首页 > 最新文献

BMC Complementary and Alternative Medicine最新文献

英文 中文
Synergistic effect of potential alpha-amylase inhibitors from Egyptian propolis with acarbose using in silico and in vitro combination analysis 利用硅学和体外组合分析从埃及蜂胶中提取的潜在α-淀粉酶抑制剂与阿卡波糖的协同效应
2区 医学 Q1 Medicine Pub Date : 2024-01-30 DOI: 10.1186/s12906-024-04348-x
Ahmed A. Nada, Aly M. Metwally, Aya M. Asaad, Ismail Celik, Reham S. Ibrahim, Safa M. Shams Eldin
Type 2 Diabetes mellitus (DM) is an affliction impacting the quality of life of millions of people worldwide. An approach used in the management of Type 2 DM involves the use of the carbohydrate-hydrolyzing enzyme inhibitor, acarbose. Although acarbose has long been the go-to drug in this key approach, it has become apparent that its side effects negatively impact patient adherence and subsequently, therapeutic outcomes. Similar to acarbose in its mechanism of action, bee propolis, a unique natural adhesive biomass consisting of biologically active metabolites, has been found to have antidiabetic potential through its inhibition of α-amylase. To minimize the need for ultimately novel agents while simultaneously aiming to decrease the side effects of acarbose and enhance its efficacy, combination drug therapy has become a promising pharmacotherapeutic strategy and a focal point of this study. Computer-aided molecular docking and molecular dynamics (MD) simulations accompanied by in vitro testing were used to mine novel, pharmacologically active chemical entities from Egyptian propolis to combat Type 2 DM. Glide docking was utilized for a structure-based virtual screening of the largest in-house library of Egyptian propolis metabolites gathered from literature, in addition to GC–MS analysis of the propolis sample under investigation. Thereafter, combination analysis by means of fixed-ratio combinations of acarbose with propolis and the top chosen propolis-derived phytoligand was implemented. Aucubin, identified for the first time in propolis worldwide and kaempferol were the most promising virtual hits. Subsequent in vitro α-amylase inhibitory assay demonstrated the ability of these hits to significantly inhibit the enzyme in a dose-dependent manner with an IC50 of 2.37 ± 0.02 mM and 4.84 ± 0.14 mM, respectively. The binary combination of acarbose with each of propolis and kaempferol displayed maximal synergy at lower effect levels. Molecular docking and MD simulations revealed a cooperative binding mode between kaempferol and acarbose within the active site. The suggested strategy seems imperative to ensure a steady supply of new therapeutic entities sourced from Egyptian propolis to regress the development of DM. Further pharmacological in vivo investigations are required to confirm the potent antidiabetic potential of the studied combination.
2 型糖尿病(DM)是一种影响全球数百万人生活质量的疾病。治疗 2 型糖尿病的一种方法是使用碳水化合物水解酶抑制剂阿卡波糖。虽然阿卡波糖长期以来一直是这种关键方法的首选药物,但它的副作用显然会对患者的依从性产生负面影响,进而影响治疗效果。蜂胶的作用机制与阿卡波糖相似,蜂胶是一种独特的天然粘合生物质,由具有生物活性的代谢物组成,通过抑制α-淀粉酶,具有抗糖尿病的潜力。为了最大限度地减少对新型药物的需求,同时降低阿卡波糖的副作用并提高其疗效,联合用药治疗已成为一种前景广阔的药物治疗策略,也是本研究的一个重点。本研究利用计算机辅助分子对接和分子动力学(MD)模拟以及体外测试,从埃及蜂胶中挖掘新型药理活性化学实体,以防治2型DM。除了对所研究的蜂胶样品进行气相色谱-质谱分析外,还利用 Glide docking 对从文献中收集的最大的埃及蜂胶内部代谢物库进行了基于结构的虚拟筛选。随后,通过将阿卡波糖与蜂胶和所选蜂胶衍生植物配体进行固定比例组合,实施了组合分析。全球首次在蜂胶中发现的杜仲甙和山奈酚是最有希望的虚拟配体。随后进行的体外α-淀粉酶抑制试验表明,这些虚拟配体能够以剂量依赖的方式显著抑制α-淀粉酶,IC50 分别为 2.37 ± 0.02 mM 和 4.84 ± 0.14 mM。阿卡波糖与蜂胶和山奈酚的二元组合在较低的效应水平下显示出最大的协同作用。分子对接和 MD 模拟显示了山奈酚和阿卡波糖在活性位点内的合作结合模式。为了确保从埃及蜂胶中获得稳定的新治疗实体,以缓解 DM 的发展,所建议的策略似乎势在必行。还需要进一步的体内药理学研究,以证实所研究的组合具有强大的抗糖尿病潜力。
{"title":"Synergistic effect of potential alpha-amylase inhibitors from Egyptian propolis with acarbose using in silico and in vitro combination analysis","authors":"Ahmed A. Nada, Aly M. Metwally, Aya M. Asaad, Ismail Celik, Reham S. Ibrahim, Safa M. Shams Eldin","doi":"10.1186/s12906-024-04348-x","DOIUrl":"https://doi.org/10.1186/s12906-024-04348-x","url":null,"abstract":"Type 2 Diabetes mellitus (DM) is an affliction impacting the quality of life of millions of people worldwide. An approach used in the management of Type 2 DM involves the use of the carbohydrate-hydrolyzing enzyme inhibitor, acarbose. Although acarbose has long been the go-to drug in this key approach, it has become apparent that its side effects negatively impact patient adherence and subsequently, therapeutic outcomes. Similar to acarbose in its mechanism of action, bee propolis, a unique natural adhesive biomass consisting of biologically active metabolites, has been found to have antidiabetic potential through its inhibition of α-amylase. To minimize the need for ultimately novel agents while simultaneously aiming to decrease the side effects of acarbose and enhance its efficacy, combination drug therapy has become a promising pharmacotherapeutic strategy and a focal point of this study. Computer-aided molecular