Phytotherapy Research最新文献

{"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":"Coffee peel polyphenols ameliorate nonalcoholic fatty liver disease by modulating cannabinoid receptor type-1-ceramide axis.","authors":"Ze-Kai Fan, Yan-Fang Chen, Wei-Wei Han, Xiao-Fei Guo, Duo Li","doi":"10.1002/ptr.8078","DOIUrl":"https://doi.org/10.1002/ptr.8078","url":null,"abstract":"<p><p>Cannabinoid receptor type-1 (CB1) signaling plays an important part in maintenance of energy homeostasis, and CB1 blockers have shown promise in the treatment of obesity-related metabolic dysfunction. Coffee peel contains abundant phytochemicals and possesses hypolipidemic and anti-inflammatory activities. The present study aimed to elucidate the preventive effect of coffee peel polyphenols (CPPs) on nonalcoholic fatty liver disease (NAFLD) from the perspective of CB1 signaling. Male C57BL/6J mice were fed a high-fat and high-cholesterol diet and CPPs (200/400 mg/kg/day) for 8 weeks. Serum biochemical indexes and liver pathological analysis were used to evaluate the effect of CPPs on NAFLD. Untargeted/targeted lipidomics analyses were used to evaluate the levels of endocannabinoid ligands and ceramides in serum and liver. The expression levels of proteins were detected by using Western blotting analysis. Administration of CPPs significantly improved hepatic steatosis, insulin resistance and biomarkers of liver function. Meanwhile, CPPs administration indicated reductions in endocannabinoid ligands, including anandamide and 2-arachidonoylglycerol levels, associated with blockade of CB1 overexpression. Blockage of CB1 signaling depleted hepatic C16:0- and C18:0-ceramide concentrations by enhancing ceramide metabolism. The reductions in hepatic ceramide concentrations contributed to down-regulating sterol regulatory element-binding protein-1c and up-regulating proliferator activated receptor alpha, leading to decrease de novo lipogenesis and increase fatty acid β-oxidation in the liver, respectively. This study demonstrated a novel mechanism that CPPs could ameliorate NAFLD through modulating CB1-ceramide axis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710946","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":"Emodin Promotes Peripheral Nerve Repair by Modulating Inflammasome Activation Through Autophagy via the EGFR/PI3K/AKT/mTOR Pathway.","authors":"Zhengyang Long, Yixun Huang, Tao Lin, Shanying Xiao, Kaiye Chen, Jiahao Ying, Ke Wang, Zhe Zhang, Long Wu","doi":"10.1002/ptr.8469","DOIUrl":"https://doi.org/10.1002/ptr.8469","url":null,"abstract":"<p><p>To investigate the potential of emodin in promoting nerve regeneration following PNI by targeting macrophage polarization, NLRP3 inflammasome activation, autophagy, and the EGFR/PI3K/Akt/mTOR pathway. A cohort of 78 male Sprague-Dawley rats was used to develop models of sciatic nerve damage, with an additional 18 rats in the sham surgery group. The rats were randomly assigned to eight groups: Sham, Control, PNI + Emodin (20 mg/kg), PNI + Emodin (80 mg/kg), PNI + MCC950 (10 mg/kg), PNI + Rapamycin (2 mg/kg), PNI + Emodin (80 mg/kg) + 3-MA (15 mg/kg), and PNI + Emodin (80 mg/kg) + NSC 228155 (5 mg/kg). Emodin was administered intragastrical daily, while the inhibitors or agonist were administered via intraperitoneal injection, as per the respective dosages and schedules. The treatment period included assessments of nerve regeneration and functional recovery, such as histological staining, immunofluorescence for cellular markers, TEM for ultrastructural changes, SFI for functional recovery, and western blot analysis for autophagy and inflammatory proteins. IF and TEM images showed that emodin enhanced axonal and myelin regeneration. Histological analysis revealed emodin reduced muscular atrophy and collagen deposition. Emodin decreased pro-inflammatory macrophage markers (CD68) while increasing M2 markers (CD206), inhibited the NLRP3 inflammasome, and reduced IL-1β and caspase-1. It activated autophagy in Schwann cells, with increased LC3-II levels. Network pharmacology and molecular docking identified EGFR in the PI3K/AKT/mTOR pathway as a key target, with emodin inhibiting EGFR activation. This study reveals that emodin promotes early nerve recovery by enhancing functional outcomes, axonal remyelination, and reducing muscle atrophy. It boosts autophagy in Schwann cells, inhibits NLRP3 inflammasome activation, and promotes M2 macrophage polarization. These effects are closely related to the EGFR/PI3K/AKT/mTOR pathway.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710947","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":"Ferulic Acid Alleviates Traumatic Brain Injury and Gastrointestinal Disorders by Promoting Ghrelin to Regulate the Microbiota-Brain-Gut Axis Inflammation and Pyroptosis.","authors":"Yawen Cai, Xiaohang Zhang, Qiantao Zhang, Li Zhou, Yunke Huang, Haotian Qian, Le Zhang, Chendong Xu, Liang Xia, Li Chen, Ping Ren, Xi Huang","doi":"10.1002/ptr.8450","DOIUrl":"https://doi.org/10.1002/ptr.8450","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a severe condition with a high mortality rate, affecting multiple organs, including the gastrointestinal (GI) tract. Ghrelin is a brain-gut peptide that regulates the microbiota-brain-gut axis, facilitating communication between the GI tract and the central nervous system. This study aimed to investigate the role of ferulic acid (FA) in regulating Ghrelin to improve TBI and GI disorders (GID) induced by controlled cortical impact (CCI). This study used CCI as the in vivo TBI model and scratch-induced injury of primary astrocytes as the in vitro TBI model. The role and mechanism of FA modulation of Ghrelin in ameliorating TBI and GID were explored using multi-omics and network pharmacology analyses. In vivo, results