Pub Date : 2024-11-01DOI: 10.1016/S1875-5364(24)60659-X
Chunmei CHEN , Xueni WANG , Wenxuan FANG , Jiaqi LIANG , Jian CAI , Dehua YANG , Xiaowei LUO , Chenghai GAO , Xiangxi YI , Yonghong LIU , Xuefeng ZHOU
Seven novel linear polyketides, talaketides A−G (1−7), were isolated from the rice media cultures of the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41027. Among these, talaketides A−E (1−5) represented unprecedented unsaturated linear polyketides with an epoxy ring structure. The structures, including absolute configurations of these compounds, were elucidated through detailed analyses of nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HR-MS) data, as well as electronic custom distributors (ECD) calculations. In the cytotoxicity screening against prostate cancer cell lines, talaketide E (5) demonstrated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines, with an IC50 value of 14.44 μmol·L−1 . Moreover, compound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase, ultimately inducing apoptosis. These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treatment for prostate cancer.
{"title":"Talaketides A−G, linear polyketides with prostate cancer cytotoxic activity from the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41027","authors":"Chunmei CHEN , Xueni WANG , Wenxuan FANG , Jiaqi LIANG , Jian CAI , Dehua YANG , Xiaowei LUO , Chenghai GAO , Xiangxi YI , Yonghong LIU , Xuefeng ZHOU","doi":"10.1016/S1875-5364(24)60659-X","DOIUrl":"10.1016/S1875-5364(24)60659-X","url":null,"abstract":"<div><div>Seven novel linear polyketides, talaketides A−G (<strong>1</strong>−<strong>7</strong>), were isolated from the rice media cultures of the mangrove sediment-derived fungus <em>Talaromyces</em> sp. SCSIO 41027. Among these, talaketides A−E (<strong>1</strong>−<strong>5</strong>) represented unprecedented unsaturated linear polyketides with an epoxy ring structure. The structures, including absolute configurations of these compounds, were elucidated through detailed analyses of nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HR-MS) data, as well as electronic custom distributors (ECD) calculations. In the cytotoxicity screening against prostate cancer cell lines, talaketide E (<strong>5</strong>) demonstrated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines, with an IC<sub>50</sub> value of 14.44 μmol·L<sup>−1</sup> . Moreover, compound <strong>5</strong> significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase, ultimately inducing apoptosis. These findings indicate that compound <strong>5</strong> may serve as a promising lead compound for the development of a potential treatment for prostate cancer.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 11","pages":"Pages 1047-1056"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/S1875-5364(24)60687-4
Simian CHEN , Binxin DAI , Dandan ZHANG , Yuexin YANG , Hairong ZHANG , Junyu ZHANG , Di LU , Caisheng WU
Natural medicines (NMs) are crucial for treating human diseases. Efficiently characterizing their bioactive components in vivo has been a key focus and challenge in NM research. High-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) systems offer high sensitivity, resolution, and precision for conducting in vivo analysis of NMs. However, due to the complexity of NMs, conventional data acquisition, mining, and processing techniques often fail to meet the practical needs of in vivo NM analysis. Over the past two decades, intelligent spectral data-processing techniques based on various principles and algorithms have been developed and applied for in vivo NM analysis. Consequently, improvements have been achieved in the overall analytical performance by relying on these techniques without the need to change the instrument hardware. These improvements include enhanced instrument analysis sensitivity, expanded compound analysis coverage, intelligent identification, and characterization of nontargeted in vivo compounds, providing powerful technical means for studying the in vivo metabolism of NMs and screening for pharmacologically active components. This review summarizes the research progress on in vivo analysis strategies for NMs using intelligent MS data processing techniques reported over the past two decades. It discusses differences in compound structures, variations among biological samples, and the application of artificial intelligence (AI) neural network algorithms. Additionally, the review offers insights into the potential of in vivo tracking of NMs, including the screening of bioactive components and the identification of pharmacokinetic markers. The aim is to provide a reference for the integration and development of new technologies and strategies for future in vivo analysis of NMs.
