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5,7,3′,4′,5′‐Pentamethoxyflavone, a Flavonoid Monomer Extracted From Murraya paniculata (L.) Jack, Alleviates Anxiety Through the A2AR/Gephyrin/GABRA2 Pathway 5,7,3′,4′,5′-五甲氧基黄酮--一种从 Murraya paniculata (L.) Jack 提取的黄酮类单体--通过 A2AR/Gephyrin/GABRA2 途径缓解焦虑症
IF 7.2 2区 医学
Phytotherapy Research Pub Date : 2024-09-12 DOI: 10.1002/ptr.8327
Wenli Ma, Dayun Sui, Weilun Sun, Ping Yu, Yuangeng Li, Meiqi Guo, Huifeng Wang, Xiaoze Zhang, Xiaofeng Yu, Wenwen Fu, Huali Xu
{"title":"5,7,3′,4′,5′‐Pentamethoxyflavone, a Flavonoid Monomer Extracted From Murraya paniculata (L.) Jack, Alleviates Anxiety Through the A2AR/Gephyrin/GABRA2 Pathway","authors":"Wenli Ma, Dayun Sui, Weilun Sun, Ping Yu, Yuangeng Li, Meiqi Guo, Huifeng Wang, Xiaoze Zhang, Xiaofeng Yu, Wenwen Fu, Huali Xu","doi":"10.1002/ptr.8327","DOIUrl":"https://doi.org/10.1002/ptr.8327","url":null,"abstract":"The sedative and hypnotic properties of 5,7,3′,4′,5′‐pentamethoxyflavone (PMF), a monomer extracted from the leaves of <jats:italic>Murraya paniculata</jats:italic> (L.) Jack, have been reported. However, the role of PMFs in the development of anxiety remains uncertain. An anxiety model was developed using chronic unpredictable mild stimulation (CUMS). Kunming mice were randomly allocated to the following groups: control, CUMS, PMF (50 mg/kg), PMF (100 mg/kg), and diazepam (3 mg/kg). The anxiolytic effects of PMFs were evaluated using elevated plus maze (EPM) test and open field test (OFT). Enzyme‐linked immunosorbent assay (ELISA) kits were used to analyze the serum levels of corticosterone (CORT), 5‐hydroxytryptamine (5‐HT), gamma‐aminobutyric acid (GABA), and cyclic adenosine monophosphate (cAMP) in the hippocampus. High‐throughput‐16S rRNA sequencing was performed to investigate its effect on the composition of the gut microbiota. Subsequently, western blotting was performed to assess the expression of GABAergic synaptic‐associated proteins. PMF effectively mitigated CUMS‐induced anxiety‐like behavior. Further examination revealed that PMF treatment ameliorated dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis and increased 5‐HT and GABA levels in the hippocampus. Notably, the ability of PMF to maintain the stability of GABAergic synapses by enhancing the species composition of the gut microbiota and acting on the adenosine a2a receptor (A<jats:sub>2A</jats:sub>R)/gephyrin/gamma‐aminobutyric acid A receptor alpha 2 (GABRA2) pathway revealed a previously unrecognized mechanism for the anxiolytic effect of PMF. These findings suggest that PMF enhances the expression of A<jats:sub>2A</jats:sub>R, preserves GABAergic synaptic stability, and reduces anxiety by modulating the microbiota composition. Thus, it holds promise as an anxiolytic agent.","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198663","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
Limitations and Challenges of Antioxidant Therapy 抗氧化疗法的局限与挑战
IF 7.2 2区 医学
Phytotherapy Research Pub Date : 2024-09-11 DOI: 10.1002/ptr.8335
Haitham Al‐Madhagi, Anwar Masoud
{"title":"Limitations and Challenges of Antioxidant Therapy","authors":"Haitham Al‐Madhagi, Anwar Masoud","doi":"10.1002/ptr.8335","DOIUrl":"https://doi.org/10.1002/ptr.8335","url":null,"abstract":"Our bodies are constantly exposed to or producing free radicals nearly on a daily basis. These highly reactive molecules are generated through a variety of internal and external processes and pathways within the body. If these free radicals are not neutralized by antioxidants, they can lead to a state of oxidative stress, which has been linked to a wide range of severe and debilitating disorders affecting various systems in the human body. This involves neurodegenerative diseases, diabetes, atherosclerosis, fatty liver, inflammation, and aging. Thankfully, the human body is armed with a repertoire of powerful antioxidants with different natures and modes of action. The recent decades witnessed the publication of enormous papers