Pub Date : 2025-01-17DOI: 10.1007/s11418-024-01872-5
Takashi Kikuchi
Steroids are physiologically important compounds for animals, plants, and fungi, and they have significantly contributed to drug discovery for many years. Fungi mainly biosynthesize ergostane-type steroids such as ergosterol. However, after the basic skeleton is biosynthesized, chemical transformations can lead to the cleavage or rearrangement of the fundamental skeleton of steroids. The cleaved (seco) and rearranged (abeo) steroids are chemically and pharmacologically intriguing because they often exhibit biological activities. As ergostane-type steroids including the normal, seco, and abeo types have been isolated from the mushrooms of the Pleurotus genus, this review focuses on them as a resource of ergostane-type steroids, providing their distribution, structure determination, and biological activity.
{"title":"Ergostane-type steroids from mushrooms of Pleurotus genus","authors":"Takashi Kikuchi","doi":"10.1007/s11418-024-01872-5","DOIUrl":"10.1007/s11418-024-01872-5","url":null,"abstract":"<div><p>Steroids are physiologically important compounds for animals, plants, and fungi, and they have significantly contributed to drug discovery for many years. Fungi mainly biosynthesize ergostane-type steroids such as ergosterol. However, after the basic skeleton is biosynthesized, chemical transformations can lead to the cleavage or rearrangement of the fundamental skeleton of steroids. The cleaved (seco) and rearranged (<i>abeo</i>) steroids are chemically and pharmacologically intriguing because they often exhibit biological activities. As ergostane-type steroids including the normal, seco, and <i>abeo</i> types have been isolated from the mushrooms of the <i>Pleurotus</i> genus, this review focuses on them as a resource of ergostane-type steroids, providing their distribution, structure determination, and biological activity.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 2","pages":"289 - 302"},"PeriodicalIF":2.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-024-01872-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), and follicular lymphoma (FL), predominantly arise from B cells undergoing germinal center (GC) reactions. The transcriptional repressor B-cell lymphoma 6 (BCL6) is indispensable for GC formation and contributes to lymphomagenesis via its BTB domain-mediated suppression of target genes. Dysregulation of BCL6 underpins the pathogenesis of GC-derived NHL. While pharmacological targeting the BCL6-BTB domain has shown therapeutic promise, natural product-based inhibitors remain underexplored. In this study, resveratrol, a polyphenolic compound derived from grapes, was identified as a potent BCL6 inhibitor through a comprehensive screen of traditional Chinese medicine monomers using Homogeneous Time-Resolved Fluorescence (HTRF) assay. As a BCL6 natural inhibitor, resveratrol effectively disrupted the BCL6/SMRT interaction, reactivated suppressed gene expression, and inhibited the proliferation of GC-derived NHL cells. It also exhibited synergistic efficacy when combined with EZH2 and PRMT5 inhibitors. In vivo, resveratrol suppressed GC formation, reduced follicular helper T-cell frequencies, impaired class-switch recombination, and disrupted immunoglobulin affinity maturation. Furthermore, it markedly inhibited the progression of GC-derived NHL in animal models. Our findings demonstrate that resveratrol functions as a natural BCL6 inhibitor with significant therapeutic potential for the treatment of GC-derived NHL.
