Phytotherapy Research最新文献

{"title":"New Roles of Artemisinins in Atherosclerosis Progression.","authors":"Hamidreza Majidiani, Maryam Musavi, Amir Abbas Momtazi-Borojeni","doi":"10.1002/ptr.8483","DOIUrl":"10.1002/ptr.8483","url":null,"abstract":"<p><p>Artemisinin is a natural compound derived from the Chinese plant Artemisia annua , which was officially approved by the FDA for its antimalarial effects. In recent years, a growing body of studies has shown the novel function of artemisinin in atherosclerosis therapy. In vivo studies have shown that artemisinin can inhibit the progression of atherosclerosis plaque. In the present review, the evidence showing the inhibitory effects of artemisinin on the progression of atherosclerosis plaque and its underlying mechanisms is discussed. Mechanistically, artemisinin and its derivatives act by modulating various atherosclerosis-mediating risk factors, including hyperlipidemia, inflammation, oxidative stress, and malfunctioning vascular smooth muscle cells (VSMCs). Notably, artesunate, but not artemisinin, can attenuate the plasma levels of TG, TC, VLDL-C, and LDL-c, along with a substantial decline in arterial lipid deposition through enhancing the LDPL activity via inducing the KFL2/NRF2/TCF7L2 axis. Artemisinin was found to ameliorate the atherosclerosis plaque inflammation by reducing monocyte adhesion and subsequent transmigration to the intima, via inhibiting the expression of ICAM-1 and VCAM-1, diminishing NLRP3 inflammasome activation, and reducing the expression of inflammatory factors such as IL-1β, IL-18, TNF-α, MCP-1, and TGF-β1 mechanistically and mainly via suppressing the by NF-κB activity. Artemisinin could exert antioxidant effects through activating the PI3K/Akt/eNOS signaling pathway and suppressing the ROS-mediated NF-κB signal pathway. Artemisinin could also improve the VSMC function in the atherosclerosis plaque. These findings can suggest artemisinin as a new therapeutic agent for treating atherosclerosis; however, future clinical trials are warranted to validate its therapeutic efficiency in patients with atherosclerosis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1847-1857"},"PeriodicalIF":6.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812085","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":"Dihydroartemisinin inhibits melanoma migration and metastasis by affecting angiogenesis.","authors":"Zhaoxiang Li, Qi Zhang, Xinyuan Zhang, Quanxin Jin, Qi Yue, Na Li, Huan Liu, Manabu Fujimoto, Guihua Jin","doi":"10.1002/ptr.8065","DOIUrl":"10.1002/ptr.8065","url":null,"abstract":"<p><p>Tumor angiogenesis is critical for tumor metastasis by providing oxygen, nutrients, and metastatic pathways. As a potential anti-angiogenic agent, Dihydroartemisinin (DHA) can effectively inhibit tumor metastasis. However, the mechanism how it regulates angiogenesis to affect tumor metastasis has not been fully clarified. To investigate the mechanisms of how DHA regulates melanoma progression. In this study, bioinformatics methods were used to analyze the correlation between angiogenesis and melanoma metastasis. Then, B16F10, A375, HUVECs and mouse metastasis models were adapted to clarify the inhibition of DHA in melanoma. GESA analysis revealed melanoma metastasis significantly positive correlated with angiogenesis. Meanwhile, DHA significantly decreased melanoma nodules and lung wet weight in metastatic tumor mice, and inhibited the expression of the angiogenic marker CD31 in vitro and in vivo. Similarly, DHA inhibited the expression of the angiogenic signal molecule VEGFR2 in A375 and B16F10 cells, and significantly suppressed the formation of their tubular structures. DHA-treated supernatants significantly inhibited the tubule-forming ability as well as lateral and longitudinal migration ability of HUVECs compared with untreated melanoma cell supernatants. Screening yielded the angiogenic pathways HIF-1α/VEGF, PI3K/ATK/mTOR associated with melanoma metastasis, and DHA may inhibit tumor metastasis by inhibiting these angiogenic pathways in melanoma cells to inhibit tumor metastasis. Further non-targeted metabolomics analysis revealed that DHA-treated model mice produced differential metabolites that were also associated with angiogenic pathways. DHA inhibits melanoma invasion and metastasis by mediating angiogenesis. These results have important implications for the potential use of DHA in treatment of melanoma.