Phytotherapy Research最新文献

{"title":"Epoxymicheliolide Reduces Radiation-Induced Senescence and Extracellular Matrix Formation by Disrupting NF-κB and TGF-β/SMAD Pathways in Lung Cancer.","authors":"Heng Zhou, Yong Chen, Ningzu Jiang, Yanxian Ren, Jiayuan Zhuang, Yue Ren, Lin Shen, Chenghao Li","doi":"10.1002/ptr.8352","DOIUrl":"10.1002/ptr.8352","url":null,"abstract":"<p><p>Lung cancer is a major cause of cancer-related mortality, and radiotherapy is often limited by tumor resistance and side effects. This study explores whether epoxymicheliolide (ECL), a compound from feverfew, can enhance radiotherapy efficacy in lung cancer. We tested ECL on A549 and PC-9 lung cancer cell lines to evaluate its effect on x-ray irradiation. We measured apoptosis, NF-κB pathway inhibition, TGF-β secretion reduction, and epithelial-mesenchymal transition suppression. In vivo, C57BL/6 mice with lung tumors received ECL and radiotherapy. ECL enhanced the antiproliferative effects of x-ray irradiation, induced apoptosis in senescent cells, inhibited the NF-κB pathway, reduced TGF-β levels, and suppressed epithelial-mesenchymal transition. ECL also inhibited tumor growth and improved survival in mice. ECL is a promising adjunct to radiotherapy for lung cancer, improving treatment outcomes by targeting multiple tumor progression mechanisms. It offers potential for enhanced management of lung cancer.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591311","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":"Lack of Efficacy of Pomegranate Supplementation on Insulin Resistance and Sensitivity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Shao Yin, Fengya Zhu, Qian Zhou, Miao Chen, Xia Wang, Qiu Chen","doi":"10.1002/ptr.8362","DOIUrl":"https://doi.org/10.1002/ptr.8362","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The objective of this study is to assess the impact of pomegranate supplements on insulin resistance (IR) and insulin sensitivity through a systematic review and meta-analysis of randomized controlled trials (RCTs). Additionally, we aim to analyze the differences in efficacy among various pomegranate extracts and the sensitivity of different diseases to pomegranate supplementation. We conducted searches in PubMed, Embase, Web of Science, and Cochrane Library up to October 30, 2023, for relevant studies published in English. The treatment group required the intake of pomegranate extract for a minimum of 4 weeks, with no restrictions on the extract type. The control group received a placebo or a treatment excluding pomegranate extract. The primary outcome was homeostatic model assessment for insulin resistance (HOMA-IR) and fasting insulin (FI), and the secondary outcome was quantitative insulin sensitivity check index (QUICKI). RoB 2 was used to assess the risk of bias in the original studies. We pre-specified subgroup analyses based on types of intervention, intervention duration, health condition, and intervention dose. Sensitivity analysis was conducted to validate result stability, utilizing Begg's test and Egger's test for publication bias. Data synthesis and analysis were performed using Stata 15.1 software. This study included a total of 15 RCTs with 673 participants conducted in 7 countries. Risk of bias results indicated an overall low risk of bias of the articles. Participants included healthy individuals, overweight and obese individuals, non-alcoholic fatty liver disease (NAFLD) patients, type 2 diabetes (T2DM) patients, polycystic ovary syndrome (PCOS) patients, metabolic syndrome (MS) patients, and individuals with hyperlipidemia. Pomegranate extract variations included pomegranate juice (PJ), pomegranate seed oil (PSO) capsule, pomegranate/pomegranate peel (PP) extract capsule, and pomegranate peel-added bread. The control groups primarily received placebo treatments with varying dosage and frequency. No adverse reactions were reported in any of the studies. The summary results showed that compared to the control groups, pomegranate extract had no significant impact on improving HOMA-IR levels in participants (WMD = -0.03, 95%CI: -0.37 to 0.31, and p = 0.851) and FI (WMD = -0.03, 95%CI: -0.42 to 0.36, and p = 0.862). Additionally, there was no significant advantage of pomegranate extract on QUICKI changes in T2DM and PCOS patients (WMD = 0.00, 95%CI: 0.00 to 0.01, and p = 0.002). Subgroup analysis results indicated that pomegranate extract could improve HOMA-IR levels in PCOS patients (WMD = -0.42, 