Kun Gao, Yunhua Liu, Kun Li, Lin Liu, Yanmo Cai, Xinxue Zhang, Zongjiang Zhao
{"title":"Nrf2-Mediated Ferroptosis Is Involved in Berberine-Induced Alleviation of Diabetic Kidney Disease.","authors":"Kun Gao, Yunhua Liu, Kun Li, Lin Liu, Yanmo Cai, Xinxue Zhang, Zongjiang Zhao","doi":"10.1002/ptr.8498","DOIUrl":"https://doi.org/10.1002/ptr.8498","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is the most common and serious complication of diabetes mellitus. Currently, there is a lack of safe and effective preventive strategies for DKD. The study aimed to explore the preventive effects and potential mechanisms of berberine (BBR) against DKD. In the in vivo experiments, we established a DKD rat model induced by the combination of high-fat diet and streptozotocin to investigate the preventive effect of BBR on DKD. Subsequently, in vitro experiments using human renal tubular epithelial cells (HK-2 cells) were performed to further validate the effect of BBR on renal tubular epithelial cell ferroptosis induced by advanced glycation end products (AGEs). In vivo, we found that BBR improved renal function and attenuated inflammatory cell infiltration, podocyte injury, and iron deposition in renal tissue in DKD rats. In addition, in vitro experiments showed that BBR attenuated HK-2 cell ferroptosis induced by AGEs. We further identified Nrf2 as a direct binding target of BBR by molecular docking and Surface Plasmon Resonance (SPR). Then, immunohistochemistry and Western Blot results demonstrated that BBR could activate the Nrf2 pathway, initiate the endogenous antioxidant system, and inhibit the occurrence of AGEs-induced ferroptosis. Moreover, silencing of Nrf2 by siRNA technology eliminated the protective effect of BBR on AGEs-induced ferroptosis. Collectively, our results supported that BBR could inhibit oxidative stress and ferroptosis by targeting activation of the Nrf2 pathway, thereby delaying the disease progression of DKD, providing a new scientific basis and perspective for the prevention and treatment of DKD.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161276","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}
Suqin Zhu, Qi Gu, Chao Meng, Jianming Liu, Xinyue Du, Bin Liao, Fanglan Liu, Chunhua Xia
{"title":"Oleanolic Acid Up-Regulated UGT1A1 and Antagonized Inflammation by Affecting the Binding of PXR and PKCα to HSP90α and SRC1.","authors":"Suqin Zhu, Qi Gu, Chao Meng, Jianming Liu, Xinyue Du, Bin Liao, Fanglan Liu, Chunhua Xia","doi":"10.1002/ptr.8515","DOIUrl":"https://doi.org/10.1002/ptr.8515","url":null,"abstract":"<p><p>Our previous studies have demonstrated that oleanolic acid (OA) can induce UGT1A1 expression in HepG2 cells by activating PXR and alleviate inflammatory damage caused by alpha-naphthyl isothiocyanate (ANIT). Activation of PKCα by phorbol-12-myristate-13-acetate (PMA) can significantly down-regulate the expression of UGT1A1 and counteract the inductive effect of OA on UGT1A1. This study aimed to explore the molecular mechanism of OA in up-regulating UGT1A1 and antagonizing inflammation based on the interaction of PXR and PKCα with HSP90α and SRC1. The expressions of PKCα, PXR, and UGT1A1, and the binding of PKCα and PXR to HSP90α and SRC1 were detected in HepG2 cells and in rats. The activation of PKCα induced by PMA or ANIT led to hyperinflammatory response and increased transfer of PKCα to the membrane, accompanied by decreased binding of PKCα to HSP90α and increased binding of PXR to HSP90α in the cytoplasm, which decreased the nuclear translocation of PXR and its binding to SRC1, and finally down-regulated the expression of UGT1A1. OA significantly inhibited the transfer of PKCα to cell membrane induced by PMA or ANIT, resulting in increased binding of PKCα to HSP90α and decreased binding of HSP90α to PXR in the cytoplasm. This facilitates PXR to enter the nucleus and increases its binding with SRC1, up-regulates UGT1A1 expression and inhibits inflammatory response. OA can affect the binding of PXR and PKCα with HSP90α and SRC1 to up-regulate the expression of UGT1A1 and finally antagonize inflammatory injury.