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1679-1693"},"PeriodicalIF":6.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138047757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Substantial Effects of Carotenoids on Skin Health: A Mechanistic Perspective.","authors":"Ressin Varghese, Arnold Emerson, Brigitte Vannier, C George Priya Doss, Rossyda Priyadharshini, Thomas Efferth, Siva Ramamoorthy","doi":"10.1002/ptr.8480","DOIUrl":"https://doi.org/10.1002/ptr.8480","url":null,"abstract":"<p><p>There has been an upsurge in the incidences of skin disorders and their mortalities owing to various environmental, hormonal, and epigenetic risk factors. Melanoma, atopic dermatitis, psoriasis, and photoaging and associated consequences are largely observed in the population globally. The social stigma, economic burden, and adverse effects from chronic medication endured by the patients emphasize the necessity of more effective natural therapeutics. Carotenoids are economically valuable tetraterpenoid pigments synthesized by plants and microorganisms, which play a paramount role in their overall growth and development. Extensive in vitro and in vivo investigations evidenced that phytopigments like carotenoids target multiple intracellular signaling pathways involving the mitogen-activated protein kinases, Janus kinase/signal transducers, and activators of transcription, apoptotic, and autophagy proteins to ameliorate melanoma. Besides, carotenoids curbed the activation and the release of immunoregulatory molecules such as cytokines and chemokines to abrogate skin immune disorders, photoaging, and associated consequences. Here, we provide a holistic discussion on the pathophysiology of prominent skin disorders and the ameliorating effects of carotenoids as evidenced in the in vitro, in vivo, and clinical interventions. We also advocate the requisite of formulating carotenoid medications after extensive clinical interventions and validation for mitigating various skin dysfunctions.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753429","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 and Phloretin Combination Mitigates Acute Kidney Injury-Diabetes Comorbidity via Regulating Mitophagy and Inflammation: A Dual-Pronged Approach.","authors":"Neha Dagar, Tahib Habshi, Vishwadeep Shelke, Hemant R Jadhav, Anil Bhanudas Gaikwad","doi":"10.1002/ptr.8489","DOIUrl":"https://doi.org/10.1002/ptr.8489","url":null,"abstract":"<p><p>Induction of PINK1/Parkin-mediated mitophagy and reducing inflammation via targeting the TLR4/NF-κB axis simultaneously could be a promising therapy for the complex pathophysiology of AKI-diabetes comorbidity. Earlier, esculetin by mitophagy activation and phloretin by inhibiting inflammation have shown promising renoprotection. Therefore, we aimed to evaluate the synergistic renoprotective ability of esculetin and phloretin combination against AKI-diabetes comorbidity. AKI-diabetes comorbidity was mimicked in vivo by bilateral ischemia/reperfusion injury (IRI) in diabetic rats and in vitro by sodium azide-induced hypoxia/reperfusion injury (HRI) under hyperglycemic conditions. The cells were pretreated with esculetin (50 μM) and phloretin (50 μM) for 24 h. Similarly, the diabetic AKI rats received esculetin (50 mg/kg/day, p.o.) and phloretin (50 mg/kg/day, p.o.) pretreatment for 4 days and 1 h before surgery. Further, the obtained samples were utilized for different experiments. Esculetin and phloretin in diabetic AKI rats preserved kidney function and prevented kidney injury, indicated by reduced plasma creatinine, blood urea nitrogen, and kidney injury molecule 1. Esculetin improved mitophagy, indicated by increased mitophagosome formation, increased PINK1, Parkin, LC3B, and decreased p62 expression. Similarly, phloretin suppressed the diabetic AKI-related increased expression of inflammatory mediators including NF-κB, TLR4, TNF-α, and MCP-1. Moreover, combination therapy showed a more pronounced effect via synergistically improving mitophagy, maintaining ΔΨm, preventing mitochondrial dysfunction, reducing inflammation, and apoptosis. Esculetin and phloretin combination ameliorated AKI-diabetes comorbidity more effectively than their monotherapies. Esculetin upregulated the PINK1/Parkin-mediated mitophagy, and phloretin reduced inflammation by inhibiting the TLR4/NF-κB axis, thereby synergistically preventing kidney dysfunction.