{"title":"Resveratrol as a BCL6 natural inhibitor suppresses germinal center derived Non-Hodgkin lymphoma cells growth","authors":"Yajing Xing, Chunbin Tan, Zhoujiang Liu, Yanqi Liu, Simei Liu, Guixue Wang, Yadong Zhong","doi":"10.1007/s11418-024-01873-4","DOIUrl":"10.1007/s11418-024-01873-4","url":null,"abstract":"<div><p>Non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), and follicular lymphoma (FL), predominantly arise from B cells undergoing germinal center (GC) reactions. The transcriptional repressor B-cell lymphoma 6 (BCL6) is indispensable for GC formation and contributes to lymphomagenesis via its BTB domain-mediated suppression of target genes. Dysregulation of BCL6 underpins the pathogenesis of GC-derived NHL. While pharmacological targeting the BCL6-BTB domain has shown therapeutic promise, natural product-based inhibitors remain underexplored. In this study, resveratrol, a polyphenolic compound derived from grapes, was identified as a potent BCL6 inhibitor through a comprehensive screen of traditional Chinese medicine monomers using Homogeneous Time-Resolved Fluorescence (HTRF) assay. As a BCL6 natural inhibitor, resveratrol effectively disrupted the BCL6/SMRT interaction, reactivated suppressed gene expression, and inhibited the proliferation of GC-derived NHL cells. It also exhibited synergistic efficacy when combined with EZH2 and PRMT5 inhibitors. In vivo, resveratrol suppressed GC formation, reduced follicular helper T-cell frequencies, impaired class-switch recombination, and disrupted immunoglobulin affinity maturation. Furthermore, it markedly inhibited the progression of GC-derived NHL in animal models. Our findings demonstrate that resveratrol functions as a natural BCL6 inhibitor with significant therapeutic potential for the treatment of GC-derived NHL.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 2","pages":"399 - 411"},"PeriodicalIF":2.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-024-01873-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06DOI: 10.1007/s11418-024-01870-7
Jisu Park, Sihyun Jang, Seung-On Lee, InWha Park, Sainan Li, A-Young Nam, Jung-Hyun Shim, MinKyun Na
In the preliminary screening, falcarinol and falcarindiol, C17 polyacetylenes from the roots of Glehnia littoralis F. Schmidt ex Miq (Umbelliferae), displayed cytotoxic activity both against oxaliplatin-sensitive/resistant colorectal cancer (CRC) and gefitinib-sensitive/resistant non-small cell lung cancer (NSCLC) cells. In this study, 13 polyacetylenes including a new (3R,11R)-11-hyroxy-isofalcarinolone (1) were isolated from G. littoralis, and the chemical structures were elucidated through NMR, HRMS, and optical rotation analysis as well as DP4 plus calculation. (3S,8S)-Oplopandiol (5) showed cytotoxic activities against oxaliplatin-sensitive and -resistant CRC (HCT116 and HCT116-OxR) cells. Unexpectedly, (3R,8S)-falcarindiol (3) and (3S)-falcarinol (12), newly purified from G. littoralis, did not show cytotoxic activity. It was confirmed that both falcarinol and falcarindiol, previously evaluated, were decomposed, which seems to be the cause of inconsistent biological results. These findings indicated that C17 polyacetylene could be a good starting compound for the development of anticancer leads against drug-resistant CRC and NSCLC cells, however, the stability of C17 polyacetylens should be considered for further studies.
Graphical Abstract
在初步筛选中，从伞形植物Glehnia littoralis F. Schmidt ex Miq（伞形植物）的根中提取的C17聚乙炔falcarinol和falcarindiol对奥沙利铂敏感/耐药的结直肠癌（CRC）和吉非替尼敏感/耐药的非小细胞肺癌（NSCLC）细胞均显示出细胞毒性活性。本研究从山茱萸中分离到了13个聚乙炔，其中包括一个新的(3R,11R)-11-羟基-异alofcarinolone(1)，并通过NMR、HRMS、旋光分析和DP4 +计算对其化学结构进行了鉴定。（3S,8S）-Oplopandiol(5)对奥沙利铂敏感和耐药的CRC （HCT116和HCT116- oxr）细胞显示细胞毒活性。出乎意料的是，从山茱萸中新纯化的(3R,8S)-镰藻醇(3)和(3S)-镰藻醇（12）没有细胞毒活性。经证实，先前评价的镰镰醇和镰镰醇均被分解，这似乎是导致生物学结果不一致的原因。这些发现表明，C17聚乙炔可能是开发抗耐药CRC和NSCLC细胞抗癌先导物的良好起始化合物，但C17聚乙炔的稳定性有待进一步研究。
{"title":"Cytotoxic activity of C17 polyacetylenes from the roots of Glehnia littoralis against drug-resistant colorectal and lung cancer cells","authors":"Jisu Park, Sihyun Jang, Seung-On Lee, InWha Park, Sainan Li, A-Young Nam, Jung-Hyun Shim, MinKyun Na","doi":"10.1007/s11418-024-01870-7","DOIUrl":"10.1007/s11418-024-01870-7","url":null,"abstract":"<div><p>In the preliminary screening, falcarinol and falcarindiol, C<sub>17</sub> polyacetylenes from the roots of <i>Glehnia littoralis</i> F. Schmidt ex Miq (Umbelliferae), displayed cytotoxic activity both against oxaliplatin-sensitive/resistant colorectal cancer (CRC) and gefitinib-sensitive/resistant non-small cell lung cancer (NSCLC) cells. In this study, 13 polyacetylenes including a new (3<i>R</i>,11<i>R</i>)-11-hyroxy-isofalcarinolone (<b>1</b>) were isolated from <i>G. littoralis</i>, and the chemical structures were elucidated through NMR, HRMS, and optical rotation analysis as well as DP4 plus calculation. (3<i>S</i>,8<i>S</i>)-Oplopandiol (<b>5</b>) showed cytotoxic activities against oxaliplatin-sensitive and -resistant CRC (HCT116 and HCT116-OxR) cells. Unexpectedly, (3<i>R</i>,8<i>S</i>)-falcarindiol (<b>3</b>) and (3<i>S</i>)-falcarinol (<b>12</b>), newly purified from <i>G</i>. <i>littoralis</i>, did not show cytotoxic activity. It was confirmed that both falcarinol and falcarindiol, previously evaluated, were decomposed, which seems to be the cause of inconsistent biological results. These findings indicated that C<sub>17</sub> polyacetylene could be a good starting compound for the development of anticancer leads against drug-resistant CRC and NSCLC cells, however, the stability of C<sub>17</sub> polyacetylens should be considered for further studies.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 2","pages":"391 - 398"},"PeriodicalIF":2.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-03DOI: 10.1007/s11418-024-01863-6
Yan Zhang, Runzhou Pan, Zhang Shou, Yongcai Zhao
Thioredoxin-interacting protein (TXNIP), as a pivotal protein in the cellular stress response, plays a significant role in the progression of diabetic nephropathy (DN). Consequently, therapeutic strategies aimed at targeting TXNIP may offer novel interventions for patients with DN. Our study is to explore the therapeutic potential of targeting TXNIP in mitigating renal tubular injury induced by hyperglycemia. Cell viability and apoptosis of renal tubular epithelial cells (RTECs) were evaluated using CCK-8, Annexin V/7-AAD, and TUNEL staining after exposure to normal glucose (NG; 5 mM), high glucose (HG; 30 mM), or treatment with TXNIP inhibitors (Xanthohumol, Xan). Furthermore, histochemical staining was utilized to assess the morphological changes in the kidney. Xan was determined to be a potential inhibitor of TXNIP due to its low binding energy value of − 7.433 kcal/mol. Both genetic inhibition of TXNIP using sh-RNA and pharmacological inhibition with Xan were found to reverse HG-induced RTEC apoptosis and inflammatory response. In diabetic mice, administration of Xan resulted in significant improvements in pathological features such as tubular atrophy, tubular injury score, and collagen deposition in the tubulointerstitium. Additionally, treatment with Xan effectively reduced the up-regulation of TXNIP protein expression caused by hyperglycemia. In conclusion, Xan, as a bioactive natural product, has been shown to attenuate hyperglycemia-induced renal tubular injury in both in vitro and in vivo models, potentially through the inhibition of TXNIP expression. Xan has the potential to serve as a therapeutic compound for the treatment of DN.
{"title":"Xanthohumol attenuates TXNIP-mediated renal tubular injury in vitro and in vivo diabetic models","authors":"Yan Zhang, Runzhou Pan, Zhang Shou, Yongcai Zhao","doi":"10.1007/s11418-024-01863-6","DOIUrl":"10.1007/s11418-024-01863-6","url":null,"abstract":"<div><p>Thioredoxin-interacting protein (TXNIP), as a pivotal protein in the cellular stress response, plays a significant role in the progression of diabetic nephropathy (DN). Consequently, therapeutic strategies aimed at targeting TXNIP may offer novel interventions for patients with DN. Our study is to explore the therapeutic potential of targeting TXNIP in mitigating renal tubular injury induced by hyperglycemia. Cell viability and apoptosis of renal tubular epithelial cells (RTECs) were evaluated using CCK-8, Annexin V/7-AAD, and TUNEL staining after exposure to normal glucose (NG; 5 mM), high glucose (HG; 30 mM), or treatment with TXNIP inhibitors (Xanthohumol, Xan). Furthermore, histochemical staining was utilized to assess the morphological changes in the kidney. Xan was determined to be a potential inhibitor of TXNIP due to its low binding energy value of − 7.433 kcal/mol. Both genetic inhibition of TXNIP using sh-RNA and pharmacological inhibition with Xan were found to reverse HG-induced RTEC apoptosis and inflammatory response. In diabetic mice, administration of Xan resulted in significant improvements in pathological features such as tubular atrophy, tubular injury score, and collagen deposition in the tubulointerstitium. Additionally, treatment with Xan effectively reduced the up-regulation of TXNIP protein expression caused by hyperglycemia. In conclusion, Xan, as a bioactive natural product, has been shown to attenuate hyperglycemia-induced renal tubular injury in both in vitro and in vivo models, potentially through the inhibition of TXNIP expression. Xan has the potential to serve as a therapeutic compound for the treatment of DN.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 2","pages":"314 - 327"},"PeriodicalIF":2.