Feibing Huang , Yong Yang , Qingling Xie , Hanwen Yuan , Muhammad Aamer , Yuqing Jian , Ye Zhang , Wei Wang
{"title":"Anti-cancer and anti-inflammatory effects of flavan-4-ol and flavan glycosides from the roots of Pronephrium penangianum","authors":"Feibing Huang , Yong Yang , Qingling Xie , Hanwen Yuan , Muhammad Aamer , Yuqing Jian , Ye Zhang , Wei Wang","doi":"10.1016/S1875-5364(25)60814-4","DOIUrl":"10.1016/S1875-5364(25)60814-4","url":null,"abstract":"<div><div>Five new flavan-4-ol glycosides jixueqiosides A-E (<strong>1</strong>-<strong>5</strong>) and two new flavan glycosides jixueqiosides F and G (<strong>6</strong> and <strong>7</strong>), along with twelve known flavan-4-ol glycosides (<strong>8</strong>-<strong>19</strong>), were isolated from the roots of <em>Pronephrium penangianum</em>. Comprehensive spectral analyses, X-ray single-crystal diffraction, and theoretical electronic circular dichroism (ECD) calculations established structures and absolute configurations. A single crystal structure of flavan-4-ol glycoside (<strong>14</strong>) was reported for the first time, while the characteristic ECD and NMR data for all isolated flavan-4-ol glycosides (<strong>1</strong>-<strong>5</strong> , <strong>8</strong>-<strong>19</strong>) were analyzed, establishing a set of empirical rules. Activity screening of these isolates showed that <strong>8</strong> and <strong>9</strong> could inhibit the proliferation of MDA-MB-231 and MCF-7 cells with IC<sub>50</sub> values of 7.93 ? 2.85 ?mol?L<sup>-1</sup> and 5.87 ? 1.58 ?mol?L<sup>-1</sup> (MDA-MB-231), and 2.21 ? 1.38 ?mol?L<sup>-1</sup> and 3.52 ? 1.55 ?mol?L<sup>-1</sup> (MCF-7), respectively. Western blotting and flow cytometry analyses demonstrated that <strong>8</strong> and <strong>9</strong> dose-dependently induced apoptosis in MDA-MB-231 cells by up-regulating BAX, activating caspase-3 and down-regulating BCL-2. Additionally, compound <strong>8</strong> affected autophagy-related proteins, increasing the ratio of LC3-II/LC3-I and Beclin-1 levels to inhibit MDA-MB-231 cell proliferation. Moreover, anti-inflammatory studies indicated that <strong>2</strong>, <strong>3</strong>, <strong>7</strong>, <strong>13</strong>, <strong>14,</strong> and <strong>18</strong> moderately inhibited tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and nitric oxide (NO) release.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 5","pages":"Pages 593-603"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068519","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}
Ruilin Wang , Cen Ji , Jiayao Chen , Xiaohan Zhang , Qinghua Hu , Chunxiao Liu
{"title":"Research advances in the treatment of arthritis from natural products (2014-present)","authors":"Ruilin Wang , Cen Ji , Jiayao Chen , Xiaohan Zhang , Qinghua Hu , Chunxiao Liu","doi":"10.1016/S1875-5364(25)60862-4","DOIUrl":"10.1016/S1875-5364(25)60862-4","url":null,"abstract":"<div><div>Arthritis, encompassing osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA), is a prevalent inflammatory disease that significantly impacts quality of life. Natural products (NPs), derived from animals, plants, marine organisms, and microorganisms, have demonstrated beneficial effects in arthritis treatment both domestically and internationally. These natural compounds offer advantages in drug discovery due to their skeletal diversity, structural complexity, and multi-effect, multi-target, and low-toxicity properties compared to conventional small-molecule medicines. However, unclear mechanisms have hindered the development and clinical application of NPs. This review summarizes recent experimental studies from the past decade on natural medicine for arthritis treatment, emphasizing key NPs with therapeutic effects on OA, RA, and GA. It examines the effects and molecular mechanisms of NPs acting on different cells to treat arthritis. Furthermore, this review provides insights into the future prospects of NP research in this field, which is crucial for advancing NP-based arthritis treatments.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 5","pages":"Pages 529-540"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068513","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}
Weimin Liang , Jindi Lu , Ping Yu , Meiqun Cai , Danni Xie , Xini Chen , Xi Zhang , Lingmin Tian , Liyan Yan , Wenxun Lan , Zhongqiu Liu , Xuefeng Zhou , Lan Tang
{"title":"Evaluation of pharmacokinetics and metabolism of three marine-derived piericidins for guiding drug lead selection","authors":"Weimin Liang , Jindi Lu , Ping Yu , Meiqun Cai , Danni Xie , Xini Chen , Xi Zhang , Lingmin Tian , Liyan Yan , Wenxun Lan , Zhongqiu Liu , Xuefeng Zhou , Lan Tang","doi":"10.1016/S1875-5364(25)60866-1","DOIUrl":"10.1016/S1875-5364(25)60866-1","url":null,"abstract":"<div><div>This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 5","pages":"Pages 614-629"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068517","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}
Yaoting Li , Yuhan Feng , Wan Guo , Yu Gao , Jiatao Zhang , Lu Yang , Chun Lei , Yun Kang , Yaqin Wang , Xudong Qu , Jianming Huang
