Phytomedicine最新文献

{"title":"Hyperoside alleviates zearalenone-induced liver injury by regulating mitochondrial calcium overload mediated excessive autophagy","authors":"Tianyu Han ,&nbsp;Lulu Wang ,&nbsp;Yan jiang ,&nbsp;Shanshan Fei ,&nbsp;Yiding Liu ,&nbsp;Zhijun Liu ,&nbsp;Tong Wang ,&nbsp;Baiwen Guan ,&nbsp;Yu Yang ,&nbsp;Guangliang Shi","doi":"10.1016/j.phymed.2025.156880","DOIUrl":"10.1016/j.phymed.2025.156880","url":null,"abstract":"<div><h3>Background</h3><div>Zearalenone (ZEA), one of the most common mycotoxins in moldy plants, can cause ferroptosis in the liver. Hyperoside (Hyp) is mainly derived from <em>Hypericum perforatum</em> and exerts hepatoprotective, neuroprotective, and cardioprotective effects. It is not known whether Hyp alleviates ZEA-induced ferroptosis-related damage</div></div><div><h3>Aim</h3><div>The protective effect of Hyp on ZEA-induced liver injury was studied and its underlying mechanisms were elucidated.</div></div><div><h3>Methods</h3><div>The protective effect of Hyp on ZEA-induced liver injury was determined based on ALT and AST levels and by using H&amp;E staining and transmission electron microscopy. The protective effect of Hyp in attenuating ferroptosis was determined by measuring mitophagy- and ferroptosis-related indices. CETSA and siRNA transfection were used to determine the targeting of Hyp to MCU protein.</div></div><div><h3>Results</h3><div>Hyp attenuated ZEA-induced ferroptosis and excessive mitophagy in hepatocytes, and use of Hyp or FUNDC1 knockdown by siRNA decreased ferroptosis in AML12 cells. Furthermore, Hyp attenuated ZEA exposure–induced Gpx4 interaction with FUNDC1 and reversed the recruitment and degradation of glutathione peroxidase 4 to mitochondria. Hyp was found to target MCU protein to attenuate mitochondrial Ca²⁺ overload and mitophagy induced by upregulated ZEA exposure. MCU knockdown reversed ZEA-induced mitophagy. Hyp also reversed ZEA-induced excessive mitochondrial fission and impairment in mitochondrial function.</div></div><div><h3>Conclusion</h3><div>Our study demonstrated that Hyp could alleviate ZEA induced ferroptosis by targeting MCU to inhibit mitochondrial Ca²⁺overloaded mitophagy.Our findings provide evidence for Hyp as an effective treatment in alleviating ferroptosis-related liver injury.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156880"},"PeriodicalIF":6.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of Gastrodia elata and its compounds in a Caenorhabditis elegans Alzheimer’s disease model","authors":"Yanqing Zhang ,&nbsp;Xiaotong Zhao ,&nbsp;Li Gong ,&nbsp;Changjiangsheng Lai ,&nbsp;Jing Liu ,&nbsp;Junbo Xie","doi":"10.1016/j.phymed.2025.156876","DOIUrl":"10.1016/j.phymed.2025.156876","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by learning and memory impairments, primarily caused by excessive β-amyloid protein (Aβ) accumulation, which induces neurotoxicity and metabolic dysfunction. Gastrodia elata (GE), a medicinal herb, has demonstrated antioxidant, antidepressant, and neuroprotective properties, making it a promising candidate for treating neurological diseases. However, systematic studies on its active compounds improving learning and memory through targeted metabolomics remain limited.</div></div><div><h3>Purpose</h3><div>This study aimed to evaluate the neuroprotective effects of Gastrodia elata (GE) and its active compounds, with a specific focus on learning and memory impairments in Alzheimer’s disease.</div></div><div><h3>Methods</h3><div>Using Caenorhabditis elegans (<em>C. elegans</em>) models of AD, the effects of GE and its active compounds were assessed through chemotaxis assays, targeted metabolomics, and LC-QQQ-MS analysis. Key neurotransmitter levels, including l-Leucine (l-Leu), l-Phenylalanine (l-Phe), γ-aminobutyric acid (GABA), and Acetylcholine (ACh), were quantified. The study also utilized principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) to investigate metabolic biomarkers.