Phytotherapy Research最新文献

{"title":"The Potential Mechanism of Soy Isoflavones in Treating Osteoporosis: Focusing on Bone Metabolism and Oxidative Stress.","authors":"Yuanyuan Zhou, Zhan Su, Gang Liu, Siwang Hu, Jiang Chang","doi":"10.1002/ptr.8451","DOIUrl":"10.1002/ptr.8451","url":null,"abstract":"<p><p>Osteoporosis is divided into primary and secondary types. Primary osteoporosis may result from estrogen deficiency in postmenopausal women, imbalanced bone remodeling in the elderly, or imbalanced adolescent-type bone development. Secondary osteoporosis can be caused by factors like long-term glucocorticoid treatment, chronic kidney disease (CKD), estrogen deprivation, oxidative stress, diabetes, and obesity. This review focuses on the therapeutic potential of soy isoflavones for osteoporosis. At the cellular level, soy isoflavones, as natural plant extracts and phytoestrogens, are crucial for osteoblastogenesis and differentiation, osteoclastogenesis, osteoclast mineralization, and bone marrow mesenchymal stromal cell differentiation. They also maintain calcium homeostasis by regulating extracellular calcium and vitamin D levels. In terms of oxidative stress, soy isoflavones mitigate it in the endoplasmic reticulum and mitochondria, thus regulating cellular senescence, autophagy, and bone remodeling processes. Moreover, soy isoflavones can relieve symptoms related to CKD and inhibit glucocorticoid secretion, which directly or indirectly benefits the treatment of osteoporosis. Overall, soy isoflavones have the potential to treat osteoporosis by enhancing bone health, regulating metabolism, and alleviating oxidative stress. Future research should explore the potential of soy isoflavones as phytoestrogens for treating osteoporosis. This exploration should focus on clarifying the safety, identifying potential side effects, determining the optimal dosage regimen, and developing strategies to mitigate any adverse reactions. In addition, further large-scale, multicenter human clinical trials are necessary to accurately evaluate the actual therapeutic effect of soy isoflavones on osteoporosis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1645-1658"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374543","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":"Multi-Targeting Phytochemicals for Alzheimer's Disease.","authors":"Radha Shree Bhattacharya, Raghuraj Singh, Archna Panghal, Ashima Thakur, Lachhman Singh, Rahul Kumar Verma, Charan Singh, Manoj Goyal, Jayant Kumar","doi":"10.1002/ptr.8435","DOIUrl":"10.1002/ptr.8435","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a type of neurodegenerative illness in which β-amyloid (Aβ) and tau protein accumulate in neurons in the form of tangles. The pathophysiological pathway of AD consists of Aβ-amyloid peptides, tau proteins, and oxidative stress in neurons and increased neuro-inflammatory response. Food and Drug Administration in the United States has authorized various drugs for the effective treatment of AD, which include galantamine, rivastigmine, donepezil, memantine, sodium oligomannate, lecanemab, and aducanumab. The major disadvantage of these drugs is that they only provide \"symptomatic\" relief. They are most effective in the early stages or for mild to moderate cases of the disease, but are not suitable for long-term use. Besides conventional therapies, phytochemicals have the potential to stop the progression of AD. According to research, the use of potential phytochemicals against AD has gained attention due to their potent anti-inflammatory, antioxidant, anti-hyperphosphorylation of the tau protein, metal chelation, and anti-amyloid properties. This study seeks to provide an up-to-date compilation of the most current and promising breakthroughs in AD therapy using phytochemicals. It could be concluded that phytochemicals light serve as an effective therapy for AD. However, more mechanistic investigations are needed to determine the clinical implications of phytochemicals in AD treatment.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1453-1483"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009866","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 Effects of Anisole on Psoriasis in Mice Based on the JAK1/STAT3 Pathway.","authors":"Qing Ning, Yingxue Yue, Xinlian Liu, Wenbo Ji, Qin Zhao, Jing Wang, Zhenhai Zhang","doi":"10.1002/ptr.8426","DOIUrl":"10.1002/ptr.8426","url":null,"abstract":"<p><p>Safe and effective treatments for psoriasis are limited. Anisole is an active ingredient in citrus and basil volatile oils; however, its potential for psoriasis treatment remains unexplored. To investigate the effects and mechanism of anisole transdermal administration as a treatment for psoriasis. Imiquimod (IMQ) was used to establish a C57 mouse psoriasis model. The severity of psoriasis lesions in each group was assessed by evaluating the thickness of skin lesions, erythema, and scales. Pathological changes within the epidermis organization were evaluated via hematoxylin and eosin (H&E) staining using light microscopy. Serum inflammatory factor levels were measured by enzyme-linked immunosorbent assays. