Pub Date : 2026-03-01Epub Date: 2026-01-14DOI: 10.1016/j.fitote.2026.107095
Meng-Jing Cong , Xue Ren , Zi-Yi Wu , Xiao-Yan Pang , Yong-Hong Liu , Peng Guo , Jun-Feng Wang
Five undescribed compounds (1–5), together with four known compounds (6–9) were isolated from the Antarctic-derived fungus Aspergillus ochraceopetaliformis SCSIO 05702. Their structures were elucidated by the nuclear magnetic resonance spectrum (NMR), mass spectrometry (MS). In addition, the absolute configurations of these compounds were determined by the combination of ECD and DP4+ calculations, chiral-phase HPLC analysis, Mosher's ester analysis and Mo2(OAc)4 induced circular dichroism method. Among them, 5 and 6 exhibited potent anti-inflammatory responses induced by LPS in RAW264.7 cells. Specifically, 5 and 6 were able to markedly inhibit the production of NO and pro-inflammatory cytokines including IL-6, TNF-α, and MCP-1 in RAW264.7 cells exposed to 0.1 μg/mL LPS. Moreover, they effectively upregulated the anti-inflammatory cytokines, such as IL-4, IL-10, and Arg-1 gene expression levels impaired by LPS without obvious cytotoxicity.
{"title":"Anti-inflammatory polyketides produced by Antarctic-derived fungus Aspergillus ochraceopetaliformis SCSIO 05702","authors":"Meng-Jing Cong , Xue Ren , Zi-Yi Wu , Xiao-Yan Pang , Yong-Hong Liu , Peng Guo , Jun-Feng Wang","doi":"10.1016/j.fitote.2026.107095","DOIUrl":"10.1016/j.fitote.2026.107095","url":null,"abstract":"<div><div>Five undescribed compounds (<strong>1</strong>–<strong>5</strong>), together with four known compounds (<strong>6</strong>–<strong>9</strong>) were isolated from the Antarctic-derived fungus <em>Aspergillus ochraceopetaliformis</em> SCSIO 05702. Their structures were elucidated by the nuclear magnetic resonance spectrum (NMR), mass spectrometry (MS). In addition, the absolute configurations of these compounds were determined by the combination of ECD and DP4<sup>+</sup> calculations, chiral-phase HPLC analysis, Mosher's ester analysis and Mo<sub>2</sub>(OAc)<sub>4</sub> induced circular dichroism method. Among them, <strong>5</strong> and <strong>6</strong> exhibited potent anti-inflammatory responses induced by LPS in RAW264.7 cells. Specifically, <strong>5</strong> and <strong>6</strong> were able to markedly inhibit the production of NO and pro-inflammatory cytokines including IL-6, TNF-<em>α</em>, and MCP-1 in RAW264.7 cells exposed to 0.1 μg/mL LPS. Moreover, they effectively upregulated the anti-inflammatory cytokines, such as IL-4, IL-10, and Arg-1 gene expression levels impaired by LPS without obvious cytotoxicity.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107095"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988919","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: 2026-01-31DOI: 10.1016/j.fitote.2026.107115
Jinwon Choi , Han-Saem Lee , Hyo Jeong Kim , Min Choi , Trina E. Tallei , Chi-Hoon Ahn , Jai-Hyun So , Moon Nyeo Park , Bonglee Kim
Magnolia officinalis Rehder et Wilson (MRW) is a traditional herbal medicine with well-documented anti-inflammatory and antioxidative properties, yet its molecular basis in cancer therapy remains incompletely defined. This study aimed to elucidate the multi-target anticancer potential of MRW against pancreatic cancer through integrated in vitro and in silico analyses. LC–MS/MS profiling identified honokiol and magnolol as the major bioactive constituents, confirmed by retention time and UV spectra. MRW treatment suppressed cell viability and induced apoptosis in PANC-1 and MIA PaCa-2 cells by promoting reactive oxygen species (ROS) generation, mitochondrial membrane potential (∆Ψm) depolarization, and caspase activation, while sparing normal epithelial cells. Mechanistically, MRW inhibited DNA methyltransferase 1 (DNMT-1) and JAK2/STAT3 signaling while restoring undifferentiated embryonic cell transcription factor 1 (UTF-1) and miR-148a-3p expression, thereby reversing the epigenetic silencing and ROS overproduction characteristic of pancreatic cancer cells. Molecular docking further demonstrated strong binding affinities of honokiol, magnolol, and magnolin toward DNMT-1, UTF-1, STAT3, JAK2, IL-6, and Survivin, forming stable hydrogen-bond and π–π stacking interactions within catalytic pockets. These interactions suggest that MRW constituents' function as non-nucleoside DNMT-1 inhibitors and ROS–immune modulators that disrupt oncogenic feedback loops and re-activate apoptotic pathways. Collectively, these findings identify MRW as a multi-target phytomedicine integrating ROS-mediated oxidative stress, epigenetic remodeling, and immune–apoptotic signaling, supporting its translational potential as a low-toxicity adjunct strategy to conventional pancreatic cancer therapies.
