Phytotherapy Research最新文献

{"title":"Essential Oils From the Fruit of Amomum villosum Lour. Alleviate LPS-Induced Neuroinflammation by Repressing PI3K-Akt and MAPK Signaling Pathways.","authors":"Hongjin Wang, Xuetong Li, Zhenhai Huang, Shanshan Luo, Jiyu Weng, Shuanghe Wang, Guofeng Shi, Yixi Zeng, Weishan Wen, Lanyue Zhang, Junxia Zheng, Hui Li","doi":"10.1002/ptr.70485","DOIUrl":"https://doi.org/10.1002/ptr.70485","url":null,"abstract":"<p><p>Amomum villosum Lour. has been traditionally valued in various cultures for its health benefits. Here, we show that the neuroprotective effects of the essential oils extracted from the fruit of Amomum villosum Lour. (AVEO) and elucidate its underlying mechanisms in lipopolysaccharide (LPS)-induced neuroinflammation. The main compounds of AVEO can cross the blood-brain barrier and significantly improve cognitive and behavioral dysfunction in LPS-induced mice, leading to a 50% enhancement in Morris water maze performance, a 60% and 80% reduction in immobility time in the tail suspension test and forced swimming test, respectively. Moreover, AVEO mitigates neuron loss and suppresses the expression of pro-inflammatory mediators, including TNF-α, IL-1β, and IL-6, while upregulating the anti-inflammatory cytokine IL-10 in brain tissue. RNA-seq and metabonomics analyses reveal that AVEO modulates multiple inflammation-related pathways and restore metabolic homeostasis in brain tissue. Remarkably, AVEO attenuates hyperactivation of the PI3K-Akt and MAPK signaling pathways in LPS-induced microglia and improves neuronal damage in LPS-induced microglia-neuron co-culture system. Altogether, our findings suggest that AVEO alleviates neural dysfunction by modulating PI3K-Akt and MAPK signaling cascades and promoting metabolic reprogramming upon neuroinflammation, thereby revealing the therapeutic potential of AVEO in several neurological disorders.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224720","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":"Gramine Suppresses Myofibroblast Activation and ECM Accumulation in Renal Fibrosis by Targeting the NF-κB/NLRP3 and TGF-β1/Smad Pathways.","authors":"Shobhit Gairola, Archana Bhatta, Tushar Mishra, Ravinder K Kaundal","doi":"10.1002/ptr.70470","DOIUrl":"https://doi.org/10.1002/ptr.70470","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is driven by persistent inflammation and progressive fibrosis, leading to irreversible renal damage. Gramine (GMN), an indole alkaloid, has broad pharmacological benefits. However, its therapeutic potential against renal fibrosis remains unexplored. This study investigates the antifibrotic potential of GMN in an experimental model of CKD. Potential therapeutic targets of GMN associated with renal fibrosis were identified through network analysis, and functional enrichment analysis revealed the mechanisms regulated by these targets. In vitro validation was conducted in transforming growth factor-β1 (TGF-β1)-induced normal rat kidney fibroblast (NRK-49F) cells. Fibrosis in the left kidney was induced by ureter obstruction, and mice received GMN orally at doses of 10 and 30 mg/kg. GMN targets 110 genes related to renal fibrosis that regulate profibrotic pathways, including TGF-β1-mediated canonical Smad signaling. GMN effectively attenuated TGF-β1-induced fibroblast-to-myofibroblast transition by inhibiting Smad signaling, resulting in downregulation of collagen I and fibronectin. In vivo, oral administration of GMN ameliorated the histopathological damage induced by UUO and significantly improved renal function. Mechanistically, GMN suppressed NF-κB-mediated priming of the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome and inhibited IL-1β maturation, thereby mitigating renal inflammation. UUO-induced fibrotic responses, characterized by upregulation of TGF-β1, TGF-β receptor type II, p-Smad2/3, connective tissue growth factor (CTGF), alpha-smooth muscle actin, and extracellular matrix (ECM) components were significantly attenuated by GMN, suggesting its ability to inhibit pathological ECM remodeling. This study demonstrates that GMN attenuates renal inflammation, suppresses myofibroblast activation and ECM remodeling by concurrently inhibiting NF-κB/NLRP3 inflammasome axis and TGF-β1/Smad pathway.