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142919051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Myelosuppression is a serious and common complication of targeted therapy for cancer patients, and there are few studies exploring the efficacy of natural drugs in this condition. Niraparib is a widely used targeted therapy for the treatment of advanced ovarian cancer. As a poly (ADP-ribose) polymerase (PARP) inhibitor, niraparib significantly improves progression-free and overall survival in patients. We aimed to explore the potential effect of red ginseng (RG) on niraparib-induced myelosuppression and to further reveal its possible molecular mechanism. Female C57BL/6 mice were divided into control, tumor, model, and RG groups (n = 6). After receiving ID8 ovarian cancer cell inoculation, the mice received niraparib treatment (80 mg/kg) for 3 days. Meanwhile, RG groups (100 and 200 mg/kg) were intragastrically treated with RG extract for 7 days. Compared with the model group, RG extract increased the counts of peripheral blood cells and enhanced the hematopoietic function of bone marrow. Furthermore, RG extract increased the colony yield of hematopoietic progenitor cells (HPCs), facilitated DNA damage repair, alleviated the G0/G1 phase cell cycle arrest, and significantly reversed the increased expression levels of p53, p21, and p27, while stimulating cyclinE1 expression levels. These findings indicate that RG might have therapeutic potential on niraparib-induced myelosuppression, which encourages further clinical trials. This study is the first to explore the efficacy and mechanism of RG in preventing myelosuppression induced by niraparib.
{"title":"Red ginseng prevents niraparib-induced myelosuppression in C57BL/6 mice via inhibiting p53-mediated upregulation of p21 and p27","authors":"Huiyan Liao, Xiangdan Hu, Shenming Chen, Zhaofeng Fan, Jing Xiao","doi":"10.1007/s11418-024-01866-3","DOIUrl":"10.1007/s11418-024-01866-3","url":null,"abstract":"<div><p>Myelosuppression is a serious and common complication of targeted therapy for cancer patients, and there are few studies exploring the efficacy of natural drugs in this condition. Niraparib is a widely used targeted therapy for the treatment of advanced ovarian cancer. As a poly (ADP-ribose) polymerase (PARP) inhibitor, niraparib significantly improves progression-free and overall survival in patients. We aimed to explore the potential effect of red ginseng (RG) on niraparib-induced myelosuppression and to further reveal its possible molecular mechanism. Female C57BL/6 mice were divided into control, tumor, model, and RG groups (n = 6). After receiving ID8 ovarian cancer cell inoculation, the mice received niraparib treatment (80 mg/kg) for 3 days. Meanwhile, RG groups (100 and 200 mg/kg) were intragastrically treated with RG extract for 7 days. Compared with the model group, RG extract increased the counts of peripheral blood cells and enhanced the hematopoietic function of bone marrow. Furthermore, RG extract increased the colony yield of hematopoietic progenitor cells (HPCs), facilitated DNA damage repair, alleviated the G0/G1 phase cell cycle arrest, and significantly reversed the increased expression levels of p53, p21, and p27, while stimulating cyclinE1 expression levels. These findings indicate that RG might have therapeutic potential on niraparib-induced myelosuppression, which encourages further clinical trials. This study is the first to explore the efficacy and mechanism of RG in preventing myelosuppression induced by niraparib.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 2","pages":"381 - 390"},"PeriodicalIF":2.5,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-024-01866-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ipomoea alba L. (Convolvulaceae) is an annual vine native to tropical America that is cultivated primarily for ornamental purposes. Its seeds are used in traditional medicine as a laxative, and young shoots are consumed as food. In this study, ten new resin glycosides, ipoalbins I (1)–X (10), were isolated from I. alba seeds. The structures of 1–10 were determined based on spectroscopic data. All compounds had intramolecular cyclic ester structures (jalapins). The sugar moieties in 1–10 were partially acylated by organic acids, including isobutyric, (E)-2-methylbut-2-enoic, and 2S-methyl-3S-hydroxybutyric acids. Notably, one of these compounds has a rare jalapin structure characterized by an ester linkage between the carboxyl group of the aglycone moiety and the hydroxyl group of an organic acid attached to the sugar moiety. In contrast, other compounds exhibited typical macrolactone structures. Furthermore, the cytotoxic activity of 1–10 against HL-60 human promyelocytic leukemia cells and their antiviral activity against herpes simplex virus type 1 (HSV-1) were evaluated. All tested compounds, except 3, were comparable to or slightly less cytotoxic than cisplatin, the positive control. In addition, all the compounds showed anti-HSV-1 activity; notably, 5 showed an EC50 value lower than that of acyclovir, the positive control. However, the selectivity indices of these compounds were lower than that of acyclovir.