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754151","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":"Mechanisms and Potential of Antitumor Therapy With Natural Products Regulating Non-Coding RNAs.","authors":"Zhuguo Wang, Fei Wang, Huiming Huang, Xinyu Qiu, Peng Tan, Xuejiao Wei, Ruoxin Zhang, Yufeng Gao, Zhongdong Hu","doi":"10.1002/ptr.8487","DOIUrl":"https://doi.org/10.1002/ptr.8487","url":null,"abstract":"<p><p>Non-coding RNAs (ncRNAs) are a distinctive class of RNA transcripts that have received extensive attention from the global scientific community due to their intricate and important roles in tumor malignancy. The dysregulated expression of ncRNAs is closely associated with the progression of different types of cancer, suggesting that ncRNAs serve as key regulatory factors and modulate numerous cancer biomarkers. The complex interactions between regulatory ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), as well as their intricate interactions with mRNAs or RNA-binding proteins, orchestrate many biological processes in tumors. Natural products, obtained from dietary or medicinal sources, are extremely safe and have stable therapeutic outcomes. These products can regulate ncRNAs, effectively inhibiting tumor cell growth and proliferation and even triggering cell death. This ability highlights that they can reduce tumor burden and enhance clinical outcomes for cancer patients. In this review we discussed the intricate mechanisms underlying ncRNAs-mediated tumor regulation and systematically highlighted the diverse antitumor applications of natural products that specifically control regulatory ncRNAs. We aimed to provide novel perspectives and methods in the field of anticancer research, focusing on the application of natural products.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743430","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":"Ganomycin C, a Ganoderma Meroterpenoid, Alleviates Pain and Absence Seizures in Mice by Targeting Ca_v3.1 and Ca_v3.2 Low-Voltage-Gated Calcium Channels.","authors":"Ding Dong, Shuqin Quan, Mingkun Wu, Shuzong Du, Hui Yan, Ye Gong, Minghua Qiu, Xingrong Peng, Yin Nian","doi":"10.1002/ptr.8486","DOIUrl":"https://doi.org/10.1002/ptr.8486","url":null,"abstract":"<p><p>Low-voltage-gated calcium channels (LVGCCs; Ca_v3.1-3.3) are promising targets for treating pain and absence seizures (ASs). Traditional Chinese medicines are potential sources of LVGCC inhibitors. In this study, we aimed to identify analgesic and anti-ASs agents targeting LVGCCs from the well-known neuropharmacological Traditional Chinese medicine Ganoderma cochlear and determine their mechanisms of action. We conducted in vitro and ex vivo electrophysiological studies to assess LVGCCs inhibition by Ganoderma meroterpenoids and the mechanism of action of the selected candidate. Molecular docking analysis was used to explore the structure-activity relationships and modes of action of these meroterpenoids. Furthermore, the antinociceptive and anti-ASs efficacies of the chosen compound were evaluated using four distinct mouse pain models and γ-butyrolactone-induced mice with ASs. Ganomycin C (GMC) was the most potent inhibitor among the eight meroterpenoids, exhibiting five-fold higher selectivity for Ca_v3.1 and Ca_v3.2 over Ca_v3.3. GMC modulated LVGCCs in a distinct manner compared to Z944, an LVGCC inhibitor currently under clinical investigation. Additionally, the side chain features of GMC and its derivatives are crucial for their activity. By preferentially inhibiting LVGCCs, GMC suppressed the evoked excitability of isolated mouse nociceptive primary afferent neurons and burst spikes highly associated with ASs in neurons from the cortico-thalamo-cortical circuits without affecting tonic firing. In three of the pain models, GMC demonstrated robust antinociception comparable to that of Z944 and outperformed ethosuximide, a standard-of-care drug for ASs, in mitigating ASs. Our findings provide insights into GMC as an analgesic and anti-AS agent targeting LVGCCs, specifically Ca_v3.1 and Ca_v3.2.