Hamidreza Majidiani, Maryam Musavi, Amir Abbas Momtazi-Borojeni
{"title":"New Roles of Artemisinins in Atherosclerosis Progression.","authors":"Hamidreza Majidiani, Maryam Musavi, Amir Abbas Momtazi-Borojeni","doi":"10.1002/ptr.8483","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-08","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":"Xanthohumol Regulates Mitophagy in Osteosarcoma Cells via AMPK-ULK1-FUNDC1 Signaling Pathway.","authors":"Qiaofeng Ge, Zhiliang Yan, Qian Tian, Jiyan Zhang, Jia Li, Fang Cai, Long Zhang, Yonggang Zhu","doi":"10.1002/ptr.8468","DOIUrl":"https://doi.org/10.1002/ptr.8468","url":null,"abstract":"<p><p>Osteosarcoma (OS) is the most common primary bone malignancy. The therapeutic efficacy for OS patients has remained stagnant in recent decades. Xanthohumol (XN), a flavonoid naturally found in hops, has demonstrated significant anticancer properties in lung and breast cancer. However, its effect on OS and the underlying molecular mechanisms remains uncertain. Therefore, the purpose of this study is to explore the relationship between XN and OS. Firstly, we assessed the impact of XN on OS cell proliferation and migration using CCK-8, wound-healing, transwell, and clonogenicity assays. Subsequently, we examined the effect of XN on mitophagy in OS cells through flow cytometry, immunofluorescence, transmission electron microscopy, and western blot analysis. Finally, we constructed siRNA targeting AMPK to validate the pathway. In vitro, we demonstrated that XN inhibited the proliferation and migration of OS cells in a concentration- and time-dependent manner. Furthermore, XN induced mitochondrial damage in OS cells and increased reactive oxygen species (ROS) levels. RNA-seq analysis suggested a potential mitophagy pathway, which we confirmed experimentally by showing that XN reduced ATP levels, altered mitochondrial membrane potential, and increased the expression of Atg5, Beclin-1, and LC3 proteins. Interestingly, the mitophagy inhibitor Mdivi-1 reversed the damage caused by XN to OS cells. Furthermore, we found that XN induced mitophagy and exerted anti-OS effects through the activation of the AMPK-ULK1-FUNDC1 signaling pathway, which was effectively reversed after AMPK knockdown. In vivo, we demonstrated the therapeutic potential of XN using a subcutaneous OS nude mouse model without any organ toxicity. XN emerges as a promising pharmaceutical agent for targeting OS.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796140","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":"Jatrorrhizine alleviates cytokine storm secondary lung injury via regulating CD39-dominant purinergic braking and downstream NLRP3 inflammasome.","authors":"Yuejia Lan, Huan Wang, Lijia Jing, Rui Li, Jiayi Sun, Xianli Meng, Jiasi Wu","doi":"10.1002/ptr.8062","DOIUrl":"https://doi.org/10.1002/ptr.8062","url":null,"abstract":"<p><p>Cytokine storm secondary lung injury (CSSLI) is a form of acute lung injury (ALI) comparable to that caused by sepsis for which there are no effective therapeutic strategies. Coptis chinensis Franch. and Scutellaria baicalensis Georgi. are two botanical medicines that exhibit anti-inflammatory properties. This study aimed to investigate the underlying therapeutic mechanism of the combination (CCSB) treatment in mice with ALI. A high dosage of lipopolysaccharide (LPS) was administered intraperitoneally to C57BL/6 mice to establish an ALI model. The AMP-Glo™ assay was applied to screen for the component with the most potent CD39-promoting enzyme activity from CCSB constituents migrating to the bloodstream. The PMA-differentiated THP-1 and RAW264.7 macrophage cell lines were stimulated with LPS and adenosine triphosphate, followed by treatment with Jatrorrhizine (JH). The administration of CCSB demonstrated a notable improvement in lung injury through the modulation of the CD39-P2X7 purinergic pathway and subsequent regulation of the NLRP3 inflammasome. The restrained CD39 and A2b were reversed by JH, leading to the suppression of the P2X7-NLRP3 signaling pathway. In addition, the utilization of a CD39 inhibitor (POM-1) attenuated the inhibitory effect of JH on the NLRP3 signaling pathway. CCSB successfully rescued CSSLI, along with its small-molecule component JH, which demonstrated the ability to inhibit the NLRP3 signaling pathway and pyroptosis, at least partially through regulating the CD39 enzyme.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796065","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}