Graphical Abstract
（旋花科）是一种一年生藤本植物，原产于热带美洲，主要用于观赏用途。它的种子在传统医学中被用作泻药，幼芽被当作食物食用。本研究从白桦种子中分离到了10个新的树脂苷，ipoalbins I (1)-X（10）。根据光谱数据确定了1-10的结构。所有化合物均具有分子内环状酯结构（jalapins）。其中1-10的糖部分被异丁酸、(E)-2-甲基丁-2-烯酸和2s -甲基- 3s -羟基丁酸等有机酸部分酰化。值得注意的是，其中一种化合物具有罕见的jalapin结构，其特征是在糖苷元部分的羧基和连接到糖部分的有机酸的羟基之间具有酯连接。相反，其他化合物表现出典型的内酯结构。此外，研究了1-10对HL-60人早幼粒细胞白血病细胞的细胞毒活性和对1型单纯疱疹病毒（HSV-1）的抗病毒活性。除3种外，所有被测化合物的细胞毒性与阳性对照顺铂相当或略低。所有化合物均具有抗hsv -1活性；其中5株的EC50值低于阳性对照阿昔洛韦。但这些化合物的选择性指标均低于阿昔洛韦。
{"title":"Ten new resin glycosides, ipoalbins I–X, from Ipomoea alba seeds","authors":"Nodoka Misuda, Mizuki Watanabe, Hirotaka Nishikawa, Shin Yasuda, Hiroyuki Miyashita, Kazumi Yokomizo, Hitoshi Yoshimitsu, Ryota Tsuchihashi, Masafumi Okawa, Junei Kinjo, Masateru Ono","doi":"10.1007/s11418-024-01868-1","DOIUrl":"10.1007/s11418-024-01868-1","url":null,"abstract":"<div><p><i>Ipomoea alba</i> L. (Convolvulaceae) is an annual vine native to tropical America that is cultivated primarily for ornamental purposes. Its seeds are used in traditional medicine as a laxative, and young shoots are consumed as food. In this study, ten new resin glycosides, ipoalbins I (<b>1</b>)–X (<b>10</b>), were isolated from <i>I. alba</i> seeds. The structures of <b>1</b>–<b>10</b> were determined based on spectroscopic data. All compounds had intramolecular cyclic ester structures (jalapins). The sugar moieties in <b>1</b>–<b>10</b> were partially acylated by organic acids, including isobutyric, (<i>E</i>)-2-methylbut-2-enoic, and 2<i>S</i>-methyl-3<i>S</i>-hydroxybutyric acids. Notably, one of these compounds has a rare jalapin structure characterized by an ester linkage between the carboxyl group of the aglycone moiety and the hydroxyl group of an organic acid attached to the sugar moiety. In contrast, other compounds exhibited typical macrolactone structures. Furthermore, the cytotoxic activity of <b>1</b>–<b>10</b> against HL-60 human promyelocytic leukemia cells and their antiviral activity against herpes simplex virus type 1 (HSV-1) were evaluated. All tested compounds, except <b>3</b>, were comparable to or slightly less cytotoxic than cisplatin, the positive control. In addition, all the compounds showed anti-HSV-1 activity; notably, <b>5</b> showed an EC<sub>50</sub> value lower than that of acyclovir, the positive control. However, the selectivity indices of these compounds were lower than that of acyclovir.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 2","pages":"341 - 356"},"PeriodicalIF":2.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-20DOI: 10.1007/s11418-024-01867-2
Satoko Sasaki, Satoshi Yokota, Yohei Sasaki
The traditional post-harvest processing method of Angelica acutiloba roots, which involves hanging the roots outdoors after being harvested, is known to promote the conversion of starch in roots into sucrose, thereby increasing sweetness. At the same time, this method increases the dilute ethanol-soluble extract (DEE) content in A. acutiloba roots to meet the standard set by the Japanese Pharmacopoeia 18th edition. However, in Hokkaido, where A. acutiloba has been cultivated in recent years, it is a challenge to practice this traditional post-harvest processing method owing to the risk of freezing. Therefore, it is necessary to determine post-harvest processing conditions to increase DEE content in A. acutiloba roots in Hokkaido. In this study, we cultivated seedlings in plug trays and the open field in Hokkaido and stored the harvested products at various temperatures and durations to determine changes in DEE content. DEE content immediately after harvest was 20.5% in roots from plug-tray seedlings and 27.8% in roots from seedlings cultivated in the open field. DEE content in roots stored at 0 °C increased slowly over 5 weeks, whereas that in roots stored at 20 °C increased rapidly. We found a strong correlation between DEE content and sucrose content, but not (Z)-ligustilide content. Our findings on the post-harvest processing conditions for roots revealed that the optimal post-harvest processing conditions are storage at 0 °C for at least two weeks during which DEE content increases stably, similar to the traditional method.
