cycle arrest. UPLC-MS/MS and network pharmacology analyses of YXCF identified 89 compounds, 20 of which are known to have anti-cancer activity. Molecular docking identified AKT1 as a potential target of one of these compounds, baicalein. In docking and CETSA analyses, baicalein binds AKT leading to inhibition of its phosphorylation and its target mTOR. Baicalein significantly inhibited proliferation of leukemic cells in culture associated with induction of apoptosis and cell cycle arrest as well as suppression of erythroleukemogenesis in vivo. YXCF is also inhibits the FLI1 oncogene, known to play a critical role in erythroleukemia, likely through kaempferol, another YXCF compound. Understanding the role of other components of YXCF may eventually enable the development of a combination drug therapy with optimal anti-leukemia activity for the treatment of AEL.
{"title":"Yuxingcao formula suppresses acute erythroleukemia through inhibition of AKT1 and FLI1","authors":"Zhongyou Yang , Jiankun Hong , Wuling Liu , Kunlin Yu , Anling Hu , Yi Kuang , Eldad Zacksenhaus , Xiao Xiao , Jingrui Song , Lei Huang , Chunlin Wang , Yanmei Li , Yaacov Ben-David","doi":"10.1016/j.fitote.2025.107079","DOIUrl":"10.1016/j.fitote.2025.107079","url":null,"abstract":"<div><div>Acute erythroid leukemia (AEL), a rare form of acute myeloid leukemia (AML), is defined as type M6 under the FAB classification, and characterized by inhibition of terminal differentiation and rapid expansion of erythroid progenitors. Despite its poor prognosis, AEL responds well to chemotherapy. Yet, the frequent emergence of resistant clones is a major concern, necessitating the development of alternative therapeutic strategies to treat this rare disease. Yuxingcao formula (YXCF), which consists of 5 herbs, is used in Traditional Chinese Medicine to treat various diseases including cancer, although the underlying mechanisms are not fully understood. Herein, we shown that in an animal model of erythroleukemia induced by Friend virus, YXCF treatment strongly inhibits leukemia progression accompanied by induction of erythroid differentiation, apoptosis and cell cycle arrest. UPLC-MS/MS and network pharmacology analyses of YXCF identified 89 compounds, 20 of which are known to have anti-cancer activity. Molecular docking identified AKT1 as a potential target of one of these compounds, baicalein. In docking and CETSA analyses, baicalein binds AKT leading to inhibition of its phosphorylation and its target mTOR. Baicalein significantly inhibited proliferation of leukemic cells in culture associated with induction of apoptosis and cell cycle arrest as well as suppression of erythroleukemogenesis in vivo. YXCF is also inhibits the FLI1 oncogene, known to play a critical role in erythroleukemia, likely through kaempferol, another YXCF compound. Understanding the role of other components of YXCF may eventually enable the development of a combination drug therapy with optimal anti-leukemia activity for the treatment of AEL.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107079"},"PeriodicalIF":2.6,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899731","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 : 2026-01-02DOI: 10.1016/j.fitote.2026.107083
Hao Yu , Qiao Wu , Siqi Chen , Yuanyuan Li , Leiling Shi , Zhonghao Sun , Haifeng Wu , Min Ma , Zhaocui Sun , Xudong Xu
Three novel meroterpenoids with unique benzo-fused 10-membered carbocycle skeletons, named tricholactones A-C (1–3), along with four known cyclic dipeptides (4–7), were isolated from the fungus Tricholoma sp. HD0815–7. Their chemical structures and absolute configurations were characterized by comprehensive analysis of HR-ESI-MS, 1D- and 2D-NMR and quantum mechanical electronic circular dichroism (ECD). Compounds 1–3 are novel natural meroterpenoids containing terpenoid scaffolds, phenols units and amino acid residues. Moreover, compound 3 features an unprecedented pentacyclic ring system (8/6/10/5/3) among these 10-membered carbocycle meroterpenoids. All isolated compounds 1–7 were tested for their cytotoxic activity. The results revealed that compound 2 exhibited strong cytotoxicity activity against HGC-27 cells with IC50 values of 2.34 ± 0.32 μM.