厚朴（Magnolia officinalis Rehder et Wilson， MRW）是一种传统的草药，具有良好的抗炎和抗氧化特性，但其在癌症治疗中的分子基础仍未完全确定。本研究旨在通过体外和计算机综合分析，阐明MRW对胰腺癌的多靶点抗癌潜力。LC-MS/MS分析鉴定其主要活性成分为厚朴酚和厚朴酚，并通过保留时间和紫外光谱进行了验证。MRW处理通过促进活性氧（ROS）生成、线粒体膜电位（∆Ψm）去极化和caspase激活，抑制PANC-1和MIA PaCa-2细胞的细胞活力，诱导细胞凋亡，同时保留正常上皮细胞。在机制上，MRW抑制DNA甲基转移酶1 （DNMT-1）和JAK2/STAT3信号传导，同时恢复未分化胚胎细胞转录因子1 （UTF-1）和miR-148a-3p的表达，从而逆转胰腺癌细胞的表观遗传沉默和ROS过量产生的特征。分子对接进一步证明了厚朴酚、厚朴酚和厚朴素对DNMT-1、UTF-1、STAT3、JAK2、IL-6和Survivin具有很强的结合亲和力，在催化口袋内形成稳定的氢键和π-π堆积相互作用。这些相互作用表明，MRW成分具有非核苷类DNMT-1抑制剂和ros免疫调节剂的功能，可破坏致癌反馈回路并重新激活凋亡途径。总之，这些发现确定MRW是一种整合ros介导的氧化应激、表观遗传重塑和免疫凋亡信号的多靶点植物药，支持其作为传统胰腺癌治疗的低毒性辅助策略的翻译潜力。
{"title":"Magnolia officinalis Lignans induce apoptosis and epigenetic reprogramming via the miR-148a-3p/DNMT-1/UTF-1 axis in pancreatic cancer cells","authors":"Jinwon Choi , Han-Saem Lee , Hyo Jeong Kim , Min Choi , Trina E. Tallei , Chi-Hoon Ahn , Jai-Hyun So , Moon Nyeo Park , Bonglee Kim","doi":"10.1016/j.fitote.2026.107115","DOIUrl":"10.1016/j.fitote.2026.107115","url":null,"abstract":"<div><div><em>Magnolia officinalis</em> Rehder et Wilson (MRW) is a traditional herbal medicine with well-documented anti-inflammatory and antioxidative properties, yet its molecular basis in cancer therapy remains incompletely defined. This study aimed to elucidate the multi-target anticancer potential of MRW against pancreatic cancer through integrated in vitro and in silico analyses. LC–MS/MS profiling identified honokiol and magnolol as the major bioactive constituents, confirmed by retention time and UV spectra. MRW treatment suppressed cell viability and induced apoptosis in PANC-1 and MIA PaCa-2 cells by promoting reactive oxygen species (ROS) generation, mitochondrial membrane potential (∆Ψm) depolarization, and caspase activation, while sparing normal epithelial cells. Mechanistically, MRW inhibited DNA methyltransferase 1 (DNMT-1) and JAK2/STAT3 signaling while restoring undifferentiated embryonic cell transcription factor 1 (UTF-1) and miR-148a-3p expression, thereby reversing the epigenetic silencing and ROS overproduction characteristic of pancreatic cancer cells. Molecular docking further demonstrated strong binding affinities of honokiol, magnolol, and magnolin toward DNMT-1, UTF-1, STAT3, JAK2, IL-6, and Survivin, forming stable hydrogen-bond and π–π stacking interactions within catalytic pockets. These interactions suggest that MRW constituents' function as non-nucleoside DNMT-1 inhibitors and ROS–immune modulators that disrupt oncogenic feedback loops and re-activate apoptotic pathways. Collectively, these findings identify MRW as a multi-target phytomedicine integrating ROS-mediated oxidative stress, epigenetic remodeling, and immune–apoptotic signaling, supporting its translational potential as a low-toxicity adjunct strategy to conventional pancreatic cancer therapies.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107115"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146104519","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: 2026-01-06DOI: 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":"2026-03-01","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 : 2026-03-01Epub Date: 2025-12-21DOI: 10.1016/j.fitote.2025.107048
Pei-Pei Zhang , Ming-Yang Cui , Shui-Yuan Yang , Bo Han , Wei Yu , Tian-Tian Wei , Ke-Wu Zeng , Peng-Fei Tu