{"title":"Optimizing post-harvest processing conditions for Angelica acutiloba roots in Hokkaido: storage temperature and duration","authors":"Satoko Sasaki, Satoshi Yokota, Yohei Sasaki","doi":"10.1007/s11418-024-01867-2","DOIUrl":"10.1007/s11418-024-01867-2","url":null,"abstract":"<div><p>The traditional post-harvest processing method of <i>Angelica acutiloba</i> roots, which involves hanging the roots outdoors after being harvested, is known to promote the conversion of starch in roots into sucrose, thereby increasing sweetness. At the same time, this method increases the dilute ethanol-soluble extract (DEE) content in <i>A. acutiloba</i> roots to meet the standard set by the Japanese Pharmacopoeia 18th edition. However, in Hokkaido, where <i>A. acutiloba</i> has been cultivated in recent years, it is a challenge to practice this traditional post-harvest processing method owing to the risk of freezing. Therefore, it is necessary to determine post-harvest processing conditions to increase DEE content in <i>A. acutiloba</i> roots in Hokkaido. In this study, we cultivated seedlings in plug trays and the open field in Hokkaido and stored the harvested products at various temperatures and durations to determine changes in DEE content. DEE content immediately after harvest was 20.5% in roots from plug-tray seedlings and 27.8% in roots from seedlings cultivated in the open field. DEE content in roots stored at 0 °C increased slowly over 5 weeks, whereas that in roots stored at 20 °C increased rapidly. We found a strong correlation between DEE content and sucrose content, but not (<i>Z</i>)-ligustilide content. Our findings on the post-harvest processing conditions for roots revealed that the optimal post-harvest processing conditions are storage at 0 °C for at least two weeks during which DEE content increases stably, similar to the traditional method.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 2","pages":"328 - 340"},"PeriodicalIF":2.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oxidative stress has been implicated as a causative factor for the development and progression of osteoporosis(OP). Ellagic acid (EA), a natural polyphenol, presents anti-oxidative and anti-inflammatory properties. However, EA’s role and molecular mechanism in osteoblasts have not yet been elucidated. In this study, exogenous supplementation with EA restored the osteoporotic bone defects in ovariectomized (OVX)-induced osteoporotic mice. Also, EA inhibited the H2O2-induced apoptosis of primary osteoblasts, prevented the production of reactive oxygen species, and restored the bone-forming potential of osteoblasts. Furthermore, EA was revealed to activate Sirtuin1 (SIRT1) and its downstream Nrf2/Heme Oxygenase 1 (HO-1) signaling pathway, and EX527 (a SIRT1 inhibitor) partially counteracted the effect of EA on bone loss. The findings suggest that EA protects against osteoporotic bone loss by activating SIRT1 and its downstream Nrf2/HO-1 signaling pathway, providing novel insights into the potential of EA as a treatment agent for osteoporosis-related bone metabolism diseases.