</div></div><div><h3>Results</h3><div>Parishin E (BG E) was identified as the most effective compound in reducing Aβ levels and modulating key biomarkers associated with learning and memory impairments. LC-QQQ-MS analysis showed that BG E restored neurotransmitter levels closer to those of healthy controls. GE extracts (100 μg/ml) and the positive control Huperzine A (Hup A, 8 μg/ml) significantly delayed paralysis in AD C. elegans models. PCA and OPLS-DA analyses confirmed that BG E normalized metabolic biomarkers and key neurotransmitter levels associated with AD.</div></div><div><h3>Conclusion</h3><div>These findings highlight the therapeutic potential of Gastrodia elata, particularly its active compound Parishin E (BG E), in mitigating learning and memory impairments in Alzheimer’s disease. This study provides a foundation for further validation in advanced models and supports the development of natural therapeutics for neurological disorders.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156876"},"PeriodicalIF":6.7,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lingguizhugan decoction ameliorates renal injury secondary to heart failure by improving pyroptosis through TLR4/NF-KB/IRE1α pathway","authors":"Jiayu Lv ,&nbsp;Zhenyue Fu ,&nbsp;Yuxin Wang ,&nbsp;Chunmei Chen ,&nbsp;Yajiao Wang ,&nbsp;Bingxuan Zhang ,&nbsp;Huaqin Wu ,&nbsp;Qingqiao Song ,&nbsp;Yumeng Li","doi":"10.1016/j.phymed.2025.156862","DOIUrl":"10.1016/j.phymed.2025.156862","url":null,"abstract":"<div><h3>Background</h3><div>Chronic heart failure (CHF) and chronic kidney disease (CKD) mutually promote the onset and progression of each other. Renal injury caused by heart failure currently lacks effective treatments. Previous studies have shown that Linggui Zhugan decoction (LGZGD) can significantly improve heart failure (HF) and cardiac remodeling, and has been reported to have renal protective effects. However, the effects and mechanisms of LGZGD in heart failure-induced renal injury remain unclear.</div></div><div><h3>Purpose</h3><div>Based on these findings, this study aims to investigate the effects and underlying mechanisms of LGZGD on renal injury secondary to HF.</div></div><div><h3>Study Design</h3><div>We used network pharmacology to predict potential targets of LGZGD in the treatment of cardiorenal syndrome (CRS). An in vivo model of CRS with right heart failure and venous congestion was established by a single intraperitoneal injection of monocrotaline (MCT). TNF-α-stimulated NRK52E cells were used as an in vitro model. We validated the effects of LGZGD in both in vivo and in vitro experiments,. Additionally, molecular docking with the components of LGZGD identified previously was performed to predict potential targets of action.</div></div><div><h3>Results</h3><div>LGZGD significantly improved heart and kidney function as well as renal histopathological changes in CRS rats. It inhibited the TLR4/NF-κB/IRE1α pathway in the kidneys and downregulated the expression of pyroptosis-related proteins (NLRP3, GSDMD, Caspase-1, IL-18, and IL-1β). Both LGZGD-containing serum and the TLR4 inhibitor (TAK-242) significantly reduced apoptosis in TNF-α-stimulated NRK52E cells and decreased the levels of TLR4/NF-κB/IRE1α pathway signaling and pyroptosis-related proteins. Molecular docking suggested that neoliquiritin (CID_51666248), enoxolon (CID_10114), and liquiritin (CID_503737) could stably bind to key targets such as IRE1α, caspase-1, and NF-κB.</div></div><div><h3>Conclusion</h3><div>This study demonstrated for the first time that LGZGD might ameliorate renal injury secondary to HF by improving pyroptosis through the TLR4/NF-κB/IRE1α pathway, which may provide valuable insights for future research in the treatment of CRS.