Recent studies have demonstrated the therapeutic potential of Astragalus membranaceus in diabetic kidney disease (DKD); however, the underlying mechanisms remain incompletely elucidated. In this study, we established a streptozotocin-induced DKD mouse model to evaluate the effects of A. membranaceus extract (AME) on glycemic control, renal function, gut microbiota composition, and metabolic profiles. Biochemical analyzes revealed that A. membranaceus significantly attenuated hyperglycemia and improved renal function, as indicated by reduced serum creatinine and blood urea nitrogen levels. Metagenomic sequencing demonstrated that A. membranaceus reversed microbial dysbiosis by suppressing pathogenic bacteria (e.g., Aerococcus urinaeequi) and enriching beneficial probiotics (e.g., Thomasclavelia cocleata). Furthermore, LC/MS-based metabolomics identified key metabolic pathways, including glycerophospholipid metabolism and bile acid synthesis, as potential mediators of the therapeutic effects. These findings underscore the crucial role of the gut-renal axis in DKD pathogenesis and provide a mechanistic basis for the clinical application of A. membranaceus.
{"title":"Astragalus membranaceus improves blood glucose and renal function in diabetic kidney disease mice via gut microbial metabolite axis","authors":"Pei-Pei Zhang , Ming-Yang Cui , Shui-Yuan Yang , Bo Han , Wei Yu , Tian-Tian Wei , Ke-Wu Zeng , Peng-Fei Tu","doi":"10.1016/j.fitote.2025.107048","DOIUrl":"10.1016/j.fitote.2025.107048","url":null,"abstract":"<div><div>Recent studies have demonstrated the therapeutic potential of <em>Astragalus membranaceus</em> in diabetic kidney disease (DKD); however, the underlying mechanisms remain incompletely elucidated. In this study, we established a streptozotocin-induced DKD mouse model to evaluate the effects of <em>A. membranaceus</em> extract (AME) on glycemic control, renal function, gut microbiota composition, and metabolic profiles. Biochemical analyzes revealed that <em>A. membranaceus</em> significantly attenuated hyperglycemia and improved renal function, as indicated by reduced serum creatinine and blood urea nitrogen levels. Metagenomic sequencing demonstrated that <em>A. membranaceus</em> reversed microbial dysbiosis by suppressing pathogenic bacteria (e.g., <em>Aerococcus urinaeequi</em>) and enriching beneficial probiotics (e.g., <em>Thomasclavelia cocleata</em>). Furthermore, LC/MS-based metabolomics identified key metabolic pathways, including glycerophospholipid metabolism and bile acid synthesis, as potential mediators of the therapeutic effects. These findings underscore the crucial role of the gut-renal axis in DKD pathogenesis and provide a mechanistic basis for the clinical application of <em>A. membranaceus</em>.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107048"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818606","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.2025.107050
Zijin Xu , Shaoxian Wang , Hao Chen , Tao Lv , Zhiwen Zhang , Faxiang Pu , Zhangfu Xie , Longfei Feng , Ping Wang
Ethnopharmacological relevance
Tetrastigma hemsleyanum Diels et Gilg (TDG), a traditional Chinese medicinal (TCM) plant, is historically used for liver injury treatment. Despite its ethnopharmacological significance, systematic studies on how processing affects its composition and efficacy remain lacking.
Aim of the study
This study aimed to compare the chemical profiles and hepatoprotective effects of extracts from TDG processed with three different Paozhi (TCM processing) methods (fresh, freeze-dried, and hot-air drying) and explore their mechanisms against drug-induced liver injury (DILI).
Materials and methods
Chemical constituents were analyzed via UPLC-Q-TOF-MS/MS. Hepatoprotection was evaluated using an acetaminophen (APAP)-induced human normal hepatocytes (LO2) cell model. Network pharmacology and molecular docking identified targets and pathways.