{"title":"Three novel meroterpenoids with unique benzo-fused 10-membered carbocycle skeletons from the fungus Tricholoma sp. HD0815–7","authors":"Hao Yu , Qiao Wu , Siqi Chen , Yuanyuan Li , Leiling Shi , Zhonghao Sun , Haifeng Wu , Min Ma , Zhaocui Sun , Xudong Xu","doi":"10.1016/j.fitote.2026.107083","DOIUrl":"10.1016/j.fitote.2026.107083","url":null,"abstract":"<div><div>Three novel meroterpenoids with unique benzo-fused 10-membered carbocycle skeletons, named tricholactones A-C (<strong>1–3</strong>), along with four known cyclic dipeptides (<strong>4–7</strong>), were isolated from the fungus <em>Tricholoma</em> sp. HD0815–7. Their chemical structures and absolute configurations were characterized by comprehensive analysis of HR-ESI-MS, 1D- and 2D-NMR and quantum mechanical electronic circular dichroism (ECD). Compounds <strong>1–3</strong> are novel natural meroterpenoids containing terpenoid scaffolds, phenols units and amino acid residues. Moreover, compound <strong>3</strong> features an unprecedented pentacyclic ring system (8/6/10/5/3) among these 10-membered carbocycle meroterpenoids. All isolated compounds <strong>1–7</strong> were tested for their cytotoxic activity. The results revealed that compound <strong>2</strong> exhibited strong cytotoxicity activity against HGC-27 cells with IC<sub>50</sub> values of 2.34 ± 0.32 μM.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107083"},"PeriodicalIF":2.6,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899701","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 : 2026-01-02DOI: 10.1016/j.fitote.2026.107084
Yadong Lv , Guiping Wu , Fenglin Gu , Xin Lu , Jinglin Zhang , Zhiqiang Niu , Xu Wang , Fei Xu , Fenglun Zhang , Xiaode Huang , Yunhe Lian , Zhanjiao Wei , Fu Li , Haifeng Wu , Weicheng Hu
Four previously undescribed alkamides (1–4) were isolated from the fruits of Piper nigrum. Their chemical structures were elucidated using HRESIMS, NMR, and optical rotation analyses. A classical NLRP3 inflammasome activation model was established by priming macrophages with LPS followed by nigericin stimulation. Compounds 1–4 exhibited markedly stronger inhibition than the reference compound piperine. Molecular docking further revealed their binding modes within the NACHT domain of NLRP3. All four derivatives displayed higher docking scores than piperine, with compound 2 showing the strongest predicted binding affinity. Molecular dynamics simulations have verified that the molecule had good binding free energy with NLRP3 and indicated the key amino acids involved in the binding. These findings enrich the structural diversity of piperine derivatives and expand the molecular scaffold available for further structure–activity relationship studies, thereby providing a solid molecular basis for the rational design and synthesis of new piperine-derived NLRP3 inhibitors.
{"title":"Alkamides from Piper nigrum and their potential inhibitory effect on NLRP3 inflammatory activation","authors":"Yadong Lv , Guiping Wu , Fenglin Gu , Xin Lu , Jinglin Zhang , Zhiqiang Niu , Xu Wang , Fei Xu , Fenglun Zhang , Xiaode Huang , Yunhe Lian , Zhanjiao Wei , Fu Li , Haifeng Wu , Weicheng Hu","doi":"10.1016/j.fitote.2026.107084","DOIUrl":"10.1016/j.fitote.2026.107084","url":null,"abstract":"<div><div>Four previously undescribed alkamides (<strong>1</strong>–<strong>4</strong>) were isolated from the fruits of <em>Piper nigrum</em>. Their chemical structures were elucidated using HRESIMS, NMR, and optical rotation analyses. A classical NLRP3 inflammasome activation model was established by priming macrophages with LPS followed by nigericin stimulation. Compounds <strong>1</strong>–<strong>4</strong> exhibited markedly stronger inhibition than the reference compound piperine. Molecular docking further revealed their binding modes within the NACHT domain of NLRP3. All four derivatives displayed higher docking scores than piperine, with compound <strong>2</strong> showing the strongest predicted binding affinity. Molecular dynamics simulations have verified that the molecule had good binding free energy with NLRP3 and indicated the key amino acids involved in the binding. These findings enrich the structural diversity of piperine derivatives and expand the molecular scaffold available for further structure–activity relationship studies, thereby providing a solid molecular basis for the rational design and synthesis of new piperine-derived NLRP3 inhibitors.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107084"},"PeriodicalIF":2.6,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899621","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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