{"title":"Advances in intelligent mass spectrometry data processing technology for in vivo analysis of natural medicines","authors":"","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":null,"pages":null},"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}
{"title":"Chiral resolution of furofuran lignans and their derivatives from the stems of Dendrobium 'Sonia'","authors":"","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":null,"pages":null},"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}
{"title":"Highly oxygenated clerodane furanoditerpenoids from the leaves and twigs of Croton yunnanensis","authors":"","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":null,"pages":null},"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}
{"title":"New insight into targeting the DNA damage response in the treatment of glioblastoma","authors":"","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":null,"pages":null},"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}
{"title":"Targeting TLR4 and regulating the Keap1/Nrf2 pathway with andrographolide to suppress inflammation and ferroptosis in LPS-induced acute lung injury","authors":"","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":null,"pages":null},"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}
{"title":"Four new diarylheptanoids and two new terpenoids from the fruits of Alpinia oxyphylla and their anti-inflammatory activities","authors":"","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":null,"pages":null},"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}
{"title":"Toosendanin: upgrade of an old agent in cancer treatment","authors":"","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":null,"pages":null},"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}
{"title":"Cyclocarysaponins A–J, dammarane-type triterpenoid glycosides from the leaves of Cyclocarya paliurus","authors":"","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":null,"pages":null},"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}
{"title":"Glasesterterpenoids A−C: three sesterterpenoids with 7-cyclohexyldecahydronaphthalene carbon skeleton isolated from the root of Lindera glauca","authors":"","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":null,"pages":null},"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}
{"title":"Rehmanniae Radix Praeparata aqueous extract improves hepatic ischemia/reperfusion injury by restoring intracellular iron homeostasis","authors":"","doi":"10.1016/S1875-5364(24)60719-3","DOIUrl":"10.1016/S1875-5364(24)60719-3","url":null,"abstract":"<div><div>Hepatic ischemia/reperfusion injury (HIRI) is a common pathophysiological condition occurring during or after liver resection and transplantation, leading to hepatic viability impairment and functional deterioration. Recently, ferroptosis, a newly recognized form of programmed cell death, has been implicated in IRI. Rehmanniae Radix Praeparata (RRP), extensively used in Chinese herbal medicine for its hepatoprotective, anti-inflammatory, and antioxidant properties, presents a potential therapeutic approach. However, the mechanisms by which RRP mitigates HIRI, particularly through the regulation of ferroptosis, remain unclear. In this study, we developed a HIRI mouse model and monocrotaline (MCT)- and erastin-induced <em>in vitro</em> hepatocyte injury models. We conducted whole-genome transcriptome analysis to elucidate the protective effects and mechanisms of RRP on HIRI. The RRP aqueous extract was characterized by the presence of acteoside, rehmannioside D, and 5-hydroxymethylfurfural. Our results demonstrate that the RRP aqueous extract ameliorated oxidative stress, reduced intracellular iron accumulation, and attenuated HIRI-induced liver damage. Additionally, RRP significantly inhibited hepatocyte death by restoring intracellular iron homeostasis both <em>in vivo</em> and <em>in vitro</em>. Mechanistically, the RRP aqueous extract reduced intrahepatocellular iron accumulation by inhibiting ZIP14-mediated iron uptake, promoting hepcidin- and ferroportin-mediated iron efflux, and ameliorating mitochondrial iron aggregation through upregulation of Cisd1 expression. Moreover, siRNA-mediated inhibition of hamp synergistically enhanced the RRP aqueous extract’s inhibitory effect on ferroptosis. In conclusion, our study elucidates the mechanisms by which RRP aqueous extracts alleviate HIRI, highlighting the restoration of iron metabolic balance. These findings position RRP as a promising candidate for clinical intervention in HIRI treatment.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315289","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}