95%CI: -0.54 to -0.29, and p &lt; 0.001) and FI levels in T2DM, PCOS, and NAFLD patients. Our results indicate that pomegranate extract only improves HOMA-IR and FI levels in PCOS patients and FI levels in T2DM and NAFLD patients. No significant difference has been found for HOMA-IR, FI, or QUICKI in other metabolic diseases. The curre","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580951","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 Comprehensive Review of Antimicrobial Agents Against Clinically Important Bacterial Pathogens: Prospects for Phytochemicals.","authors":"Soumyadip Ghosh, Soumya Basu, Anand Anbarasu, Sudha Ramaiah","doi":"10.1002/ptr.8365","DOIUrl":"https://doi.org/10.1002/ptr.8365","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) hinders the effective treatment of a range of bacterial infections, posing a serious threat to public health globally, as it challenges the currently available antimicrobial drugs. Among the various modes of antimicrobial action, antimicrobial agents that act on membranes have the most promising efficacy. However, there are no consolidated reports on the shortcomings of these drugs, existing challenges, or the potential applications of phytochemicals that act on membranes. Therefore, in this review, we have addressed the challenges and focused on various phytochemicals as antimicrobial agents acting on the membranes of clinically important bacterial pathogens. Antibacterial phytochemicals comprise diverse group of agents found in a wide range of plants. These compounds have been found to disrupt cell membranes, inhibit enzymes, interfere with protein synthesis, generate reactive oxygen species, modulate quorum sensing, and inhibit bacterial adhesion, making them promising candidates for the development of novel antibacterial therapies. Recently, polyphenolic compounds have been reported to have proven efficacy against nosocomial multidrug-resistant pathogens. However, more high-quality studies, improved standards, and the adoption of rules and regulations are required to firmly confirm the clinical efficacy of phytochemicals derived from plants. Identifying potential challenges, thrust areas of research, and considering viable approaches is essential for the successful clinical translation of these compounds.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576537","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":"Therapeutic Potential of Polyphenols in Cellular Reversal of Patho-Mechanisms of Alzheimer's Disease Using In Vitro and In Vivo Models: A Comprehensive Review.","authors":"Monalisha Samal, Varsha Srivastava, Muzayyana Khan, Areeba Insaf, Naveen Reddy Penumallu, Aftab Alam, Bushra Parveen, Shahid Hussain Ansari, Sayeed Ahmad","doi":"10.1002/ptr.8344","DOIUrl":"https://doi.org/10.1002/ptr.8344","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is considered one of the most common neurological conditions associated with memory and cognitive impairment and mainly affects people aged 65 or above. Even with tremendous progress in modern neuroscience, a permanent remedy or cure for this crippling disease is still unattainable. Polyphenols are a group of naturally occurring potent compounds that can modulate the neurodegenerative processes typical of AD. The present comprehensive study has been conducted to find out the preclinical and clinical potential of polyphenols and elucidate their possible mechanisms in managing AD. Additionally, we have reviewed different clinical studies investigating polyphenols as single compounds or cotherapies, including those currently recruiting, completed, terminated, withdrawn, or suspended in AD treatment. Natural polyphenols were systematically screened and identified through electronic databases including Google Scholar, PubMed, and Scopus based on in vitro cell line studies and preclinical data demonstrating their potential for neuroprotection. A total of 63 significant polyphenols were identified. A multimechanistic pathway for polyphenol's mode of action has been proposed in the study. Out of 63, four potent polyphenols have been identified as promising potential candidates, based on their reported clinical efficacy. Polyphenols hold tremendous scope for the development of a future drug molecule as a phytopharmaceutical that may be incorporated as an adjuvant to the therapeutic regime. However, more high-quality studies with novel delivery methods and combinatorial approaches are required to overcome obstacles such as bioavailability and blood-brain barrier crossing to underscore the therapeutic potential of these compounds in AD management.