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151393","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":"Erucin Alleviates Cardiac Hypertrophy by Improving Mitochondrial Function via Nrf2-Sirt3 Pathway.","authors":"Shushu Jiang, Cheng Wang, Yin Dong, Long Chen, Menghao Shi, Fengxiao Zhang, Zhaohui Wang, Minglu Liang","doi":"10.1002/ptr.8458","DOIUrl":"https://doi.org/10.1002/ptr.8458","url":null,"abstract":"<p><p>Numerous studies have documented erucin's anticancer and vasodilatory properties, yet its impact on pathological cardiac hypertrophy remains to be fully understood. This study aimed to explore the therapeutic potential of erucin in cardiac hypertrophy induced by pressure overload. Cardiac hypertrophy was induced in mice by transverse aortic constriction (TAC) surgery, and in neonatal rat cardiomyocytes via phenylephrine (PE) treatment. Cardiac function and remodeling were evaluated using echocardiography, histological assessment, and molecular analyses. Mitochondrial function was assessed by measuring mitochondrial respiration, ATP concentration, the NAD+/NADH ratio, and reactive oxygen species (ROS) levels. Molecular docking was performed to identify erucin's downstream effector. Nrf2 and Sirt3 were silenced using siRNAs, and their activities were inhibited with ML385 and 3-TYP, respectively. Here, we found that erucin improved cardiac function and remodeling in TAC-induced hypertrophic mice, mitigated PE-induced cell hypertrophy, and restored mitochondrial function. Molecular docking analysis identified Nrf2 as a target protein of erucin. Erucin increased Nrf2 protein levels and activated the Nrf2 signaling pathway, which in turn promoted Sirt3 transcription. This effect was blocked by silencing Nrf2 or using ML385. Additionally, silencing Nrf2 and Sirt3 or using ML385 and 3-TYP abolished erucin's protective effects. This study is the first to demonstrate that erucin protects against cardiac hypertrophy by improving mitochondrial function through the activation of the Nrf2-Sirt3 pathway. Erucin may emerge as a promising therapeutic candidate for treating cardiac hypertrophy.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143302","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}
Elvan Wiyarta, Refael Alfa Budiman, Devina Ravelia Tiffany Subroto, Moon Nyeo Park, Nelly Mayulu, Nurpudji Astuti Taslim, Raymond Rubianto Tjandrawinata, Trina Ekawati Tallei, Hardinsyah Hardinsyah, Fahrul Nurkolis, Bonglee Kim
{"title":"Plant-Derived Natural Products for Dietary Intervention in Overweight and Obese Individuals: A Systematic Review and Network Meta-Analysis.","authors":"Elvan Wiyarta, Refael Alfa Budiman, Devina Ravelia Tiffany Subroto, Moon Nyeo Park, Nelly Mayulu, Nurpudji Astuti Taslim, Raymond Rubianto Tjandrawinata, Trina Ekawati Tallei, Hardinsyah Hardinsyah, Fahrul Nurkolis, Bonglee Kim","doi":"10.1002/ptr.8490","DOIUrl":"https://doi.org/10.1002/ptr.8490","url":null,"abstract":"<p><p>Growing rates of overweight and obesity worldwide call for novel approaches to treatment, and plant-derived natural products present a promising therapeutic option. Evaluate the efficacy of plant-derived natural products as dietary interventions for overweight and obesity through a systematic review and network meta-analysis. We conduct a systematic review and network meta-analysis following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. We searched from five databases and registries up to March 2024, selecting randomized controlled trials examining dietary interventions with plant-derived natural products for adults with obesity or overweight. The frequentist approach was used