revealed that FA is the main active component of the Guanxin II compound and mimics its function. Significant improvement in GI hypomotility and brain injury was observed in the FA group compared to the CCI group. Concurrently, FA ameliorated intestinal barrier impairment triggered by CCI-induced reduction in the expression of Ghrelin and reduces the inflammatory response. Furthermore, 16S rRNA results indicated that CCI-induced TBI worsened gut microflora imbalance via the brain-gut axis, while gut dysbiosis aggravated brain injury. FA improved the dysbiosis of Bacteroidetes and Odoribacter mainly by targeting the Ghrelin-mediated inflammatory response. RNA-seq and network pharmacology analyses revealed that FA mainly affects inflammation-mediated pyroptosis pathways in the brain-gut axis. Additionally, experimental evidence demonstrated that FA reversed CCI-induced pyroptosis in rats and scratch injury-induced pyroptosis in astrocytes by promoting the binding of Ghrelin to GHSR, which suppressed the TLR4/NF-κB/NLRP3 pathway. Conclusively, FA could alleviate TBI and GID by promoting Ghrelin to regulate the microbiota-brain-gut axis inflammation via the Ghrelin/TLR4/NLRP3 pathway.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review of Biologically Active Natural Products on Human Papillomavirus (HPV) at a Glance.","authors":"Mahsa Sadat Hosseini, Amirreza Sadeqi, Zinat Heidari, Motahareh Boozari","doi":"10.1002/ptr.8444","DOIUrl":"https://doi.org/10.1002/ptr.8444","url":null,"abstract":"<p><p>Human papillomavirus (HPV) is widespread known as the sexually transmitted infection, which is responsible, for genital warts and certain types of cancer. Low-risks HPV types are responsible for genital warts. Genital warts can be treated through various medical and surgical methods. High-risks HPV types may cause dangerous cancers such as cervical cancer. The clinical approach in treatment of HPV-related cancers were different depending on the diseases stage ranging from surveillance and minor procedures for dysplasia to chemotherapy for more advanced cases. It is crucial to vaccinate adolescents against HPV to prevent infections from high risk strains. Researchers have explored natural products as potential solutions against viral infections with eight biologically active compounds. Including EGCG, curcumin, podophyllotoxin, resveratrol, pterostilbene, tanshinone IIA, indole-3-carbinol, and carrageenan. They are showing promising therapeutic effects in treating different stages of HPV-related diseases. Clinical trials have demonstrated the effectiveness of EGCG and podophyllotoxin in treating warts while other compounds, like curcumin, resveratrol, pterostilbene, indole-3-carbinol, and tanshinone IIA offer benefits in combating cervical cancer. In addition, carrageenan shows promising effects in HPV transmission prevention. It appears that compounds from nature may have an impact, on different phases of the HPV infection like genital warts treatment, disease transmission prevention, and healing-related cancers. These findings highlight the potential of natural products as valuable sources to combat HPV infection and related cancers. Further more extensive studies are necessary to discover the effective mechanism of these natural compounds as anti-HPV agents.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701280","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":"Protective Effect of Dietary Fiber on Blood Pressure and Vascular Dysfunction Through Regulation of Sympathetic Tone and Immune Response in Genetic Hypertension.","authors":"Cristina González-Correa, Javier Moleón, Sofía Miñano, Iñaki Robles-Vera, Néstor de la Visitación, Eduardo Guerra-Hernández, Marta Toral, Rosario Jiménez, Juan Duarte, Miguel Romero","doi":"10.1002/ptr.8484","DOIUrl":"https://doi.org/10.1002/ptr.8484","url":null,"abstract":"<p><p>The mechanisms underlying the antihypertensive effect of dietary fibers remain poorly understood. This study investigates whether dietary fiber supplementation can prevent cardiovascular damage and high blood pressure in a genetic model of neurogenic hypertension. Six-week-old male spontaneously hypertensive rats (SHR) and their respective normotensive control, Wistar Kyoto rats (WKY), were divided into four groups: Untreated WKY, untreated SHR, SHR treated with resistant starch (SHR + RS), and SHR treated with inulin-type fructans (SHR + ITF) for 12 weeks. Additionally, a faecal microbiota transplantation (FMT) experiment was conducted, transferring faecal content from treated SHR donors to recipient SHRs. A diet rich in RS fiber reduced vascular oxidative stress, inflammation, and high blood pressure. These protective effects were associated with a reshaped gut microbiota, leading to increased short-chain fatty acid production, reduced endotoxemia, decreased sympathetic activity, and a restored balance between Th17 and Treg lymphocytes in mesenteric lymph nodes and aorta. Elevated plasma levels of acetate and butyrate in the SHR + RS group correlated with increased expression of aortic GPR41, GRP43 and PPARδ. Conversely, ITF treatment failed to prevent hypertension or endothelial dysfunction in SHR. FMT from the SHR + RS group to recipient SHR partially replicated these beneficial effects. This study highlights the antihypertensive benefits of dietary insoluble RS fiber, which are attributed to enhanced short-chain fatty acids production in the gut. This leads to improved gut permeability, reduced sympathetic tone, and diminished vascular T-cell accumulation. Therefore, dietary interventions with RS fiber may offer promising therapeutic strategies for preventing hypertension.</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":"143693012","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}