{"title":"Advances in intelligent mass spectrometry data processing technology for in vivo analysis of natural medicines","authors":"Simian CHEN , Binxin DAI , Dandan ZHANG , Yuexin YANG , Hairong ZHANG , Junyu ZHANG , Di LU , Caisheng WU","doi":"10.1016/S1875-5364(24)60687-4","DOIUrl":"10.1016/S1875-5364(24)60687-4","url":null,"abstract":"<div><div>Natural medicines (NMs) are crucial for treating human diseases. Efficiently characterizing their bioactive components <em>in vivo</em> has been a key focus and challenge in NM research. High-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) systems offer high sensitivity, resolution, and precision for conducting <em>in vivo</em> analysis of NMs. However, due to the complexity of NMs, conventional data acquisition, mining, and processing techniques often fail to meet the practical needs of <em>in vivo</em> NM analysis. Over the past two decades, intelligent spectral data-processing techniques based on various principles and algorithms have been developed and applied for <em>in vivo</em> NM analysis. Consequently, improvements have been achieved in the overall analytical performance by relying on these techniques without the need to change the instrument hardware. These improvements include enhanced instrument analysis sensitivity, expanded compound analysis coverage, intelligent identification, and characterization of nontargeted <em>in vivo</em> compounds, providing powerful technical means for studying the <em>in vivo</em> metabolism of NMs and screening for pharmacologically active components. This review summarizes the research progress on <em>in vivo</em> analysis strategies for NMs using intelligent MS data processing techniques reported over the past two decades. It discusses differences in compound structures, variations among biological samples, and the application of artificial intelligence (AI) neural network algorithms. Additionally, the review offers insights into the potential of <em>in vivo</em> tracking of NMs, including the screening of bioactive components and the identification of pharmacokinetic markers. The aim is to provide a reference for the integration and development of new technologies and strategies for future <em>in vivo</em> analysis of NMs.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 10","pages":"Pages 900-913"},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/S1875-5364(24)60725-9
Kaimei QIU , Hao QIU , Yanqiao XIE , Siyu ZHANG , Qian ZHANG , Zhengtao WANG , Zhuzhen HAN , Li YANG
Five new furofuran lignans and their derivatives, (−)-glaberide I 4-O-β-D-glucopyranoside (1a), (+)-glaberide I 4-O-β-D-glucopyranoside (1b), (+)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside (2a), (−)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside (2b), and (−)-isoeucommin A (3b), along with fifteen known analogs were isolated from the stems of Dendrobium 'Sonia'. These compounds were classified into ten pairs of enantiomers or diastereoisomers via chiral resolution, and their structures were determined based on extensive spectroscopic data. Their absolute configurations were determined by hydrolysis, comparison of experimental and calculated electronic circular dichroism (ECD) data, and single-crystal X-ray diffraction analysis. The isolates were evaluated for their ability to inhibit nitric oxide (NO) production in RAW264.7 cells. Among them, syringaresinol (5) exhibited prominent inhibition activity, with an IC50 value of 28.4 ± 3.0 μmol·L−1, and there was a slight difference between 5a, 5b and the racemic mixture 5.