proving antioxidant activity of a novel synthesized compound, plant extract, or a purified drug in vitro, in vivo, and even on human beings. However, the efficacy of antioxidant therapies in clinical trials, including selenium, vitamin C, vitamin E, and vitamin A, has been notably inconsistent. This inconsistency can be primarily ascribed to different factors related to the nature of free radical generation, purpose and the specific type of therapy employed, and the intricate oxidative stress connected network, among others. Collectively, these factors will be explored in this review article to decipher the observed shortcomings in the application of antioxidant therapies within clinical settings.","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198638","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
Phytoconstituents as modulator of inflammatory pathways for COVID-19: A comprehensive review and recommendations. 作为 COVID-19 炎症途径调节剂的植物成分:全面回顾与建议。
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2024-09-09 DOI: 10.1002/ptr.8302
Pragati Gupta, Kamal Dev, Gurjot Kaur
{"title":"Phytoconstituents as modulator of inflammatory pathways for COVID-19: A comprehensive review and recommendations.","authors":"Pragati Gupta, Kamal Dev, Gurjot Kaur","doi":"10.1002/ptr.8302","DOIUrl":"https://doi.org/10.1002/ptr.8302","url":null,"abstract":"<p><p>SARS-CoV-2 infection causes disruptions in inflammatory pathways, which fundamentally contribute to COVID-19 pathophysiology. The present review critically evaluates the gaps in scientific literature and presents the current status regarding the inflammatory signaling pathways in COVID-19. We propose that phytoconstituents can be used to treat COVID-19 associated inflammation, several already formulated in traditional medications. For this purpose, extensive literature analysis was conducted in the PubMed database to collect relevant in vitro, in vivo, and human patient studies where inflammation pathways were shown to be upregulated in COVID-19. Parallelly, scientific literature was screened for phytoconstituents with known cellular mechanisms implicated for inflammation or COVID-19 associated inflammation. Studies with insufficient evidence on cellular pathways for autophagy and mitophagy were considered out of scope and excluded from the study. The final analysis was visualized in figures and evaluated for accuracy. Our findings demonstrate the frequent participation of NF-κB, a transcription factor, in inflammatory signaling pathways linked to COVID-19. Moreover, the MAPK signaling pathway is also implicated in producing inflammatory molecules. Furthermore, it was also analyzed that the phytoconstituents with flavonoid and phenolic backbones could inhibit either the TLR4 receptor or its consecutive signaling molecules, thereby, decreasing NF-κB activity and suppressing cytokine production. Although, allopathy has treated the early phase of COVID-19, anti-inflammatory phytoconstituents and existing ayurvedic formulations may act on the COVID-19 associated inflammatory pathways and provide an additional treatment strategy. Therefore, we recommend the usage of flavonoids and phenolic phytoconstituents for the treatment of inflammation associated with COVID-19 infection and similar viral ailments.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154834","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
Quercetin supplementation prevents kidney damage and improves long-term prognosis in hypertensive patients. 补充槲皮素可预防高血压患者的肾损伤并改善长期预后。
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2024-09-07 DOI: 10.1002/ptr.8306
Yawei Zheng, Yuan Fang, Li Li, Huihui Wang, Siqi Zhang, Yuan Zhu, Yating Wang, Xianze Meng, Zhen Fang, Yu Luo, Zhuyuan Fang