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576541","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":"Therapeutic Potential of Ocimum basilicum L. Extract in Alleviating Autistic-Like Behaviors Induced by Maternal Separation Stress in Mice: Role of Neuroinflammation and Oxidative Stress.","authors":"Hossein Amini-Khoei, Nafiseh Taei, Hossein Tahmasebi Dehkordi, Zahra Lorigooini, Elham Bijad, Anahita Farahzad, Mohammad Rahimi Madiseh","doi":"10.1002/ptr.8360","DOIUrl":"https://doi.org/10.1002/ptr.8360","url":null,"abstract":"<p><p>A confluence of genetic, environmental, and epigenetic factors shapes autism spectrum disorder (ASD). Early-life stressors like MS play a contributing role in this multifaceted neurodevelopmental disorder. This research was to explore the efficacy of Ocimum basilicum L. (O.B.) extract in mitigating behaviors reminiscent of autism prompted by maternal separation (MS) stress in male mice, focusing on its impact on neuroinflammation and oxidative stress. MS mice were treated with O.B. extract at varying dosages (20, 40, and 60 mg/kg) from postnatal days (PND) 51-53 to PND 58-60. Behavioral experiments, including the Morris water maze, three-chamber test, shuttle box, and resident-intruder test, were conducted post-treatment. The method of maternal separation involved separating the pups from their mothers for 3 h daily, from PND 2 to PND 14. Molecular analysis of hippocampal tissue was performed to assess gene expression of Toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Hippocampal and serum malondialdehyde (MDA) levels and total antioxidant capacity (TAC) were measured. O.B. extract administration resulted in the amelioration of autistic-like behaviors in MS mice, as evidenced by improved spatial and passive avoidance memories and social interactions, as well as reduced aggression in behavioral tests. O.B. extract attenuated oxidative stress and neuroinflammation, as indicated by decreased MDA and increased TAC levels, as well as downregulation of TLR4, TNF-α, and IL-1β expression in the hippocampus. O.B. extract may offer a novel therapeutic avenue for ASD, potentially mediated through its anti-inflammatory and antioxidant properties.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576539","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 Systematic Review and Meta-Analysis of the Effects of Dietary Isoflavones on Female Hormone-Dependent Cancers for Benefit-Risk Evaluation.","authors":"Bandana Chakravarti, Swati Rajput, Anubhav Srivastava, Lokendra Kumar Sharma, Rohit Anthony Sinha, Naibedya Chattopadhyay, Jawed Akhtar Siddiqui","doi":"10.1002/ptr.8358","DOIUrl":"10.1002/ptr.8358","url":null,"abstract":"<p><p>Female hormone-dependent cancers depend on estrogen for their growth. Numerous studies have explored the antitumor effect of dietary isoflavones on female hormone-dependent cancers. Still, few clinical evidence supports the use of isoflavones in female hormone-dependent cancer patients. This study was performed to examine the impact of dietary isoflavones on tumor growth of female hormone-dependent cancers and accelerate the transformation of research from bench to bedside. We searched PubMed Medline, Web of Science, and Google Scholar for relevant articles related to the effect of dietary isoflavone on tumor growth of experimental animal models of female hormone-dependent cancers from 1998 to 2024. The effects of dietary isoflavones on tumor growth were analyzed between the control and treatment groups using comprehensive meta-analysis software (CMA). We included 30 studies describing tumor growth focused on female hormone-dependent cancer types, including breast, ovarian, and uterine cancers. Overall, a pooled analysis revealed that dietary isoflavones reduced tumor volume (Hedge's g = -1.151, 95% CI = -1.717 to -0.585, p = 0.000) and tumor weight (Hedge's g = -2.584, 95% CI = -3.618 to -1.549, p = 0.000). On the other hand, dietary isoflavones increased tumor area (Hedge's g = 1.136, 95% CI = 0.752 to 1.520, p = 0.000). Dietary isoflavones have potential benefits and risks in female hormone-dependent cancers. Therefore, caution should be exercised when considering the intake of dietary isoflavones in female hormone-dependent cancer patients, particularly in the form of supplements.