Results
Thirty-two compounds were identified across TDG extracts, with 13 shared and 19 unique to specific formulations. All extracts alleviated liver injury, but freeze-dried TDG (TDG-b) showed the strongest effect. Quercetin, procyanidin B1, catechins, kaempferol, and isorhamnetin emerged as key active constituents in TDG-b, targeting DILI through cancer, lipid and atherosclerosis, Hypoxia-Inducible Factor 1 (HIF-1), and Tumor Necrosis Factor (TNF) signaling pathways. Molecular docking confirmed robust binding between these compounds and core therapeutic targets.
Conclusions
TDG-b, a freeze-dried extract, optimally preserves bioactive constituents and demonstrates superior anti-DILI activity, validating traditional processing wisdom. This study bridges ethnopharmacological knowledge and mechanistic evidence, guiding TDG-based therapeutic optimization.
民族药理学相关性：四柱草（Tetrastigma hemsleyanum Diels et Gilg， TDG）是一种传统的中药植物，历史上被用于肝损伤治疗。尽管其具有民族药理学意义，但加工过程如何影响其成分和功效的系统研究仍然缺乏。目的：本研究旨在比较三种中药泡治方法（新鲜、冷冻干燥和热风干燥）炮制的龙胆提取物的化学成分和肝保护作用，并探讨其抗药物性肝损伤（DILI）的机制。材料与方法：化学成分分析采用UPLC-Q-TOF-MS/MS法。采用对乙酰氨基酚（APAP）诱导的人正常肝细胞（LO2）细胞模型评估肝保护作用。网络药理学和分子对接确定靶点和途径。结果：在TDG提取物中鉴定出32种化合物，其中13种是共有的，19种是独特的。所有提取物均能减轻肝损伤，但冻干TDG （TDG-b）的作用最强。槲皮素、原花青素B1、儿茶素、山奈酚和异鼠李素是TDG-b中的关键活性成分，通过癌症、脂质和动脉粥样硬化、缺氧诱导因子1 （HIF-1）和肿瘤坏死因子（TNF）信号通路靶向DILI。分子对接证实了这些化合物与核心治疗靶点之间的强大结合。结论：冻干提取物TDG-b具有较好的保存生物活性成分和抗dili活性，验证了传统的加工智慧。本研究将民族药理学知识与机制证据相结合，指导基于tdg的治疗优化。
{"title":"A comparative study of the hepatoprotective effects of the three processed products of Tetrastigma hemsleyanum Diels et Gilg: in vitro pharmacological investigation and integrating Network pharmacology","authors":"Zijin Xu , Shaoxian Wang , Hao Chen , Tao Lv , Zhiwen Zhang , Faxiang Pu , Zhangfu Xie , Longfei Feng , Ping Wang","doi":"10.1016/j.fitote.2025.107050","DOIUrl":"10.1016/j.fitote.2025.107050","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Tetrastigma hemsleyanum</em> Diels et Gilg (TDG), a traditional Chinese medicinal (TCM) plant, is historically used for liver injury treatment. Despite its ethnopharmacological significance, systematic studies on how processing affects its composition and efficacy remain lacking.</div></div><div><h3>Aim of the study</h3><div>This study aimed to compare the chemical profiles and hepatoprotective effects of extracts from TDG processed with three different Paozhi (TCM processing) methods (fresh, freeze-dried, and hot-air drying) and explore their mechanisms against drug-induced liver injury (DILI).</div></div><div><h3>Materials and methods</h3><div>Chemical constituents were analyzed <em>via</em> UPLC-Q-TOF-MS/MS. Hepatoprotection was evaluated using an acetaminophen (APAP)-induced human normal hepatocytes (LO2) cell model. Network pharmacology and molecular docking identified targets and pathways.</div></div><div><h3>Results</h3><div>Thirty-two compounds were identified across TDG extracts, with 13 shared and 19 unique to specific formulations. All extracts alleviated liver injury, but freeze-dried TDG (TDG-b) showed the strongest effect. Quercetin, procyanidin B1, catechins, kaempferol, and isorhamnetin emerged as key active constituents in TDG-b, targeting DILI through cancer, lipid and atherosclerosis, Hypoxia-Inducible Factor 1 (HIF-1), and Tumor Necrosis Factor (TNF) signaling pathways. Molecular docking confirmed robust binding between these compounds and core therapeutic targets.</div></div><div><h3>Conclusions</h3><div>TDG-b, a freeze-dried extract, optimally preserves bioactive constituents and demonstrates superior anti-DILI activity, validating traditional processing wisdom. This study bridges ethnopharmacological knowledge and mechanistic evidence, guiding TDG-based therapeutic optimization.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107050"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827046","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: 2026-01-02DOI: 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":"2026-03-01","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}
Pub Date : 2026-03-01Epub Date: 2026-01-02DOI: 10.1016/j.fitote.2026.107082
Abdoulaye Segda , Priya Tufail , Roland Nâg-Tiéro Méda , Aneela Fayaz , Benjamin Kouliga Koama , Georges Anicet Ouédraogo , Humera Jahan , M. Iqbal Choudhary