{"title":"Quercetin supplementation prevents kidney damage and improves long-term prognosis in hypertensive patients.","authors":"Yawei Zheng, Yuan Fang, Li Li, Huihui Wang, Siqi Zhang, Yuan Zhu, Yating Wang, Xianze Meng, Zhen Fang, Yu Luo, Zhuyuan Fang","doi":"10.1002/ptr.8306","DOIUrl":"https://doi.org/10.1002/ptr.8306","url":null,"abstract":"<p><p>Quercetin has shown potential antihypertensive-like activities in several studies. The present study aimed to test the effect of quercetin supplementation on kidney damage and long-term prognosis in hypertensive patients. The data of enrolled hypertensive patients were acquired from the NHANES dataset. The flavanol intake data was extracted from the FNDDS flavonoid database. Information regarding mortality was extracted from the NCHS. A total of 5801 hypertensive patients were included in this study. Preliminary analysis found that the total flavanols intake dosage was the independent influence factor of the kidney damage prevalence in hypertension, and it was found that only the quercetin supplementation was the protective factor for kidney damage after stratification analysis. For every 10 mg/d increase in quercetin intake, the kidney damage prevalence decreased by 8% [OR = 0.92, 95% CI: 0.85-0.99, p = 0.032]. The comprehensive analysis results suggested that hypertensive patients in the quercetin-high group had a lower kidney damage prevalence and a higher survival probability than those in the quercetin-low group. The urine microalbumin of hypertensive patients in the quercetin-high group was significantly lower than that of hypertensive patients in the quercetin-low group. In addition, at a median follow-up time of 122 months, the mortality decreased by 9% [HR = 0.91, 95% CI: 0.84-0.99, p = 0.031] for every 10 mg/d increase in quercetin intake. The findings suggested that high quercetin intake was associated with low kidney damage prevalence and high survival probability. Based on the existing evidence, promoting quercetin supplementation as a supplementary treatment for hypertensive patients was warranted.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146153","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
N-palmitoyl-d-glucosamine limits mucosal damage and VEGF-mediated angiogenesis by PPARα-dependent suppression of pAkt/mTOR/HIF1α pathway and increase in PEA levels in AOM/DSS colorectal carcinoma in mice. 通过 PPARα 依赖性抑制 pAkt/mTOR/HIF1α 通路和增加 PEA 水平,N-棕榈酰-d-氨基葡萄糖可限制 AOM/DSS 大肠癌小鼠粘膜损伤和血管内皮生长因子介导的血管生成。
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2024-09-05 DOI: 10.1002/ptr.8303
Irene Palenca, Silvia Basili Franzin, Aurora Zilli, Luisa Seguella, Anna Troiani, Federico Pepi, Martina Vincenzi, Giuseppe Giugliano, Viviana Catapano, Italia Di Filippo, Giovanni Sarnelli, Giuseppe Esposito
{"title":"N-palmitoyl-d-glucosamine limits mucosal damage and VEGF-mediated angiogenesis by PPARα-dependent suppression of pAkt/mTOR/HIF1α pathway and increase in PEA levels in AOM/DSS colorectal carcinoma in mice.","authors":"Irene Palenca, Silvia Basili Franzin, Aurora Zilli, Luisa Seguella, Anna Troiani, Federico Pepi, Martina Vincenzi, Giuseppe Giugliano, Viviana Catapano, Italia Di Filippo, Giovanni Sarnelli, Giuseppe Esposito","doi":"10.1002/ptr.8303","DOIUrl":"https://doi.org/10.1002/ptr.8303","url":null,"abstract":"<p><p>Chronic intestinal inflammation and neo-angiogenesis are interconnected in colorectal carcinoma (CRC) pathogenesis. Molecules reducing inflammation and angiogenesis hold promise for CRC prevention and treatment. N-Palmitoyl-d-glucosamine (PGA), a natural glycolipid analog with anti-inflammatory properties, has shown efficacy against acute colitis. Micronized PGA (mPGA) formulations exhibit superior anti-inflammatory activity. This study investigates the in vivo anti-angiogenic and protective effects of mPGA in a mouse model of colitis-associated CRC induced by azoxymethane/dextran sodium sulfate (AOM/DSS). CRC was induced in C57BL/6J mice using intraperitoneal azoxymethane followed by three cycles of 2.5% dextran sodium sulfate (DSS) in drinking water. Mice were treated with mPGA (30-150 mg/kg) with or without the PPARα inhibitor MK886 (10 mg/kg). At Day 70 post-azoxymethane injection, mice underwent anesthetized endoscopic colon