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were performed to analyze the mRNA levels of relevant inflammatory factors and the expression of key proteins at the skin lesion sites in psoriatic mice. In model mice, applying anisole hydrogels significantly reduced the serum levels of pro-inflammatory factors interleukin (IL)-17A, (IL)-23, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. H&E staining revealed significantly attenuated stratum spinosum thickening and lymphocyte infiltration in the treatment group. RT-qPCR results further demonstrated that the skin tissues from the treatment group exhibited significantly reduced Il1b, Il17a, Il22, and Tnfa mRNA expression. Western blotting revealed inhibition of the JAK1/STAT3 signaling pathway within anisole-treated psoriatic tissues. Anisole potentially reduces psoriatic-associated inflammation through the JAK1/STAT3 signaling pathway, alleviating IMQ-induced psoriasis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1344-1354"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932137","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":"Effects, Mechanisms of Action and Application of Vitex agnus-castus for Improvement of Health and Female Reproduction.","authors":"Alexander V Sirotkin","doi":"10.1002/ptr.8438","DOIUrl":"10.1002/ptr.8438","url":null,"abstract":"<p><p>This narrative review describes the provenance and chemical composition of Vitex agnus-castus , as well as the currently available knowledge concerning its action. To search the related articles, Cochrane Library, PubMed, Web of Science, SCOPUS databases between the years 1995 and 2024, and the keywords \"Vitex,\" \"review,\" \"fertility,\" \"ovarian\" and \"mechanisms\" were used in various combinations. The data listed in this review demonstrate that Vitex agnus-castus and its constituents (isoflavones and essential oils) affect a number of physiological actions via multiple extra- and intracellular mechanisms of action. This makes it an efficient drug in both traditional and modern medicine for the treatment of a number of illnesses. The main described target of Vitex agnus-castus is female reproduction. It can up-regulate ovarian cycle and fecundity via a wide spectrum of mediators from hypothalamic, pituitary and ovarian hormones up to intracellular regulators of proliferation, apoptosis, oxidation and dopamine receptors. These effects determine its potential action as protector and medicine against a number of female reproductive disorders and reproduction-related health problems including menstrual disorders, premenstrual syndrome, cyclic mastalgia, corpus luteum insufficiency, abnormal production of progesterone and prolactin, low fertility and infertility, hyperandrogenism and polycystic ovarian syndrome. Nevertheless, further high-quality studies are needed to firmly establish the biological and clinical efficacy of this plant.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1484-1493"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033610","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":"Epigallocatechin-3-Gallate Promotes Recanalization in Deep Vein Thrombosis by Modulating Endothelial Progenitor Cell Ferroptosis Through the Nrf2 Pathway.","authors":"Da Li, Youjun Mao, Xiaosong Zhang, Yusheng Wang, Hao Tang, He Huang, Xiaomin Huang, Honggang Zhang","doi":"10.1002/ptr.8457","DOIUrl":"10.1002/ptr.8457","url":null,"abstract":"<p><p>Endothelial progenitor cells (EPCs) provide a promising therapeutic choice for deep venous thrombosis (DVT). Their number is increased by epigallocatechin-3-gallate (EGCG) in patients with diabetes. Although EGCG is effective against doxorubicin-induced ferroptosis and cardiotoxicity, its efficacy in DVT treatment has not been well studied. This study was aimed at assessing the effects of EGCG on EPC ferroptosis and recanalization in a DVT model. EPCs were treated with EGCG, and their proliferation and migration, angiogenesis, and apoptosis were evaluated using cell counting kit-8 and colony formation, Transwell, tube formation, and flow cytometry