The present study investigated the antiglycation activities of extracts and fractions of Phyllanthus amarus, Chrysanthellum americanum, Striga hermonthica and, based on cytotoxicity results, evaluated the anti-inflammatory potential of the ethyl acetate fraction of Striga hermonthica (EtOAc-Sh) in AGE-challenged THP-1 monocytes. The in vitro methylglyoxal (MGO)-bovine serum albumin (BSA) assay revealed notable inhibition of AGE formation by EtOAc-Sh (IC50 = 100.1 ± 0.001 μg/mL; quercetin 1.23 μM, gallic acid 0.131 μM, rutin 0.0021 μM), with rutin used as the standard (IC50 = 402 ± 0.30 μM). Cell metabolic assay showed EtOAc-Sh was non-cytotoxic to HepG2 hepatocytes (∼ 94 % cell viability at 250 μg/mL), and THP-1 monocytes (≥ 90 % cell viability at 500 μg/mL). Moreover, EtOAc-Sh significantly (p < 0.001) reduced the AGE-mediated ROS production (83 % at 100 μg/mL), as compared to apocynin (69 % at 100 μM). Furthermore, EtOAc-Sh suppressed the NF-κB (p65) (RFU: 9.18 at 100 μg/mL) activation, as compared to PDTC (RFU: 6.97) at 100 μM. EtOAc-Sh also significantly (p < 0.001) reduced the COX-2 levels (1.52-fold decrease at 100 μg/mL; PDTC, 1.68-fold decrease) in THP-1 monocytes, while significantly (p < 0.001) reversing the AGE-induced suppression of COX-1 levels (1.89-fold increase at 100 μg/mL; PDTC, 1.88-fold increase) at 100 μM. HPLC-UV analysis identified quercetin, gallic acid, and rutin, as the active constituents of the EtOAc-Sh fraction. These findings suggest that EtOAc-Sh fraction as a potential antiglycation, and anti-inflammatory agent, which supporting the traditional use of Striga hermonthica in diabetes management in Burkina Faso.
{"title":"Ethyl acetate fraction of Striga hermonthica (Delile) Benth. inhibits AGEs-mediated inflammatory markers in THP-1 monocytes","authors":"Abdoulaye Segda , Priya Tufail , Roland Nâg-Tiéro Méda , Aneela Fayaz , Benjamin Kouliga Koama , Georges Anicet Ouédraogo , Humera Jahan , M. Iqbal Choudhary","doi":"10.1016/j.fitote.2026.107082","DOIUrl":"10.1016/j.fitote.2026.107082","url":null,"abstract":"<div><div>The present study investigated the antiglycation activities of extracts and fractions of <em>Phyllanthus amarus</em>, <em>Chrysanthellum americanum</em>, <em>Striga hermonthica</em> and, based on cytotoxicity results, evaluated the anti-inflammatory potential of the ethyl acetate fraction of <em>Striga hermonthica</em> (<em>EtOAc-Sh</em>) in AGE-challenged THP-1 monocytes. The <em>in vitro</em> methylglyoxal (MGO)-bovine serum albumin (BSA) assay revealed notable inhibition of AGE formation by <em>EtOAc-Sh</em> (IC<sub>50</sub> = 100.1 ± 0.001 μg/mL; quercetin 1.23 μM, gallic acid 0.131 μM, rutin 0.0021 μM), with rutin used as the standard (IC<sub>50</sub> = 402 ± 0.30 μM). Cell metabolic assay showed <em>EtOAc-Sh</em> was non-cytotoxic to HepG2 hepatocytes (∼ 94 % cell viability at 250 μg/mL), and THP-1 monocytes (≥ 90 % cell viability at 500 μg/mL). Moreover, <em>EtOAc-Sh</em> significantly (<em>p <</em> 0.001) reduced the AGE-mediated ROS production (83 % at 100 μg/mL), as compared to apocynin (69 % at 100 μM). Furthermore, <em>EtOAc-Sh</em> suppressed the NF-κB (p<sup>65</sup>) (RFU: 9.18 at 100 μg/mL) activation, as compared to PDTC (RFU: 6.97) at 100 μM. <em>EtOAc-Sh</em> also significantly (<em>p</em> < 0.001) reduced the COX-2 levels (1.52-fold decrease at 100 μg/mL; PDTC, 1.68-fold decrease) in THP-1 monocytes, while significantly (<em>p</em> < 0.001) reversing the AGE-induced suppression of COX-1 levels (1.89-fold increase at 100 μg/mL; PDTC, 1.88-fold increase) at 100 μM. HPLC-UV analysis identified quercetin, gallic acid, and rutin, as the active constituents of the <em>EtOAc-Sh</em> fraction. These findings suggest that <em>EtOAc-Sh</em> fraction as a potential antiglycation, and anti-inflammatory agent, which supporting the traditional use of <em>Striga hermonthica</em> in diabetes management in Burkina Faso.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107082"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899631","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.2025.107067
Wen Pan , Ze-Fei Jia , Xiao-Bin Deng , Liang-Ying Li , Shu-Li Man , Shi-Qiang Tan , Jing Hu