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183745","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":"Cinnamic Acid Attenuates Ethanol-Exacerbated Hepatocyte Pyroptosis in Type 2 Diabetes via AMPK-Mediated NLRP3/GSDMD Inhibition.","authors":"Huaiying Tang, Qin Xiang, Yue Zhang, Yu Zhang, Xiangxiang Fu, Liming Tan, Yongli Zhang, Siqi Li, Dong Gong, Xu Guo, Yonghong Zhang, Li Chen, Tao Zheng, Qibin Wang","doi":"10.1002/ptr.70479","DOIUrl":"https://doi.org/10.1002/ptr.70479","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is frequently accompanied by chronic ethanol (ET) consumption, which worsens metabolic dysregulation and organ damage. Cinnamic acid (CA), a natural compound with anti-diabetic and hepatoprotective effects, shows therapeutic potential, but its role in mitigating ET-exacerbated hepatocyte injury in diabetes remains unclear. This study thus investigated whether CA protects against ET-induced hepatocyte pyroptosis under diabetic conditions and explored the underlying mechanisms. In vitro, HepG2 cells cultured under high-glucose (HG) conditions were exposed to ET to simulate a diabetic state with concomitant alcohol intake. Pyroptosis was evaluated by morphological examination and annexin V/PI staining. The involvement of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3)/gasdermin D (GSDMD) pathway and AMP-activated protein kinase (AMPK) activation was assessed via immunoblotting, reactive oxygen species (ROS) detection, and molecular docking. In vivo, a T2DM mouse model was established using a high-fat diet combined with streptozotocin injection, followed by ET exposure and CA treatment. Metabolic parameters, histopathological changes, and hepatic signaling pathways were analyzed. Our results showed that ET exposure significantly increased pyroptotic body formation, ROS production, and NLRP3/GSDMD pathway activation in HG-treated HepG2 cells-all of which were reversed by CA in a concentration-dependent manner. Mechanistically, CA directly bound to and activated AMPK, and the protective effects were abolished by the AMPK inhibitor Compound C. In T2DM mice, ET exposure aggravated insulin resistance, dyslipidemia, hepatic steatosis, and histopathological abnormalities, whereas CA intervention ameliorated these adverse effects and modulated the AMPK-NLRP3/GSDMD signaling axis in liver tissue. Collectively, these findings demonstrate that CA alleviates ET-exacerbated hepatocyte pyroptosis under diabetic conditions by activating AMPK and subsequently inhibiting the NLRP3/GSDMD signaling cascade. This study provides novel insights into the therapeutic potential of CA in T2DM complicated by alcoholic hepatocellular injury.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183765","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":"Correction to \"Morusin Alleviates Spinal Cord Injury in Rats by Regulating Macrophage Reprogramming through Targeting RELA and NRF2\".","authors":"","doi":"10.1002/ptr.70453","DOIUrl":"https://doi.org/10.1002/ptr.70453","url":null,"abstract":"","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183812","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":"Mogroside V Promotes Brown Adipose Thermogenesis via FTO-m⁶A-LETMD1-UCP1 Pathway to Combat Obesity.","authors":"Yuan-Hai Sun, Ling-Huan Li, Ya-Qian Feng, Teng-Jiao Zhao, Min-You Qi, Han-Bing Li","doi":"10.1002/ptr.70480","DOIUrl":"https://doi.org/10.1002/ptr.70480","url":null,"abstract":"<p><p>Obesity is a chronic, recurrent, and progressive disease caused by energy imbalance. N⁶-methyladenosine (m⁶A) modification regulates fat thermogenesis, potentially counteracting obesity. Mogroside V (MV) is a triterpene glycoside extracted from Siraitia grosvenorii and has shown beneficial effects in models of obesity. However, its underlying mechanism remains unknown. The objective of this study is to investigate the effects of MV on adipose thermogenesis and explore the mechanism of m⁶A modifications in mediating these effects. Mitochondrial respiration analysis, histological and molecular biological methods were used to investigate the thermogenesis in differentiated C3H10T1/2 brown adipocytes and adipose tissue in high-fat diet (HFD)-fed mouse models, respectively. Stable cell models with overexpression or knockdown of fat mass and obesity-associated protein (FTO) were generated to investigate the effects of FTO on m⁶A modification and thermogenesis in brown adipocytes. Methylated RNA immunoprecipitation-quantitative-PCR (MeRIP-qPCR) and RIP-qPCR analysis were used to reveal the potential downstream molecular targets of FTO. MV improved HFD-induced obesity and metabolic dysfunction in mice. MV also increased uncoupling protein 1 (UCP1) expression in brown adipose tissue and enhanced mitochondrial respiration and expression of peroxisome proliferator activated receptor γ coactivator 1α (PGC1α) and UCP1 in differentiated C3H10T1/2 cells. Further analysis of the relevant molecular mechanisms showed that MV suppressed FTO expression, thereby increasing m⁶A modification of LETM1 domain-containing protein 1 (Letmd1) mRNA. The m⁶A-modified Letmd1 transcript was recognized by the m⁶A reader YTH domain-containing protein 2 (YTHDC2), thereby increasing the stability of Letmd1 mRNA. The increased Letmd1 mRNA levels were correlated with increased LETMD1 protein abundance, which subsequently enhanced the expression of PGC1α and UCP1, ultimately promoting brown adipocyte thermogenesis. MV promoted brown adipocyte thermogenesis through the FTO-m⁶A-LETMD1-UCP1 axis, suggesting a potential therapeutic strategy for obesity.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168275","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":"Modulation of Arachidonic Acid Metabolism by Pinoresinol Diglucoside Ameliorates Osteogenic Dysfunction via Coordinated NF-κB Suppression and GSK3β/β-Catenin Activation in Diabetic Osteoporosis.","authors":"Wenqi Jin, Yujing Tan, Lei Zhang, Weigeng She, Yunhang Chu, Xuenan Chen, Shuai Zhang, Liwei Sun","doi":"10.1002/ptr.70468","DOIUrl":"https://doi.org/10.1002/ptr.70468","url":null,"abstract":"<p><p>Diabetic osteoporosis (DOP) is characterized by chronic low-grade inflammation and impaired bone formation. Pinoresinol diglucoside (PDG), a bioactive compound derived from Eucommia ulmoides Oliv., has shown therapeutic potential in metabolic bone disorders; however, its direct molecular targets and integrated mechanisms remain unclear. This study aimed to elucidate the metabolic basis and molecular targets through which PDG protects against high glucose (HG)-induced osteoblast dysfunction and diabetic bone loss. Osteogenic effects of PDG were evaluated in HG-exposed osteoblasts, with untargeted metabolomics, qPCR, Western blotting, molecular docking, SPR, and siRNA-mediated knockdown applied to identify altered pathways and validate target necessity. In vivo, PDG was administered to db/db mice with DOP for 8 weeks, followed by micro-CT, bone metabolism factors, histomorphometry, and immunofluorescence analyses. Metabolomic profiling identified arachidonic acid metabolism as the central pathway dysregulated in HG conditions and rescued by PDG. PDG directly bound and inhibited both p65 (NF-κB) and GSK3β. Mechanistically, p65 knockdown abolished the anti-inflammatory effect of PDG without affecting osteogenesis, whereas GSK3β knockdown abrogated β-catenin activation and osteogenic differentiation without affecting anti-inflammatory responses, indicating that they function as parallel and independent branches. Simultaneous knockdown of both completely blocked the functional recovery of osteoblast differentiation. In DOP mice, PDG significantly improved trabecular microarchitecture and bone metabolic homeostasis, reduced local PGE2 levels with an effect directly targeting bone, inhibited p65 nuclear translocation, and restored β-catenin nuclear localization. PDG ameliorates DOP by dual targeting p65 and GSK3β, coordinately inhibiting NF-κB-mediated inflammation and activating the β-catenin osteogenic program, highlighting its therapeutic potential for DOP.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167453","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":"Astragaloside IV Restores Autophagy and Inhibits Apoptosis for Podocyte Protection in Diabetic Nephropathy by Inhibiting Notch1 Signaling via SIRT6-Mediated Deacetylation.","authors":"Qiyu Yue, Chen Yong, Xinran Wang, Yang Shu, Min Yao, Yongfei Yu, Yubai Xue, Rong Deng, Tianlu Chu, Weiwei Tao, Min Zhao, Enchao Zhou","doi":"10.1002/ptr.70472","DOIUrl":"https://doi.org/10.1002/ptr.70472","url":null,"abstract":"<p><p>Astragaloside IV (AS-IV) has demonstrated efficacy in ameliorating proteinuria and attenuating renal tubular damage in preclinical diabetic nephropathy (DN) models. Despite these multi-target benefits, the molecular mechanisms underlying its podocyte-protective effects remain largely uncharacterized, particularly its potential epigenetic regulatory capacity within glomerular cells. This study aimed to test the hypothesis that AS-IV protects against DN by activating the deacetylase sirtuin 6 (SIRT6). Specifically, AS-IV activates SIRT6, which deacetylates Histone H3 at Lysine 9 (H3K9) at the Notch1 promoter, thereby suppressing Notch1 expression. This suppression is expected to enhance autophagy and reduce apoptosis, ultimately repairing renal filtration barrier injury. A murine model of DN was