assays. Levels of iron, ferroptosis markers, and reactive oxygen species (ROS), and mitochondrial membrane potential (ΔΨm) were measured. Expression of ferroptosis-related genes and proteins was analyzed using qRT-PCR and western blotting, respectively. Promoter activation was evaluated using a dual-luciferase reporter system. Thrombus recanalization was examined in the DVT mouse model via hematoxylin and eosin staining and digital subtraction angiography. EGCG promoted EPC proliferation, migration, and angiogenesis and suppressed apoptosis. It attenuated ferroptosis by reducing iron and ROS accumulation, increasing ΔΨm, and regulating the expression of ferroptosis-related genes and proteins (ALOX15, ACSL4, and FTH1). EGCG enhanced the expression of Nrf2 and its targets, Slc7A11, HO-1, and GPX4. EGCG inhibited thrombogenesis and promoted recanalization in DVT mice, an effect mediated through the Nrf2 pathway and enhanced upon EPC transplantation. Transplantation of EGCG-pretreated EPCs facilitates DVT resolution via ferroptosis blockade. EGCG-pretreated EPC-based therapy may provide a novel option for patients with DVT.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1632-1644"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365503","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":"Berberine Inhibits Migration and Apoptosis of Rat Podocytes in Diabetic Nephropathy via the Novel lncRNA LOC102549726 Related Pathway.","authors":"Chen Wang, Hao Wu, Yongsheng Xie, Jiajia Wang, Lingzhi Huang, Xiayun Ni, Shujun Deng, Yang Zhang, Xinyi Chen, Huihui Zhang, Siming Yuan, Liqin Tang","doi":"10.1002/ptr.8452","DOIUrl":"10.1002/ptr.8452","url":null,"abstract":"<p><strong>Background: </strong>Diabetic nephropathy (DN) stands as one of the most severe complications of diabetes. Podocytes injury, particularly its attachment to the lateral glomerular basement membrane, serves as a crucial indicator of DN. Growing evidence suggests that berberine (BBR) can mitigate the onset and progression of DN. However, the molecular mechanisms through which BBR exerts its beneficial effects in the treatment of DN remain incompletely elucidated.</p><p><strong>Purpose: </strong>To explore the underlying mechanisms by which BBR exerts its therapeutic effects in DN.</p><p><strong>Methods: </strong>High-throughput lncRNA sequencing on the renal cortex of both the DN model group and the normal SD group was performed to dig for differentially expressed lncRNAs. The expression of LOC102549726 was evaluated using qPCR. The biological functions of LOC102549726 were analyzed in podocyets and DN rats. The bioinformatics techniques, qPCR and WB were used to explore the potential molecular mechanisms.</p><p><strong>Results: </strong>We found that lncRNA LOC102549726 was highly expressed in renal cortex of DN rats and podocytes subjected to high glucose conditions. Silencing LOC102549726 inhibited migration and apoptosis of podocytes. Mechanistically, LOC102549726 was identified as a facilitator of the expression of EGF and forkhead box O1 (FOXO1). BBR, a known therapeutic agent for DN, exhibited the ability to diminish the level of LOC102549726, EGF and FOXO1 in both DN rats and podocytes.</p><p><strong>Conclusion: </strong>Our findings suggested that BBR suppresses migration and apoptosis of podocytes in DN through targeting the LOC102549726/EGF/FOXO1 axis. This sheds light on a potential therapeutic avenue for mitigating the impact of DN on podocyte function.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1615-1631"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365497","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":"Deciphering the Power of Resveratrol in Mitophagy: From Molecular Mechanisms to Therapeutic Applications.","authors":"Hongmei Liu, Yixuan Song, Huan Wang, Ying Zhou, Min Xu, Jiaxun Xian","doi":"10.1002/ptr.8433","DOIUrl":"10.1002/ptr.8433","url":null,"abstract":"<p><p>Resveratrol (RES), a natural polyphenolic compound, has garnered significant attention for its therapeutic potential in various pathological conditions. This review explores how RES modulates mitophagy-the selective autophagic degradation of mitochondria essential for maintaining cellular homeostasis. RES promotes the initiation and execution of mitophagy by enhancing PINK1/Parkin-mediated mitochondrial clearance, reducing reactive oxygen species production, and mitigating apoptosis, thereby preserving mitochondrial integrity. Additionally, RES regulates mitophagy through the activation of key molecular targets such as AMP-activated protein kinase (AMPK), the mechanistic target of