Croton tiglium L. (Crotonis Fructus, CF), a classic toxic but valued Chinese herb used for over 2000 years, requires detoxification processing for clinical safety. Crotonis Semen Pulveratum (CP) is the most common processed product of CF, which has been utilized since the Song Dynasty. Nevertheless, the detoxification mechanisms underlying CP processing is still unclear. Therefore, this study investigated toxicity differences between raw and processed CF in rats and preliminarily predicted the potential attenuation mechanism after processing. UPLC-Q-Exactive-MS characterized CF and CP constituents, and 16S rRNA sequencing analyzed gut microbiota changes. Additionally, serum metabolomics was adopted to identify differential biomarkers and principal metabolic pathways associated with CP toxicity attenuation. The results show that chemical profiling identified 18 compounds that differentiated CP from CF. Histopathology showed processing significantly alleviated CF-induced gut damage in normal rats. CP restored colonic mucosa, reversing CF-induced damage to epithelium, crypts, and goblet cells. Moreover, CP treatment exhibited substantial regulatory effects on inflammatory and oxidative markers. Gut microbiota studies revealed that processing-mediated toxicity attenuation was closely associated with the restoration of gut microbial diversity and specific modulation of key bacterial taxa, including Eubacterium_coprostanoligenes_group, Escherichia-Shigella and Lactobacillus. Processing ameliorated CF-induced serum metabolic disorders, identifying 12 biomarkers linked to glycerolipid, lysine, and arginine/proline metabolism pathways. Additionally, quantitative analysis indicated that the reduction of crotonane diterpenoids after processing might contribute to the observed detoxification effects of CP. This study provides new insights into the possible processing-mediated toxicity attenuation of CP, offering a scientific foundation for its quality optimization and safe clinical application.
{"title":"Gut microbiota combined with metabolomics approach to investigate the processing-based detoxification mechanism of processed cream of Croton tiglium L. seeds","authors":"Wen Pan , Ze-Fei Jia , Xiao-Bin Deng , Liang-Ying Li , Shu-Li Man , Shi-Qiang Tan , Jing Hu","doi":"10.1016/j.fitote.2025.107067","DOIUrl":"10.1016/j.fitote.2025.107067","url":null,"abstract":"<div><div><em>Croton tiglium</em> L. (Crotonis Fructus, CF), a classic toxic but valued Chinese herb used for over 2000 years, requires detoxification processing for clinical safety. Crotonis Semen Pulveratum (CP) is the most common processed product of CF, which has been utilized since the Song Dynasty. Nevertheless, the detoxification mechanisms underlying CP processing is still unclear. Therefore, this study investigated toxicity differences between raw and processed CF in rats and preliminarily predicted the potential attenuation mechanism after processing. UPLC-Q-Exactive-MS characterized CF and CP constituents, and 16S rRNA sequencing analyzed gut microbiota changes. Additionally, serum metabolomics was adopted to identify differential biomarkers and principal metabolic pathways associated with CP toxicity attenuation. The results show that chemical profiling identified 18 compounds that differentiated CP from CF. Histopathology showed processing significantly alleviated CF-induced gut damage in normal rats. CP restored colonic mucosa, reversing CF-induced damage to epithelium, crypts, and goblet cells. Moreover, CP treatment exhibited substantial regulatory effects on inflammatory and oxidative markers. Gut microbiota studies revealed that processing-mediated toxicity attenuation was closely associated with the restoration of gut microbial diversity and specific modulation of key bacterial taxa, including Eubacterium_coprostanoligenes_group, Escherichia-Shigella and Lactobacillus. Processing ameliorated CF-induced serum metabolic disorders, identifying 12 biomarkers linked to glycerolipid, lysine, and arginine/proline metabolism pathways. Additionally, quantitative analysis indicated that the reduction of crotonane diterpenoids after processing might contribute to the observed detoxification effects of CP. This study provides new insights into the possible processing-mediated toxicity attenuation of CP, offering a scientific foundation for its quality optimization and safe clinical application.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107067"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846173","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.2025.107052
