Chinese Journal of Natural Medicines最新文献

{"title":"Combination of Astragalus−Salvia and Ophiopogon−Dendrobium herb pairs alleviates Sjögren’s Syndrome via inhibiting the JAK1/STAT3 and PI3K/AKT pathways in NOD/Ltj mice","authors":"Peng Sun ,&nbsp;Lili Zhu ,&nbsp;Yang Yu ,&nbsp;Sijing Hu ,&nbsp;Mengyi Shan ,&nbsp;Xuan Zhao ,&nbsp;Xinchang Wang ,&nbsp;Qiaoyan Zhang ,&nbsp;Luping Qin","doi":"10.1016/S1875-5364(25)60892-2","DOIUrl":"10.1016/S1875-5364(25)60892-2","url":null,"abstract":"<div><div>Sjögren’s syndrome (SS) is an autoimmune disease characterized primarily by oral and periocular dryness. <em>Astragalus-Salvia</em> (AS) and <em>Ophiopogon</em>-<em>Dendrobium</em> (OD) represent two frequently utilized herb pairs in SS treatment. While the combination of AS-OD herb pairs demonstrates clinical efficacy in alleviating SS symptoms, its underlying mechanism remains unclear. This investigation sought to assess the therapeutic effects and elucidate the potential mechanisms of AS-OD in non-obese diabetic (NOD)/Ltj mice with SS. The study utilized NOD/Ltj mice as SS models, administering AS-OD treatment for 10 weeks at doses of 113.1, 226.2, and 339.3 mg·d⁻¹·20 g⁻¹. Results demonstrated that AS-OD improved SS symptoms, evidenced by enhanced salivary flow rate, decreased anti-SSA/Ro and anti-SSB/La antibody levels, increased swimming duration, and reduced lactate (LA) and blood urea nitrogen (BUN) levels in NOD/Ltj mice. AS-OD reduced lymphocyte infiltration, enhanced Aquaporin-5 (AQP5) expression in the submandibular gland, decreased inflammatory cytokine levels in the submandibular gland, and reduced the T helper type 17/regulatory T lymphocyte (Th17/Treg) cell ratio in the spleen. Transcriptomic and proteomic analyses indicated AS-OD’s involvement in regulating phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and Janus kinase 3/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways, with inhibitory effects validated in both NOD/Ltj mice submandibular gland and A-253 cells. Furthermore, AS-OD enhanced cell viability and reduced A-253 cell apoptosis through the PI3K/AKT pathway. In A-253 cells, AS-OD reduced inflammatory cytokine levels, CXC chemokine ligand 9/10 (CXCL9/10), and T-cell chemotaxis by inhibiting the JAK1/STAT3 pathway. AS-OD mitigates SS by suppressing inflammation and immune responses through the PI3K/AKT and JAK1/STAT3 pathways.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 6","pages":"Pages 733-741"},"PeriodicalIF":4.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331319","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":"Emerging evidence of inter-organ interaction on drug transporters under liver injury","authors":"Ling Jiang ,&nbsp;Ying Deng ,&nbsp;Ruijing Mu ,&nbsp;Wenke Feng ,&nbsp;Xiaonan Liu ,&nbsp;Li Liu","doi":"10.1016/S1875-5364(25)60888-0","DOIUrl":"10.1016/S1875-5364(25)60888-0","url":null,"abstract":"<div><div>Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury. Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain, eye, liver, intestine, and kidney. Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury, particularly those associated with bilirubin, reactive oxygen species, ammonia, bile acid, and inflammatory factors. Notably, the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood. Additional research is necessary to fully comprehend these effects and their therapeutic implications. The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs, including both traditional Chinese and Western medicines, to patients with liver dysfunction. This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions. Furthermore, when utilizing transporter inducers or inhibitors clinically, consideration of their long-term effects on transporters and subsequent therapeutic impact is essential. Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters. Similarly, prudent use of inducers or inducer-type therapeutic drugs is necessary to prevent enhanced drug resistance. This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 6","pages":"Pages 687-699"},"PeriodicalIF":4.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331403","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":"Salidroside inhibits osteoclast differentiation based on osteoblast-osteoclast interaction via HIF-1a pathway","authors":"Yutong Jin ,&nbsp;Yao Wang ,&nbsp;Chuan Wang ,&nbsp;Lingling Zhang ,&nbsp;Dandan Gao ,&nbsp;Haizhao Liu ,&nbsp;Qingwen Cao ,&nbsp;Chenchen Tian ,&nbsp;Yuhong Bian ,&nbsp;Yue Wang","doi":"10.1016/S1875-5364(25)60864-8","DOIUrl":"10.1016/S1875-5364(25)60864-8","url":null,"abstract":"<div><div>This study investigated the regulatory potential of salidroside (SAL), a primary active compound in <em>Rhodiola rosea</em> L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis <em>in vivo</em>. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. <em>In vivo</em>, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 5","pages":"Pages 572-584"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068420","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":"Progress on the functions and mechanisms of natural products in anti-glioma therapy","authors":"Yanting Li ,&nbsp;Shuhui Qu ,&nbsp;Jiayi Zuo ,&nbsp;Haoping Long ,&nbsp;Feng Cao ,&nbsp;Feng Jiang","doi":"10.1016/S1875-5364(25)60815-6","DOIUrl":"10.1016/S1875-5364(25)60815-6","url":null,"abstract":"<div><div>Glioma, the most prevalent primary tumor of the central nervous system (CNS), is also the most lethal primary malignant tumor. Currently, there are limited chemotherapeutics available for glioma treatment, necessitating further research to identify and develop new chemotherapeutic agents. A significant approach to discovering anti-glioma drugs involves isolating antitumor active ingredients from natural products (NPs) and optimizing their structures. Additionally, targeted drug delivery systems (TDDSs) are employed to enhance drug solubility and stability and overcome the blood-brain barrier (BBB). TDDSs can penetrate deep into the brain, increase drug concentration and retention time in the CNS, and improve the targeting efficiency of NPs, thereby reducing adverse effects and enhancing anti-glioma efficacy. This paper reviews the research progress of anti-glioma activities of NPs, including alkaloids, polyphenols, flavonoids, terpenoids, saponins, quinones, and their synthetic derivatives over the past decade. The review also summarizes anti-glioma mechanisms, such as suppression of related protein expression, regulation of reactive oxygen species (ROS) levels, control of apoptosis signaling pathways, reduction of matrix metalloproteinases (MMPs) expression, blocking of vascular endothelial growth factor (VEGF), and reversal of immunosuppression. Furthermore, the functions and advantages of NP-based TDDSs in anti-glioma therapy are examined. The key information presented in this review will be valuable for the research and development of NP-based anti-glioma drugs and related TDDSs.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 5","pages":"Pages 541-559"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068412","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":"Lingguizhugan Decoction improves chronic heart failure by synergistically modulating ?1-AR/Gs/GRKs/?-arrestin signaling bias","authors":"Shuting Guo ,&nbsp;Lei Xia ,&nbsp;Songru Yang ,&nbsp;Yueyang Liang ,&nbsp;Xiaoli Shan ,&nbsp;Pei Zhao ,&nbsp;Wei Guo ,&nbsp;Chen Zhang ,&nbsp;Ming Xu ,&nbsp;Ning Sun ,&nbsp;Rong Lu ,&nbsp;Huihua Chen","doi":"10.1016/S1875-5364(25)60863-6","DOIUrl":"10.1016/S1875-5364(25)60863-6","url":null,"abstract":"<div><div>Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. <em>In vivo</em>, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system <em>via</em> multiple pathways.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 5","pages":"Pages 560-571"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068419","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":"Anti-cancer and anti-inflammatory effects of flavan-4-ol and flavan glycosides from the roots of Pronephrium penangianum","authors":"Feibing Huang ,&nbsp;Yong Yang ,&nbsp;Qingling Xie ,&nbsp;Hanwen Yuan ,&nbsp;Muhammad Aamer ,&nbsp;Yuqing Jian ,&nbsp;Ye Zhang ,&nbsp;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 IC₅₀ values of 7.93 ? 2.85 ?mol?L^-1 and 5.87 ? 1.58 ?mol?L^-1 (MDA-MB-231), and 2.21 ? 1.38 ?mol?L^-1 and 3.52 ? 1.55 ?mol?L^-1 (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}