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156862"},"PeriodicalIF":6.7,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network pharmacology and in-depth blood proteomics reveal the mechanism of Buqi Tongluo capsules in treating bone destruction in osteoarthritis","authors":"Haishan Li ,&nbsp;Jiasheng Yang ,&nbsp;Wei Deng ,&nbsp;Tengpeng Zhou ,&nbsp;Danqing Guo ,&nbsp;Yongxian Li ,&nbsp;Guoye Mo ,&nbsp;Guangwei Wen ,&nbsp;Jiake Xu ,&nbsp;Yiyi Lai ,&nbsp;Shuncong Zhang","doi":"10.1016/j.phymed.2025.156867","DOIUrl":"10.1016/j.phymed.2025.156867","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Osteoarthritis (OA) is the most prevalent form of arthritis, characterized by a rapidly increasing global incidence. Once OA develops, it initiates an irreversible process of bone destruction, which can lead to joint dysfunction or disability, and currently, no cure exists. Traditional Chinese medicine formulations, such as Buqi Tongluo Capsule (BQTL), are known for their ability to promote blood circulation, relieve pain, and unblock meridians, and are widely used to treat pain-related conditions. However, the effects of BQTL on OA-related bone destruction remain unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aims to investigate the safety and efficacy of BQTL in treating OA bone destruction using a multi-method approach, including bioinformatics analysis, network pharmacology, in-depth blood proteomics, and an ACLT-induced OA rat model. The study also seeks to identify active components of BQTL using UHPLC&lt;img&gt;HRMS, LC-MS/MS and SPR techniques and to explore its potential mechanisms of action in BMMs-induced osteoclasts.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Network pharmacology analysis was used to predict the main active ingredients, key pathways, and targets of BQTL for OA treatment. An ACLT-induced OA rat model was employed to evaluate the &lt;em&gt;in vivo&lt;/em&gt; efficacy of BQTL. Articular bone destruction and serum marker expression were assessed using Micro CT and ELISA. Hepatotoxicity and nephrotoxicity were evaluated via ELISA and HE staining. Key protein expression related to cartilage, osteoclastogenesis, and inflammation was detected using TRAP staining, Safranin O-Fast Green staining, and immunohistochemistry. UHPLC&lt;img&gt;HRMS and LC-MS/MS was used to identify potential active components and compound concentrations of BQTL &lt;em&gt;in vivo&lt;/em&gt;. Surface plasmon resonance (SPR), molecular docking, and dynamics simulations were employed to validate interactions between active ingredients and key targets. In-depth blood proteomics was used to explore the mechanism of action of BQTL in OA treatment. Cytotoxicity of Buqi Tongluo capsule-containing serum (BQTLS) was assessed using the CCK-8 assay. The inhibitory effects of BQTLS on osteoclastogenesis were evaluated in an osteoclast model induced by BMMs, with TRAP staining used to analyze osteoclast number and average area. F-actin staining and immunofluorescence were used to assess osteoclast morphology, function, and ROS production. IF, WB, and RT-PCR were employed to detect protein expression related to key signaling pathways, osteoclastogenesis, and ROS. Lentiviral transfection with overexpressed RAGE was used for rescue verification of the molecular mechanism of upstream and downstream pathways.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;&lt;em&gt;In vivo&lt;/em&gt; findings demonstrated that BQTL reduced proteins associated with osteoclast activity and inflammation in subchondral bone, decreased osteoclastogenesis, and mitigated articular cartilage degradation. Oral administr","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156867"},"PeriodicalIF":6.7,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary microvascular endothelial glycocalyx degradation as a key driver in COPD progression and its protection by Tongxinluo","authors":"Jing Guo ,&nbsp;Jiemeng Sun ,&nbsp;Mingyu Xiong ,&nbsp;Le Wang ,&nbsp;Ningxin Han ,&nbsp;Tongxing Wang ,&nbsp;Zhuo He ,&nbsp;Caiyun Yuan ,&nbsp;Yan Ma ,&nbsp;Hui Qi ,&nbsp;Yunlong Hou ,&nbsp;Zhenhua Jia","doi":"10.1016/j.phymed.2025.156878","DOIUrl":"10.1016/j.phymed.2025.156878","url":null,"abstract":"<div><h3>Background</h3><div>Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality worldwide. Pulmonary microvascular endothelial glycocalyx (PMEG) has been found to be significantly reduced in COPD, but the mechanism, cause, and effect of the reduction on COPD progression are inconclusive.