Phytotherapy Research最新文献

{"title":"Ginsenoside Rg1, a Natural Lysosomal Enhancer, Alleviates Parkinson's Disease Pathology via Cathepsin D-Dependent Regulation of α-Synuclein Homeostasis.","authors":"Ya-Nan Fei, Ming-Yang Hao, Jia-Qiang Liu, Yin-Song Dong, Hui-Ning Zou, Xiao-Xi Guo, Su An, Jun Sang, Tian-Rui Xu","doi":"10.1002/ptr.70392","DOIUrl":"10.1002/ptr.70392","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron loss and α-synuclein (α-syn) aggregation, often linked to lysosomal dysfunction. Cathepsin D (CTSD), a lysosomal hydrolase essential for α-syn clearance, becomes functionally impaired when its maturation is disrupted, exacerbating proteostatic stress. This study investigated whether ginsenoside Rg1(Rg1) restores CTSD maturation and lysosomal function to mitigate PD pathology. MPTP-induced zebrafish and mouse PD models, as well as MPP+-treated SH-SY5Y cells, animals and cells were treated with Rg1 at different concentrations. Motor behavior, dopaminergic neuron survival, α-syn clearance, CTSD maturation, lysosomal activity, endoplasmic reticulum (ER) stress, oxidative stress, autophagic flux, and apoptosis were systematically evaluated. Rg1 improved locomotor performance and preserved dopaminergic neurons, promoted α-syn clearance, and enhanced CTSD maturation in lysosomes. These effects coincided with reduced ER and oxidative stress, normalized autophagic flux, and decreased apoptosis. Rg1 functions as a natural lysosomal enhancer, restoring lysosome-ER homeostasis and counteracting multiple pathogenic pathways in PD. The findings reveal a CTSD-dependent regulatory axis in α-syn homeostasis and highlight Rg1 as a promising multi-target therapeutic candidate for PD.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"5357-5373"},"PeriodicalIF":8.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176678","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":"Neohesperidin Regulates Lipid Metabolism and Ameliorates MASLD by Targeting ECHS1.","authors":"Hongyan Zhu, Tong Zhu, Min Yang, Xiaohui Huang, Shengwang Gao, Mingfei Li, Yang Shu, Xinran Yu, Xisong Ke, Jian Zhang, Jia Qi","doi":"10.1002/ptr.70400","DOIUrl":"10.1002/ptr.70400","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver condition globally, closely linked to disrupted lipid metabolism, yet effective targeted therapies remain elusive. While we previously reported the efficacy of ShuGan-QieZhi Capsule against fatty liver disease, the therapeutic potential of its active component, Neohesperidin (NH), in MASLD was unknown. Here, we demonstrate that NH effectively alleviates lipid accumulation in high-fat diet (HFD)-induced mice and palmitic acid (PA)-treated hepatocytes. Mechanistically, NH directly binds to PHE248 of ECHS1, a key enzyme in fatty acid β-oxidation, and inhibits its ubiquitin-proteasome-mediated degradation, thereby stabilizing ECHS1 and promoting lipid catabolism. Additionally, NH modulates the PPARα signaling pathway, contributing to its overall therapeutic effect. Our findings not only identify ECHS1 as a promising therapeutic target for MASLD but also propose NH as a first-in-class small molecule that directly stabilizes ECHS1, providing a novel strategy against MASLD by targeting protein stability to restore lipid homeostasis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"5585-5600"},"PeriodicalIF":8.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346071","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":"Liver Disease and Plant-Derived Phytoconstituents: From Ethnopharmacology to Modern Medicine.","authors":"Bipindra Pandey, Sagun Kharel, Anjila Shrestha, Biswash Sapkota, Laxman Subedi, Sushil Panta","doi":"10.1002/ptr.70383","DOIUrl":"10.1002/ptr.70383","url":null,"abstract":"<p><p>Liver diseases such as viral hepatitis, fatty liver disease, autoimmune and genetic disorders, drug-induced liver injury, hepatocellular carcinoma, and cirrhosis represent a major global health burden, while current pharmacotherapies remain limited by suboptimal efficacy, adverse effects, and poor accessibility. Ethnopharmacological use of medicinal plants offers a rich resource for discovering novel hepatoprotective agents, particularly secondary metabolites including alkaloids, flavonoids, terpenoids, glycosides, tannins, and saponins that target key pathogenic processes such as oxidative stress, inflammation, fibrosis, apoptosis, and metabolic dysregulation. This review systematically integrates traditional knowledge with modern evidence from in vitro, in