Ting Ye, Yang Ge, Jing Zhang, Hang Gao, Peng-Cheng Zhang, Rui Shen, Can Peng, Bin Liu, Hang Song
{"title":"Inhibition of Hepatoblastoma by Ganoderma Lucidum Polysaccharide via the Induction of HDAC4-p16-RB Axis-Mediated Cellular Senescence.","authors":"Ting Ye, Yang Ge, Jing Zhang, Hang Gao, Peng-Cheng Zhang, Rui Shen, Can Peng, Bin Liu, Hang Song","doi":"10.1002/ptr.8493","DOIUrl":"https://doi.org/10.1002/ptr.8493","url":null,"abstract":"<p><p>Hepatoblastoma (HB), the most common primary malignant liver tumor in children, is characterized by high metastatic potential and poor prognosis. Ganoderma lucidum polysaccharide (GLP), the main bioactive compound of Ganoderma lucidum, has not been fully investigated for its therapeutic effects on HB. This study aimed to evaluate the anti-tumor effects of GLP on HB cells and explore the underlying biological mechanisms. GLP was chemically characterized using ultraviolet-visible spectroscopy, monosaccharide composition analysis, Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy. The effects of GLP on the malignant phenotype of HB cells were assessed using CCK-8, EdU, Transwell assays, and other standard in vitro techniques. Mechanistic investigations included proteomics, western blotting, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays. In vivo anti-HB effects of GLP were evaluated through animal models. Crude GLP, exhibiting anti-tumor activity, was prepared through water extraction, alcohol precipitation, and column chromatography. In vitro, GLP inhibited proliferation, invasion, and induced apoptosis in HuH6 and HepG2 cells. In vivo, GLP suppressed tumor growth in a dose-dependent manner. Mechanistically, GLP induced cellular senescence by downregulating histone deacetylase 4 (HDAC4) expression and enhancing p16 histone acetylation, which activated the p16-retinoblastoma (p16-RB) pathway and suppressed the malignant phenotype of HB cells. Furthermore, overexpression of HDAC4 reversed the senescence-inducing effects of GLP. GLP inhibits HB progression by promoting cellular senescence via the HDAC4-p16-RB axis. These findings establish a mechanistic link between GLP's anti-tumor activity and cellular senescence, providing new insights for its potential clinical application.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796064","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":"Chrysophanol Attenuates Cardiac Fibrosis and Arrhythmia by Suppressing the Endoplasmic Reticulum Stress/Pyroptosis Axis and Inflammation.","authors":"Chengyin Liu, Shuang Qiu, Xiaoqiong Liu, Rui Huang, Zhao Fang","doi":"10.1002/ptr.8476","DOIUrl":"https://doi.org/10.1002/ptr.8476","url":null,"abstract":"<p><p>Chrysophanol (CHR), one of the principal bioactive compounds extracted from the rhizome of Rheum palmatum L., is known for its anti-inflammatory, antioxidative, anti-cancer, and cardioprotective effects. However, the effect of CHR on cardiac fibrosis remains elusive. In this study, mice were administered isoproterenol (ISO) to induce cardiac fibrosis in vivo, and cardiac fibroblasts were pretreated with transforming growth factor-β1 (TGF-β1) to induce the transformation of fibroblasts into myofibroblasts in vitro. Western blot and reverse transcription-quantitative polymerase chain reaction analyses were performed to evaluate the endoplasmic reticulum (ER) stress and pyroptosis. Immunohistochemistry staining and ELISA analyses were used to detect the inflammation level. In vivo electrophysiological studies were conducted to assess arrhythmia susceptibility. Our findings revealed that CHR treatment ameliorated cardiac dysfunction and fibrosis in ISO-challenged mice. Moreover, CHR reduced susceptibility to ventricular fibrillation by reducing ventricular electrical remodeling and increasing the expression of gap junction proteins and ion channels. Additionally, CHR inhibited the TGF-β1-stimulated transformation of cardiac fibroblasts into myofibroblasts in vitro. CHR inhibited ER stress, pyroptosis, and inflammation in vivo and in vitro. Furthermore, tunicamycin (TM)-induced activation of ER stress abolished the protective effects of CHR. CHR treatment attenuates cardiac fibrosis and arrhythmia by suppressing the ER stress/pyroptosis axis and inflammation.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788766","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}