{"title":"A CYP80B enzyme from Stephania tetrandra enables the 3'-hydroxylation of N-methylcoclaurine and coclaurine in the biosynthesis of benzylisoquinoline alkaloids","authors":"Yaoting Li , Yuhan Feng , Wan Guo , Yu Gao , Jiatao Zhang , Lu Yang , Chun Lei , Yun Kang , Yaqin Wang , Xudong Qu , Jianming Huang","doi":"10.1016/S1875-5364(25)60867-3","DOIUrl":"10.1016/S1875-5364(25)60867-3","url":null,"abstract":"<div><div>Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (<em>S</em>)-<em>N</em>-methylcoclaurine, with the <em>N</em>-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (<em>StCYP80B</em>) from <em>Stephania tetrandra</em> (<em>S. tetrandra</em>) and identified its function using a yeast heterologous expression system. Both <em>in vivo</em> yeast feeding and <em>in vitro</em> enzyme analysis demonstrated that <em>St</em>CYP80B could catalyze <em>N</em>-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, <em>St</em>CYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an <em>N</em>-methyl group for hydroxylase activity. Furthermore, <em>St</em>CYP80B displayed a clear preference for the (<em>S</em>)-configuration. Co-expression of <em>St</em>CYP80B with the CYP450 reductases (CPRs, <em>St</em>CPR1, and <em>St</em>CPR2), also cloned from <em>S. tetrandra</em>, significantly enhanced the catalytic activity towards (<em>S</em>)-coclaurine. Site-directed mutagenesis of <em>St</em>CYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, <em>St</em>CYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 5","pages":"Pages 630-640"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068518","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}
Mengyuan Feng , Anjie Zhang , Jingyi Wu , Xinran Cheng , Qingyu Yang , Yunlai Gong , Xiaohui Hu , Wentao Ji , Xianjun Yu , Qun Zhao
{"title":"Pristimerin induces Noxa-dependent apoptosis by activating the FoxO3a pathway in esophageal squamous cell carcinoma","authors":"Mengyuan Feng , Anjie Zhang , Jingyi Wu , Xinran Cheng , Qingyu Yang , Yunlai Gong , Xiaohui Hu , Wentao Ji , Xianjun Yu , Qun Zhao","doi":"10.1016/S1875-5364(25)60865-X","DOIUrl":"10.1016/S1875-5364(25)60865-X","url":null,"abstract":"<div><div>Pristimerin, which is one of the compounds present in <em>Celastraceae</em> and <em>Hippocrateaceae</em>, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC <em>in vitro</em> and <em>in vivo</em>. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin <em>in vivo</em>. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin <em>in vitro</em> and <em>in vivo</em> were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 5","pages":"Pages 585-592"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068421","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}
{"title":"Advances in nanocarriers for targeted drug delivery and controlled drug release","authors":"Yuqian Wang , Renqi Huang , Shufan Feng , Ran Mo","doi":"10.1016/S1875-5364(25)60861-2","DOIUrl":"10.1016/S1875-5364(25)60861-2","url":null,"abstract":"<div><div>Nanocarrier-based drug delivery systems (nDDSs) present significant opportunities for improving disease treatment, offering advantages in drug encapsulation, solubilization, stability enhancement, and optimized pharmacokinetics and biodistribution. nDDSs, comprising lipid, polymeric, protein, and inorganic nanovehicles, can be guided by or respond to biological cues for precise disease treatment and management. Equipping nanocarriers with tissue/cell-targeted ligands enables effective navigation in complex environments, while functionalization with stimuli-responsive moieties facilitates site-specific controlled release. These strategies enhance drug delivery efficiency, augment therapeutic efficacy, and reduce side effects. This article reviews recent strategies and ongoing advancements in nDDSs for targeted drug delivery and controlled release, examining lesion-targeted nanomedicines through surface modification with small molecules, peptides, antibodies, carbohydrates, or cell membranes, and controlled-release nanocarriers responding to endogenous signals such as pH, redox conditions, enzymes, or external triggers like light, temperature, and magnetism. The article also discusses perspectives on future developments.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 5","pages":"Pages 513-528"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068512","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}
Qingqing Chen , Yuhang Ding , Zhongyi Li , Xingyu Chen , Aliya Fazal , Yahan Zhang , Yudi Ma , Changyi Wang , Liu Yang , Tongming Yin , Guihua Lu , Hongyan Lin , Zhongling Wen , Jinliang Qi , Hongwei Han , Yonghua Yang
{"title":"Comprehensive analysis of the antibacterial activity of 5,8-dihydroxy-1,4-naphthoquinone derivatives against methicillin-resistant Staphylococcus aureus","authors":"Qingqing Chen , Yuhang Ding , Zhongyi Li , Xingyu Chen , Aliya Fazal , Yahan Zhang , Yudi Ma , Changyi Wang , Liu Yang , Tongming Yin , Guihua Lu , Hongyan Lin , Zhongling Wen , Jinliang Qi , Hongwei Han , Yonghua Yang","doi":"10.1016/S1875-5364(25)60818-1","DOIUrl":"10.1016/S1875-5364(25)60818-1","url":null,"abstract":"<div><div>Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive <em>in vitro</em> and <em>in vivo</em> analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant <em>Staphylococcus aureus</em> (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an <em>in vivo</em> mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 5","pages":"Pages 604-613"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068516","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}
