Phytotherapy Research最新文献

{"title":"Multifaceted Therapeutic Impacts of Cucurbitacin B: Recent Evidences From Preclinical Studies.","authors":"Meenal Sahu, Tripti Paliwal, Smita Jain, Kanika Verma, Dipjyoti Chakraborty, Shivangi Jaiswal, Jaya Dwivedi, Swapnil Sharma","doi":"10.1002/ptr.8454","DOIUrl":"10.1002/ptr.8454","url":null,"abstract":"<p><p>The most prevalent and bioactive cucurbitacin is Cucurbitacin B (CuB, C₃₂H₄₆O₈), which is a tetracyclic triterpene chiefly present in the Cucurbitaceae family. CuB has a wide spectrum of pharmacological properties namely antioxidant, anticancer, hepatoprotective, anti-inflammatory, antiviral, hypoglycaemic, insecticidal, and neuroprotective properties, owing to its ability to regulate several signaling pathways, including the Janus kinase/signal transducer and activator of transcription-3 (JAK/STAT3), AMP-activated protein kinase (AMPK), nuclear factor (NF)-κB, nuclear factor erythroid 2-related factor-2/antioxidant responsive element (Nrf2/ARE), phosphoinositide 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK), Hippo-Yes-associated protein (YAP), focal adhesion kinase (FAK), cancerous inhibitor of protein phosphatase-2A/protein phosphatase-2A (CIP2A/PP2A), Wnt and Notch pathways. The present review highlights the medicinal attributes of Cucurbitacin B (CuB) with special emphasis on their signaling pathways to provide key evidence of its therapeutic utility in the near future.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1966-1995"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441663","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":"Macelignan Improves Functional Recovery After Spinal Cord Injury by Augmenting Autophagy via the AKT-mTOR-TFEB Signaling Pathway.","authors":"Yuxuan Zhu, Shu Yang, Shenkai Su, Yeheng Huang, Yuli Chen, Haibo Liang, Jiansen Miao, Zhouwei Wu, Xiang Li, Jian Xiao, Xiangyang Wang","doi":"10.1002/ptr.8473","DOIUrl":"10.1002/ptr.8473","url":null,"abstract":"<p><p>Spinal cord injury (SCI) presents considerable therapeutic challenges due to its complex pathophysiology, and effective treatments are currently lacking. Macelignan (Mace) has shown therapeutic effects in some neurological disorders, but its potential to enhance functional recovery in SCI and the underlying mechanisms are not well understood. This research endeavors to explore the therapeutic value of Mace in SCI and its underlying mechanism of action. A mouse model of SCI was established, and the mice were randomly divided into 13 groups: Sham, Sham + Mace, SCI, SCI + 25 mg/kg Mace, SCI + Mace, SCI + 75 mg/kg Mace, SCI + 100 mg/kg Mace, SCI + 3MA, SCI + Mace/3MA, SCI + Mace/Scramble shRNA, SCI + Mace/TFEB shRNA, SCI + SC79, and SCI + Mace/SC79. Histological examinations were conducted using hematoxylin and eosin (HE), Masson's trichrome, and Nissl staining techniques. Functional recovery post-injury was evaluated through footprint analysis and the Basso Mouse Scale (BMS). The levels of proteins associated with pyroptosis and autophagy were quantified using qPCR, protein immunoblotting, and immunofluorescence (IF). Network pharmacology techniques were applied to elucidate the signaling pathways modulated by Mace. Mace facilitated functional recovery following SCI by augmenting autophagy and diminishing pyroptosis, with these effects being partially counteracted by 3-Methyladenine (3MA). It was noted that Mace induced autophagy via inhibition of the AKT-mTOR signaling pathway, leading to an increase in TFEB expression. As an autophagy activator, Mace induces TFEB-mediated autophagy and inhibits pyroptosis, which supports functional recovery post-SCI, indicating its potential clinical relevance.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2091-2109"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586473","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":"The Effects of Polyphenols on Doxorubicin-Induced Nephrotoxicity by Modulating Inflammatory Cytokines, Apoptosis, Oxidative Stress, and Oxidative DNA Damage.","authors":"Lang Wang, Can Wei, Junfeng Jing, Mingmin Shao, Zhen Wang, Bo Wen, Mingming Lu, Zhenzhen Jia, Yanbin Zhang","doi":"10.1002/ptr.8470","DOIUrl":"10.1002/ptr.8470","url":null,"abstract":"<p><p>Doxorubicin (DOX) is an anthracyclic antibiotic with anti-neoplastic activity that has been found to be a highly effective and commonly used chemotherapeutic agent in the treatment of a variety of solid and hematologic malignancies. However, its effectiveness has been limited by the occurrence of dose-related renal, myocardial, and bone marrow toxicities. The clinical use of DOX is associated with nephrotic syndrome characterized by heavy proteinuria, hypoalbuminemia, and hyperlipidemia. DOX-induced changes in the renal tissue of rats include increased glomerular capillary permeability and tubular atrophy. Several lines of evidence suggest that reactive oxygen species and oxidative stress have been associated with DOX-induced renal damage. The mechanism of DOX-induced nephrotoxicity is believed to be mediated through free radical formation, iron-dependent oxidative damage of biological macromolecules, and membrane lipid peroxidation. Polyphenols are present in high concentration in fruits and vegetables. They have been shown to have potent antioxidant and cytoprotective effects in preventing endothelial apoptosis caused by oxidants. Treatment with polyphenols has been shown to prevent liver damage and suppress overexpression of inducible nitric oxide synthase, which is induced by various inflammatory stimuli. In addition, epidemiological studies have suggested that the intake of polyphenols may be associated with a reduced risk of DOX-induced nephrotoxicity by modulating inflammatory cytokines, apoptosis, oxidative stress, and oxidative DNA damage. Therefore, in the present review, we examined the influence of polyphenols on DOX-induced nephrotoxicity.