vivo, preclinical, and clinical studies to highlight plant-derived phytoconstituents with demonstrated benefits across the spectrum of liver diseases, including clinically investigated agents such as silymarin, glycyrrhizin, curcumin, resveratrol, and ginsenosides. Mechanistic sections summarize disease progression from inflammation to fibrosis, cirrhosis, and hepatocellular carcinoma, and delineate how specific phytoconstituents modulate signaling pathways, redox homeostasis, lipid metabolism, and cell death programs, while pharmacokinetic data address absorption, distribution, metabolism, excretion, and strategies to overcome low oral bioavailability. The article also contrasts the limitations of current synthetic drugs with regulatory advances for botanical products across major agencies (FDA, EMA, WHO, and Asian regulators), and outlines methodological innovations including high-throughput screening, cheminformatics, in silico docking, organoid and liver-on-chip models, and nanotechnology-based delivery systems that can accelerate phytoconstituent-driven drug development. Overall, this review provides a comprehensive framework that links ethnomedicinal use, experimental validation, regulatory context, and technological progress, and identifies priority phytoconstituents and research directions for translating plant-based hepatoprotective agents into standardized, clinically effective therapies for liver disease.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"5441-5500"},"PeriodicalIF":8.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258786","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":"Cryptotanshinone Directly Targets MEK1 to Inhibit Migration and Invasion of Breast Cancer Cells Through Down-Regulating ERK/EMT Axis.","authors":"Min Qian, Xin Liu, Zhuoran Chai, Mengyao Li, Xiaoxiao Wang, Jiahui Du, Shuhui You, Min Xiang, Xin Ju, Liangzhi Li, Yuyang Zhou, Songbai Liu, Yuefeng Bi, Weiqiang Guo","doi":"10.1002/ptr.70395","DOIUrl":"10.1002/ptr.70395","url":null,"abstract":"<p><p>Cryptotanshinone (CPT) exerts inhibitory effects on breast cancers (BC). However, its effect and potential mechanism on breast cancer cell migration and invasion are not well understood. This study aims to investigate the potential mechanism of CPT on migration and invasion by network pharmacology and experiments. Wound healing and Transwell Matrigel invasion assays were performed to analyze the effects of CPT on migration and invasion in breast cancer cell lines MCF-7 and 4 T1. Western blot and immunofluorescence analyses were performed to verify the effect of CPT on epithelial-mesenchymal transition (EMT). Network pharmacology and experiments were used to explore the potential mechanism of CPT on EMT in breast cancer. Molecular docking, molecular dynamics (MD) simulation, cellular thermal shift assays (CETSA), drug affinity responsive target stability (DARTS), transfection, and mutagenesis were performed to confirm the direct binding effect of CPT on MEK1. Finally, BC nude mouse xenografts were established to explore the anti-metastasis effect of CPT in vivo. We found that CPT inhibited the EMT process to attenuate the migration and invasion of BC cells in a dose-dependent manner. Subsequently, network pharmacology, CETSA, DARTS, and enzyme activity assays confirmed that CPT directly binds MEK1 to inhibit its phosphorylation and kinase activity. Moreover, the molecular docking, MD, and mutagenesis results showed that CPT bound to MEK1 at Gly80 and Asp208. Moreover, MEK inhibitor (AZD-6244) intervention studies confirmed that CPT inhibits EMT by targeting the MEK pathway. Finally, the mouse tail vein injection model showed that CPT can effectively inhibit BC metastasis in vivo. Our results demonstrated that CPT modulates breast cancer migration and invasion via the MEK/ERK/EMT axis by directly targeting MEK1. Our study provides evidence suggesting that CPT may serve as a potential agent for suppressing breast cancer metastasis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"5374-5388"},"PeriodicalIF":8.