for the network meta-analysis, assessing 13 metabolic and obesity-related outcomes. Our review included 39 studies with 2513 participants with PROSPERO registration ID CRD42024520305. African Mango emerged as the most effective intervention, reducing body weight (MD: -10.00 kg, 95% CI: -16.74 to -3.26), waist circumference (MD: -11.70 cm, 95% CI: -17.15 to -6.25), total cholesterol (MD: -44.01 mg/dL, 95% CI: -58.95 to -29.08), triglycerides (MD: -42.65 mg/dL, 95% CI: -79.70 to -5.60), and random blood glucose (MD: -14.95 mg/dL, 95% CI: -18.60 to -11.30). Green coffee led to the largest reduction in body fat percentage (MD: -2.90%, 95% CI: -4.88 to -0.92) and BMI (MD: -3.08 kg/m<sup>2</sup>, 95% CI: -6.35 to 0.19). Ephedra was most effective in reducing fasting blood glucose (MD: -4.60 mg/dL, 95% CI: -5.49 to -3.71) and HOMA-IR (MD: -16.20, 95% CI: -18.66 to -13.74). There were too few direct comparisons between various metabolites; thus, most of the comparisons were indirect comparisons through placebo. Plant-derived natural products significantly impact obesity management, notably in body weight, waist circumference, and lipid profile reduction; however, further high-quality and rigorous studies were needed to establish the clinical efficacy of the plant-derived natural products.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151400","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}
Amirhossein Niknejad, Niusha Esmaealzadeh, Amirreza Peyrovinasab, Shirin Sirouskabiri, Mahsa Gholami, Aytak Vahdat Khajeh Pasha, Saleh Shahri, Dietrich Büsselberg, Amir Hossein Abdolghaffari
{"title":"Phytochemicals Alleviate Tumorigenesis by Regulation of M1/M2 Polarization: A Systematic Review of the Current Evidence.","authors":"Amirhossein Niknejad, Niusha Esmaealzadeh, Amirreza Peyrovinasab, Shirin Sirouskabiri, Mahsa Gholami, Aytak Vahdat Khajeh Pasha, Saleh Shahri, Dietrich Büsselberg, Amir Hossein Abdolghaffari","doi":"10.1002/ptr.8522","DOIUrl":"https://doi.org/10.1002/ptr.8522","url":null,"abstract":"<p><p>Cancers are increasingly common and significantly impact patients' quality of life and longevity. The role of macrophages in tumorigenesis is critical, and natural compounds have long been recognized as valuable sources of bioactive agents for treating this condition. However, no systematic review has been performed on the role of phytochemicals impacting tumorigenesis by M1/M2 macrophage polarization. The aim of this study is to systematically review phytochemicals that relieve tumorigenesis by impacting M1/M2 macrophage polarization and investigate related signaling pathways. This systematic review adheres to PRISMA 2020 guidelines and statements. Scientific databases, MEDLINE, Scopus, and Web of Science, have been searched from inception to October 2023. This review includes English original articles on the role of phytochemicals, whole plant extracts, and polyherbal formulas in ameliorating tumorigenesis through M1/M2 polarization while excluding non-English articles, non-original research, and unrelated studies according to title, abstract, and full-text screening. Shreds of evidence were gathered from cellular and animal studies about the beneficial impacts of phytochemicals against tumorigenesis by impacting M1/M2 macrophage polarization. Critical assessment of in vitro and in vivo studies was performed by the CRIS and ARRIVE guidelines. Due to the high level of heterogeneity of the collected data, only a narrative synthesis was performed. Of 741 collected articles, only 35 remained. Polyphenols are the most highlighted group. Phytochemicals affect cytokines related to M1, such as CD80, CD86, CD64, and iNOS, and M2, like CXCR-1, CXCR-2, and TGF-β, in various cancer models. Together, these compounds exerted protective effects against tumorigenesis in preclinical cancer models. Furthermore, high-quality clinical experiments are recommended to cover the limitations of the current study, which are reliance on preclinical evidence, lack of clinical trials, and exclusion of non-English and grey literature.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111318","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}
