Phytotherapy Research最新文献

Triptolide Promotes Ferroptosis in Cervical Cancer Cell via NRF2/xCT/GPX4.

IF 6.1 2区医学

Phytotherapy Research Pub Date : 2024-12-19 DOI: 10.1002/ptr.8398

Miaomiao Feng, Haiwang Wu, Ling Zhu, Jie Gao, Gaopi Deng

{"title":"Triptolide Promotes Ferroptosis in Cervical Cancer Cell via NRF2/xCT/GPX4.","authors":"Miaomiao Feng, Haiwang Wu, Ling Zhu, Jie Gao, Gaopi Deng","doi":"10.1002/ptr.8398","DOIUrl":"https://doi.org/10.1002/ptr.8398","url":null,"abstract":"Cervical cancer (CC) is a serious risk to women's health; it is necessary to explore less toxic and more effective therapies to cure CC. Triptolide (Tri) is the principal active constituent found in \"Tripterygium Wilford,\" has been shown to have antitumor effects. This study set up to demonstrate whether Tri is capable of inducing ferroptosis in CC cells and its potential mechanism. In vitro, Tri was used to treat CC cells, and lipid peroxidation levels in CC cells were detected by flow cytometry, immunofluorescence, and other experiments; the molecular mechanism of Tri treatment of CC was explored by western blot; moreover, the regulatory effects of Tri on the NRF2/GPX4/xCT axis were verified by overexpressing NRF2 in reverse. In vivo, CC cells tumor-bearing mice were constructed to observe the effect of Tri treatment on tumor growth. In vitro, we have demonstrated that Tri prevents the growth and migration of CC cells. Further investigation revealed that Tri substantially enhances ferroptosis in CC cells by increasing lipid peroxidation accumulation. Mechanically, Tri significantly reduced the expression of NRF2, leading to a corresponding repression of the NRF2 downstream targets GPX4 and xCT. Moreover, overexpressing of NRF2 effectively reversed the impact of Tri on ferroptosis in CC cells. Additionally, animal experiments indicted that Tri markedly inhibited tumor size in nude mice by inhibiting the NRF2/GPX4/xCT axis. Tri exerts antitumor effects by triggering ferroptosis in CC cells through the NRF2/GPX4/xCT axis.","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855097","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}

引用次数: 0

Ilexgenin A Alleviates Myocardial Ferroptosis in Response to Ischemia Reperfusion Injury via the SIRT1 Pathway.

IF 6.1 2区医学

Phytotherapy Research Pub Date : 2024-12-19 DOI: 10.1002/ptr.8414

Bo Yang, Xiao-Yu Jue, Shang-Fei Luo, Zhang-Bin Tan, Li-Ning Yang, Yun-Ting Feng, Yong-Zhen Tan, Bin Liu, Jing-Zhi Zhang, Bo Deng, Wei-Wei Wu, Shuang-Wei Zhang

{"title":"Ilexgenin A Alleviates Myocardial Ferroptosis in Response to Ischemia Reperfusion Injury via the SIRT1 Pathway.","authors":"Bo Yang, Xiao-Yu Jue, Shang-Fei Luo, Zhang-Bin Tan, Li-Ning Yang, Yun-Ting Feng, Yong-Zhen Tan, Bin Liu, Jing-Zhi Zhang, Bo Deng, Wei-Wei Wu, Shuang-Wei Zhang","doi":"10.1002/ptr.8414","DOIUrl":"https://doi.org/10.1002/ptr.8414","url":null,"abstract":"Myocardial ischemia-reperfusion (I/R) injury has emerged as an increasingly serious cardiovascular health concern worldwide, with ferroptosis playing a pivotal role as the underlying pathogenic process. This study aimed to investigate the pharmacological effect and mechanism of Ilexgenin A on cardiomyocyte ferroptosis induced by myocardial I/R injury. In vivo, we established a murine anterior descending artery ligation/recanalization model to evaluate the cardioprotective effect of Ilexgenin A. Bioinformatics analysis, molecular docking, and Surface Plasmon Resonance imaging were conducted to predict the pharmacological targets of Ilexgenin A. In vitro experiments, the neonatal rat cardiomyocytes (NRCMs) were utilized to further explore the mechanism of Ilexgenin A in inhibiting ferroptosis using chemiluminescence and immunofluorescence staining, electron microscopy, biochemical assay, RT-qPCR, western blotting, and so on. The results showed that Ilexgenin A protected against cardiac dysfunction, ameliorated myocardial ferroptosis and mitochondrial damage induced by murine myocardial I/R injury via the silence information regulator 1 (SIRT1) pathway, the trend was consistently observed in NRCMs. Additionally, the SIRT1 knockdown by siRNA delivery partially abrogated the beneficial effects of Ilexgenin A on ameliorating mitochondrial damage, and then aggravated erastin-induced ferroptosis in NRCMs. Overall, Our research demonstrated that the inhibition of ferroptosis via the SIRT1 pathway was one of the mechanisms by which Ilexgenin A exerted cardioprotective effect.","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855094","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}