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205633","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":"In Vivo Evidence of Human Organic Anion Transporting Polypeptide (OATP) 1B1 and OATP1B3 Mediated Disposition of Glycyrrhizin and Its Drug-Drug Interactions in Humanized Mice.","authors":"Jiajia Dong, Jiajing Zhong, Xiangnan Wang, Doudou Geng, Chunqin Mao, Zhipeng Chen, Tulin Lu","doi":"10.1002/ptr.70394","DOIUrl":"10.1002/ptr.70394","url":null,"abstract":"<p><p>Organic anion-transporting polypeptide (OATP) transporters have a significant influence on the disposition of drugs, significantly influencing their efficacy and toxicity. Humans express two transporters (OATP1B1 and OATP1B3), while murine possess only a single ortholog (Oatp1b2). To elucidate the impact of OATP1B1 and 1B3 on the pharmacokinetics of the hepatoprotective agent glycyrrhizin and its potential drug-drug interactions, we conducted a study utilizing wild-type, murine Oatp1b2 knockout, and newly generated humanized OATP1B1 and OATP1B3 transgenic mice (Slco1b2 ^-/- ; 1B1/1B3 ^tg ). These models were characterized physiologically and biochemically, followed by intravenous administration of glycyrrhizin for pharmacokinetic analysis. Compared to wild-type controls, Oatp1b2 knockout mice exhibited a 2-fold decrease in liver AUC_0-7h and up to 26.9-fold reduction in liver-to-plasma ratios, indicating impaired hepatic uptake of glycyrrhizin. Additionally, the absence of Oatp1b2 resulted in a 2.8-fold increase in plasma AUC_0-7h and enhanced renal distribution of glycyrrhizin. However, the knock-in of human OATP1B1 and OATP1B3 partially or fully restored the impaired hepatic uptake and reduced plasma levels of glycyrrhizin in Oatp1b2 knockout mice. Furthermore, we evaluated drug-drug interactions between glycyrrhizin and glecaprevir/pibrentasvir, a clinically relevant combination. Glecaprevir/pibrentasvir inhibited OATP1B1/1B3-mediated hepatic uptake of glycyrrhizin at therapeutic concentrations, increasing systemic exposure and highlighting drug-drug interaction risks. Our study provides the first in vivo evidence of glycyrrhizin hepatic transport by human OATP1B1 and OATP1B3, emphasizing the need for careful dosing in patients with variable OATP1B/1B3 activity due to transporter-mediated drug-drug interactions. Additionally, this humanized mouse model can serve as a robust in vivo tool for the prediction of human OATP1B1 and 1B3 function.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"5405-5419"},"PeriodicalIF":8.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212286","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":"Ruta graveolens L. in Evidence-Based Phytotherapy: Pharmacological Activities, Bioactive Compounds and Safety.","authors":"Tetiana Serhiienko, Victoriya Georgiyants, Liudas Ivanauskas, Olha Mykhailenko","doi":"10.1002/ptr.70434","DOIUrl":"https://doi.org/10.1002/ptr.70434","url":null,"abstract":"<p><p>Ruta graveolens L. is widely used in traditional European, Asian, African, and South American medicine for digestive, nervous, cardiovascular, respiratory, and reproductive disorders. Despite its long-standing ethnomedical relevance, the translation into evidence-based phytotherapy remains limited due to fragmented pharmacological data and well-documented safety concerns. This review critically synthesizes ethnomedical use, phytochemical composition, pharmacological activities, and toxicological risks of R. graveolens, aiming to evaluate its therapeutic potential and identify key research gaps. A systematic search and critical analysis were conducted following PRISMA guidelines using PubMed, ScienceDirect, and Google Scholar. Ethnomedicinal data were reviewed without time limits, while phytochemical and pharmacological studies published between 2014 and 2025 were analysed in detail. More than 160 compounds (including furanocoumarins, alkaloids, flavonoids, and others) have been identified by HPLC, CC, GC-MS, and NMR methods, of which 38 are characteristic markers. The plant exhibits a wide spectrum of activity, from antimicrobial to antitumor. However, due to the content of furanocoumarins and alkaloids, the extracts have phototoxic, abortifacient, hepatotoxic, and nephrotoxic effects, which highlights safety concerns in the absence of dosage control. Although R. graveolens represents a chemically diverse source of bioactive compounds with promising pharmacological potential, its integration into modern phytotherapy requires rigorous toxicological evaluation, extract standardization, and well-designed preclinical and clinical studies. Future research should prioritize development of standardized extracts with defined phytochemical profiles, comprehensive dose-dependent toxicological assessment, and translational studies bridging experimental findings with clinical applications with particular attention to safe therapeutic windows and less toxic bioactive constituents.