Khadra Afaf Bendrihem, Aicha Mouane, Manel Azzi, Mohamed Aimene Mihoubi, Maria Atanassova, Barbara Sawicka, Wafa Zahnit, Mohammed Messaoudi
{"title":"The Role of Medicinal Plants in Modulating Epigenetic Mechanisms: Implications for Cancer Prevention and Therapy.","authors":"Khadra Afaf Bendrihem, Aicha Mouane, Manel Azzi, Mohamed Aimene Mihoubi, Maria Atanassova, Barbara Sawicka, Wafa Zahnit, Mohammed Messaoudi","doi":"10.1002/ptr.8481","DOIUrl":"https://doi.org/10.1002/ptr.8481","url":null,"abstract":"<p><p>Cancer remains a significant global health challenge, with its progression driven by both genetic mutations and reversible epigenetic modifications. This review highlights the potential of phytochemicals to modulate epigenetic mechanisms for cancer prevention and treatment. Natural compounds such as quercetin, EGCG, genistein, and β-elemene interact with key processes such as DNA methylation, histone modifications, and non-coding RNA regulation. These mechanisms enable the reactivation of tumor suppressor genes, increased sensitivity to conventional therapy and mitigation of drug resistance. For instance, EGCG improves the efficacy of cisplatin by altering DNA methylation patterns, while genistein influences breast cancer progression through HER2 pathway regulation. However, challenges such as low bioavailability, variability in compound composition, and the need for robust clinical validation remain. Further high-quality clinical trials are required to confirm the efficacy and safety of these compounds in cancer prevention and therapy.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780934","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":"Unlocking the Therapeutic Potential of Autophagy Modulation by Natural Products in Tackling Non-Alcoholic Fatty Liver Disease.","authors":"Farshad Niazpour, Reza Meshkani","doi":"10.1002/ptr.8463","DOIUrl":"https://doi.org/10.1002/ptr.8463","url":null,"abstract":"<p><p>It is widely recognized that there is currently no established treatment for individuals with Non-alcoholic Fatty Liver Disease (NAFLD). In recent years, there has been a surge of interest in natural products derived from plants, driven by their minimal toxicity and notable efficacy. It was reported that natural products could ameliorate NAFLD via various mechanisms. On the other hand, autophagy has been suggested to be involved in the pathogenesis of NAFLD. The aim of this review is to understand whether the beneficial effects of natural products on NAFLD are mediated by affecting autophagy pathways. In this review, we have compiled data elucidating how these natural products exhibit the potential to improve NAFLD by modulating core autophagic pathways. Specifically, we demonstrate that these natural products, including resveratrol, berberine, curcumin, quercetin, punicalagin, epigallocatechin-3-gallate, apigenin, and many others, regulate autophagy through key signaling pathways, such as AMPK/SIRT1/mTOR. Interestingly, these compounds might activate or inhibit autophagy, depending on the context. We explore how autophagy activation promotes the degradation of lipid droplets and alleviates liver injury, while autophagy inhibition contributes to reducing inflammation, apoptosis, and pyroptosis, and also resulting in improved NAFLD outcomes. Taken together, these findings suggest that targeting autophagy with natural products presents a promising mechanism for preventing and treating NAFLD.