Renchao Dong, Jun Wei, Shuo Tian, Yu Ma, Jie Wang, Xinyi Tu, Gang Li, Yanqiu Liu
{"title":"Asperosaponin VI Promotes Osteoporotic Fracture Healing by Targeting Piezo1 to Enhance the Coupling of LEPR<sup>+</sup> BMSCs and PODXL<sup>+</sup> ECs.","authors":"Renchao Dong, Jun Wei, Shuo Tian, Yu Ma, Jie Wang, Xinyi Tu, Gang Li, Yanqiu Liu","doi":"10.1002/ptr.8523","DOIUrl":"https://doi.org/10.1002/ptr.8523","url":null,"abstract":"<p><p>Osteoporotic fracture (OPF) has garnered significant attention due to its high incidence of delayed or nonunion, which severely impacts quality of life. However, the pathogenesis remains mysterious, and therapeutic options are limited. The current study aimed to elucidate the molecular pathogenesis of OPF, thereby proposing a novel treatment protocol. In this study, single-cell RNA sequencing analysis was conducted to identify the role of Piezo1 in the osteogenic capacity of LEPR<sup>+</sup> BMSCs in the healing process of fracture. Single-cell trajectory analysis and pseudo-time ordering were used to elucidate the differentiation trajectory of LEPR<sup>+</sup> BMSCs and Piezo1 expression. Molecular docking, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTs) were performed to assess the interaction between Piezo1 and ASP. The ovariectomized (OVX) model combined with femoral bone fracture was utilized to evaluate the osteoprotective effect of ASP in vivo. The alkaline phosphatase (ALP) assay and alizarin red S (ARS) staining were applied to evaluate the osteogenic differentiation potential of LEPR<sup>+</sup> BMSCs. The three-dimensional culture was utilized to assess the proliferation and sphere-forming ability of LEPR<sup>+</sup> BMSCs. The scratch wound healing and tube formation assay were employed to detect the angiogenesis of endothelial cells (ECs). Furthermore, western blotting, immunofluorescence staining, and flow cytometry assays were utilized to detect the relevant protein expression. Initially, single-cell RNA sequencing analysis was utilized to identify Piezo1 as a key factor in osteogenic differentiation of LEPR<sup>+</sup> BMSCs during fracture healing. By molecular docking, CETSA, and DARTs analysis, Asperosaponin VI (ASP) was identified as a potentially effective monomer for Piezo1. Histologically, ASP enhanced the coupling of PODXL<sup>+</sup> ECs and LEPR<sup>+</sup> BMSCs within the callus of osteoporotic fractures. Notably, ASP improved LEPR<sup>+</sup> BMSCs' osteogenic potential and PODXL<sup>+</sup> ECs' angiogenesis. The augmented angiogenic capacity of PODXL<sup>+</sup> ECs was mediated by vascular endothelial growth factor (VEGF), an effect nullified by siPiezo1 in LEPR<sup>+</sup> BMSCs. Further, ASP significantly elevated P-ERK1/2, YAP, and VEGF expression, the downstream molecules of Piezo1 in the LEPR<sup>+</sup> BMSCs.This study initially revealed that the findings suggest that ASP may facilitate the coupling of LEPR<sup>+</sup> BMSCs and PODXL<sup>+</sup> ECs by activating the Piezo1/ERK1/2/YAP/VEGF signaling pathway in LEPR<sup>+</sup> BMSCs, thus indicating a promising therapeutic strategy for osteoporotic fracture management.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111315","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}
Xuemin Yao, Shuangpan Zhang, Guoxin Zhang, Ying Liu, Yongping Zhu, Wenli Wang, Chunyan Zhu, Na Lin
