Chinese Journal of Natural Medicines最新文献

{"title":"Intervention of natural products targeting novel mechanisms after myocardial infarction","authors":"Guangjie Tai ,&nbsp;Renhua Liu ,&nbsp;Tian Lin ,&nbsp;Jiancheng Yang ,&nbsp;Xiaoxue Li ,&nbsp;Ming Xu","doi":"10.1016/S1875-5364(25)60816-8","DOIUrl":"10.1016/S1875-5364(25)60816-8","url":null,"abstract":"<div><div>Myocardial infarction is a cardiovascular disease (CVD) with high morbidity and mortality, which can trigger a cascade of cardiac pathophysiological changes, including fibrosis, inflammation, ischemia-reperfusion injury (IRI), and ventricular remodeling, ultimately leading to heart failure (HF). While conventional pharmacological treatments and clinical reperfusion therapy may enhance short-term prognoses and emergency survival rates, both approaches have limitations and adverse effects. Natural products (NPs) are extensively utilized as therapeutics globally, with some demonstrating potentially favorable therapeutic effects in preclinical and clinical pharmacological studies, positioning them as potential alternatives to modern drugs. This review comprehensively elucidates the pathophysiological mechanisms during myocardial infarction and summarizes the mechanisms by which NPs exert cardiac beneficial effects. These include classical mechanisms such as inhibition of inflammation and oxidative stress, alleviation of cardiomyocyte death, attenuation of cardiac fibrosis, improvement of angiogenesis, and emerging mechanisms such as cardiac metabolic regulation and histone modification. Furthermore, the review emphasizes the modulation by NPs of novel targets or signaling pathways in classical mechanisms, including other forms of regulated cell death (RCD), endothelial-mesenchymal transition, non-coding ribonucleic acids (ncRNAs) cascade, and endothelial progenitor cell (EPC) function. Additionally, NPs influencing a particular mechanism are categorized based on their chemical structure, and their relevance is discussed. Finally, the current limitations and prospects of NPs therapy are considered, highlighting their potential for use in myocardial infarction management and identifying issues that require urgent attention.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 6","pages":"Pages 658-672"},"PeriodicalIF":4.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331402","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":"Oroxylin A inhibits UVB-induced non-melanoma skin cancer by regulating XPA degradation","authors":"Renjie Dou ,&nbsp;Jiarui Sun ,&nbsp;Hang Yang ,&nbsp;Yufen Zheng ,&nbsp;Kang Yuan ,&nbsp;Lei Qiang ,&nbsp;Run Ma ,&nbsp;Yunyao Liu","doi":"10.1016/S1875-5364(25)60893-4","DOIUrl":"10.1016/S1875-5364(25)60893-4","url":null,"abstract":"<div><div>Oroxylin A (OA), a natural compound extracted from <em>Scutellaria baicalensis</em>, demonstrates preventive potential against ultraviolet B (UVB)-induced non-melanoma skin cancer (NMSC), the most prevalent cancer worldwide with increasing incidence. Utilizing SKH-1 hairless mice exposed to UVB, this study showed that OA delayed NMSC onset and alleviated acute skin damage. Mechanistic investigations revealed its dual action: inhibiting inflammation and enhancing nucleotide excision repair (NER) by stabilizing XPA, a crucial deoxyribonucleic acid (DNA) repair protein. This stabilization occurred through OA’s interaction with glucose-regulated protein 94 (GRP94), which disrupted murine double minute 2 (MDM2)-mediated XPA ubiquitination and proteasomal degradation. By maintaining XPA levels, OA expedited photoproduct clearance and diminished genomic instability, ultimately impeding NMSC development. These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 6","pages":"Pages 742-753"},"PeriodicalIF":4.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331320","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":"Advancements and applications in radiopharmaceutical therapy","authors":"Shiya Wang ,&nbsp;Mingyi Cao ,&nbsp;Yifei Chen ,&nbsp;Jingjing Lin ,&nbsp;Jiahao Li ,&nbsp;Xinyu Wu ,&nbsp;Zhiyue Dai ,&nbsp;Yuhan Pan ,&nbsp;Xiao Liu ,&nbsp;Xian Liu ,&nbsp;Liang-Ting Lin ,&nbsp;Jianbing Wu ,&nbsp;Ji Liu ,&nbsp;Qifeng Zhong ,&nbsp;Zhenwei Yuan","doi":"10.1016/S1875-5364(25)60887-9","DOIUrl":"10.1016/S1875-5364(25)60887-9","url":null,"abstract":"<div><div>Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 6","pages":"Pages 641-657"},"PeriodicalIF":4.