</div></div><div><h3>Objective</h3><div>This study aims to explore the mechanisms and consequences underlying PMEG degradation in COPD. Additionally, we strive to ascertain whether Tongxinluo (TXL)’s protective role in COPD is mediated through the preservation of PMEG integrity.</div></div><div><h3>Methods</h3><div>A staged cigarette smoke (CS) exposure model was employed to investigate the timeline, trajectory, mechanisms, and causes of glycocalyx degradation, with in vitro validation. The in vivo glycocalyx degradation model was induced by intravenous injection of glycocalyx hydrolase along with CS exposure. The protective effect of TXL on glycocalyx integrity was examined in CS-exposed mice treated with TXL.</div></div><div><h3>Results</h3><div>PMEG degradation occurs as early as 2 weeks after CS exposure and worsens as the disease advances. Multiple glycocalyx degrading enzyme upregulation at different time points collectively results in consistent glycocalyx component degradation. Mechanistically, CS or reactive oxygen species (ROS) exposure elevates pro-inflammatory cytokine secretion, leading to an increase in glycocalyx hydrolysis expression and subsequent PMEG degradation on the endothelial cell (EC) surface. PMEG degradation further promotes inflammatory cell infiltration and accelerates endothelial apoptosis, ultimately driving disease progression in COPD. TXL alleviates oxidative stress, reverses the upregulation of PMEG degrading enzyme, preserves PMEG integrity, reduces endothelial cell apoptosis, and mitigates COPD pathology.</div></div><div><h3>Conclusion</h3><div>In summary, this study provides groundbreaking insights into the role of PMEG degradation in COPD pathogenesis and introduces TXL as a novel therapeutic agent with the potential to preserve PMEG integrity and mitigate COPD progression. These findings significantly advance our understanding of COPD and offer innovative directions for future research and therapeutic development.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156878"},"PeriodicalIF":6.7,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angoroside C: A potent AMPK activator in the aqueous extract of Scrophularia ningpoensis, alleviates metabolic syndrome in db/db mice","authors":"Xiaohan Li ,&nbsp;Yue Zhang ,&nbsp;Chunxiao Yu ,&nbsp;Xu Guo ,&nbsp;Xiangxiang Fu ,&nbsp;Shiqi Chen ,&nbsp;Yanguo Gao ,&nbsp;Yu Zhang ,&nbsp;Qin Xiang ,&nbsp;Wei Lu ,&nbsp;Yonghong Zhang ,&nbsp;Qibin Wang ,&nbsp;Li Chen ,&nbsp;Tao Zheng","doi":"10.1016/j.phymed.2025.156873","DOIUrl":"10.1016/j.phymed.2025.156873","url":null,"abstract":"<div><h3>Background</h3><div><em>Scrophularia ningpoensis</em> Hemsl. (SN) is a traditional herbal medicine used for treating diabetes mellitus (DM). Previous studies indicated that the aqueous extract of SN (AESN) improves type 2 DM (T2DM) by activating AMP-activated protein kinase (AMPK), but the active components were unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to identify the compound in AESN responsible for AMPK activation and to verify its therapeutic effects on T2DM.</div></div><div><h3>Methods</h3><div>Rats were administered AESN intragastrically. The absorbed compounds in serum samples were analyzed using LC-MS/MS and subjected to molecular docking with AMPK. The compound with the highest docking score was further verified using SPR, CETSA, and TR-FRET to confirm its effects on AMPK activation. Primary mouse hepatocytes were used to examine the effects of angoroside C (ANC) on AMPK activity, Akt/GSK3β signaling, NLRP3 inflammasome activation, and lipid accumulation. An AMPK inhibitor was used to determine whether the effects were AMPK-dependent. In type 2 diabetic <em>db/db</em> mice, various dosages of ANC were administered intragastrically to observe its therapeutic effects.