rapamycin (mTOR), deacetylases (SIRT1 and SIRT3), and mitochondrial quality control (MQC) pathways, demonstrating substantial therapeutic effects in multiple disease models. We provide a detailed account of the biosynthetic pathways, pharmacokinetics, and metabolic characteristics of RES, focusing on its role in mitophagy modulation and implications for medical applications. Potential adverse effects associated with its clinical use are also discussed. Despite its promising therapeutic properties, the clinical application of RES is limited by issues of bioavailability and pharmacokinetic profiles. Future research should concentrate on enhancing RES bioavailability and developing derivatives that precisely modulate mitophagy, thereby unlocking new avenues for disease therapy.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1319-1343"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927756","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":"Bergapten Ameliorates Renal Fibrosis by Inhibiting Ferroptosis.","authors":"Li Li, Wenqian Cai, Hao Zhang, Jiuren Tang, Yongjie Yang, Yang Huang, Qing Xi, Rongxin Zhang","doi":"10.1002/ptr.8425","DOIUrl":"10.1002/ptr.8425","url":null,"abstract":"<p><p>Renal fibrosis is the most common pathway for the development of end-stage renal disease (ESRD) in various kidney diseases. Currently, the treatment options for renal fibrosis are limited. Ferroptosis is iron-mediated lipid peroxidation, triggered mainly by iron deposition and ROS generation. Notably, the kidney is the most sensitive of all tissues to iron-dependent ferroptosis, and the inhibition of ferroptosis is an effective therapeutic strategy for the treatment of kidney fibrosis. Nonetheless, the pathways involved in ferroptosis in renal fibrosis are still unclear. Bergapten, a natural coumarin derivative, is mainly found in bergapten essential oil, grapefruit juice, and other commonly used plants, and it has various pharmacological effects. However, the role that ferroptosis plays in renal fibrosis and the potential therapeutic benefits of bergapten remain unclear. In this study, we investigated the therapeutic effects of bergapten on renal fibrosis and its mechanisms. We investigated the anti-fibrotic effects of bergapten in in vivo and in vitro models of renal fibrosis. Initially, network pharmacological analysis was employed to predict the potential therapeutic impact of bergapten on renal fibrosis. We then explored the potential therapeutic role of bergapten in obstructive nephropathy, which is due to unilateral ureteral obstruction (UUO). Furthermore, RNA-Seq was conducted to investigate the possible mechanism of bergapten against renal fibrosis. Additionally, Bergapten demonstrated a significant improvement in TGF-β1-induced fibrosis and RSL3-induced renal tubular epithelial cell ferroptosis; these findings are consistent with those of the in vivo studies. Our findings indicate that bergapten is a potential treatment for renal fibrosis. Treatment with bergapten significantly reduced the expression of fibronectin and α-SMA in the damaged kidneys of UUO mice, thereby improving fibrosis. Meanwhile, bergapten protected against fibrosis caused by TGF-β1 and ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibitor RSL3. Significantly, bergapten therapy alleviated renal fibrosis by modulating ferroptosis. We found that bergapten inhibited PI3K phosphorylation and indirectly restored GPX4 expression. In conclusion, we have revealed the nephroprotective effect of bergapten, whose mechanism of action is related to the inhibition of ferroptosis, and it is expected that it will be developed as a therapeutic agent for the treatment of renal fibrosis. This study aims to explore the effect of bergapten on renal fibrosis ferroptosis. Collectively, these results demonstrate that bergapten is an inhibitor of ferroptosis and provides a new treatment strategy for diseases associated with ferroptosis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":"39 3","pages":"1355-1371"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586493","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":"Effects of Cornus mas L. Supplementation on Anthropometric and Metabolic Characteristics in Patients With Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.","authors":"Dong Li, Yuzhe Liu, Qiang Fu, Rui Han, Jinlin Wu, Qinglan Zhang, Fang Fang, Danping Zhu","doi":"10.1002/ptr.8445","DOIUrl":"10.1002/ptr.8445","url":null,"abstract":"<p><p>The high prevalence of metabolic syndrome (MetS) is threatening the health of people around the world. The fruit of Cornus mas L. (CM) is