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780939","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 Progress of Flavonoids in Spinal Cord Injury: Therapeutic Mechanisms and Drug Delivery Strategies.","authors":"Shizhe Li, Shutao Gao, Yukun Hu, Jingsheng Feng, Weibin Sheng","doi":"10.1002/ptr.8488","DOIUrl":"https://doi.org/10.1002/ptr.8488","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a serious neurological disease with an extremely high disability rate. Most patients show a loss of motor and sensory functions below the level of injury. Current treatment protocols are based on early surgical decompression and pharmacotherapy. However, the efficacy of these interventions is suboptimal. Due to its complex pathophysiological mechanisms and the difficulty of central nervous system (CNS) regeneration, exploring effective therapeutic interventions remains daunting. Flavonoids are secondary metabolites unique to plants that have attracted attention in recent years for their potential efficacy and are now commonly used in the treatment of inflammation, tumors, and other diseases. For SCI, related studies are still exploring; some compounds, such as quercetin, fisetin, and hesperetin, have shown good anti-inflammatory and anti-apoptotic properties, which help to restore the function of the injured spinal cord. However, flavonoids exhibit certain disadvantages, including poor solubility, low bioavailability, and the inability to achieve long-term controlled release. Some studies have proposed potential drug delivery strategies-including nanoparticles, hydrogels, and collagen scaffolds-to enhance efficacy. In this paper, we summarize the therapeutic mechanisms and drug delivery strategies of flavonoids in SCI by searching the relevant literature in recent years and propose future research directions to provide new ideas for the multimodal treatment of SCI.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764610","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":"Gut Microbiota and Bile Acid Metabolism in the Mechanism of Ginsenoside Re Against Nonalcoholic Fatty Liver Disease.","authors":"Yanfang Zheng, Jiaying Chen, Ying Zhang, Huaying Guan, Shan Deng, Dennis Chang, Yitao Wang, JinJian Lu, Xian Zhou, Qin Xie, Jianyuan Song, Mingqing Huang","doi":"10.1002/ptr.8474","DOIUrl":"https://doi.org/10.1002/ptr.8474","url":null,"abstract":"<p><p>Gut microbiota and bile acid metabolism play crucial roles in the progression of nonalcoholic fatty liver disease (NAFLD). Early evidence demonstrates that Ginsenoside Re (Re) possesses pharmacological effects on NAFLD, but its mechanisms of action are not well understood. This study aimed to investigate the hepatic protective effects of Re in NAFLD and elucidate relevant mechanisms. The effects of Re treatments (10, 20, or 40 mg/kg) against high-fat diet-induced NAFLD were initially tested on male C57BL/6 mice. Then, a separate mouse group received Re with or without antibiotics to confirm the regulatory role of microbiota in the effect of Re. Finally, another group of mice received fecal microbiota transplantation (FMT) from the initial experiment of NAFLD mice to further investigate the mechanistic role of gut microbiota. Re significantly improved liver function by reducing hepatic lipid accumulation, injury and hepatocyte steatosis, and inflammation. The liver protection was mediated by the regulation of gut microbiota as evidenced by restored intestinal barrier integrity, normalized Firmicutes/Bacteroidota ratio, enhanced abundances of Adlercreutzia equolifaciens, and reduced Faecalibaculum rodentium. Following that, Re reduced total and primary bile acids and downregulated bile acid synthesis genes and proteins such as farnesoid X receptor and cytochrome P450 family 7 subfamily A member 1. The co-administration of antibiotic cocktail counteracted the effect of Re against NAFLD. Further, the results obtained from the FMT animal study confirmed that Re's liver protective effects were at least partly driven by the regulation of gut microbiota. Re modulated bile salt hydrolase-related microbial genera to alter bile acid synthesis pathways, thereby inhibiting NAFLD progression.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764597","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}
Ressin Varghese, Arnold Emerson, Brigitte Vannier, C George Priya Doss, Rossyda Priyadharshini, Thomas Efferth, Siva Ramamoorthy
{"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}