{"title":"Celastrol Mediated Regulation of the HnRNPA1-Thyroxine Axis in the Amygdala Alleviates High Fat Diet-Induced Demyelination and Cognitive Deficits in Mice.","authors":"Xuemin Yao, Shuangpan Zhang, Guoxin Zhang, Ying Liu, Yongping Zhu, Wenli Wang, Chunyan Zhu, Na Lin","doi":"10.1002/ptr.8520","DOIUrl":"https://doi.org/10.1002/ptr.8520","url":null,"abstract":"<p><p>High fat diet (HFD) is closely linked to demyelination and cognitive deficiency. Previously, we reported that the covalent binding and downregulation of heterogeneous nuclear ribonucleoprotein A1 (HnRNPA1) were responsible for the effectiveness of celastrol against high fat diet (HFD) induced obesity. However, little is known about cognitive functions. This study aimed to evaluate the effectiveness and mechanism of celastrol on cognitive functions and demyelination in HFD mice. In HFD mice, the anti-cognitive dysfunction and anti-demyelination effects of celastrol and HnRNPA1-shRNA were evaluated by Morris water maze and luxol-fast-blue staining. Then, the common biological pathway of celastrol and HnRNPA1-shRNA was clarified by the transcriptomic and metabolomic analyses of amygdala tissue and verified in the amygdala and in cultured MO3.13 cells. Celastrol and HnRNPA1-shRNA alleviated cognitive impairments and amygdala demyelination in HFD mice. By transcriptome analysis, genes co-regulated by celastrol and HnRNPA1-shRNA were focused on the myelin generating cells-oligodendrocyte. Celastrol and HnRNPA1-shRNA alleviated oligodendrocyte differentiation disorder and myelin loss induced by HFD. Association analysis of metabolome and transcriptome indicated that the enhanced central transport and inhibited inactivation of thyroxine may underlie celastrol and HnRNPA1-shRNA mediated regulation of oligodendrocyte. In MO3.13 cells, celastrol mediated downregulation of HnRNPA1. In addition, the pro-maturation effects of celastrol and HnRNPA1-shRNA were confirmed by the downregulation of Dio3 and O1, as well as the upregulation of MBP. Through HnRNPA1-thyroxine axis, celastrol protects against HFD-induced demyelination and cognitive deficits.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041988","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}
Solmaz Asnaashari, Ali Jahanban-Esfahlan, Ryszard Amarowicz
{"title":"Harnessing Essential Oils for Acetylcholinesterase Inhibition: A Literature Review.","authors":"Solmaz Asnaashari, Ali Jahanban-Esfahlan, Ryszard Amarowicz","doi":"10.1002/ptr.8512","DOIUrl":"https://doi.org/10.1002/ptr.8512","url":null,"abstract":"<p><p>Aromatherapy, a branch of herbal and alternative medicine, has emerged as a promising non-pharmacological approach to treating Alzheimer's disease (AD) due to its potential to enhance cognitive function. This comprehensive review evaluates the inhibitory effects of various plant essential oils (EOs) on acetylcholinesterase (AChE) activity, a key enzyme implicated in the pathophysiology of AD. Our analysis highlights EOs from the Lamiaceae family, particularly rosemary (Salvia rosmarinus) and lavender (Lavandula officinalis), which demonstrated the most potent AChE inhibitory effects. Key chemical constituents such as α- and β-pinene, limonene, linalool, 1,8-cineole, caryophyllene, estragole, eugenol, and asarone were identified as the primary active components responsible for these effects. Additionally, we discuss the biochemical mechanisms underlying the neuroprotective properties of these EOs and their potential role in developing effective therapies for AD. Our findings underscore the therapeutic promise of specific EOs and their constituents in managing cognitive decline associated with neurodegenerative disorders.