引用次数: 0

Isoliquiritigenin Exhibits Anti-Inflammatory Responses in Acute Lung Injury by Covalently Binding to the Myeloid Differentiation Protein-2 Domain.

IF 6.1 2区医学

Phytotherapy Research Pub Date : 2024-12-19 DOI: 10.1002/ptr.8411

Liu Yang, Haoran Nie, Yan Du, Xuyang Liu, Bangrong Cai, Jiansheng Li

{"title":"Isoliquiritigenin Exhibits Anti-Inflammatory Responses in Acute Lung Injury by Covalently Binding to the Myeloid Differentiation Protein-2 Domain.","authors":"Liu Yang, Haoran Nie, Yan Du, Xuyang Liu, Bangrong Cai, Jiansheng Li","doi":"10.1002/ptr.8411","DOIUrl":"https://doi.org/10.1002/ptr.8411","url":null,"abstract":"Acute lung injury (ALI), a systemic inflammatory response with high morbidity, lacks effective pharmacological therapies. Myeloid differentiation protein-2 (MD2) has emerged as a promising therapeutic target for ALI. Herein, we aimed to evaluate the ability of isoliquiritigenin (ISL), a natural flavonoid found in licorice as a novel MD2 inhibitor, to inhibit lipopolysaccharide (LPS)-induced ALI. We established a mouse ALI model and a RAW 264.7 cell injury model through LPS administration. Then, lung injury was assessed through histopathological examination, and the effects of ISL were evaluated using immunofluorescence, western blotting, reverse transcription-quantitative polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assays. In addition, the interaction between ISL and MD2 was investigated through co-immunoprecipitation and LPS displacement assays. Molecular docking and liquid chromatography/mass spectrometry analyses were employed to predict the ISL-binding domain of MD2. We found that ISL covalently bound to the Cysteine 133 residue of MD2, disrupting the formation of the LPS/MD2/toll-like receptor 4 complex, and ISL significantly suppressed proinflammatory cytokine production and reactive oxygen species generation in LPS-induced RAW264.7 cells. Moreover, ISL significantly alleviated lung injury in LPS-induced mice, reducing pulmonary microvascular permeability, inflammatory cell infiltration, and inflammatory cytokine expression. The underlying mechanism of ISL involved the inhibition of nuclear factor kappa B and the p38 mitogen-activated protein kinase pathway. Our findings supported that MD2 is the direct target of ISL in mediating its anti-inflammatory response in vivo and in vitro, and it holds potential as a therapeutic candidate for treating ALI and other inflammatory diseases.","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855095","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}

引用次数: 0

Natural Compounds and Their Analogs as Antivirals Against Dengue Virus: A Review.

IF 6.1 2区医学

Phytotherapy Research Pub Date : 2024-12-19 DOI: 10.1002/ptr.8408

Amalina Ghaisani Komarudin, Azis Adharis, R Tedjo Sasmono

引用次数: 0

Unlocking Natural Potential: Antibody-Drug Conjugates With Naturally Derived Payloads for Cancer Therapy.