</div></div><div><h3>Results</h3><div>Among the 17 absorbed prototype compounds, ANC exhibited the strongest binding ability to AMPK. SPR, CETSA, and TR-FRET assays confirmed that ANC binds to and activates AMPK. In hepatocytes, ANC activated the Akt/GSK3β signaling, suppressed NLRP3 inflammasome activation, and inhibited lipid accumulation in an AMPK-dependent manner. In <em>db/db</em> mice, ANC intervention improved glucose and lipid metabolic disorders, insulin resistance, and histopathological abnormalities in a dose-dependent manner, while activating AMPK and alleviating lipid metabolic disorders and metabolic inflammatory responses.</div></div><div><h3>Conclusion</h3><div>ANC can treat T2DM by directly binding to and activating AMPK.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156873"},"PeriodicalIF":6.7,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voacamine initiates the PI3K/mTOR/Beclin1 pathway to induce autophagy and potentiate apoptosis in acute myeloid leukemia","authors":"Yuening Cao ,&nbsp;Yan Wang ,&nbsp;Ying Chen ,&nbsp;Xuejian Zhang ,&nbsp;Yi Zuo ,&nbsp;Xian Ge ,&nbsp;Chen Sun ,&nbsp;Bo Ren ,&nbsp;Yilan Liu ,&nbsp;Maolin Wang ,&nbsp;Jun Lu","doi":"10.1016/j.phymed.2025.156859","DOIUrl":"10.1016/j.phymed.2025.156859","url":null,"abstract":"<div><h3>Background</h3><div>Acute myeloid leukemia (AML) is notoriously prevalent as a malignant hematological neoplasm, and commonly prescribed combination chemotherapeutic treatments invariably involve unanticipated toxicities. Therefore, identifying potential single agent with definitive multi-target and multi-pathway anti-tumor properties is an emerging strategy for the effective treatment of AML.</div></div><div><h3>Purpose</h3><div>The present study aimed to investigate how voacamine (VOA) regulated apoptosis and autophagy to suppress the progression of AML.</div></div><div><h3>Methods</h3><div>Molecular docking, western blot, CTESA, gene silencing, and immunohistochemistry were employed to demonstrate the <em>in vivo</em> and <em>in vitro</em> anti-AML capacity of VOA and to elucidate the mechanism by which VOA coordinately regulates autophagy and apoptosis.</div></div><div><h3>Results</h3><div>Mechanistically, VOA was identified as a direct target for PI3K to suppress the PI3K/Akt/mTOR signaling pathway, thereby triggering autophagic cell death and mitochondrial pathway apoptosis in AML cells. Additionally, VOA bound and enabled Beclin1, a pivotal protein in the autophagy and apoptosis regulation, further inducing autophagy and intensifying the apoptotic process, prompting the dual pathway of AML cell death. Autophagy induced by VOA, especially the autophagosomes generation, was an essential process for apoptosis. Moreover, mTOR inhibition contributed to the Beclin1 accumulation, which, in combination with the direct Beclin1 stimulation by VOA, dramatically elevated autophagy level in AML cells. Furthermore, overexpressed Beclin1 was cleaved by Caspase protease to augment Bax expression, to promote Cyt-C release from mitochondria, and to initiate a Caspase cascade to profoundly deepen apoptosis in the mitochondrial pathway. Inspiringly, <em>in vivo</em>, the enhanced autophagy level in tumor tissues conversely facilitated VOA to exert its anti-AML capability.</div></div><div><h3>Conclusion</h3><div>VOA was initially identified as a novel apoptosis and autophagy activator to trigger dual-pathway programmed cell death in AML cells by targeting the regulation of the PI3K/Akt/mTOR signaling pathway and activating Beclin1.