evaluation. Post-mortem analysis of tumorigenesis and angiogenesis was performed using histological, immunohistochemical, and immunoblotting techniques. mPGA improved disease progression and survival rates in a dose- and PPARα-dependent manner in AOM/DSS-exposed mice. It reduced polyp formation, decreased pro-angiogenic CD31, pro-proliferative Ki67, and pro-inflammatory TLR4 expression levels, and inhibited VEGF and MMP-9 secretion by disrupting the pAkt/mTOR/HIF1α pathway. mPGA increased colon PEA levels, restoring anti-tumoral PPARα and wtp53 protein expression. Given its lack of toxicity, mPGA shows potential as a nutritional intervention to counteract inflammation-related angiogenesis in CRC.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133464","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
Gardenia jasminoides Ellis. Polysaccharides Alleviated Cholestatic Liver Injury by Increasing the Production of Butyric Acid and FXR Activation. 栀子花多糖(Gardenia jasminoides Ellis.多糖通过增加丁酸的产生和 FXR 激活缓解胆汁淤积性肝损伤
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2024-09-05 DOI: 10.1002/ptr.8326
Tianming Wang, Tian Tian, Zhenyun Zhu, Su Fang, Lincong Zhang, Xiaotian Peng, Rong Shi, Yuanyuan Li, Jiasheng Wu, Yueming Ma
{"title":"Gardenia jasminoides Ellis. Polysaccharides Alleviated Cholestatic Liver Injury by Increasing the Production of Butyric Acid and FXR Activation.","authors":"Tianming Wang, Tian Tian, Zhenyun Zhu, Su Fang, Lincong Zhang, Xiaotian Peng, Rong Shi, Yuanyuan Li, Jiasheng Wu, Yueming Ma","doi":"10.1002/ptr.8326","DOIUrl":"https://doi.org/10.1002/ptr.8326","url":null,"abstract":"<p><p>Gardenia jasminoides Ellis. polysaccharide (GPS) can protect against cholestatic liver injury (CLI) by regulating nuclear farnesoid X receptor (FXR).However, the mechanism via which GPS mediates the FXR pathway remains unclear. The aim of this study was to investigate the mechanism. Firstly, an alpha-naphthylisothiocyanate-induced cholestatic mouse model was administered with GPS to evaluate its hepatoprotective effects. The metabolic pathways influenced by GPS in cholestatic mice were detected by serum metabolomics. The effect of GPS on bile acid (BA) homeostasis, FXR expression, and liver inflammation were investigated. Second, the intestinal bacteria metabolites affected by GPS in vivo and in vitro were determined. The activation of FXR by sodium butyrate (NaB) was measured. Finally, the effects of NaB on cholestatic mice were demonstrated. The main pathways influenced by GPS involved BA biosynthesis. GPS upregulated hepatic FXR expression, improved BA homeostasis, reduced F4/80<sup>+</sup> and Ly6G<sup>+</sup> positive areas in the liver, and inhibited liver inflammation in cholestatic mice. Butyric acid was the most notable intestinal bacterial metabolite following GPS intervention. NaB activated the transcriptional activity of FXR in vitro, upregulated hepatic FXR and its downstream efflux transporter expression, and ameliorated disordered BA homeostasis in CLI mice. NaB inhibited the toll-like receptor 4/nuclear factor (TLR4/NF-κB) pathway and reduced inflammation and CLI in mice. An FXR antagonist suppressed the effects. In conclusion, GPS increased butyric acid production, which can activate hepatic FXR, reverse BA homeostasis disorder, and inhibit the TLR4/NF-κB inflammatory pathway, exerting protective effects against CLI.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140798","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
Thonningianin A from Penthorum chinense Pursh as a targeted inhibitor of Alzheimer's disease-related β-amyloid and Tau proteins. 从 Penthorum chinense Pursh 中提取的 Thonningianin A 作为阿尔茨海默氏症相关 β 淀粉样蛋白和 Tau 蛋白的靶向抑制剂。
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2024-09-03 DOI: 10.1002/ptr.8060
Lu Yu, Huimiao Wang, Qianfang Yao, Keru Li, Liqun Qu, Bin Tang, Wu Zeng, Gan Qiao, Yong Tang, Guishan Hu, Guangqiang Hu, Vincent Kam-Wai Wong, Qiong Wang, Dalian Qin, Jianming Wu, Xiaogang Zhou, Xiaolei Sun, Betty Yuen-Kwan Law, Anguo Wu