氧化应激被认为是骨质疏松症（OP）发生和发展的一个致病因素。鞣花酸（EA）是一种天然多酚，具有抗氧化和抗炎特性。然而，EA在成骨细胞中的作用和分子机制尚未阐明。在这项研究中，外源性补充 EA 可恢复卵巢切除（OVX）诱导的骨质疏松小鼠的骨质疏松性骨缺损。此外，EA 还能抑制 H2O2 诱导的原发性成骨细胞凋亡，防止活性氧的产生，并恢复成骨细胞的成骨潜能。此外，EA还能激活Sirtuin1（SIRT1）及其下游的Nrf2/Heme氧化酶1（HO-1）信号通路，而EX527（一种SIRT1抑制剂）能部分抵消EA对骨质流失的影响。研究结果表明，EA通过激活SIRT1及其下游的Nrf2/HO-1信号通路来防止骨质疏松性骨丢失，为EA作为骨质疏松相关骨代谢疾病的治疗药物提供了新的见解。
{"title":"Ellagic acid prevents ovariectomy-induced bone loss and attenuates oxidative damage of osteoblasts by activating SIRT1","authors":"Liwei Guo, Pengcheng Wei, Shijie Li, Lulu Zhou, Yunjie Yan, Duan Li","doi":"10.1007/s11418-024-01859-2","DOIUrl":"10.1007/s11418-024-01859-2","url":null,"abstract":"<p>Oxidative stress has been implicated as a causative factor for the development and progression of osteoporosis(OP). Ellagic acid (EA), a natural polyphenol, presents anti-oxidative and anti-inflammatory properties. However, EA’s role and molecular mechanism in osteoblasts have not yet been elucidated. In this study, exogenous supplementation with EA restored the osteoporotic bone defects in ovariectomized (OVX)-induced osteoporotic mice. Also, EA inhibited the H<sub>2</sub>O<sub>2</sub>-induced apoptosis of primary osteoblasts, prevented the production of reactive oxygen species, and restored the bone-forming potential of osteoblasts. Furthermore, EA was revealed to activate Sirtuin1 (SIRT1) and its downstream Nrf2/Heme Oxygenase 1 (HO-1) signaling pathway, and EX527 (a SIRT1 inhibitor) partially counteracted the effect of EA on bone loss. The findings suggest that EA protects against osteoporotic bone loss by activating SIRT1 and its downstream Nrf2/HO-1 signaling pathway, providing novel insights into the potential of EA as a treatment agent for osteoporosis-related bone metabolism diseases.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 2","pages":"371 - 380"},"PeriodicalIF":2.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Radiotherapy is a primary treatment method for lung cancer, and radiation-induced lung injury has been widely studied. However, the lung and intestines are closely related, and patients receiving lung radiotherapy often experience gastrointestinal reactions. Huanglian Decoction has proven effective in treating intestinal diseases, but its role in radiation-induced intestinal injury in lung cancer has not yet been demonstrated. The study investigated the potential protective mechanisms of Huanglian Decoction against radiation-induced intestinal injury in lung cancer. In vivo experiments were conducted to examine the morphological changes. Changes in endoplasmic reticulum stress-related proteins were assessed using electron microscopy, immunohistochemistry, immunofluorescence, and Western blotting. In vitro studies involved the overexpression of TRPA1 protein in NCM460 cells via lentiviral vectors. Tumor-bearing mice exhibited severe damage to both lung and colon tissues following radiotherapy, with elevated levels of IL-33, increased expression of ST2L and TRPA1 in colon tissues, higher levels of endoplasmic reticulum stress-related proteins, and the presence of apoptosis and inflammatory responses. Huanglian Decoction reduced radiation-induced intestinal injury by lowering IL-33 levels, which in turn reduced endoplasmic reticulum stress response in colon tissues. In TRPA1-overexpressing NCM460 cells, Huanglian Decoction decreased TRPA1 expression levels and significantly alleviated endoplasmic reticulum stress response. Conclusively, the results indicate that Huanglian Decoction alleviates radiation-induced intestinal endoplasmic reticulum stress by reducing IL-33 levels, subsequently inhibiting the expression of ST2L and TRPA1 in colon tissues. This demonstrates the protective effect of Huanglian Decoction on the intestines during lung cancer radiotherapy, highlighting its promising clinical application in radiation protection.
{"title":"Huanglian decoction prevents and treats radiation-induced intestinal injury in lung cancer by regulating endoplasmic reticulum stress","authors":"Liang-liang Shi, Ya-ping Chen, Hao-ming Guo, Xue-peng Wang, Yang-yang Li, Shuai-zhe Wang, Shang-zu Zhang, Qi-hong Zhuo, Yong-qi Liu, Ben-jun Wei, Li-ying Zhang","doi":"10.1007/s11418-024-01860-9","DOIUrl":"10.1007/s11418-024-01860-9","url":null,"abstract":"<div><p>Radiotherapy is a primary treatment method for lung cancer, and radiation-induced lung injury has been widely studied. However, the lung and intestines are closely related, and patients receiving lung radiotherapy often experience gastrointestinal reactions. Huanglian Decoction has proven effective in treating intestinal diseases, but its role in radiation-induced intestinal injury in lung cancer has not yet been demonstrated. The study investigated the potential protective mechanisms of Huanglian Decoction against radiation-induced intestinal injury in lung cancer. In vivo experiments were conducted to examine the morphological changes. Changes in endoplasmic reticulum stress-related proteins were assessed using electron microscopy, immunohistochemistry, immunofluorescence, and