五种新的呋喃木脂素及其衍生物：(-)-木脂素 I 4-O-β-D-吡喃葡萄糖苷(1a)、(+)-木脂素 I 4-O-β-D-吡喃葡萄糖苷(1b)、(+)-木脂素 I 7'-乙氧基-4-O-β-D-吡喃葡萄糖苷(2a)、(-)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside (2b)、(-)-isoeucommin A (3b)以及 15 种已知的类似物都是从铁皮石斛'Sonia'的茎中分离出来的。通过手性解析，这些化合物被分为十对对映体或非对映异构体，并根据大量光谱数据确定了它们的结构。通过水解、比较实验和计算的电子圆二色性（ECD）数据以及单晶 X 射线衍射分析，确定了它们的绝对构型。对这些分离物抑制 RAW264.7 细胞产生一氧化氮（NO）的能力进行了评估。其中，丁香树脂醇（5）的抑制活性突出，其 IC50 值为 28.4 ± 3.0 μmol-L-1，且 5a、5b 和外消旋混合物 5 之间存在微小差异。
{"title":"Chiral resolution of furofuran lignans and their derivatives from the stems of Dendrobium 'Sonia'","authors":"Kaimei QIU , Hao QIU , Yanqiao XIE , Siyu ZHANG , Qian ZHANG , Zhengtao WANG , Zhuzhen HAN , Li YANG","doi":"10.1016/S1875-5364(24)60725-9","DOIUrl":"10.1016/S1875-5364(24)60725-9","url":null,"abstract":"<div><div>Five new furofuran lignans and their derivatives, (−)-glaberide I 4-<em>O</em>-<em>β</em>-D-glucopyranoside (<strong>1a</strong>), (+)-glaberide I 4-<em>O</em>-<em>β</em>-D-glucopyranoside (<strong>1b</strong>), (+)-glaberide I 7'-ethoxy-4-<em>O</em>-<em>β</em>-D-glucopyranoside (<strong>2a</strong>), (−)-glaberide I 7'-ethoxy-4-<em>O</em>-<em>β</em>-D-glucopyranoside (<strong>2b</strong>), and (−)-isoeucommin A (<strong>3b</strong>), along with fifteen known analogs were isolated from the stems of <em>Dendrobium</em> 'Sonia'. These compounds were classified into ten pairs of enantiomers or diastereoisomers <em>via</em> chiral resolution, and their structures were determined based on extensive spectroscopic data. Their absolute configurations were determined by hydrolysis, comparison of experimental and calculated electronic circular dichroism (ECD) data, and single-crystal X-ray diffraction analysis. The isolates were evaluated for their ability to inhibit nitric oxide (NO) production in RAW264.7 cells. Among them, syringaresinol (<strong>5</strong>) exhibited prominent inhibition activity, with an IC<sub>50</sub> value of 28.4 ± 3.0 μmol·L<sup>−1</sup>, and there was a slight difference between <strong>5a</strong>, <strong>5b</strong> and the racemic mixture <strong>5</strong>.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 10","pages":"Pages 937-944"},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/S1875-5364(24)60722-3
Didi WANG , Fang MEI , Jinchun NIE , Zhenwei LI , Daidi ZHANG , Dean GUO , Wei LI
The phytochemical investigation of the leaves and twigs of Croton yunnanensis resulted in the isolation of eight new clerodane furanoditerpenoids, named croyunfuranoids A−H (1−8), along with three known analogs (9−11). The structures of these compounds were elucidated using spectroscopic analyses, and their absolute configurations were determined through a combination of electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction. Notably, Croyunfuranoid D (4) is identified as a rare 18,19-dinor-clerodane diterpenoid. Additionally, the structure of a previously reported diterpenoid, crotonyunnan B, was revised. All isolated compounds were evaluated for their inhibitory activities on nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages. Among them, compounds 5 and 6 demonstrated significant inhibitory effects, with IC50 values of 20.33 ± 2.31 and 22.80 ± 1.31 μmol·L−1, respectively.