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156859"},"PeriodicalIF":6.7,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of puerarin alleviating myocardial remodeling through NSUN2-mediated m5C methylation modification","authors":"Yahua Wu ,&nbsp;Xiaomin Huang ,&nbsp;Yun He ,&nbsp;Junjie Chang ,&nbsp;Xiaoxia Fang ,&nbsp;Pengju Kang ,&nbsp;Na Feng ,&nbsp;Rui Liu ,&nbsp;Pingping Xiao ,&nbsp;Dandan Shi ,&nbsp;Qiufang Zhang ,&nbsp;Yan Ding ,&nbsp;Wenjun Zhang ,&nbsp;Xiju He","doi":"10.1016/j.phymed.2025.156849","DOIUrl":"10.1016/j.phymed.2025.156849","url":null,"abstract":"<div><h3>Background</h3><div>Myocardial remodeling is a primary contributor to the development and progression of heart failure. Reversing this process is crucial for the prevention and treatment of heart failure. Puerarin (Pue), a traditional Chinese medicine, has been widely utilized in the management of cardiovascular diseases; however, its potential mechanisms for reversing myocardial remodeling remain unclear.</div></div><div><h3>Aim of the study</h3><div>To investigate the effect of Pue in myocardial remodeling and the potential mechanism with m5C methylation.</div></div><div><h3>Materials and methods</h3><div>A transverse aortic coarctation (TAC)-induced myocardial hypertrophy model was established in vivo, while angiotensin II (AngII)-induced cardiomyocyte hypertrophy was examined in vitro using H9c2 and NRCM cells. Various doses of Pue were administered to assess their effects. Myocardial remodeling was evaluated through echocardiography, H&amp;E staining, WGA staining, Masson staining, PSR staining, and Western Blot (WB) analysis in mice, alongside mean cell area measurement and WB analysis in cultured cells. The m5C level was quantified using Dot Blot and immunohistochemistry (IHC). RNA sequencing, molecular docking, microscale thermophoresis (MST), transfection, immunofluorescence (IF), and WB were employed to confirm that Pue reverses myocardial remodeling via NSUN2-mediated m5C methylation modification in both in vitro and in vivo settings. The methylation modification was further validated using methylation immunoprecipitation (MeRIP-qPCR).</div></div><div><h3>Results</h3><div>In both in vitro and in vivo experiments, we found that long-term administration of Pue can alleviate myocyte hypertrophy and fibrosis while improving both diastolic and systolic function in mice. Additionally, Pue was shown to upregulate the m5C modification level in cardiomyocytes. RNA sequencing, along with docking and MST assays, revealed that Pue upregulates and targets NSUN2. Furthermore, the protective effect of Pue was diminished by the knockdown of NSUN2 expression. Pue was found to inhibit the activation of NF-κB, and the knockdown of NSUN2 prolonged the half-life of NF-κB mRNA. The enrichment of m5C mRNA was confirmed through MeRIP-qPCR.</div></div><div><h3>Conclusion</h3><div>This study suggests that Pue enhances the m5C methylation of NF-κB mRNA by targeting NSUN2. The m5C methylation facilitates the degradation of NF-κB mRNA and suppresses NF-κB activation, thereby modulating the expression of factors related to myocardial remodeling. Consequently, this process alleviates myocardial remodeling and prevents the progression of heart failure, providing a novel perspective for the clinical treatment of heart failure.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156849"},"PeriodicalIF":6.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cinnamic acid-GPR109A pathway improves skeletal muscle hypertrophy and metabolism","authors":"Zewei Ma ,&nbsp;Penglin Li ,&nbsp;Xiaohua Feng ,&nbsp;Yunlong Zhu ,&nbsp;Fan Li ,&nbsp;Guli Xu ,&nbsp;Lina Wang ,&nbsp;Songbo Wang ,&nbsp;Ruifan Wu ,&nbsp;Canjun Zhu ,&nbsp;Ping Gao ,&nbsp;Qingyan Jiang ,&nbsp;Gang Shu","doi":"10.1016/j.phymed.2025.156851","DOIUrl":"10.1016/j.phymed.2025.156851","url":null,"abstract":"<div><h3>Background</h3><div>Cinnamic acid (CA), a phenylalanine metabolite found in various plants, such as <em>Cinnamomi ramulus</em>, a key role in regulating biological process, like proliferation, osteoblast differentiation, glucose and lipid metabolism, angiogenesis, and the activation of brown adipocytes. However, its physiological role in manipulating skeletal muscle phenotype is unclear.