induced with streptozotocin and a high-fat diet. To simulate diabetic damage, MPC-5 podocytes were subjected to high glucose (HG, 33 mM). Renal function metrics were extensively evaluated, and glomerular histopathological and ultrastructural changes were assessed by hematoxylin and eosin staining and electron microscopy. Subsequently, downstream mechanisms involving podocyte autophagy and apoptosis were investigated by immunofluorescence staining and Western blotting. To confirm that SIRT6 directly regulates Notch1 transcription via histone deacetylation, our study utilized chromatin immunoprecipitation (ChIP). Our results showed that AS-IV treatment alleviated renal biochemical and pathological abnormalities in DN mice and attenuated podocyte injury, evidenced by restoring nephrin and podocin expression and reducing glomerular basement membrane thickness (p < 0.01). Functionally, AS-IV treatment reversed HG-induced podocyte apoptosis and autophagy dysfunction (p < 0.01). Mechanistically, AS-IV was confirmed to directly bind to SIRT6 (Kd = 0.164 μM). ChIP assays demonstrated increased SIRT6 occupancy and consequently reduced H3K9ac enrichment at the Notch1 promoter (p < 0.01). In summary, AS-IV may ameliorate DN by activating the SIRT6/H3K9ac/Notch1 epigenetic axis, providing a strong molecular basis for AS-IV as a promising therapeutic agent against DN.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137577","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":"Ganoderic Acids Alleviate Dexamethasone-Induced Muscle Atrophy Potentially via Regulating Protein Synthesis/Degradation, Attenuating Oxidative Stress, and Antagonizing Glucocorticoid Receptor.","authors":"Kecheng Tang, Yan Yu, Yiru Chen, Zhizhen Huang, Hang Zhang, Yun Tian, Min Li, Yue Yin, Shaowei Li, Bingchuan Liu, Baoxue Yang","doi":"10.1002/ptr.70476","DOIUrl":"https://doi.org/10.1002/ptr.70476","url":null,"abstract":"<p><p>Ganoderic acids (GA), a class of specific triterpenoids found exclusively in Ganoderma lucidum, have broad pharmacological activities. The purpose of this study was to determine whether GA attenuates dexamethasone (DEX)-induced muscle atrophy and to explore the underlying mechanisms. The therapeutic effect of GA (at intraperitoneal doses of 3.125, 12.5, and 50 mg/kg) and its active monomers were assessed in DEX-treated C57BL/6 mice and C2C12 myotubes. Experimental results showed that GA significantly protected muscle function and mass and reduced muscle damage. Interestingly, GA significantly inhibited protein degradation by suppressing muscle atrophy F-box protein (Atrogin-1)/muscle RING finger protein 1 (MuRF1) expression and promoted protein synthesis by enhancing protein kinase B (AKT)/ribosomal S6 kinase (S6K) phosphorylation in the gastrocnemius muscle. GA also significantly reduced oxidative stress by decreasing 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), enhancing activities of superoxide dismutase (SOD) and catalase (CAT), and upregulating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H dehydrogenase quinone 1 (NQO1) pathway. In DEX-induced C2C12 cells, both GA and ganoderic acid-A (GA-A) markedly attenuated myotube atrophy, with GA-A further regulating protein synthesis/degradation and reducing oxidative stress in vitro. Moreover, the binding of GA-A to the glucocorticoid receptor (GR) was supported by molecular docking, dynamics simulation, surface plasmon resonance (SPR), microscale thermophoresis (MST), and cellular thermal shift assays (CETSA). A glucocorticoid response element (GRE)-driven luciferase reporter assay further revealed that GA-A suppressed DEX-induced GR transcriptional activity, suggesting functional antagonism of GR signaling. In conclusion, our study found that GA alleviated DEX-induced muscle atrophy, potentially via regulating protein synthesis/degradation, attenuating oxidative stress, and functionally antagonizing GR.