Fui-Ling Voon , Yu Zhao Lee , Xiao Ying Ooi , Charlotte Zi Ern Tay , Ji Wei Tan , Chau Ling Tham , Yu-Cheng Ho , Ming Tatt Lee
Purpurin, a naturally occurring anthraquinone pigment, has gained attention for its promising anticancer properties. This systematic-narrative hybrid review summarises current preclinical evidence on its mechanisms of action, pharmacology, and translational potential. Literature searches were conducted using PubMed, Web of Science, Scopus, and Google Scholar up to June 2025. Purpurin demonstrates selective cytotoxicity across multiple cancer models through redox imbalance, mitochondrial dysfunction, inhibition of PI3K/AKT signalling, and upregulation of the tumour suppressor LHPP. It also interferes with amino acid and glutamine metabolism and suppresses oncogenic protein aggregation. As a photosensitiser, purpurin enhances photodynamic therapy through light-activated ROS generation. Despite these promising mechanistic insights, its clinical applicability remains limited by poor aqueous solubility, rapid metabolism, and insufficient pharmacokinetic and toxicological data. Early in vivo studies indicate favourable safety, and emerging nanoparticle-based delivery systems show potential to improve bioavailability and tumour targeting. Collectively, current findings highlight purpurin as a compelling candidate for further development in oncology, particularly as part of combination or photo-enhanced therapeutic approaches. Continued research is required to address existing pharmacological gaps and to evaluate purpurin in clinically relevant models.
紫癜素是一种天然存在的蒽醌色素，因其具有良好的抗癌特性而受到关注。这篇系统叙述的混合综述总结了目前关于其作用机制、药理学和转化潜力的临床前证据。截至2025年6月，使用PubMed、Web of Science、Scopus和谷歌Scholar进行文献检索。Purpurin通过氧化还原失衡、线粒体功能障碍、抑制PI3K/AKT信号和上调肿瘤抑制因子LHPP，在多种癌症模型中显示出选择性细胞毒性。它还干扰氨基酸和谷氨酰胺代谢，抑制致癌蛋白聚集。作为一种光敏剂，紫癜素通过光激活ROS的产生来增强光动力治疗。尽管这些有希望的机制见解，但其临床适用性仍然受到水溶性差，代谢快，药代动力学和毒理学数据不足的限制。早期体内研究表明良好的安全性，新兴的基于纳米颗粒的递送系统显示出提高生物利用度和肿瘤靶向性的潜力。总的来说，目前的研究结果突出了紫癜蛋白作为肿瘤学进一步发展的引人注目的候选者，特别是作为联合或光增强治疗方法的一部分。需要继续研究以解决现有的药理学空白，并在临床相关模型中评估紫癜蛋白。
{"title":"Purpurin as a promising anticancer agent: A review of preclinical evidence","authors":"Fui-Ling Voon , Yu Zhao Lee , Xiao Ying Ooi , Charlotte Zi Ern Tay , Ji Wei Tan , Chau Ling Tham , Yu-Cheng Ho , Ming Tatt Lee","doi":"10.1016/j.fitote.2025.107052","DOIUrl":"10.1016/j.fitote.2025.107052","url":null,"abstract":"<div><div>Purpurin, a naturally occurring anthraquinone pigment, has gained attention for its promising anticancer properties. This systematic-narrative hybrid review summarises current preclinical evidence on its mechanisms of action, pharmacology, and translational potential. Literature searches were conducted using PubMed, Web of Science, Scopus, and Google Scholar up to June 2025. Purpurin demonstrates selective cytotoxicity across multiple cancer models through redox imbalance, mitochondrial dysfunction, inhibition of PI3K/AKT signalling, and upregulation of the tumour suppressor LHPP. It also interferes with amino acid and glutamine metabolism and suppresses oncogenic protein aggregation. As a photosensitiser, purpurin enhances photodynamic therapy through light-activated ROS generation. Despite these promising mechanistic insights, its clinical applicability remains limited by poor aqueous solubility, rapid metabolism, and insufficient pharmacokinetic and toxicological data. Early <em>in vivo</em> studies indicate favourable safety, and emerging nanoparticle-based delivery systems show potential to improve bioavailability and tumour targeting. Collectively, current findings highlight purpurin as a compelling candidate for further development in oncology, particularly as part of combination or photo-enhanced therapeutic approaches. Continued research is required to address existing pharmacological gaps and to evaluate purpurin in clinically relevant models.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107052"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801955","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: 2026-01-20DOI: 10.1016/j.fitote.2026.107104