</div></div><div><h3>Purpose</h3><div>In this study, we summarize its amazing role in skeletal muscle hypertrophy and mitochondrial metabolism and briefly clarify the mechanical function of GPR109A/PKA pathway under those process.</div></div><div><h3>Methods</h3><div>In vivo, C57BL/6 mice were subjected to acute and chronic CA supplement to investigate its function on skeletal muscle development, exercise capacity and systemic metabolism. In vitro, C2C12 cells was used to quantify protein synthesis, mitochondrial biogenesis and intracellular ATP dynamics.</div></div><div><h3>Results</h3><div>Chronic CA supplementation effectively increased energy expenditure and significantly altered lean fat mass and gut microbiota composition in mice, while acute addition of CA enhanced the tibialis anterior muscle index, tricarboxylic acid cycle activation, and exercise capacity. Mechanically, we demonstrated that CA induces myotube hypertrophy by promoting protein synthesis in <em>vitro</em>. Meanwhile, the mitochondrial content and intracellular ATP level were significantly accumulated through the activation of GPR109A and its downstream PKA/CREB signalling pathway, and which is also could regulated by CA directly binding.</div></div><div><h3>Conclusion</h3><div>These results firstly reveal the critical role of CA in promoting skeletal muscle hypertrophy and mitochondrial metabolism via the GPR109A/PKA pathway, which shows experimental basic for CA to be a potential food source for improving metabolism. Most importantly form a treatment standpoint, CA could be a newly treatment for sarcopenia.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156851"},"PeriodicalIF":6.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydroxysafflower yellow A mitigates renal ischemia-reperfusion injury by inhibiting the CCR4-mediated apoptosis pathway","authors":"Rui-Yu Wang,&nbsp;Dan Jia,&nbsp;Wen-Qiang Zhang,&nbsp;Hao Wu,&nbsp;Tong Yang,&nbsp;Tao Xu,&nbsp;Lei Wang,&nbsp;Bao-Shan Gao","doi":"10.1016/j.phymed.2025.156857","DOIUrl":"10.1016/j.phymed.2025.156857","url":null,"abstract":"<div><h3>Background</h3><div>Renal ischemia-reperfusion injury (RIRI) is a major contributor to acute kidney injury (AKI), associated with high mortality in intensive care units. Hydroxysafflower yellow A (HSYA), with known anti-inflammatory and antioxidant properties, may protect against AKI caused by RIRI.</div></div><div><h3>Purpose</h3><div>This study investigates HSYA’s mechanisms in AKI protection through transcriptome sequencing and functional validation.</div></div><div><h3>Methods</h3><div>Cell viability under OGD/R conditions was assessed using the lactate dehydrogenase (LDH) assay. The role of HSYA in CCR4-associated pathways was explored by transcriptome analysis, molecular docking, and rescue studies. A mouse RIRI model was established, and serum creatinine and blood urea nitrogen (BUN) were detected to evaluate the degree of renal injury.</div></div><div><h3>Results</h3><div>HSYA enhanced the viability of HK-2 renal tubular epithelial cells and inhibited OGD/R-induced apoptosis. Transcriptome analysis revealed HSYA’s regulatory effects on G protein-coupled receptor (GPCR) pathways, particularly via downregulation of CCR4. Molecular docking predicted a direct interaction between HSYA and CCR4, which was experimentally supported by reduced CCR4 expression. HSYA inhibited IP3R/PLCβ signaling through the p38/JNK pathway, maintained calcium homeostasis, and reduced apoptosis. In vivo, HSYA significantly decreased creatinine and BUN levels, alleviating renal injury; these effects were reversed by the CCR4 agonist CCL17.</div></div><div><h3>Conclusion</h3><div>HSYA mitigates renal injury by modulating CCR4-associated signaling pathways and stabilizing intracellular calcium levels. This study is the first to propose CCR4 as a direct molecular target of HSYA in the context of RIRI.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156857"},"PeriodicalIF":6.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}