rich in bioactive compounds that have the potential to promote health and improve chronic diseases associated with MetS. This systematic review aimed to compile data on the effects of CM supplementation on anthropometric and metabolic characteristics in patients with MetS. Scopus, Web of Sciences, PubMed, Embase, and the Cochrane library were employed to identify the eligible randomized controlled trials (RCTs) that assessed the effects of CM on anthropometric parameters, glycemia, and lipid profiles up to December 2024. The included articles were subjected to assessment using the Cochrane risk-of-bias tool and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. A heterogeneity test was conducted on the included trials using the I ² statistic. A random-effects model was applied based on the results of the heterogeneity tests, and the pooled data were presented as the mean difference with a 95% confidence interval (CI). A total of five RCTs were included in the analysis, with a total sample size of 313 human subjects. The results indicated that CM had a significant effect on lowering body mass index (BMI) (MD: -0.31; 95% CI: -0.46 to -0.16, p < 0.0001, I ² = 15%), hip circumference (HC) (MD: -0.84; 95% CI: -1.31 to -0.37, p = 0.0005, I ² = 19%), fasting blood glucose (FBG) (MD: -4.85; 95% CI: -7.80 to -1.91, p = 0.001, I ² = 24%), and total cholesterol (TC) levels (MD: -13.40; 95% CI: -18.93 to -7.87, p < 0.00001, I ² = 30%). Furthermore, a notable elevation in high-density lipoprotein cholesterol (HDL-c) was observed in CM interventions (MD: 2.08; 95% CI: 0.03-4.13, p = 0.05, I ² = 0%). Compared to the control group, the reduction in insulin (MD: -3.20; 95% CI: -5.25 to -1.15, p = 0.002, I ² = 83%), glycosylated hemoglobin A1c (HbA1C) (MD: -0.36; 95% CI: -0.67 to -0.04, p = 0.03, I ² = 89%), triglyceride (TG) (MD: -36.47, 95% CI: -62.03 to -10.91, p = 0.005, I ² = 76%), and low-density lipoprotein cholesterol (LDL-c) (MD: -15.35; 95% CI: -25.63 to -5.06, p = 0.003, I ² = 52%) were observed in CM interventions, although there was considerable heterogeneity in the results. In conclusion, the present findings suggest the beneficial effects of CM supplementation on MetS and related disorders. However, in order to establish a robust link between CM and MetS, further trials with adequate sample sizes are warranted.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1565-1577"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080851","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":"Dihydrotanshinone I Attenuates Diet-Induced Nonalcoholic Fatty Liver Disease via Up-Regulation of IRG1.","authors":"Yang Xiang, Ge Kuang, Xia Gong, Huang Xie, Yan Lin, Xijian Zhang, Zhongpei Chen, Jingyuan Wan, Zhenhan Li","doi":"10.1002/ptr.8443","DOIUrl":"10.1002/ptr.8443","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, but effective therapeutic drugs are still lacking. Dihydrotanshinone I (DHTS), a natural product isolated from Salvia miltiorrhiza , has been shown to have ameliorative effects on NAFLD. The aim of this study was to investigate the hepatoprotective effect of DHTS on NAFLD and its mechanism. A model of NAFLD and DHTS treatment was established using a Western diet to observe the effect of DHTS on NAFLD, which were detected by immunohistochemical, immunofluorescence, and other experiments. The mechanism was further explored by constructing immune responsive gene 1 (IRG1) knockout mice, RNA sequence, and molecular docking. The results revealed that DHTS significantly improved diet-induced metabolic disorders in mice, notably alleviating liver inflammation, oxidative stress, and fibrosis. Further analysis revealed that the intervention of DHTS was associated with the activation of IRG1. Subsequent experiments confirmed that IRG1 gene deletion reversed the above protective effects of DHTS in NAFLD. Mechanistically, DHTS enhanced the antioxidant nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway through IRG1/itaconate and blocked the oxidative stress response in the liver. In addition, DHTS also inhibited the activation of NACHT-, leucine-rich repeat (LRR)-, and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome via IRG1/itaconate, blocking the inflammatory amplification effect in the liver. The study suggests that DHTS may be a potential drug for the treatment of NAFLD, which exerts protective regulatory effects mainly through the IRG1/itaconate molecular pathway.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1531-1548"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033606","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}