通过对云南巴豆的叶片和小枝进行植物化学研究，分离出了八种新的萜类呋喃二萜化合物，命名为云南巴豆呋喃二萜 A-H（1-8），以及三种已知的类似物（9-11）。通过光谱分析阐明了这些化合物的结构，并结合电子圆二色性（ECD）计算和单晶 X 射线衍射确定了它们的绝对构型。值得注意的是，Croyunfuranoid D (4) 被鉴定为一种罕见的 18,19-二邻氯二萜类化合物。此外，以前报道过的一种二萜类化合物巴豆呋喃烷 B 的结构也得到了修正。对所有分离出的化合物进行了评估，以确定它们对 LPS 诱导的 RAW 264.7 巨噬细胞产生一氧化氮（NO）的抑制活性。其中，化合物 5 和 6 具有显著的抑制作用，IC50 值分别为 20.33 ± 2.31 和 22.80 ± 1.31 μmol-L-1。
{"title":"Highly oxygenated clerodane furanoditerpenoids from the leaves and twigs of Croton yunnanensis","authors":"Didi WANG , Fang MEI , Jinchun NIE , Zhenwei LI , Daidi ZHANG , Dean GUO , Wei LI","doi":"10.1016/S1875-5364(24)60722-3","DOIUrl":"10.1016/S1875-5364(24)60722-3","url":null,"abstract":"<div><div>The phytochemical investigation of the leaves and twigs of <em>Croton yunnanensis</em> resulted in the isolation of eight new clerodane furanoditerpenoids, named croyunfuranoids A−H (<strong>1</strong>−<strong>8</strong>), along with three known analogs (<strong>9</strong>−<strong>11</strong>). The structures of these compounds were elucidated using spectroscopic analyses, and their absolute configurations were determined through a combination of electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction. Notably, Croyunfuranoid D (<strong>4</strong>) is identified as a rare 18,19-<em>dinor</em>-clerodane diterpenoid. Additionally, the structure of a previously reported diterpenoid, crotonyunnan B, was revised. All isolated compounds were evaluated for their inhibitory activities on nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages. Among them, compounds <strong>5</strong> and <strong>6</strong> demonstrated significant inhibitory effects, with IC<sub>50</sub> values of 20.33 ± 2.31 and 22.80 ± 1.31 μmol·L<sup>−1</sup>, respectively.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 10","pages":"Pages 945-954"},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/S1875-5364(24)60694-1
Tengfei ZHEN , Tianyu SUN , Baichen XIONG , Hui LIU , Lei WANG , Yao CHEN , Haopeng SUN
Glioblastoma (GBM) is the most common invasive malignant tumor in human brain tumors, representing the most severe grade of gliomas. Despite existing therapeutic approaches, patient prognosis remains dismal, necessitating the exploration of novel strategies to enhance treatment efficacy and extend survival. Due to the restrictive nature of the blood-brain barrier (BBB), small-molecule inhibitors are prioritized in the treatment of central nervous system tumors. Among these, DNA damage response (DDR) inhibitors have garnered significant attention due to their potent therapeutic potential across various malignancies. This review provides a detailed analysis of DDR pathways as therapeutic targets in GBM, summarizes recent advancements, therapeutic strategies, and ongoing clinical trials, and offers perspectives on future directions in this rapidly evolving field. The goal is to present a comprehensive outlook on the potential of DDR inhibitors in improving GBM management and outcomes.
