Chinese Journal of Natural Medicines最新文献

{"title":"Advances in nanocarriers for targeted drug delivery and controlled drug release","authors":"Yuqian Wang ,&nbsp;Renqi Huang ,&nbsp;Shufan Feng ,&nbsp;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}

{"title":"Comprehensive analysis of the antibacterial activity of 5,8-dihydroxy-1,4-naphthoquinone derivatives against methicillin-resistant Staphylococcus aureus","authors":"Qingqing Chen ,&nbsp;Yuhang Ding ,&nbsp;Zhongyi Li ,&nbsp;Xingyu Chen ,&nbsp;Aliya Fazal ,&nbsp;Yahan Zhang ,&nbsp;Yudi Ma ,&nbsp;Changyi Wang ,&nbsp;Liu Yang ,&nbsp;Tongming Yin ,&nbsp;Guihua Lu ,&nbsp;Hongyan Lin ,&nbsp;Zhongling Wen ,&nbsp;Jinliang Qi ,&nbsp;Hongwei Han ,&nbsp;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}

{"title":"Emd-D inhibited ovarian cancer progression via PFKFB4-dependent glycolysis and apoptosis","authors":"Xin Zhao ,&nbsp;Chao Chen ,&nbsp;Xuefei Feng ,&nbsp;Haoqi Lei ,&nbsp;Lingling Qi ,&nbsp;Hongxia Zhang ,&nbsp;Haiying Xu ,&nbsp;Jufeng Wan ,&nbsp;Yan Zhang ,&nbsp;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 ,&nbsp;Jing Zeng ,&nbsp;Laifeng Zeng ,&nbsp;Xianmei Li ,&nbsp;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 Fe²⁺, 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}

{"title":"Mass spectral database-based methodologies for the annotation and discovery of natural products","authors":"Fengyao Yang ,&nbsp;Zeyuan Liang ,&nbsp;Haoran Zhao ,&nbsp;Jiayi Zheng ,&nbsp;Lifang Liu ,&nbsp;Huipeng Song ,&nbsp;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}