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546774","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":"Curcumin on Human Health: A Comprehensive Systematic Review and Meta-Analysis of 103 Randomized Controlled Trials.","authors":"Ali Jafari, Maryam Abbastabar, Alireza Alaghi, Javad Heshmati, Francesca L Crowe, Mahdi Sepidarkish","doi":"10.1002/ptr.8340","DOIUrl":"https://doi.org/10.1002/ptr.8340","url":null,"abstract":"<p><p>The aim of this meta-analysis was to determine the effect of curcumin on a range of health outcomes. PubMed, EMBASE, Scopus, and Web of Science were searched from inception until September 2023. Randomized clinical trials (RCTs) that compared the effect of Curcuma longa L. with placebo were considered eligible. The risk of bias and overall certainty of evidence were assessed using the Newcastle-Ottawa Scale and Grading of Recommendations Assessment, Development, and Evaluation (GRADE), respectively. We meta-analyzed the effect sizes across eligible studies using the random-effects model. In total, 103 RCTs on 42 outcomes were included, incorporating a total population of 7216 participants. Overall, 23 out of 42 (55%) outcomes reported statistically significant effect sizes. The credibility of the evidence was rated as high for fasting blood sugar (FBS), C-reactive protein (CRP), high-density lipoprotein (HDL), and weight. The remaining outcomes presented moderate (waist circumference [WC], hip circumference [HC], body mass index [BMI], insulin, Homeostatic Model Assessment for Insulin Resistance [HOMA-IR], quantitative insulin-sensitivity check index [QUICKI], leptin, gamma-glutamyl transferase [GGT], glutathione [GSH], and superoxide dismutase [SOD]), low (14 outcomes), or very low (14 outcomes) evidence. In conclusion, curcumin supplementation can modify FBS and some glycemic indices, lipid parameters, as well as inflammatory and oxidative parameters. This updated summary of the accumulated evidence may help inform clinicians and future guidelines regarding medical and scientific interest in curcumin. However, due to limitations in the methodological quality of the included studies, well-designed and long-term RCTs with large sample sizes are needed. Trial registration: PROSPERO: CRD42021251969.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546776","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 Ginseng on Cognitive Function: A Systematic Review and Meta-Analysis.","authors":"Maogui Zeng, Kuan Zhang, Juan Yang, Yu Zhang, Pengcheng You, Lin Yan, Yiling Weng","doi":"10.1002/ptr.8359","DOIUrl":"https://doi.org/10.1002/ptr.8359","url":null,"abstract":"<p><p>Ginseng is a kind of traditional Chinese medicine. It is widely believed that ginseng can improve cognitive function, but its clinical efficacy is still controversial. This study aimed to systematically evaluate the effects of ginseng on cognitive function improvement. This is a systematic review and meta-analysis of the randomized controlled trials (RCTs). Searching PubMed, Web of Science, the Cochrane Library, and Medline databases to collect RCTs of ginseng on the effects of human cognitive function. The time range is from the establishment of the database to December 2023. The main intervention in the trials was ginseng preparation. The Cochrane risk-of-bias tool 2.0 (RoB2.0) and Jadad scale were used to assess the risk of bias and evaluate the quality of the included articles. After data extraction, meta-analysis was performed using Stata 17.0 software. A total of 15 RCTs were included, and 671 patients were analyzed. The subjects included healthy people, patients of cognitive impairment, schizophrenia, hospitalized, and Alzheimer's disease. The intervention measures were mainly ginseng preparations. The meta-analysis results indicated that ginseng has a significant effect on memory improvement (SMD = 0.19, 95%CI: 0.02-0.36, p < 0.05), especially at high doses (SMD = 0.33, 95%CI: 0.04-0.61, p < 0.05). Ginseng did not have a positive effect on overall cognition, attention, and executive function (SMD = 0.06, 95%CI: -0.64-0.77, p = 0.86; SMD = 0.06, 95%CI: -0.12 to 0.23, p = 0.54; SMD = -0.03, 95%CI: -0.28 to 0.21, p = 0.79). Ginseng has some positive effects on cognitive improvement, especially on memory improvement. But in the future, more high-quality studies are needed to determine the effects of ginseng on cognitive function. Trial Registration: Prospero: CRD42024514231.