Western blotting. In vitro studies involved the overexpression of TRPA1 protein in NCM460 cells via lentiviral vectors. Tumor-bearing mice exhibited severe damage to both lung and colon tissues following radiotherapy, with elevated levels of IL-33, increased expression of ST2L and TRPA1 in colon tissues, higher levels of endoplasmic reticulum stress-related proteins, and the presence of apoptosis and inflammatory responses. Huanglian Decoction reduced radiation-induced intestinal injury by lowering IL-33 levels, which in turn reduced endoplasmic reticulum stress response in colon tissues. In TRPA1-overexpressing NCM460 cells, Huanglian Decoction decreased TRPA1 expression levels and significantly alleviated endoplasmic reticulum stress response. Conclusively, the results indicate that Huanglian Decoction alleviates radiation-induced intestinal endoplasmic reticulum stress by reducing IL-33 levels, subsequently inhibiting the expression of ST2L and TRPA1 in colon tissues. This demonstrates the protective effect of Huanglian Decoction on the intestines during lung cancer radiotherapy, highlighting its promising clinical application in radiation protection.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 1","pages":"143 - 161"},"PeriodicalIF":2.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alzheimer disease (AD) is the most common type of dementia and accounts for the largest proportion of dementia cases. The amyloid cascade hypothesis is known for the pathogenesis of AD, in which excessive accumulation of amyloid-β (Aβ) leads to the formation of senile plaques and ultimately to AD. Inhibition of β-secretase (BACE1) may contribute to the treatment of AD by suppressing Aβ production. In this study, we isolated and characterized the activity of new and known BACE1-inhibiting compounds from two mushrooms of the Boletales order, Suillus bovinus and Boletinus cavipes, using a BACE1-inhibitory activity-guided separation approach. Three compounds (1–3) were isolated from Suillus bovinus CHCl3 extract and three compounds (4–6) were isolated from Boletinus cavipes CHCl3 extract. Compound 1 was a new compound. The structures were elucidated using MS, IR, and NMR. Compounds 1–6 showed BACE1-inhibitory activity (IC50; 21.2, 17.8, 1.0, 1.6, 23.7, and 22.8 μM, respectively). To examine the structure–activity relationship, we also evaluated the activity of geranylgerniol, farnesol, 2,5-dihydroxy-1,4-benzoquinone and mesaconic acid. These compounds showed no activity, and these results indicate that chain terpenes alone do not show BACE1-inhibitory activity, but only when mesaconic acid or a quinone with a hydroxyl group is bound. In addition, the mode of inhibition of 2 and 3 were competitive and 4 was uncompetitive inhibition, respectively, as determined by analysis of Lineweaver–Burk and Dixon plots.
{"title":"Meroterpenoids with BACE1-inhibitory activity from the fruiting bodies of Suillus bovinus and Boletinus cavipes","authors":"Takamasa Yamaguchi, Hiroaki Sasaki, Genki Yatsu, Kiyotaka Koyama, Kaoru Kinoshita","doi":"10.1007/s11418-024-01862-7","DOIUrl":"10.1007/s11418-024-01862-7","url":null,"abstract":"<div><p>Alzheimer disease (AD) is the most common type of dementia and accounts for the largest proportion of dementia cases. The amyloid cascade hypothesis is known for the pathogenesis of AD, in which excessive accumulation of amyloid-β (Aβ) leads to the formation of senile plaques and ultimately to AD. Inhibition of β-secretase (BACE1) may contribute to the treatment of AD by suppressing Aβ production. In this study, we isolated and characterized the activity of new and known BACE1-inhibiting compounds from two mushrooms of the Boletales order, <i>Suillus bovinus</i> and <i>Boletinus cavipes</i>, using a BACE1-inhibitory activity-guided separation approach. Three compounds (<b>1</b>–<b>3</b>) were isolated from <i>Suillus bovinus</i> CHCl<sub>3</sub> extract and three compounds (<b>4–6</b>) were isolated from <i>Boletinus cavipes</i> CHCl<sub>3</sub> extract. Compound <b>1</b> was a new compound. The structures were elucidated using MS, IR, and NMR. Compounds <b>1</b>–<b>6</b> showed BACE1-inhibitory activity (IC<sub>50</sub>; 21.2, 17.8, 1.0, 1.6, 23.7, and 22.8 μM, respectively). To examine the structure–activity relationship, we also evaluated the activity of geranylgerniol, farnesol, 2,5-dihydroxy-1,4-benzoquinone and mesaconic acid. These compounds showed no activity, and these results indicate that chain terpenes alone do not show BACE1-inhibitory activity, but only when mesaconic acid or a quinone with a hydroxyl group is bound. In addition, the mode of inhibition of <b>2</b> and <b>3</b> were competitive and <b>4</b> was uncompetitive inhibition, respectively, as determined by analysis of Lineweaver–Burk and Dixon plots.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 1","pages":"233 - 241"},"PeriodicalIF":2.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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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