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2147-2164"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649911","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":"Natural Compounds Exert Anti-Obesity Effects by Regulating Cytokines.","authors":"Yu Zhang, Guize Feng, Weidong Zhang, Xia Liu","doi":"10.1002/ptr.8508","DOIUrl":"https://doi.org/10.1002/ptr.8508","url":null,"abstract":"<p><p>Obesity, along with its associated health risks such as hypertension, hyperlipidemia, Type 2 diabetes, stroke, metabolic syndrome, asthma, and cancer, constitutes a significant global health burden, contributing substantially to morbidity and mortality. Cytokines, a group of secreted signaling proteins, are crucial in initiating, maintaining, and resolving immune and metabolic responses. Although cytokines have unique advantages in regulating immune and metabolic functions, their therapeutic application for obesity remains limited in clinical practice. Natural compounds, known for their structural diversity and low toxicity, have become a valuable resource for drug development. Many natural compounds have shown anti-obesity effects. This review comprehensively examines the mechanisms underlying obesity, with a specific focus on the roles of cytokines, such as inflammatory cytokines, adipokines, and growth factors. Additionally, it highlights the regulatory interactions between gut microbiota and cytokines in obesity. The review critically analyzes current anti-obesity pharmacological interventions and summarizes advanced methodologies for identifying potential natural compounds. Finally, it identifies promising natural compounds that modulate cytokine activity to prevent or treat obesity and assesses their potential as complementary or alternative therapies.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994135","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":"Identification of 5-Geranyloxy-7-Methoxy-Coumarin as Antiadipogenic Constituent of Peels From Citrus limon.","authors":"Franz Bucar, Lisa Raimann, Gabriele Schoiswohl, Alexander Kollau, Bernd Mayer, Astrid Schrammel","doi":"10.1002/ptr.8391","DOIUrl":"10.1002/ptr.8391","url":null,"abstract":"","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1879-1882"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391501","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":"Aurantio-Obtusin Regulates Gut Microbiota and Serum Metabolism to Alleviate High-Fat Diet-Induced Obesity-Associated Non-Alcoholic Fatty Liver Disease in Mice.","authors":"Zhaoyong Li, Yao Jin, Huashan Zhao, Yuyan Gu, Yaxin Zhang, Saibo Cheng, Lifang Zhang, Peikun He, Xiaoyu Liu, Yuhua Jia","doi":"10.1002/ptr.8459","DOIUrl":"10.1002/ptr.8459","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) is a progressive condition with limited effective treatments. This study investigated the therapeutic effects of Aurantio-obtusin (AO), a bioactive compound from Cassiae Semen, on obesity-associated NAFLD. An obesity-related NAFLD model was established in ApoE ^-/- mice fed a high-fat diet (HFD) for 24 weeks, with AO administered during the last 16 weeks. Mouse body weight, adipose tissue weights, liver weights, serum lipid levels, hepatic steatosis, inflammatory damage, and colonic tissue barrier integrity were evaluated. Gut microbial communities and serum metabolic profiles were analyzed using 16S rRNA sequencing and untargeted metabolomics. Hepatic lipid metabolism-related gene expression was assessed using molecular biology techniques. AO treatment significantly ameliorated HFD-induced adiposity, hyperlipidemia, and NAFLD symptoms. It preserved intestinal barrier integrity, modulated gut microbial composition by enriching beneficial taxa, and improved serum metabolic profiles. AO favorably adjusted hepatic lipid metabolism by upregulating PPARα and CPT1A while downregulating SREBP1, FASN, and SCD1. Correlation analysis revealed significant associations among gut microbial composition, serum metabolites, and disease indicators. AO's therapeutic benefits in NAFLD might be attributed to its ability to modulate gut microbial community composition and serum metabolic profile, enhance intestinal barrier function, and regulate hepatic lipid metabolism gene expression. AO presents a promising therapeutic agent for obesity-associated NAFLD, warranting further investigation into its potential clinical applications.