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731232","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":"Synergistic Strategies for Lung Cancer Immunotherapy: Combining Phytochemicals and Immune-Checkpoint Inhibitors.","authors":"Quan Gao, Hao Wu, Zhengjun Li, Zijing Yang, Lin Li, Xueni Sun, Qibiao Wu, Xinbing Sui","doi":"10.1002/ptr.8482","DOIUrl":"https://doi.org/10.1002/ptr.8482","url":null,"abstract":"<p><p>Lung cancer remains one of the most widespread and deadliest malignant tumors globally, with a particularly high mortality rate among all cancers. Recently, immunotherapy, particularly immune checkpoint inhibitors (ICIs), has emerged as a crucial treatment strategy for lung cancer patients, following surgical intervention, radiotherapy, chemotherapy, and targeted drug therapies. However, the therapeutic limitations are caused owing to their low response rate and undesirable side effects such as immune-related pneumonitis. Therefore, developing new strategies to improve the efficacy of ICIs while minimizing immune-related adverse events will be crucial for cancer immunotherapy. The tumor immune microenvironment plays a significant role in the success of lung cancer immunotherapy, and the immunosuppressive characteristics of the immune microenvironment are one of the major obstacles to the poor immunotherapeutic effect. Phytochemicals, naturally occurring compounds in plants, have shown promise in enhancing cancer immunotherapy by remodeling the immunosuppressive microenvironment, offering the potential to increase the efficacy of ICIs. Therefore, this review summarizes the associated mechanisms of phytochemicals remodeling the immunosuppressive microenvironment in lung cancer. Additionally, the review will focus on the synergistic effects of combining phytochemicals with ICIs, aiming to improve anticancer efficacy and reduce side effects, which may hopefully offer novel strategies to overcome current limitations in immunotherapy.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693021","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":"Effects of Dietary Polyphenols on Vasculogenic Erectile Dysfunction: A Systematic Review of Pre-Clinical Studies.","authors":"Rafaela Geraldo, Catarina Castro, Elisabete Pinto, Marta W Vasconcelos, Delminda Neves","doi":"10.1002/ptr.8477","DOIUrl":"https://doi.org/10.1002/ptr.8477","url":null,"abstract":"<p><p>Erectile dysfunction (ED) is a medical condition characterized by the inability to achieve or maintain a satisfactory erection, primarily treated with oral phosphodiesterase type 5 inhibitors. Treatment effectiveness is diminished in severe vasculogenic ED, particularly in patients with diabetes mellitus, highlighting the need for exploring alternative/complementary interventions. Among them, dietary phenolic compounds are known for their antioxidant and anti-inflammatory properties. This systematic review focuses on catechin (EGCG), quercetin, resveratrol, and curcumin and their influence on the pathophysiology of ED. Following PRISMA 2020 guidelines (PROSPERO registration number CRD42023402016) searches across PubMed, Scopus, and Web of Science until October 2024 were conducted using relevant keywords. Inclusion criteria required original articles in English, while in silico studies, review articles, editorials, and original studies lacking essential polyphenol administration information were excluded. After an initial search that located 409, 445, and 285 publications in each database respectively, rigorous screening resulted in 26 publications comprising animal, ex vivo, and in vitro studies. Their quality was assessed using GRADE and SYRCLE ROB tools, revealing an overall \"medium-high\" or \"high quality.\" These polyphenols consistently demonstrated improvements in erectile function, encompassing behavioral, functional, molecular, and hormonal aspects. However, limitations were identified, such as the predominant reliance on animal models and in vitro trials, which may not precisely reflect human physiological responses. Further clinical investigations are needed to ascertain data translational potential, standardize dosages, and establish safe and effective prescription recommendations. Prioritizing clinical trials is essential for validating the widespread applicability and efficacy of polyphenols in managing ED.