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875360","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":"Integrative Approaches in Cardiovascular Disease: The Role of Nutraceuticals in Heart Failure, Atrial Fibrillation, and Related Conditions.","authors":"Laura Beatrice Mattioli, Ivan Corazza, Roberta Budriesi, Luca Camarda, Maria Carelli, Alberto Spadotto, Igor Diemberger","doi":"10.1002/ptr.70433","DOIUrl":"https://doi.org/10.1002/ptr.70433","url":null,"abstract":"<p><p>Heart failure (HF) and atrial fibrillation (AF) are among the most prevalent cardiovascular diseases, often coexisting and sharing common pathophysiological pathways such as systemic inflammation, oxidative stress, mitochondrial dysfunction, and endothelial impairment. Despite substantial progress in pharmacological treatment, including renin-angiotensin-aldosterone system (RAAS) inhibitors, beta-blockers, sodium-glucose cotransporter 2 (SGLT2) inhibitors, mineralocorticoid receptor antagonists (MRAs), diuretics, and antiarrhythmic drugs, many patients continue to experience residual symptoms and drug-related adverse effects. Nutraceuticals have emerged as potential adjuncts to conventional therapy due to their ability to modulate key biological processes involved in HF and AF. Polyphenols from Olea europaea, Hibiscus sabdariffa, Camellia sinensis, and Vitis vinifera (resveratrol) exhibit antioxidant, anti-inflammatory, and vasoprotective effects. Omega-3 fatty acids and astaxanthin contribute to inflammation control and redox balance, while Orthosiphon stamineus and Taraxacum officinale show mild diuretic activity. Moreover, anthocyanins, ursolic acid, and Rhodiola crenulata may exert antifibrotic and antiarrhythmic properties. This review provides a mechanistic comparison between pharmacological agents and nutraceuticals with overlapping mechanisms of action, highlighting their potential role in integrative cardiovascular care. While nutraceuticals are not substitutes for established therapies, emerging evidence supports their complementary use in improving treatment response, reducing side effects, and enhancing patient outcomes. Future research should focus on large-scale trials, improved bioavailability, standardized formulations, and the development of personalized therapeutic strategies. Challenges related to dosage consistency, clinical validation, and regulatory oversight are also addressed to guide innovation in integrative cardiology.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866480","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":"Brassinin Inhibits Cell Survival and Autophagy via Modulation of ROS Production and the AMPKα-beclin1 Signaling Pathway in Gliomas.","authors":"Sunil Rauniyar, Yuhui Wang, Qiaoshan Zhang, Shicheng Zhang, Jiale Yin, Tong Zhang, Shangfeng Gao, Rutong Yu","doi":"10.1002/ptr.70420","DOIUrl":"https://doi.org/10.1002/ptr.70420","url":null,"abstract":"<p><p>Brassinin, a phytoalexin compound derived mainly from Chinese cabbage, shows anticancer activity against several types of cancer. In this study, we aimed to investigate the role of brassinin in glioma progression and reveal the underlying mechanism. CCK8 assays were used to investigate the dose- and time-dependent effects of brassinin on the growth of different glioma cell lines, and then colony formation assays were employed to measure cell proliferation. Next, we used flow cytometry/Western blotting to assess cell cycle progression, apoptosis, and reactive oxygen species (ROS) production, and employed Western blotting/fluorescence staining for LC3, p62, and other signaling molecules to evaluate autophagy. Finally, we confirmed the in vitro findings in both the subcutaneous and intracranial glioma models using hematoxylin and eosin staining, immunohistochemistry, and immunofluorescence. Brassinin blocked cell cycle progression, inhibited proliferation, and promoted apoptosis in glioma cells. Brassinin inhibited autophagy, induced ROS overproduction, and suppressed the expression/activity of AMPKα-beclin1 signaling. The effect of brassinin on cell growth and survival was partially reversed by an ROS scavenger or an autophagy activator in glioma cells. Brassinin regulated the AMPKα/beclin1 signaling and autophagy via promoting ROS production in glioma cells. The anticancer role of brassinin was confirmed in subcutaneous and intracranial glioma models, and brassinin administration prolonged the survival of tumor-bearing mice. Brassinin inhibited cell survival and autophagy in glioma cells via modulation of ROS production and the AMPKα-beclin1 signaling pathway. Our study identified a promising botanical drug for the treatment of gliomas.