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1946-1965"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426042","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":"Sinigrin Selectively Mitigates the Acute-Cardiac Inflammatory Response Through an AMPK-Dependent Mechanism.","authors":"Anjali Veeram, Rohan R Patekar, Sandip B Bharate, Sai Balaji Andugulapati, Ramakrishna Sistla","doi":"10.1002/ptr.8453","DOIUrl":"10.1002/ptr.8453","url":null,"abstract":"<p><p>Inflammatory cardiomyopathy is an inflammatory condition characterised by infiltrating inflammatory cells into the heart, which causes impaired myocardial function. Sinigrin (SNG) has been reported to possess antioxidant and anti-inflammatory properties. This study aimed to investigate the therapeutic benefit of SNG against endotoxin/Poly(I:C)-induced acute-cardiac inflammation using in vitro and in vivo models. Experimental procedure: THP-1, HCF and H9C2 cells were employed as an in vitro model, while lipopolysaccharide (LPS)/Poly(I:C)-induced cardiac inflammation model served as an in vivo to examine the anti-inflammatory potential of SNG using molecular biology techniques, cardiac function and histological assessments. The network pharmacological approach revealed that SNG could target the myocarditis-responsible genes. mRNA/protein expression studies showed that SNG treatment significantly mitigated the LPS + Poly(I:C)-induced expression of pro-inflammatory and myocarditis-responsive genes. Further analysis revealed that SNG treatment significantly reduced the LPS + Poly(I:C)-induced elevation of neutrophil, lymphocyte count, AST, ALT, LDH and CK-MB levels; infiltration of inflammatory cells, cardiomyocyte degeneration, cardiac troponin and macrophage markers, on the other hand, improved the platelet levels. Cardiac functional parameters by Langendorff indicated that SNG potentially ameliorated the LPS + Poly(I:C)-induced elevation of LVP and other parameters and improved cardiac functions. Molecular docking studies demonstrated that sinigrin forms a H-bond with Asn-111 (significant interaction) and binds to the activator site of AMPK with a docking score of -8.88 kcal/mol. The current study reveals that sinigrin exerts potent anti-inflammatory and antioxidant activities by modulating AMPK signalling. These findings support sinigrin's potential as a promising option for treating acute myocardial inflammation and open avenues for translational research.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2017-2037"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503329","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":"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":"2291-2311"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","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":"Exploring the Therapeutic Potential and Underlying Mechanism of Bergapten in Renal Fibrosis: Network Pharmacology, Molecular Docking, and Experimental Validation.","authors":"Shobhit Gairola, Montu Saini, Archana Bhatta, Ravinder K Kaundal","doi":"10.1002/ptr.8460","DOIUrl":"10.1002/ptr.8460","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is characterized by progressive interstitial fibrosis, contributing to high global mortality due to limited treatment options. Contemporary findings highlight the potential of natural compounds for CKD treatment. Bergapten (BGT), a bioactive furocoumarin, is recognized for its antioxidant and anti-inflammatory properties but remains unexplored as an antifibrotic agent. The potential targets of BGT were identified using network pharmacology and in silico approaches. The antifibrotic effects of BGT were evaluated in transforming growth factor (TGF)-β1-induced normal rat kidney fibroblast (NRK-49F) cells. For in vivo validation, CKD was induced in mice using unilateral ureteral obstruction (UUO). Immunocytochemistry, histopathological analysis, and immunoblotting were conducted to assess the effects of BGT on fibroblast activation, renal microstructural changes, and expression of profibrotic markers. Network pharmacology analysis revealed 119 BGT-target genes involved in renal fibrosis, including those in the TGF-β1 signaling pathway. Molecular docking confirmed the interaction of BGT with TGF-β receptor 1 (TGFR1). In vitro studies demonstrated that BGT (30 μM) inhibited TGF-β1-induced fibrotic response in NRK-49F cells by inhibiting TGF-β1/Smad signaling. In vivo, oral administration of BGT (20 mg/kg) improved kidney function and alleviated histological damage, and pathological collagen deposition while mitigating renal inflammation. BGT suppressed the TGF-β1/Smad signaling pathway, reduced the expression of extracellular matrix (ECM) proteins, and mitigated oxidative stress by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme-oxygenase-I (HO-I) signaling pathway. This study demonstrated the therapeutic potential of BGT in alleviating renal fibrosis in experimental models of CKD. The observed effects were attributed to the inhibition of TGF-β1/Smad signaling and activation of the Nrf2 pathway.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2131-2146"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634108","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":"Adverse Reactions to Ginkgo biloba Medicinal Products Released in European Countries.","authors":"Ilaria Ammendolia, Everaldo Attard, Carmen Mannucci, Emanuela Esposito, Gioacchino Calapai, Mariaconcetta Currò, Paola Midiri, Tamara Attard, Luigi Cardia, Fabrizio Calapai","doi":"10.1002/ptr.8475","DOIUrl":"10.1002/ptr.8475","url":null,"abstract":"","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2197-2201"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649908","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}