{"title":"Thonningianin A from Penthorum chinense Pursh as a targeted inhibitor of Alzheimer's disease-related β-amyloid and Tau proteins.","authors":"Lu Yu, Huimiao Wang, Qianfang Yao, Keru Li, Liqun Qu, Bin Tang, Wu Zeng, Gan Qiao, Yong Tang, Guishan Hu, Guangqiang Hu, Vincent Kam-Wai Wong, Qiong Wang, Dalian Qin, Jianming Wu, Xiaogang Zhou, Xiaolei Sun, Betty Yuen-Kwan Law, Anguo Wu","doi":"10.1002/ptr.8060","DOIUrl":"https://doi.org/10.1002/ptr.8060","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by complex pathogenesis mechanisms. Among these, β-amyloid plaques and hyperphosphorylated Tau protein tangles have been identified as significant contributors to neuronal damage. This study investigates thonningianin A (TA) from Penthorum chinense Pursh (PCP) as a potential inhibitor targeting these pivotal proteins in AD progression. The inhibitory potential of PCP and TA on Aβ fibrillization was initially investigated. Subsequently, ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry and biolayer interferometry were employed to determine TA's affinity for both Aβ and Tau. The inhibitory effects of TA on the levels and cytotoxicity of AD-related proteins were then assessed. In 3xTg-AD mice, the therapeutic potential of TA was evaluated. Additionally, the molecular interactions between TA and either Aβ or Tau were explored using molecular docking. We found that PCP-total ethanol extract and TA significantly inhibited Aβ fibrillization. Additionally, TA demonstrated strong affinity to Aβ and Tau, reduced levels of amyloid precursor protein and Tau, and alleviated mitochondrial distress in PC-12 cells. In 3xTg-AD mice, TA improved cognition, reduced Aβ and Tau pathology, and strengthened neurons. Moreover, molecular analyses revealed efficient binding of TA to Aβ and Tau. In conclusion, TA, derived from PCP, shows significant neuroprotection against AD proteins, highlighting its potential as an anti-AD drug candidate.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120372","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
Oroxylin A alleviates myocardial ischemia-reperfusion injury by quelling ferroptosis via activating the DUSP10/MAPK-Nrf2 pathway. Oroxylin A可通过激活DUSP10/MAPK-Nrf2通路抑制铁变态反应,从而减轻心肌缺血再灌注损伤。
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2024-09-03 DOI: 10.1002/ptr.8315
Yifeng Jin, Mingyue Tan, Yunfei Yin, Chen Lin, Yongjian Zhao, Jun Zhang, Tingbo Jiang, Hongxia Li, Mingqing He
{"title":"Oroxylin A alleviates myocardial ischemia-reperfusion injury by quelling ferroptosis via activating the DUSP10/MAPK-Nrf2 pathway.","authors":"Yifeng Jin, Mingyue Tan, Yunfei Yin, Chen Lin, Yongjian Zhao, Jun Zhang, Tingbo Jiang, Hongxia Li, Mingqing He","doi":"10.1002/ptr.8315","DOIUrl":"https://doi.org/10.1002/ptr.8315","url":null,"abstract":"<p><p>Reperfusion therapy is the primary treatment strategy for acute myocardial infarction (AMI). Paradoxically, it can lead to myocardial damage, namely myocardial ischemia/reperfusion injury (MIRI). This study explored whether oroxylin A (OA) protects the myocardium after MIRI by inhibiting ferroptosis and the underlying mechanism. In vivo, we established an MIRI model to investigate the protective effect of OA. In vitro, H9C2 cells were used to explore the regulation of ferroptosis by OA through immunofluorescence staining, western blotting, assay kits, etc. Additionally, RNA sequencing analysis (RNA-seq) and network pharmacology analyses were conducted to elucidate the molecular mechanisms. Our results showed that MIRI caused cardiac structural and functional damage in rats. MIRI promoted ferroptosis, which was consistently observed in vitro. However, pretreatment with OA reversed these effects. The mitogen-activated protein kinases (MAPK) signaling pathway participated in the MIRI process, with dual-specificity phosphatase 10 (DUSP10) found to regulate it. Further confirmation was provided by knocking down DUSP10 using small interfering RNA (siRNA), demonstrating the activation of the DUSP10/MAPK-Nrf2 pathway by OA to protect H9C2 cells from ferroptosis. Our research has demonstrated the mitigating effect of OA on MIRI and the improvement of myocardial function for the first time. The inhibition of ferroptosis has been identified as one of the mechanisms through which OA exerts its myocardial protective effects. Moreover, we have first unveiled that DUSP10 serves as an upstream target involved in mediating ferroptosis, and the regulation of the DUSP10/MAPK-Nrf2 pathway by OA is crucial in inhibiting ferroptosis to protect the myocardium.