{"title":"Pure drug nanomedicines - where we are?","authors":"Yaoyao Lai,&nbsp;Bing Xie,&nbsp;Wanting Zhang,&nbsp;Wei He","doi":"10.1016/S1875-5364(25)60851-X","DOIUrl":"10.1016/S1875-5364(25)60851-X","url":null,"abstract":"<div><div>Pure drug nanomedicines (PDNs) encompass active pharmaceutical ingredients (APIs), including macromolecules, biological compounds, and functional components. They overcome research barriers and conversion thresholds associated with nanocarriers, offering advantages such as high drug loading capacity, synergistic treatment effects, and environmentally friendly production methods. This review provides a comprehensive overview of the latest advancements in PDNs, focusing on their essential components, design theories, and manufacturing techniques. The physicochemical properties and <em>in vivo</em> behaviors of PDNs are thoroughly analyzed to gain an in-depth understanding of their systematic characteristics. The review introduces currently approved PDN products and further explores the opportunities and challenges in expanding their depth and breadth of application. Drug nanocrystals, drug-drug cocrystals (DDCs), antibody-drug conjugates (ADCs), and nanobodies represent the successful commercialization and widespread utilization of PDNs across various disease domains. Self-assembled pure drug nanoparticles (SAPDNPs), a next-generation product, still require extensive translational research. Challenges persist in transitioning from laboratory-scale production to mass manufacturing and overcoming the conversion threshold from laboratory findings to clinical applications.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 385-409"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860294","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":"Novel araucarene diterpenes from Agathis dammara exert hypoglycemic activity by promoting pancreatic β cell regeneration and glucose uptake","authors":"Zhewei Yu ,&nbsp;Yi Zhang ,&nbsp;Wenhui Wang ,&nbsp;XinYi Wu ,&nbsp;Shunzhi Liu ,&nbsp;Yanlin Bin ,&nbsp;Hongsheng Li ,&nbsp;Bangping Cai ,&nbsp;Zheng Wang ,&nbsp;Meijuan Fang ,&nbsp;Rong Qi ,&nbsp;Mingyu Li ,&nbsp;Yingkun Qiu","doi":"10.1016/S1875-5364(25)60856-9","DOIUrl":"10.1016/S1875-5364(25)60856-9","url":null,"abstract":"<div><div>In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of <em>Agathis dammara</em>, including 11 previously unreported compounds: dammaradione (<strong>1</strong>), dammarones D−G (<strong>2</strong>, <strong>5</strong>, <strong>14</strong>, <strong>15</strong>), dammaric acids B−F (<strong>8</strong>−<strong>12</strong>), and dammarol (<strong>16</strong>). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure–activity relationship (SAR) analysis was conducted. Araucarone (<strong>3</strong>) and dammaric acid C (<strong>9</strong>), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic <em>β</em> cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into <em>β</em> cells in zebrafish.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 492-503"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860289","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":"Structurally diverse sesquiterpenoids with anti-MDR cancer activity from Penicillium roqueforti","authors":"Shuyuan Mo ,&nbsp;Nanjin Ding ,&nbsp;Zhihong Huang ,&nbsp;Jun Yao ,&nbsp;Weiguang Sun ,&nbsp;Jianping Wang ,&nbsp;Yonghui Zhang ,&nbsp;Zhengxi Hu","doi":"10.1016/S1875-5364(25)60857-0","DOIUrl":"10.1016/S1875-5364(25)60857-0","url":null,"abstract":"<div><div>Five novel <em>nor</em>-eremophilane-type sesquiterpenoids, peniroqueforins E–H and J (<strong>1</strong>–<strong>4</strong> and <strong>7</strong>), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (<strong>5</strong> and <strong>8</strong>), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (<strong>9</strong>), along with four known compounds (<strong>6</strong> and <strong>10</strong>–<strong>12</strong>), were isolated and characterized from fungus <em>Penicillium roqueforti</em> (<em>P. roqueforti</em>). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC₅₀) value of paclitaxel (PTX) combined with <strong>1</strong> in SW620/Ad300 cells was 50.36 nmol·L⁻¹, which was 65-fold more potent than PTX alone (IC₅₀ 3.26 μmol·L⁻¹). Subsequent molecular docking studies revealed an affinity between compound <strong>1</strong> and P-glycoprotein (P-gp), suggesting that this <em>nor</em>-eremophilane-type sesquiterpenoid (<strong>1</strong>) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 504-512"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860290","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":"Andrographolide sulfonate alleviates rheumatoid arthritis by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation","authors":"Chunhong Jiang ,&nbsp;Xi Zeng ,&nbsp;Jia Wang ,&nbsp;Xiaoqian Wu ,&nbsp;Lijuan Song ,&nbsp;Ling Yang ,&nbsp;Ze Li ,&nbsp;Ning Xie ,&nbsp;Xiaomei Yuan ,&nbsp;Zhifeng Wei ,&nbsp;Yi Guan","doi":"10.1016/S1875-5364(25)60855-7","DOIUrl":"10.1016/S1875-5364(25)60855-7","url":null,"abstract":"<div><div>Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from <em>Andrographis paniculata</em> (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. <em>In vitro</em>, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals <em>in vivo</em> and <em>in vitro</em>, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 480-491"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860291","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":"Xiaohuang Qudan decoction alleviates ANIT-induced cholestatic liver injury by inhibiting the JAK2/STAT3 pathway and regulating TH17/Treg","authors":"Zhangkui Tan ,&nbsp;Lifeng Chen ,&nbsp;Zhiqin Ye ,&nbsp;Qiping Lu","doi":"10.1016/S1875-5364(25)60854-5","DOIUrl":"10.1016/S1875-5364(25)60854-5","url":null,"abstract":"<div><div>Xiaohuang Qudan decoction (XHQDD) is a classical traditional Chinese medicine (TCM) formula widely used in the treatment of cholestatic liver injury. Despite its widespread use, the protective mechanism of XHQDD against cholestatic liver injury remains incompletely understood. The aim of this study was to investigate whether XHQDD mediates its beneficial effects by inhibiting the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway and regulating TH17/Treg balance. To this end, the researchers used Sprague-Dawley (SD) rats and established a cholestatic liver injury model by oral administration of alpha-naphthylisothiocyanate (ANIT). The experimental group was divided into six groups: Control (CON), ANIT, ursodeoxycholic acid (UDCA), XHQDD-low dose (XHQDD-L) group, XHQDD-medium dose (XHQDD-M) group, and XHQDD-high dose (XHQDD-H) groups. Then, after 7 d of treatment, various tests were performed to verify the results. Firstly, XHQDD and its drug-containing serum were analyzed by ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS), and 14 blood-entry components were identified. Then, bile flow was monitored and found to be significantly reduced in the model group, which was significantly reversed in the UDCA and XHQDD groups. To further assess ANIT-induced liver injury, hematoxylin and eosin (H&amp;E) and Sirius red staining, alongside transmission electron microscopy (TEM), were employed to observe liver tissues, revealing hepatocellular injury, cholestasis, and hepatic fibrotic changes. Serum inflammatory factors and liver injury indicators were assessed using enzyme-linked immunosorbent assay (ELISA), indicating an inflammatory state in ANIT-induced liver injury rats. The expression levels of JAK2/STAT3-related genes and proteins in liver and intestinal tissues were measured <em>via</em> quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, immunofluorescence (IF) staining, and Western blottting (WB) assays. These studies revealed that the inflammatory state of liver-injured rats was inextricably linked to the inflammatory cascade associated with the JAK2/STAT3 pathway and that XHQDD may exert anti-inflammatory efficacy by inhibiting the JAK2/STAT3 pathway. Flow cytometry was used to determine the percentage of T helper 17 (Th17)/regulatory T (Treg) cells in serum and hepatocytes, and it was further found that XHQDD was able to regulate Th17/Treg immune homeostasis in liver-injured rats. The findings suggest that XHQDD markedly alleviates inflammation in ANIT rats, potentially treating cholestasis and liver injury through JAK2/STAT3 inhibition and Th17/Treg balance regulation.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 457-470"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860288","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}