{"title":"Research advances in the treatment of arthritis from natural products (2014-present)","authors":"Ruilin Wang ,&nbsp;Cen Ji ,&nbsp;Jiayao Chen ,&nbsp;Xiaohan Zhang ,&nbsp;Qinghua Hu ,&nbsp;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}

{"title":"Evaluation of pharmacokinetics and metabolism of three marine-derived piericidins for guiding drug lead selection","authors":"Weimin Liang ,&nbsp;Jindi Lu ,&nbsp;Ping Yu ,&nbsp;Meiqun Cai ,&nbsp;Danni Xie ,&nbsp;Xini Chen ,&nbsp;Xi Zhang ,&nbsp;Lingmin Tian ,&nbsp;Liyan Yan ,&nbsp;Wenxun Lan ,&nbsp;Zhongqiu Liu ,&nbsp;Xuefeng Zhou ,&nbsp;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 &gt; GPA &gt; 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}

{"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 ,&nbsp;Yuhan Feng ,&nbsp;Wan Guo ,&nbsp;Yu Gao ,&nbsp;Jiatao Zhang ,&nbsp;Lu Yang ,&nbsp;Chun Lei ,&nbsp;Yun Kang ,&nbsp;Yaqin Wang ,&nbsp;Xudong Qu ,&nbsp;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}

{"title":"Pristimerin induces Noxa-dependent apoptosis by activating the FoxO3a pathway in esophageal squamous cell carcinoma","authors":"Mengyuan Feng ,&nbsp;Anjie Zhang ,&nbsp;Jingyi Wu ,&nbsp;Xinran Cheng ,&nbsp;Qingyu Yang ,&nbsp;Yunlai Gong ,&nbsp;Xiaohui Hu ,&nbsp;Wentao Ji ,&nbsp;Xianjun Yu ,&nbsp;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}