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546777","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":"Co-Micronized Palmitoylethanolamide and Rutin Associated With Hydroxytyrosol Recover Diabesity-Induced Hepatic Dysfunction in Mice: In Vitro Insights Into the Synergistic Effect.","authors":"S Melini, C Pirozzi, A Lama, F Comella, N Opallo, F Del Piano, E Di Napoli, M P Mollica, O Paciello, M C Ferrante, G Mattace Raso, R Meli","doi":"10.1002/ptr.8361","DOIUrl":"https://doi.org/10.1002/ptr.8361","url":null,"abstract":"<p><p>Metabolic dysfunction-associated fatty liver disease (MAFLD) and diabesity (diabetes related to obesity) are interrelated since glucose and lipid alterations play a vital role in the development of both disorders. Due to their multi-variant metabolic features, more than one drug or natural product may be required to achieve proper therapeutic effects. This study aimed to evaluate the effectiveness of a formulation containing co-micronized palmitoylethanolamide and rutin (PEA-Rut) associated with hydroxytyrosol (HT), namely NORM3, against hepatic damage and metabolic alterations in high-fat diet (HFD)-induced diabesity in mice. NORM3 decreased the body weight and fat mass of obese mice. The formulation improved HFD-altered insulin sensitivity and hepatic glucose production and metabolism, as shown by glucose, insulin, pyruvate tolerance tests, Western blot, and real-time PCR. In the liver, NORM3 limited macro- and micro-vacuolar steatosis, as revealed by morphological analysis, and reduced the associated hepatic inflammation. NORM3 counteracted lipid dysfunctions of HFD animals, activating AMPK, a key cellular energy sensor, and normalizing the expression of carnitine palmitoyl-transferase (CPT)1, a rate-limiting enzyme of fatty acid β-oxidation, and other genes involved in lipid homeostasis. Relevantly, the hepatic antioxidant activity of NORM3 was proved (reduced ROS and increased detoxifying factors and enzymes). Finally, in vitro synergistic protective effects of the components (PEA-Rut and HT) on H₂O₂-induced oxidative challenge in HepG2 were determined (ROS production, inflammation, and antioxidant defense). Our results show the beneficial effect of NORM3 and its potential as an innovative phytotherapeutic combination in limiting hepatic damage progression and counteracting glucose and lipid dysmetabolism associated with diabesity.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546775","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":"Formononetin Induces Ferroptosis in Activated Hepatic Stellate Cells to Attenuate Liver Fibrosis by Targeting NADPH Oxidase 4.","authors":"Ming-Xuan Liu, Ying-Ying Gu, Wen-Yuan Nie, Xiao-Ming Zhu, Meng-Jing Qi, Rui-Min Zhao, Wei-Zhong Zhu, Xiao-Ling Zhang","doi":"10.1002/ptr.8338","DOIUrl":"https://doi.org/10.1002/ptr.8338","url":null,"abstract":"<p><p>Ferroptosis is a newly discovered type of cell death that exerts a crucial role in hepatic fibrosis. Formononetin (FMN), a natural isoflavone compound mainly isolated from Spatholobus suberectus Dunn, shows multiple biological activities, including antioxidant, anti-inflammatory, and hepatoprotection. This research aims to explore the regulatory mechanism of FMN in liver fibrosis and the relationship between NADPH oxidase 4 (NOX4) and ferroptosis. The effects of FMN on HSC ferroptosis were evaluated in rat model of CCl₄-induced hepatic fibrosis. In vitro, N-acetyl-L-cysteine (NAC) and deferoxamine (DFO) were used to block ferroptosis and then explored the anti-fibrotic effect of FMN. The target protein of FMN was identified by bio-orthogonal click chemistry reaction as well as drug affinity responsive target stability (DARTS), cellular thermal shift (CETSA), surface plasmon resonance (SPR) assays, and isothermal titration calorimetry (ITC) analysis. Here, we found that FMN exerted anti-fibrotic effects via inducing ferroptosis in activated HSCs. NAC and DFO prevented FMN-induced ferroptotic cell death and collagen reduction. Furthermore, FMN bound directly to NOX4 through possible active amino acid residues sites, and increased NOX4-based NADPH oxidase activity to enhance levels of NADP⁺/NADPH, thus promoting ferroptosis of activated HSCs and relieving liver fibrosis. These results demonstrate that the direct target and mechanism by which FMN improves liver fibrosis, suggesting that FMN may be a natural candidate for further development of liver fibrosis therapy.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546779","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}