IF 6.1 2区医学

Phytotherapy Research Pub Date : 2024-12-17 DOI: 10.1002/ptr.8407

Xue Jiang, Wan Najbah Nik Nabil, Yufei Ze, Rongchen Dai, Zhichao Xi, Hongxi Xu

{"title":"Unlocking Natural Potential: Antibody-Drug Conjugates With Naturally Derived Payloads for Cancer Therapy.","authors":"Xue Jiang, Wan Najbah Nik Nabil, Yufei Ze, Rongchen Dai, Zhichao Xi, Hongxi Xu","doi":"10.1002/ptr.8407","DOIUrl":"https://doi.org/10.1002/ptr.8407","url":null,"abstract":"Natural compound-derived chemotherapies remain central to cancer treatment, however, they often cause off-target side effects that negatively impact patients' quality of life. In contrast, antibody-drug conjugates (ADCs) combine cytotoxic payloads with antibodies to specifically target cancer cells. Most approved and clinically investigated ADCs utilize naturally derived payloads, while those with conventional synthetic molecular payloads remain limited. This review focuses on approved ADCs that enhance the efficacy of naturally derived payloads by linking them with antibodies. We provide an overview of the core components of ADCs, their working mechanisms, and FDA-approved ADCs featuring naturally derived payloads, such as calicheamicin, camptothecin, dolastatin 10, maytansine, pyrrolbenzodiazepine (PBD), and the immunotoxin Pseudomonas exotoxin A. This review also explores recent clinical advancements aimed at broadening the therapeutic potential of ADCs, their applicability in treating heterogeneously composed tumors and their potential use beyond oncology. Additionally, this review highlights naturally derived payloads that are currently being clinically investigated but have not yet received approval. By summarizing the current landscape, this review provides insights into promising avenues for exploration and contributes to the refinement of treatment protocols for improved patient outcomes.","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838624","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}

引用次数: 0

Herbal Approaches to Diabetes Management: Pharmacological Mechanisms and Omics-Driven Discoveries.

IF 6.1 2区医学

Phytotherapy Research Pub Date : 2024-12-17 DOI: 10.1002/ptr.8410

Debajyoti Roy, Maitrayee Ghosh, Naresh Kumar Rangra

{"title":"Herbal Approaches to Diabetes Management: Pharmacological Mechanisms and Omics-Driven Discoveries.","authors":"Debajyoti Roy, Maitrayee Ghosh, Naresh Kumar Rangra","doi":"10.1002/ptr.8410","DOIUrl":"https://doi.org/10.1002/ptr.8410","url":null,"abstract":"Diabetes mellitus is a chronic metabolic disorder marked by hyperglycemia, resistance to insulin, and impaired function of the pancreatic β-cells; it advances into more serious complications like nephropathy, neuropathy, cardiovascular disease, and retinopathy; herbal medicine has indicated promise in not just mitigating the symptoms but also in managing the complications. This review would aim to evaluate the pharmacological aspect of the botanical therapies Anacardium occidentale, Allium sativum, Urtica dioica, and Cinnamomum zeylanicum, as well as their bioactive phytochemicals, quercetin, resveratrol, berberine, and epigallocatechin gallate (EGCG). In this review, we discuss their mechanisms for secreting the insulin sensitizers, carbohydrate-hydrolyzing enzymes, reduction in oxidative stress and effectiveness against diabetic complications-all through sensitivity to insulin. Great emphasis is laid on the integration of multi-omics technologies such as genomics, proteomics, metabolomics, and transcriptomics in the discovery of bioactive compounds. The nature of the technologies can evaluate the intrinsic complexities of herbal pharmacology and even identify therapeutic candidates. Finally, the review refers to the meagre clinical trials on the efficiency of these compounds in the metabolism of humans. High-quality future research, such as human large-scale trials, would be emphasized; improvement in the clinical validity of a drug might come from improved study design, better selection of potentially usable biomarkers, and enhanced safety profiles to guarantee efficacy with lessened risks.","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838580","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}

引用次数: 0

Beta-Caryophyllene Augments Radiotherapy Efficacy in GBM by Modulating Cell Apoptosis and DNA Damage Repair via PPARγ and NF-κB Pathways. 通过PPARγ和NF-κB途径调节细胞凋亡和DNA损伤修复，β-卡里叶烯可增强GBM放疗疗效