{"title":"New insight into targeting the DNA damage response in the treatment of glioblastoma","authors":"Tengfei ZHEN , Tianyu SUN , Baichen XIONG , Hui LIU , Lei WANG , Yao CHEN , Haopeng SUN","doi":"10.1016/S1875-5364(24)60694-1","DOIUrl":"10.1016/S1875-5364(24)60694-1","url":null,"abstract":"<div><div>Glioblastoma (GBM) is the most common invasive malignant tumor in human brain tumors, representing the most severe grade of gliomas. Despite existing therapeutic approaches, patient prognosis remains dismal, necessitating the exploration of novel strategies to enhance treatment efficacy and extend survival. Due to the restrictive nature of the blood-brain barrier (BBB), small-molecule inhibitors are prioritized in the treatment of central nervous system tumors. Among these, DNA damage response (DDR) inhibitors have garnered significant attention due to their potent therapeutic potential across various malignancies. This review provides a detailed analysis of DDR pathways as therapeutic targets in GBM, summarizes recent advancements, therapeutic strategies, and ongoing clinical trials, and offers perspectives on future directions in this rapidly evolving field. The goal is to present a comprehensive outlook on the potential of DDR inhibitors in improving GBM management and outcomes.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 10","pages":"Pages 869-886"},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/S1875-5364(24)60727-2
Yichen LI , Liting HUANG , Jilang LI , Siyuan LI , Jianzhen LV , Guoyue ZHONG , Ming GAO , Shilin YANG , Shan HAN , Wenhui HAO
Acute lung injury (ALI) is a severe inflammatory condition with a high mortality rate, often precipitated by sepsis. The pathophysiology of ALI involves complex mechanisms, including inflammation, oxidative stress, and ferroptosis, a novel form of regulated cell death. This study explores the therapeutic potential of andrographolide (AG), a bioactive compound derived from Andrographis, in mitigating Lipopolysaccharide (LPS)-induced inflammation and ferroptosis. Our research employed in vitro experiments with RAW264.7 macrophage cells and in vivo studies using a murine model of LPS-induced ALI. The results indicate that AG significantly suppresses the production of pro-inflammatory cytokines and inhibits ferroptosis in LPS-stimulated RAW264.7 cells. In vivo, AG treatment markedly reduces lung edema, decreases inflammatory cell infiltration, and mitigates ferroptosis in lung tissues of LPS-induced ALI mice. These protective effects are mediated via the modulation of the Toll-like receptor 4 (TLR4)/Kelch-like ECH-associated protein 1(Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Molecular docking simulations identified the binding sites of AG on the TLR4 protein (Kd value: −33.5 kcal·mol−1), and these interactions were further corroborated by Cellular Thermal Shift Assay (CETSA) and SPR assays. Collectively, our findings demonstrate that AG exerts potent anti-inflammatory and anti-ferroptosis effects in LPS-induced ALI by targeting TLR4 and modulating the Keap1/Nrf2 pathway. This study underscores AG’s potential as a therapeutic agent for ALI and provides new insights into its underlying mechanisms of action.
急性肺损伤（ALI）是一种严重的炎症，死亡率很高，通常由败血症诱发。急性肺损伤的病理生理学涉及复杂的机制，包括炎症、氧化应激和铁变态反应（一种新的细胞死亡调节形式）。本研究探讨了穿心莲内酯（AG）（一种从穿心莲中提取的生物活性化合物）在减轻脂多糖（LPS）诱导的炎症和铁细胞凋亡方面的治疗潜力。我们的研究采用了 RAW264.7 巨噬细胞体外实验和 LPS 诱导 ALI 的小鼠模型体内研究。结果表明，AG 能明显抑制促炎细胞因子的产生，并能抑制 LPS 刺激的 RAW264.7 细胞中的铁蛋白沉积。在体内，AG 治疗可明显减轻 LPS 诱导的 ALI 小鼠肺组织的肺水肿、减少炎性细胞浸润并减轻铁细胞沉着。这些保护作用是通过调节 Toll 样受体 4 (TLR4)/Kelch-like ECH-associated protein 1(Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) 信号通路介导的。分子对接模拟确定了 AG 在 TLR4 蛋白上的结合位点（Kd 值：-33.5 kcal-mol-1），细胞热移试验（CETSA）和 SPR 试验进一步证实了这些相互作用。总之，我们的研究结果表明，AG 通过靶向 TLR4 和调节 Keap1/Nrf2 通路，在 LPS 诱导的 ALI 中发挥了强有力的抗炎和抗铁细胞生成作用。这项研究强调了 AG 作为 ALI 治疗药物的潜力，并对其潜在的作用机制提供了新的见解。