Shaymaa Ahmed Gouda , E.A. Gamal , Hanaa Mohamed Gouda , Ahmed A.M.A. Selim
The emergence of microbial resistance to antimicrobial agents emphasizes the need to discover new ones. The potential use of endophytic fungi as a source of antimicrobial agents and their mode of action has not been fully explored. Thus, this research aimed to evaluate the antimicrobial activity of 16 endophytic fungal species isolated from some plants collected from Wadi Hagul, Egypt, along with assessing the mechanism of action of the most active one. Alternaria E15 was the most effective fungus against S. aureus with an MIC of 321.5 μgmL−1, E. coli, A. niger with MICs of 1250 μgmL−1, and C. albicans with an MIC of 2500 μgmL−1. It was identified morphologically and molecularly as Alternaria alternata (accession no. PX106371). Sorbitol protection and ergosterol-binding assays indicated that its ethyl acetate extract does not target the fungal cell wall but acts through direct ergosterol binding in the fungal membrane. LC/MS analysis of A. alternata extract revealed seventeen major compounds belonging to different antimicrobial chemical classes. The docking studies on CYP51 and Penicillin-Binding Protein 3 showed that Okanin4-(6-acetylglucoside) and alternariol (docking scores −11.957 and − 7.009, respectively) may inhibit fungal ergosterol biosynthesis, while Okanin4-(6-acetylglucoside) and altenusin may inhibit bacterial cell wall synthesis (docking scores −8.537 and − 8.019, respectively). This study highlights, for the first time to our knowledge, the investigation of Egyptian endophytic fungi isolated from certain plants as a potential source for antimicrobial products, with an understanding of the responsible compounds and their mechanisms supporting their potential use in developing novel medicinal applications.
{"title":"Bioprospecting of endophytic fungi from medicinal plants as a source of antimicrobial agents: In vitro evaluation, metabolite profiling, and docking-based elucidation","authors":"Shaymaa Ahmed Gouda , E.A. Gamal , Hanaa Mohamed Gouda , Ahmed A.M.A. Selim","doi":"10.1016/j.fitote.2026.107104","DOIUrl":"10.1016/j.fitote.2026.107104","url":null,"abstract":"<div><div>The emergence of microbial resistance to antimicrobial agents emphasizes the need to discover new ones. The potential use of endophytic fungi as a source of antimicrobial agents and their mode of action has not been fully explored. Thus, this research aimed to evaluate the antimicrobial activity of 16 endophytic fungal species isolated from some plants collected from Wadi Hagul, Egypt, along with assessing the mechanism of action of the most active one. <em>Alternaria</em> E15 was the most effective fungus against <em>S. aureus</em> with an MIC of 321.5 μgmL<sup>−1</sup>, <em>E. coli</em>, <em>A. niger</em> with MICs of 1250 μgmL<sup>−1</sup>, and <em>C. albicans</em> with an MIC of 2500 μgmL<sup>−1</sup>. It was identified morphologically and molecularly as <em>Alternaria alternata</em> (accession no. PX106371). Sorbitol protection and ergosterol-binding assays indicated that its ethyl acetate extract does not target the fungal cell wall but acts through direct ergosterol binding in the fungal membrane. LC/MS analysis of <em>A. alternata</em> extract revealed seventeen major compounds belonging to different antimicrobial chemical classes. The docking studies on CYP51 and Penicillin-Binding Protein 3 showed that Okanin4-(6-acetylglucoside) and alternariol (docking scores −11.957 and − 7.009, respectively) may inhibit fungal ergosterol biosynthesis, while Okanin4-(6-acetylglucoside) and altenusin may inhibit bacterial cell wall synthesis (docking scores −8.537 and − 8.019, respectively). This study highlights, for the first time to our knowledge, the investigation of Egyptian endophytic fungi isolated from certain plants as a potential source for antimicrobial products, with an understanding of the responsible compounds and their mechanisms supporting their potential use in developing novel medicinal applications.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"189 ","pages":"Article 107104"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023302","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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