IF 6.1 2区医学

Phytotherapy Research Pub Date : 2024-12-13 DOI: 10.1002/ptr.8413

Hui-Wen Chan, Wei-Chan Lin, Deng-Yu Kuo, Hui-Yen Chuang

{"title":"Beta-Caryophyllene Augments Radiotherapy Efficacy in GBM by Modulating Cell Apoptosis and DNA Damage Repair via PPARγ and NF-κB Pathways.","authors":"Hui-Wen Chan, Wei-Chan Lin, Deng-Yu Kuo, Hui-Yen Chuang","doi":"10.1002/ptr.8413","DOIUrl":"https://doi.org/10.1002/ptr.8413","url":null,"abstract":"Glioblastoma multiforme (GBM) is a highly aggressive brain malignancy with limited treatment options. Radiotherapy (RT) is often used for treating unresectable GBM; however, the outcomes are often limited due to the radioresistance of GBM. Therefore, the discovery of potential radiosensitizers to enhance GBM responses to RT is crucial. Beta-caryophyllene (BCP), a natural cannabinoid, promotes cancer apoptosis by upregulating the PPARγ signaling pathway and can cross the blood-brain barrier due to its lipophilic nature. This study aimed to evaluate the radiosensitizing potential of BCP in GBM cells. U87MG and GL261 cells and a GL261 tumor-bearing model were treated with RT, BCP, or both. Treatment efficacy was assessed using the MTT assay and tumor growth tracking, and the underlying mechanisms were investigated using western blotting, immunofluorescence staining, and other analyses. BCP synergistically enhanced the efficacy of RT in cell culture, as evidenced by the combination index determined through the MTT assay. This enhancement was mediated by the BCP-induced deceleration of DNA damage repair, as demonstrated by sustained γH2AX signal, upregulated PPARγ levels, and reduced expression of pAKT, pERK, and NF-κB, indicating apoptosis induction and inhibition of survival pathways. BCP significantly inhibited tumor growth in GL261 tumor-bearing mice with no discernible side effects. These findings indicate that BCP may serve as a potential radiosensitizer for improving RT outcomes in GBM by inhibiting DNA repair, inducing apoptosis, and suppressing anti-apoptotic and survival pathways.","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818959","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}

引用次数: 0

Role of Flavonoids in Mitigating the Pathological Complexities and Treatment Hurdles in Alzheimer's Disease.

IF 6.1 2区医学

Phytotherapy Research Pub Date : 2024-12-11 DOI: 10.1002/ptr.8406

Shivani Chib, Bhaskar Jyoti Dutta, Rishabh Chalotra, Md Abubakar, Puneet Kumar, Thakur Gurjeet Singh, Randhir Singh

{"title":"Role of Flavonoids in Mitigating the Pathological Complexities and Treatment Hurdles in Alzheimer's Disease.","authors":"Shivani Chib, Bhaskar Jyoti Dutta, Rishabh Chalotra, Md Abubakar, Puneet Kumar, Thakur Gurjeet Singh, Randhir Singh","doi":"10.1002/ptr.8406","DOIUrl":"https://doi.org/10.1002/ptr.8406","url":null,"abstract":"With the passage of time, people step toward old age and become more prone to several diseases associated with the age. One such is Alzheimer's disease (AD) which results into neuronal damage and dementia with the progression of age. The existing therapeutics has been hindered by various enkindles like less eminent between remote populations, affordability issues and toxicity profiles. Moreover, lack of suitable therapeutic option further worsens the quality of life in older population. Developing an efficient therapeutic intervention to cure AD is still a challenge for medical fraternity. Recently, alternative approaches attain the attention of researchers to focus on plant-based therapy in mitigating AD. In this context, flavonoids gained centrality as a feasible treatment in modifying various neurological deficits. This review mainly focuses on the pathological facets and economic burden of AD. Furthermore, we have explored the possible mechanism of flavonoids with the preclinical and clinical aspects for curing AD. Flavonoids being potential therapeutic, target the pathogenic factors of AD such as oxidative stress, inflammation, metal toxicity, Aβ accumulation, modulate neurotransmission and insulin signaling. In this review, we emphasized on potential neuroprotective effects of flavonoids in AD pathology, with focus on both experimental and clinical findings. While preclinical studies suggest promising therapeutic benefits, clinical data remains limited and inconclusive. Thus, further high-quality clinical trials are necessary to validate the efficacy of flavonoids in AD. The study aim is to promote the plant-based therapies and encourage people to add flavonoids to regular diet to avail the beneficial effects in preventive therapy for AD.","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807852","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}

引用次数: 0

Smart Polymer-Based Delivery Systems for Curcumin in Colon Cancer Therapy: A Review.