Xin Zhao , Chao Chen , Xuefei Feng , Haoqi Lei , Lingling Qi , Hongxia Zhang , Haiying Xu , Jufeng Wan , Yan Zhang , Baofeng Yang
{"title":"Emd-D inhibited ovarian cancer progression via PFKFB4-dependent glycolysis and apoptosis","authors":"Xin Zhao , Chao Chen , Xuefei Feng , Haoqi Lei , Lingling Qi , Hongxia Zhang , Haiying Xu , Jufeng Wan , Yan Zhang , Baofeng Yang","doi":"10.1016/S1875-5364(25)60843-0","DOIUrl":"10.1016/S1875-5364(25)60843-0","url":null,"abstract":"<div><div>Ovarian cancer poses a significant threat to women’s health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. <em>In vivo</em> experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D’s potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 431-442"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860353","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}
{"title":"Esculetin triggers ferroptosis via inhibition of the Nrf2-xCT/GPx4 axis in hepatocellular carcinoma","authors":"Zhixin Qu , Jing Zeng , Laifeng Zeng , Xianmei Li , Fenghua Zhang","doi":"10.1016/S1875-5364(25)60853-3","DOIUrl":"10.1016/S1875-5364(25)60853-3","url":null,"abstract":"<div><div>Esculetin, a natural dihydroxy coumarin derived from the Chinese herbal medicine <em>Cortex Fraxini</em>, has demonstrated significant pharmacological activities, including anticancer properties. Ferroptosis, an iron-dependent form of regulated cell death, has garnered considerable attention due to its lethal effect on tumor cells. However, the exact role of ferroptosis in esculetin-mediated anti-hepatocellular carcinoma (HCC) effects remains poorly understood. This study investigated the impact of esculetin on HCC cells both <em>in vitro</em> and <em>in vivo</em>. The findings indicate that esculetin effectively inhibited the growth of HCC cells. Importantly, esculetin promoted the accumulation of intracellular Fe<sup>2+</sup>, leading to an increase in ROS production through the Fenton reaction. This event subsequently induced lipid peroxidation (LPO) and triggered ferroptosis within the HCC cells. The occurrence of ferroptosis was confirmed by the elevation of malondialdehyde (MDA) levels, the depletion of glutathione peroxidase (GSH-Px) activity, and the disruption of mitochondrial morphology. Notably, the inhibitor of ferroptosis, ferrostatin-1 (Fer-1), attenuated the anti-tumor effect of esculetin in HCC cells. Furthermore, the findings revealed that esculetin inhibited the Nrf2-xCT/GPx4 axis signaling in HCC cells. Overexpression of Nrf2 upregulated the expression of downstream SLC7A11 and GPX4, consequently alleviating esculetin-induced ferroptosis. In conclusion, this study suggests that esculetin exerts an anti-HCC effect by inhibiting the activity of the Nrf2-xCT/GPx4 axis, thereby triggering ferroptosis in HCC cells. These findings may contribute to the potential clinical use of esculetin as a candidate for HCC treatment.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 443-456"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860287","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}
Fengyao Yang , Zeyuan Liang , Haoran Zhao , Jiayi Zheng , Lifang Liu , Huipeng Song , Guizhong Xin
{"title":"Mass spectral database-based methodologies for the annotation and discovery of natural products","authors":"Fengyao Yang , Zeyuan Liang , Haoran Zhao , Jiayi Zheng , Lifang Liu , Huipeng Song , Guizhong Xin","doi":"10.1016/S1875-5364(25)60852-1","DOIUrl":"10.1016/S1875-5364(25)60852-1","url":null,"abstract":"<div><div>Natural products (NPs) have long held a significant position in various fields such as medicine, food, agriculture, and materials. The chemical space covered by NPs is extensive but often underexplored. Therefore, high-throughput and efficient methodologies for the annotation and discovery of NPs are desired to address the complexity and diversity of NP-based systems. Mass spectrometry (MS) has emerged as a powerful platform for the annotation and discovery of NPs. MS databases provide vital support for the structural characterization of NPs by integrating extensive mass spectral data and sample information. Additionally, the released annotation methodologies, based on a variety of informatics tools, continuously improve the ability to annotate the structure and properties of compounds. This review examines the current mainstream databases and annotation methodologies, focusing on their advantages and limitations. Prospects for future technological advancements are then discussed in terms of novel applications and research objectives. Through a systematic overview, this review aims to provide valuable insights and a reference for MS-based NPs annotation, thereby promoting the discovery of novel natural entities.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 410-420"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860293","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}