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A New Perspective on Signaling Pathways and Structure-Activity Relationships of Natural Active Ingredients in Metabolic Crosstalk Between Liver and Brown Adipose Tissue: A Narrative Review.","authors":"Qi-Cong Chen, Wei-Feng Cai, Qian Ni, Song-Xia Lin, Cui-Ping Jiang, Yan-Kui Yi, Li Liu, Qiang Liu, Chun-Yan Shen","doi":"10.1002/ptr.8521","DOIUrl":"https://doi.org/10.1002/ptr.8521","url":null,"abstract":"<p><p>Obesity has become a major global health problem, and strategies to improve metabolic disorders are urgently needed. This review focused on the roles of natural active ingredients in regulating metabolic communication between the liver and brown adipose tissue (BAT), especially highlighting the associated signaling pathways and structure-activity relationship (SAR). Natural polyphenols, flavonoids, terpenoids, and their potential in modulating metabolism were elaborated. Particularly, some signaling factor pathways including insulin, adiponectin, leptin, NRG4, FGF21, inflammatory factor, and BMP were summarized, detailing how natural active ingredients modulated the liver-BAT metabolic crosstalk, such as celastrol, genistein, sesamin, etc. FGF21 and NRG4 acted as key signaling factors, playing important transduction roles in the metabolic crosstalk between the liver and BAT. More importantly, SAR of flavonoids, phenolic acids, polysaccharides, and terpenoid compounds was discussed. The presence of functional groups, hydroxyl or methoxyl substituents, and molecular size were analyzed in relation to the interaction between compounds and biological targets. Furthermore, how structural modifications enhanced bioactivity and bioavailability while reducing side effects was elucidated. In conclusion, natural active ingredients played an important role in modulating metabolic crosstalk between the liver and BAT, underscoring the potential of these components in treating metabolic disorders. Further research on SAR of different natural active ingredients and their long-term health impacts are still needed to provide more effective and safer natural solutions for metabolic diseases prevention and treatment.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040020","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}
Igor Ferraz da Silva, Celina D'Ávila Felipe, Alexandre Dantas Alves, Pollyana Peixoto, Lívia Carla de Melo Rodrigues
{"title":"Behavioral and Neuroprotective Properties of the Phytoestrogen 8-Prenylnaringenin (8-PN) in Ovariectomized Mice.","authors":"Igor Ferraz da Silva, Celina D'Ávila Felipe, Alexandre Dantas Alves, Pollyana Peixoto, Lívia Carla de Melo Rodrigues","doi":"10.1002/ptr.8500","DOIUrl":"https://doi.org/10.1002/ptr.8500","url":null,"abstract":"<p><p>8-Prenylnaringenin (8-PN) is one of the most potent phytoestrogens identified to date. Despite its role as an estrogen receptor modulator and its vast therapeutic potential, the effects of this molecule on the brain and behavior of females remain largely unexplored. This study hypothesized that 8-PN exerts cognitive effects by preventing oxidative damage in the brain and promoting the expression of neurotrophins. Female mice were divided into five groups and received acute treatments with LPS (1 mg/kg), 8-PN (1 or 2 mg/kg), a combination of LPS and 8-PN doses, or a combination of vehicle solutions. Recognition memory, spatial memory, and social behavior were assessed using behavioral protocols. Prefrontal cortex and hippocampus samples were collected and analyzed for lipid peroxidation levels using the TBARS assay and for BDNF protein expression using western blot. A single injection of 8-PN at both doses attenuated the behavioral impairments caused by LPS exposure in recognition memory, spatial memory, and social behavior tasks. 8-PN at both doses protected the prefrontal cortex and hippocampus against lipid peroxidation, and 8-PN at 2 mg/kg promoted increased BDNF protein expression in the hippocampus. This study demonstrates that 8-PN has potential neuroprotective effects in the female brain in vivo and may be a promising drug candidate for preventing cognitive impairments in women.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038065","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}