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331401","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":"Harmonizing tradition and technology: Liposomal nanocarriers unlocking the power of natural herbs in Traditional Chinese Medicine","authors":"Ibrahim Shaw ,&nbsp;Aaron Albert Aryee ,&nbsp;Yimer Seid Ali ,&nbsp;George Frimpong Boafo ,&nbsp;Jingjing Tian ,&nbsp;Ronald Mlambo ,&nbsp;Songwen Tan ,&nbsp;Chuanpin Chen","doi":"10.1016/S1875-5364(25)60889-2","DOIUrl":"10.1016/S1875-5364(25)60889-2","url":null,"abstract":"<div><div>Natural herbs demonstrate significant therapeutic potential in managing chronic and complex diseases; however, their clinical application faces limitations due to low bioavailability, instability, toxicity, and herb-drug interactions. Furthermore, insufficient standardized evidence and global acceptance impede their widespread adoption. Liposomes, nanocarriers consisting of a phospholipid bilayer enclosing an aqueous core, present a promising approach for enhancing the pharmacokinetics and therapeutic efficacy of herbal compounds. These adaptable systems can encapsulate both hydrophilic and hydrophobic agents, enabling targeted drug delivery and enhanced stability. Moreover, liposomes can be modified to carry diagnostic and imaging agents, enabling precise disease detection and monitoring. While liposomes offer potential as an innovative delivery technology for herbal remedies, their application in Traditional Chinese Medicine (TCM) remains relatively unexplored. TCM, with its holistic, energy-based approach to health and organ function, presents distinct challenges regarding formulation and delivery. This review examines the therapeutic potential of herbal medicines, emphasizing how liposomes address delivery challenges within the TCM framework. It also investigates the integration of TCM with Western medical practices, demonstrating how liposomal systems may bridge these approaches. The review analyzes key formulation techniques for TCM-loaded liposomes, particularly the microfluidic method, which demonstrates superior control over particle size and encapsulation efficiency compared to conventional methods. The analysis addresses barriers to integrating liposomal delivery systems with TCM, including physicochemical properties, scalability issues, and regulatory challenges. Finally, this review provides strategic recommendations for overcoming these obstacles and identifies future research directions to maximize the potential of liposomal technology in enhancing TCM therapies.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 6","pages":"Pages 700-713"},"PeriodicalIF":4.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331404","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":"Diphenylemestrins A−E: diketopiperazine-diphenyl ether hybrids from Aspergillus nidulans","authors":"Aimin Fu ,&nbsp;Qin Li ,&nbsp;Yang Xiao ,&nbsp;Jiaxin Dong,&nbsp;Yuanyang Peng,&nbsp;Yu Chen,&nbsp;Qingyi Tong,&nbsp;Chunmei Chen,&nbsp;Yonghui Zhang,&nbsp;Hucheng Zhu","doi":"10.1016/S1875-5364(25)60891-0","DOIUrl":"10.1016/S1875-5364(25)60891-0","url":null,"abstract":"<div><div>A chemical investigation of secondary metabolites (SMs) from <em>Aspergillus nidulans</em> resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A−E (<strong>1</strong>−<strong>5</strong>). These compounds <strong>1</strong>−<strong>5</strong> represent the first known dimers combining DKP and diphenyl ether structures, with compound <strong>4</strong> featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (<strong>3</strong>) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L⁻¹, and induced apoptosis at higher concentrations.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 6","pages":"Pages 727-732"},"PeriodicalIF":4.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331318","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":"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}