{"title":"Targeting TLR4 and regulating the Keap1/Nrf2 pathway with andrographolide to suppress inflammation and ferroptosis in LPS-induced acute lung injury","authors":"Yichen LI , Liting HUANG , Jilang LI , Siyuan LI , Jianzhen LV , Guoyue ZHONG , Ming GAO , Shilin YANG , Shan HAN , Wenhui HAO","doi":"10.1016/S1875-5364(24)60727-2","DOIUrl":"10.1016/S1875-5364(24)60727-2","url":null,"abstract":"<div><div>Acute lung injury (ALI) is a severe inflammatory condition with a high mortality rate, often precipitated by sepsis. The pathophysiology of ALI involves complex mechanisms, including inflammation, oxidative stress, and ferroptosis, a novel form of regulated cell death. This study explores the therapeutic potential of andrographolide (AG), a bioactive compound derived from <em>Andrographis</em>, in mitigating Lipopolysaccharide (LPS)-induced inflammation and ferroptosis. Our research employed <em>in vitro</em> experiments with RAW264.7 macrophage cells and <em>in vivo</em> studies using a murine model of LPS-induced ALI. The results indicate that AG significantly suppresses the production of pro-inflammatory cytokines and inhibits ferroptosis in LPS-stimulated RAW264.7 cells. <em>In vivo</em>, AG treatment markedly reduces lung edema, decreases inflammatory cell infiltration, and mitigates ferroptosis in lung tissues of LPS-induced ALI mice. These protective effects are mediated <em>via</em> the modulation of the Toll-like receptor 4 (TLR4)/Kelch-like ECH-associated protein 1(Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Molecular docking simulations identified the binding sites of AG on the TLR4 protein (Kd value: −33.5 kcal·mol<sup>−1</sup>), and these interactions were further corroborated by Cellular Thermal Shift Assay (CETSA) and SPR assays. Collectively, our findings demonstrate that AG exerts potent anti-inflammatory and anti-ferroptosis effects in LPS-induced ALI by targeting TLR4 and modulating the Keap1/Nrf2 pathway. This study underscores AG’s potential as a therapeutic agent for ALI and provides new insights into its underlying mechanisms of action.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 10","pages":"Pages 914-928"},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/S1875-5364(24)60723-5
Jie DONG , Haibo LI , Mi ZHOU , Xinsheng YAO , Jianliang GENG , Yang YU
Four previously unreported diarylheptanoids (1a/1b−2a/2b), one undescribed sesquiterpenoid (8), one new diterpenoid (12), and twelve known analogs were isolated from the fruits of Alpinia oxyphylla. The structural elucidation of these compounds was achieved through a comprehensive analysis of spectroscopic data, single-crystal X-ray diffraction, electronic circular dichroism (ECD), and modified Mosher’s method. Enantiomeric mixtures (1a/1b, 2a/2b, 3a/3b, 4a/4b, and 5a/5b) were separated on a chiral column using acetonitrile-water mixtures as eluents. Among them, compounds 3a/3b and 4a/4b were isolated as optically pure enantiomers in the initial chiral separation. Furthermore, most of the isolates were evaluated for their inhibitory effects against the production of nitric oxide (NO) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Interestingly, 2 and 4 showed significant inhibitory activities against NO production with IC50 values of 33.65 and 9.88 μmol·L−1 (hydrocortisone: IC50 34.26 μmol·L−1), respectively. Additionally, they also partially reduced the secretion of IL-6.