IF 6.1 2区医学

Phytotherapy Research Pub Date : 2024-12-11 DOI: 10.1002/ptr.8394

Adithya Jayaprakash Kamath, Asawari Dilip Donadkar, Bhagyalakshmi Nair, Ayana R Kumar, M Sabitha, Gautam Sethi, Abhay Singh Chauhan, Lekshmi R Nath

{"title":"Smart Polymer-Based Delivery Systems for Curcumin in Colon Cancer Therapy: A Review.","authors":"Adithya Jayaprakash Kamath, Asawari Dilip Donadkar, Bhagyalakshmi Nair, Ayana R Kumar, M Sabitha, Gautam Sethi, Abhay Singh Chauhan, Lekshmi R Nath","doi":"10.1002/ptr.8394","DOIUrl":"https://doi.org/10.1002/ptr.8394","url":null,"abstract":"Curcumin, a well-known bioactive component, has profound effects against colon cancer. However, the limitations are poor systemic absorption, off-target distribution, chemical instability, short half-life, and less concentration reaching tumor tissues. Several drug delivery systems have been evaluated so far to deliver effective concentrations of curcumin to the malignant tissues. This review aims to explore the role of smart polymers in overcoming limitations in curcumin delivery against colon cancer. Literature of the past 10 years was collected from Scopus, PubMed/Medline, Google Scholar, and Science Direct using specific keywords. Several preclinical and clinical studies of curcumin against colon cancer with the inclusion of smart polymers were screened using keywords like \"FDA-approved biomaterials,\" \"stimuli-responsive polymer,\" \"smart biomaterial,\" and so forth. Smart polymer phrase is used to describe all the mentioned polymers in the manuscript. Stimuli-responsive polymers, including poly-lactic-co-glycolic acid (PLGA), polyethylene glycol (PEG), Eudragit, cyclodextrin, and chitosan, have emerged as promising candidates for curcumin delivery against colon cancer. These polymers facilitate controlled drug release in response to stimuli such as temperature, pH, and enzymes, while offering biocompatibility, biodegradability, and safety. The five selected FDA-approved smart polymers exhibit the potential for enhancing curcumin delivery against colon cancer.","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807853","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}

引用次数: 0

Astragaloside IV Alleviates Acute Hepatic Injury by Regulating Macrophage Polarization and Pyroptosis via Activation of the AMPK/SIRT1 Signaling Pathway.

IF 6.1 2区医学

Phytotherapy Research Pub Date : 2024-12-11 DOI: 10.1002/ptr.8403

Gang Kuang, Yisi Zhao, Liuyang Wang, Tingyu Wen, Panting Liu, Bei Ma, Qiaozhi Peng, Fang Xu, Lin Ye, Jing Fan

{"title":"Astragaloside IV Alleviates Acute Hepatic Injury by Regulating Macrophage Polarization and Pyroptosis via Activation of the AMPK/SIRT1 Signaling Pathway.","authors":"Gang Kuang, Yisi Zhao, Liuyang Wang, Tingyu Wen, Panting Liu, Bei Ma, Qiaozhi Peng, Fang Xu, Lin Ye, Jing Fan","doi":"10.1002/ptr.8403","DOIUrl":"https://doi.org/10.1002/ptr.8403","url":null,"abstract":"Acute hepatic injury (AHI) is associated with poor prognosis in sepsis patient; however, to date, no specific therapeutic approach has been established for this disease. Therefore, we aimed to explore the effects and action mechanisms of Astragaloside IV (AS) on AHI. C57BL/6 mice, RAW264.7 cells, and bone marrow-derived macrophages were used in this study. Sepsis-associated AHI model mice were established using lipopolysaccharide + D-galactosamine. Pathological examination of liver tissues and serum alanine aminotransferase/aspartate aminotransferase was performed to evaluate the liver function. Moreover, inflammatory cytokine levels, proportion of M1/M2 macrophages and their marker levels, and cell pyroptosis-related indicator levels were determined in the liver of the AHI model mice with or without AS treatment. AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) expression was determined after AS treatment. Additionally, inflammatory cytokine levels, liver injury, and macrophage polarization were evaluated after inhibiting the AMPK/SIRT1 pathway. AS alleviated lipopolysaccharide + D-galactosamine-induced AHI and inhibited inflammatory reactions in the blood and liver of mice. AS also promoted the M1-to-M2 phenotypic transformation of macrophages in the liver of AHI model mice and in vitro, thereby decreasing the pro-inflammatory cytokine levels and increasing the anti-inflammatory cytokine levels. AS increased AMPK and SIRT1 levels in the liver and macrophages. Furthermore, AS improved liver injury by elevating the expression of the AMPK/SIRT1 signaling pathway and inhibiting pyroptosis in macrophages. Overall, AS alleviated AHI by promoting M1-to-M2 macrophage transformation and inhibiting macrophage pyroptosis via activation of the AMPK/SIRT1 signaling pathway.","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807839","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}

引用次数: 0