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120451","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
Organosulfur Compounds, S-Allyl-L-Cysteine and S-Ethyl-L-Cysteine, Target PCSK-9/LDL-R-Axis to Ameliorate Cardiovascular, Hepatic, and Metabolic Changes in High Carbohydrate and High Fat Diet-Induced Metabolic Syndrome in Rats. 有机硫化合物 S-烯丙基-L-半胱氨酸和 S-乙基-L-半胱氨酸靶向 PCSK-9/LDL-R-Axis,改善高碳水化合物和高脂肪饮食诱发的大鼠代谢综合征的心血管、肝脏和代谢变化。
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2024-09-03 DOI: 10.1002/ptr.8323
Parvej Ahmad, Arunim Shah, Mohd Waiz, Chandra P Chaturvedi, Sahir Sultan Alvi, M Salman Khan
{"title":"Organosulfur Compounds, S-Allyl-L-Cysteine and S-Ethyl-L-Cysteine, Target PCSK-9/LDL-R-Axis to Ameliorate Cardiovascular, Hepatic, and Metabolic Changes in High Carbohydrate and High Fat Diet-Induced Metabolic Syndrome in Rats.","authors":"Parvej Ahmad, Arunim Shah, Mohd Waiz, Chandra P Chaturvedi, Sahir Sultan Alvi, M Salman Khan","doi":"10.1002/ptr.8323","DOIUrl":"https://doi.org/10.1002/ptr.8323","url":null,"abstract":"<p><p>Metabolic syndrome (MetS) is an ever-evolving set of diseases that poses a serious health risk in many countries worldwide. Existing evidence illustrates that individuals with MetS have a 30%-40% higher chance of acquiring type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), or both. This study was undertaken to uncover the regulatory role of natural organosulfur compounds (OSCs), S-allyl-L-cysteine (SAC), and S-ethyl-L-cysteine (SEC), in targeting high carbohydrate high fat (HCHF)-diet-induced MetS-associated risk management. Our findings suggested that SAC and SEC ameliorated HCHF-diet-induced diabetic profiles, plasma lipid and lipoprotein level, liver function, oxidative-stress, inflammatory cytokines, and chemokines including monocyte chemoattractant protein-1 (MCP-1), lipid peroxidation, plasma proprotein convertase subtilisin/kexin type-9 (PCSK-9), and high-sensitivity C-reactive protein (hs-CRP). Moreover, the assessment of the hepatic mRNA expression of the key genes involved in cholesterol homeostasis depicted that SAC and SEC downregulated the PCSK-9 mRNA expression via targeting the expression of HNF-1α, a transcriptional activator of PCSK-9. On the other hand, the LDL-receptor (LDL-R) expression was upregulated through the activation of its transcriptional regulator sterol regulatory element binding protein-2 (SREBP-2). In addition, the activity and the mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme-A reductases (HMG-R) and peroxisome proliferator-activated receptors (PPARs) were also improved by the treatment of SAC and SEC. We concluded that SAC and SEC can protect against MetS via improving the lipid and lipoprotein content, glycemic indices, hepatic function, targeting the inflammatory cascades, and oxidative imbalance, regulation of the mRNA expression of PCSK-9, LDL-R, SREBP-2, HNF-1α, PPARs, and inflammatory biomarkers.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120450","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
Resveratrol: Challenges and prospects in extraction and hybridization with nanoparticles, polymers, and bio-ceramics. 白藜芦醇:白藜芦醇:提取以及与纳米颗粒、聚合物和生物陶瓷杂交的挑战与前景。
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2024-09-03 DOI: 10.1002/ptr.8319
Roua Ben Dassi, Salah Ibidhi, Hedya Jemai, Ameur Cherif, Rim Driouich Chaouachi
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