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866540","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":"Liquiritigenin Ameliorates High-Fat Diet-Induced Hepatic Steatosis by Promoting Lipid Droplet Catabolism via PLIN2-ATGL Regulation.","authors":"Zhuoya Xu, Jingmiao Chen, Hong Qin, Yansong Fu, Cunqi Lv, Zhipeng Wang, Xi Liu, Wenya Zheng","doi":"10.1002/ptr.70440","DOIUrl":"https://doi.org/10.1002/ptr.70440","url":null,"abstract":"<p><p>Metabolic-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD) has caused a significant health burden. Glycyrrhiza uralensis Fisch. is a traditional Chinese medicinal herb used to prevent and treat numerous diseases. Liquiritigenin (LQ), a flavonoid isolated from Glycyrrhiza uralensis Fisch., has shown potential benefits in regulating lipid metabolism. This study aimed to analyze whether LQ was involved in ameliorating hepatic steatosis and elucidate the specific molecular mechanisms. A high-fat diet (HFD) model of male C57BL/6J mice was established to evaluate the effects of LQ on regulating hepatic steatosis. The potential molecular mechanisms of LQ on promoting lipid droplet catabolism were assessed in vitro using HepG2 cells treated with palmitic acid (PA) and/or LQ. The impact of the PLIN2-ATGL signaling in lipid droplet catabolism was elucidated by treating HepG2 cells with NG-497 (an ATGL inhibitor), the inhibitor of ATGL, and by constructing Plin2-overexpressed HepG2 cell lines. Both in vivo and in vitro experiments demonstrated that LQ alleviated excessive lipid accumulation, enhanced lipolysis and lipophagy, down-regulated PLIN2 expression and up-regulated CGI-58 expression. Further, inhibiting lipolysis with NG-497, the inhibitor of ATGL, attenuated the effects of LQ on increasing the phosphorylation of HSL and promoting lipophagy. The results also showed that transfecting HepG2 cells with a Plin2-overexpressing vector reduced the effects of LQ on up-regulating the expression of CGI-58, as well as proteins related to lipolysis and lipophagy. LQ promoted lipid droplet catabolism through the activation of lipolysis and lipophagy by regulating PLIN2-ATGL signaling, which provided evidence for developing LQ as a functional compound in food for ameliorating hepatic steatosis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866510","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":"Breaking Alzheimer's Disease Barrier: The Role of Xanthoceras sorbifolia Bunge Oil in Gut-Brain Axis and TLR4/Myd88/MAPK Pathway Inhibition.","authors":"Lijing Du, Shikai Yan, Xiaopeng Ren, Syed Shams Ul Hassan, Yuanfang Sun, Yu Gan, Xue Xiao, Shasha Li, Huizi Jin","doi":"10.1002/ptr.70432","DOIUrl":"https://doi.org/10.1002/ptr.70432","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with cognitive decline and neuroinflammation. Xanthoceras sorbifolia Bunge oil (XSBO), a woody plant oil rich in bioactive fatty acids, has shown potential health benefits. This study aimed to investigate the neuroprotective effects and underlying mechanisms of XSBO in AD. A scopolamine-induced AD rat model was established to evaluate the effects of XSBO on cognitive function, pathological changes, and neuroinflammation. Gut microbiota alterations were analyzed by 16S rDNA sequencing. Fecal microbiota transplantation (FMT) and short-chain fatty acid (SCFA) supplementation experiments were performed to explore the role of gut microbiota-derived metabolites. The TLR4/MyD88/MAPK signaling pathway was further examined. XSBO treatment improved cognitive deficits, reduced neuronal damage and neuroinflammation, and enhanced intestinal barrier integrity in AD rats. XSBO restored gut microbiota dysbiosis and increased SCFA-producing bacteria. FMT and SCFA supplementation confirmed that microbiota-derived metabolites contributed to XSBO-mediated cognitive improvement and neuroprotection. Mechanistically, XSBO inhibited lipopolysaccharide-induced neuroinflammation by suppressing TLR4/MyD88/MAPK signaling activation. XSBO alleviates AD-related cognitive impairment and neuroinflammation by modulating the gut microbiota-SCFA axis and inhibiting TLR4/MyD88/MAPK-mediated inflammatory responses. These findings suggest that XSBO may serve as a promising dietary intervention for neurodegenerative disease management.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808968","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}