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137587","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":"Dietary Flavonoid Hyperoside Ameliorates High-Fat Diet-Induced Type 2 Diabetes Mellitus by Enhancing Brown Adipose Tissue Thermogenesis, White Adipose Tissue Browning, and Gut Microbiota Remodeling.","authors":"WeiFeng Cai, WenXin Zeng, Yu Luo, Qiang Liu, CuiPing Jiang, YanKui Yi, JieYu Chen, ChunYan Shen","doi":"10.1002/ptr.70478","DOIUrl":"https://doi.org/10.1002/ptr.70478","url":null,"abstract":"<p><p>Hyperoside, a natural dietary flavonoid widely found in a variety of fruits, vegetables, and medicinal plants, exhibits hypoglycemic as well as hepatorenal protective activities. However, its effects on type 2 diabetes mellitus (T2DM) and the underlying mechanisms remain poorly understood. In this study, T2DM mice were established after 8 weeks of high-fat diet (HFD) feeding and were subsequently treated with hyperoside for 6 weeks. Then, indices of glucose and lipid metabolism, energy expenditure, hepatic histopathology, brown adipose tissue (BAT) thermogenesis, inguinal white adipose tissue (iWAT) browning, macrophage polarization in iWAT, and gut microbiota composition were evaluated. Hyperoside significantly reduced HFD-induced body weight gain in T2DM mice without suppressing appetite. HFD-induced insulin resistance, dyslipidemia, hepatic steatosis, and fibrosis were markedly ameliorated by hyperoside. Hyperoside also increased oxygen consumption, carbon dioxide production, and energy expenditure, and decreased the respiratory exchange ratio. In addition, hyperoside treatment was accompanied by increased UCP1 and PGC-1α protein expression and upregulated mRNA expression of PGC-1α, UCP1, PRDM16, and Cidea in BAT and iWAT, consistent with enhanced BAT thermogenic activity and an iWAT browning-related phenotype. Flow cytometry analysis further revealed that hyperoside inhibited M1 macrophage polarization and reduced the M1/M2 ratio in iWAT. Moreover, hyperoside partially modulated gut microbial diversity and taxonomic composition in T2DM mice, increased the relative abundance of Bacteroidetes and the Bacteroidetes/Firmicutes ratio, and partially restored the relative abundance of Muribaculaceae and Lachnospiraceae_NK4A136_group. In conclusion, hyperoside ameliorated metabolic dysfunction in HFD-induced T2DM mice, accompanied by enhanced BAT thermogenic activity, iWAT browning-related changes, modulation of macrophage polarization in iWAT, and remodeling of the gut microbiota. These findings suggest that hyperoside may represent a potential natural product candidate with metabolic benefits, although further pharmacokinetic, safety, long-term, and clinical validation is required.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137627","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":"Suppression of PKM2 by Leonurine Attenuates Alcoholic Hepatitis Through Regulating Glycolytic Reprogramming.","authors":"Xuan-Xuan Zhang, Gao-Feng Pan, Hong Fang, Xiao-Peng Liu, Jing Sun, Ji-Xiang Chen, Xin Fan, Jia-Hao Feng","doi":"10.1002/ptr.70471","DOIUrl":"https://doi.org/10.1002/ptr.70471","url":null,"abstract":"<p><p>Alcoholic hepatitis (AH) is a liver disease caused by long-term heavy drinking. In the early stages, it usually manifests as fatty liver, which can then develop into liver fibrosis and cirrhosis. Kupffer cells are liver resident macrophages and the effect of glycolytic reprogramming on the polarization of macrophages plays an important role in hepatitis, which maybe a possibility therapeutic target for treating AH. Leonurine (Leo) is a natural alkaloid from Leonurus japonicus Houtt. and has been commonly used to ameliorate metabolic disorders. However, the protective effects and underlying mechanisms of Leo against alcoholic liver disease remain unclear. The study aimed to investigate the novel role of PKM2 on AH, and whether targeting PKM2-mediated glycolytic reprogramming is the underlying mechanism for the anti-inflammatory effects of Leo to regulate the AH. To investigate the potential role of Leo and its mechanisms on AH, we established an alcohol-induced C57BL/6 mice and LPS&IFN-γ-induced kupffer cell model to evaluate its pharmacological activity and mechanisms on AH in vivo and vitro. Our results showed that Leo treatment could restrain liver inflammation and inhibit PKM2 expression in vivo and in vitro, reducing the upregulated glycolysis. Additionally, treatment of Leo ameliorated extensive vacuolar degeneration and reduced lipid droplet accumulation in AH mice. The decrease of PKM2 expression apparently attenuated glycolysis and liver inflammation in vivo and in vitro. Leo interacted with PKM2 to modulate glycolysis for switching glycolytic reprogramming, thereby suppressing liver inflammation during AH. Our data highlighted that inhibition of PKM2 may be an effective strategy for treating AH. Leo possesses a beneficial amelioration effect on AH through inhibiting PKM2-mediated glycolytic reprogramming. These findings demonstrate an experimental basis for the clinical application of Leo in the treatment of AH.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128311","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}