{"title":"Four new diarylheptanoids and two new terpenoids from the fruits of Alpinia oxyphylla and their anti-inflammatory activities","authors":"Jie DONG , Haibo LI , Mi ZHOU , Xinsheng YAO , Jianliang GENG , Yang YU","doi":"10.1016/S1875-5364(24)60723-5","DOIUrl":"10.1016/S1875-5364(24)60723-5","url":null,"abstract":"<div><div>Four previously unreported diarylheptanoids (<strong>1a</strong>/<strong>1b</strong>−<strong>2a</strong>/<strong>2b</strong>), one undescribed sesquiterpenoid (<strong>8</strong>), one new diterpenoid (<strong>12</strong>), and twelve known analogs were isolated from the fruits of <em>Alpinia oxyphylla</em>. The structural elucidation of these compounds was achieved through a comprehensive analysis of spectroscopic data, single-crystal X-ray diffraction, electronic circular dichroism (ECD), and modified Mosher’s method. Enantiomeric mixtures (<strong>1a</strong>/<strong>1b</strong>, <strong>2a</strong>/<strong>2b</strong>, <strong>3a</strong>/<strong>3b</strong>, <strong>4a</strong>/<strong>4b</strong>, and <strong>5a</strong>/<strong>5b</strong>) were separated on a chiral column using acetonitrile-water mixtures as eluents. Among them, compounds <strong>3a</strong>/<strong>3b</strong> and <strong>4a</strong>/<strong>4b</strong> were isolated as optically pure enantiomers in the initial chiral separation. Furthermore, most of the isolates were evaluated for their inhibitory effects against the production of nitric oxide (NO) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Interestingly, <strong>2</strong> and <strong>4</strong> showed significant inhibitory activities against NO production with IC<sub>50</sub> values of 33.65 and 9.88 μmol·L<sup>−1</sup> (hydrocortisone: IC<sub>50</sub> 34.26 μmol·L<sup>−1</sup>), respectively. Additionally, they also partially reduced the secretion of IL-6.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 10","pages":"Pages 929-936"},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/S1875-5364(24)60693-X
Shuwei LI , Qingyi XIONG , Yiwen SHEN , Jiayi LIN , Lijun ZHANG , Ye WU , Jinmei JIN , Xin LUAN
Toosendanin (TSN), a tetracyclic triterpenoid derived from Melia toosendan and M. azedarach, demonstrates broad application prospects in cancer treatment. Although previously employed as a pesticide, recent studies have revealed its potential therapeutic value in treating various types of cancer. TSN exerts an anticancer effect via mechanisms including proliferation inhibition, apoptosis induction, migration suppression, and angiogenesis inhibition. However, TSN’s toxicity, particularly its hepatotoxicity, significantly limits its therapeutic application. This review explored the dual nature of TSN, evaluating both its anticancer potential and toxicological risks, emphasizing the importance of balancing these aspects in therapeutic applications. Furthermore, we investigated the incorporation of TSN into novel therapeutic strategies, such as Proteolysis-targeting chimeras (PROTAC) technology and nanotechnology-based drug delivery systems (DDS), which enhance treatment efficacy while mitigating toxicity in normal tissues.
{"title":"Toosendanin: upgrade of an old agent in cancer treatment","authors":"Shuwei LI , Qingyi XIONG , Yiwen SHEN , Jiayi LIN , Lijun ZHANG , Ye WU , Jinmei JIN , Xin LUAN","doi":"10.1016/S1875-5364(24)60693-X","DOIUrl":"10.1016/S1875-5364(24)60693-X","url":null,"abstract":"<div><div>Toosendanin (TSN), a tetracyclic triterpenoid derived from <em>Melia toosendan</em> and <em>M. azedarach</em>, demonstrates broad application prospects in cancer treatment. Although previously employed as a pesticide, recent studies have revealed its potential therapeutic value in treating various types of cancer. TSN exerts an anticancer effect <em>via</em> mechanisms including proliferation inhibition, apoptosis induction, migration suppression, and angiogenesis inhibition. However, TSN’s toxicity, particularly its hepatotoxicity, significantly limits its therapeutic application. This review explored the dual nature of TSN, evaluating both its anticancer potential and toxicological risks, emphasizing the importance of balancing these aspects in therapeutic applications. Furthermore, we investigated the incorporation of TSN into novel therapeutic strategies, such as Proteolysis-targeting chimeras (PROTAC) technology and nanotechnology-based drug delivery systems (DDS), which enhance treatment efficacy while mitigating toxicity in normal tissues.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 10","pages":"Pages 887-899"},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/S1875-5364(24)60646-1
Huiting XI , Mingming YUAN , Jianhua XIE , Yuanxing WANG
Ten previously undescribed dammarane-type triterpenoid glycosides, cyclocarysaponins A–J (1–10), were isolated from the leaves of Cyclocarya paliurus (Batal.) Iljinskaja. The structures of these compounds were characterized through detailed spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The cytotoxic activities of all isolates were assessed against five human cancer cell lines (Bel-7402, Caski, BGC-823, A2780, and HCT-116). Of the tested compounds, compounds 1, 7, and 9 exhibited selective cytotoxicity against one or more human cancer cell lines.