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649909","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":"Pueraria Radix and Its Major Constituents Against Metabolic Diseases: Pharmacological Mechanisms and Potential Applications.","authors":"Yicheng Lei, Ruiyuan Zhang, Yan Li, Huiwen Pang, Qiang Fu, Chen Chen, Fang Liu","doi":"10.1002/ptr.8464","DOIUrl":"https://doi.org/10.1002/ptr.8464","url":null,"abstract":"<p><p>Metabolic diseases (MD), a series of chronic disorders, severely decrease the quality of life for patients but also cause a heavy economic burden. The ancient Chinese herb Pueraria Radix (PR) plays an important role in curing MD. Up to now, the bioactive compounds found in PR demonstrate effective actions in treating various metabolic disorders. This paper systematically summarizes the recent research advances on the pharmacological activities of PR and its constituents, explains the underlying mechanisms of preventing and treating MD. Besides, phytochemicals, drug delivery systems, clinical application, and safety of PR have been researched, hoping to provide valuable information for the future application, development, and improvement of PR as well as MD treatment. The information about PR was collected from various sources including classic books about Chinese herbal medicine and scientific databases including Web of Science, PubMed, ScienceDirect, Springer, ACS, SCOPUS, CNKI, Google Scholar, X-MOL, and WANFANG using keywords given and terms like pharmacological and phytochemical details of this plant. The chemical constituents isolated and identified from PR, such as isoflavones including puerarin, formononetin, daidzin, daidzein, genistein, and so forth, polysaccharides, alkaloids, starch, and other components have been proved to have the effect of anti-diabetic, anti-obesity, anti-atherosclerotic, anti-osteoporotic, anti-hypertensive, anti-hyperlipidemia, and anti-nonalcoholic fatty liver disease (NAFLD) through PI3K/Akt, Nrf2/HO-1, LOX-1/ROS/Akt/eNOS, ERK1/2-Nrf2, GLP-1R, Caspase, MAPK, NF-κB, and other anti-inflammatory and anti-oxidant signaling pathways. Also, the active contents of PR have been designed as drug delivery systems to improve the therapeutic effects of MD. It provides a preclinical basis for the efficacy of PR as an effective therapeutic agent for the prevention and treatment of MD. Even so, further studies are still needed to enhance bioavailability and expand clinical application.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658184","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":"Poncirus trifoliata Extract and Its Active Coumarins Alleviate Dexamethasone-Induced Skeletal Muscle Atrophy by Regulating Protein Synthesis, Mitochondrial Biogenesis, and Gut Microbiota.","authors":"Hyejin Ko, Tam Thi Le, Ngoc Bao Nguyen, Suk Woo Kang, Kwang Hyun Cha, Nain Yang, Sang Hoon Jung, Myungsuk Kim","doi":"10.1002/ptr.8478","DOIUrl":"https://doi.org/10.1002/ptr.8478","url":null,"abstract":"<p><p>Sarcopenia, an age-related decline in skeletal muscle mass and function, contributes to frailty and increased morbidity in the elderly. This necessitates the development of effective interventions to combat muscle atrophy. This study investigated the therapeutic potential of Poncirus trifoliata ethanol extract (PT) and its coumarin derivatives against dexamethasone (DEX)-induced muscle atrophy. We employed in vitro and in vivo models of DEX-induced muscle atrophy. C2C12 myotubes were used for mechanistic studies. C57BL/6J mice received DEX injections and oral PT supplementation (50 mg/kg/day) to evaluate effects on muscle mass, function, gene expression, and gut microbiota composition. In vitro, PT enhanced protein synthesis, mitochondrial biogenesis, and myogenic differentiation in DEX-exposed myotubes, with auraptene, ponciol, and triphasiol identified as key bioactive coumarins. In vivo, PT significantly attenuated DEX-induced muscle atrophy, increasing tibialis anterior muscle mass by 36% (p < 0.01), grip strength by 31% (p < 0.001), and maximal running speed by 18% (p < 0.05). Mechanistically, PT upregulated genes associated with muscle function and mitochondrial health. Furthermore, PT modulated gut microbiota composition, notably increasing Phocaeicola vulgatus abundance 2.2-fold, which correlated with improved muscle performance (R = 0.58, p < 0.01). These findings suggest that PT and its coumarin derivatives, particularly auraptene, ponciol, and triphasiol, hold promise as therapeutic agents for combating muscle atrophy. The observed benefits may be mediated through enhanced protein synthesis, improved mitochondrial function, and modulation of the gut-muscle axis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634154","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}