{"title":"Cyclocarysaponins A–J, dammarane-type triterpenoid glycosides from the leaves of Cyclocarya paliurus","authors":"Huiting XI , Mingming YUAN , Jianhua XIE , Yuanxing WANG","doi":"10.1016/S1875-5364(24)60646-1","DOIUrl":"10.1016/S1875-5364(24)60646-1","url":null,"abstract":"<div><div>Ten previously undescribed dammarane-type triterpenoid glycosides, cyclocarysaponins A–J (<strong>1–10</strong>), were isolated from the leaves of <em>Cyclocarya paliurus</em> (Batal.) Iljinskaja. The structures of these compounds were characterized through detailed spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The cytotoxic activities of all isolates were assessed against five human cancer cell lines (Bel-7402, Caski, BGC-823, A2780, and HCT-116). Of the tested compounds, compounds <strong>1</strong>, <strong>7</strong>, and <strong>9</strong> exhibited selective cytotoxicity against one or more human cancer cell lines.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 10","pages":"Pages 955-964"},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/S1875-5364(24)60657-6
Shiting HE , Qinghui ZOU , Qi ZHANG , Yingming LUO , Die YAN , Jingxin HE , Yena LIU , Hui CUI
Three novel sesterterpenoids glasesterterpenoids A−C (1−3), featuring an unprecedented 7-cyclohexyldecahydronaphthalene carbon skeleton, were isolated from the root of Lindera glauca (L. glauca). Their structures were elucidated by quantum chemical calculations and spectroscopic methods. The biogenetic pathway for 1−3 is proposed. In the bioassay, glasesterterpenoid C exhibited DNA topoisomerase 1 (Top1) inhibitory activity compared with the positive control, camptothecin. These findings represent the first examples of sesterterpenoids with a 7-cyclohexyldecahydronaphthalene carbon skeleton from the root of L. glauca.
从 Lindera glauca（林达草）的根中分离出了三种新的酯类化合物 glasesterterpenoids A-C（1-3），它们具有前所未有的 7-Cyclohexyldecahydronaphthalene 碳骨架。通过量子化学计算和光谱方法阐明了它们的结构。提出了 1-3 的生物发生途径。在生物测定中，与阳性对照喜树碱相比，glasesterpenoid C 具有 DNA 拓扑异构酶 1（Top1）抑制活性。这些发现代表了从鳞茎草根中首次发现具有 7-环己基十氢萘碳骨架的酯类化合物。
{"title":"Glasesterterpenoids A−C: three sesterterpenoids with 7-cyclohexyldecahydronaphthalene carbon skeleton isolated from the root of Lindera glauca","authors":"Shiting HE , Qinghui ZOU , Qi ZHANG , Yingming LUO , Die YAN , Jingxin HE , Yena LIU , Hui CUI","doi":"10.1016/S1875-5364(24)60657-6","DOIUrl":"10.1016/S1875-5364(24)60657-6","url":null,"abstract":"<div><div>Three novel sesterterpenoids glasesterterpenoids A−C (<strong>1</strong>−<strong>3</strong>), featuring an unprecedented 7-cyclohexyldecahydronaphthalene carbon skeleton, were isolated from the root of <em>Lindera glauca</em> (<em>L. glauca</em>). Their structures were elucidated by quantum chemical calculations and spectroscopic methods. The biogenetic pathway for <strong>1</strong>−<strong>3</strong> is proposed. In the bioassay, glasesterterpenoid C exhibited DNA topoisomerase 1 (Top1) inhibitory activity compared with the positive control, camptothecin. These findings represent the first examples of sesterterpenoids with a 7-cyclohexyldecahydronaphthalene carbon skeleton from the root of <em>L. glauca</em>.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 9","pages":"Pages 864-868"},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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