docking and molecular dynamics (MD) simulations accompanied by in vitro testing were used to mine novel, pharmacologically active chemical entities from Egyptian propolis to combat Type 2 DM. Glide docking was utilized for a structure-based virtual screening of the largest in-house library of Egyptian propolis metabolites gathered from literature, in addition to GC–MS analysis of the propolis sample under investigation. Thereafter, combination analysis by means of fixed-ratio combinations of acarbose with propolis and the top chosen propolis-derived phytoligand was implemented. Aucubin, identified for the first time in propolis worldwide and kaempferol were the most promising virtual hits. Subsequent in vitro α-amylase inhibitory assay demonstrated the ability of these hits to significantly inhibit the enzyme in a dose-dependent manner with an IC50 of 2.37 ± 0.02 mM and 4.84 ± 0.14 mM, respectively. The binary combination of acarbose with each of propolis and kaempferol displayed maximal synergy at lower effect levels. Molecular docking and MD simulations revealed a cooperative binding mode between kaempferol and acarbose within the active site. The suggested strategy seems imperative to ensure a steady supply of new therapeutic entities sourced from Egyptian propolis to regress the development of DM. Further pharmacological in vivo investigations are required to confirm the potent antidiabetic potential of the studied combination.","PeriodicalId":9132,"journal":{"name":"BMC Complementary and Alternative Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139580471","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
The PD-Ballet study: study protocol for a randomised controlled single-blind hybrid type 2 clinical trial evaluating the effects of ballet dancing on motor and non-motor symptoms in Parkinson’s disease 帕金森病芭蕾舞研究:评估芭蕾舞对帕金森病运动和非运动症状影响的随机对照单盲混合型 2 类临床试验的研究方案
2区 医学 Q1 Medicine Pub Date : 2024-01-17 DOI: 10.1186/s12906-023-04296-y
Aleksandra M. Podlewska, Lucia Batzu, Tayana Soukup, Nick Sevdalis, Ioannis Bakolis, Fleur Derbyshire-Fox, Alison Hartley, Andy Healey, Anthony Woods, Nikki Crane, Carmine Pariante, K Ray Chaudhuri
To date, beneficial effects of multimodal exercise programmes on Parkinson’s disease (PD) have focused on motor symptoms and little attention has been paid to the potential effects of such programmes on the non-motor symptoms of PD, which are now universally known as one of the key drivers of quality of life and a key unmet need. We aim to explore clinical effectiveness of a ballet-based dance programme in addressing non-motor and motor symptoms of Parkinson’s disease across all stages of progression. A randomised, single-blind, controlled trial of 160 people with Parkinson’s across all motor stages (Participants will be stratified into three groups of motor advancement: Hoehn and Yahr (HY) stages I and II being Mild Group, HY Stage III being Moderate Group and HY Stages IV and V being Severe Group) will be randomly allocated to either an intervention or a control group using an independent randomisation body. The primary outcome is an improvement in non-motor symptoms as measured by the Movement Disorders Society Non-Motor Scale (MDS-NMS). The intervention protocol consists of 12 one-weekly dance sessions led by English National Ballet. Each session is followed by a ‘tea and biscuit’ social time. Control group follows standard clinical pathway and joins the ‘tea and biscuit’ to control for any positive effects of social interactions. All participants are assessed at baseline, immediately after completion of the intervention and 3–6 months later to explore any potential longitudinal effects. To our knowledge, no adequately powered study has explored the effects of a dance-based intervention on non-motor symptoms of Parkinson’s disease, assessing these on both holistic and granular levels. We also aim to stratify participants in accordance with their motor state as assessed by. HY staging to explore specific effects on the symptoms at the initial, moderate and complex stages of the disease. If successful, this trial provides first evidence on clinical effectiveness of a ballet-based dance intervention for symptoms of Parkinson’s disease, assessed in a robust, rigorous manner. NCT04719468.
迄今为止,多模式锻炼计划对帕金森病(PD)的有益影响主要集中在运动症状上,很少有人关注此类计划对帕金森病非运动症状的潜在影响。我们的目标是探索以芭蕾舞为基础的舞蹈课程在解决帕金森病各进展阶段的非运动症状和运动症状方面的临床效果。这是一项随机、单盲、对照试验,对象为 160 名帕金森病患者,涵盖所有运动阶段(参与者将根据运动进展情况分为三组:Hoehn and Yahr(HY)I期和II期为轻度组,HY III期为中度组,HY IV期和V期为重度组),他们将被随机分配到干预组或对照组。主要结果是通过运动障碍协会非运动量表(MDS-NMS)测量非运动症状的改善情况。干预方案包括由英国国家芭蕾舞团领导的 12 节舞蹈课,每节课为期一周。每节课后都有 "茶和饼干 "社交时间。对照组遵循标准临床路径并参加 "茶和饼干 "活动,以控制社交互动的积极影响。对所有参与者进行基线评估、干预结束后立即评估以及 3-6 个月后的评估,以探讨任何潜在的纵向影响。据我们所知,目前还没有一项充分的研究探讨了舞蹈干预对帕金森病非运动症状的影响,并对这些症状进行了整体和细化的评估。我们的目标还包括根据参与者的运动状态进行分层。我们还将根据帕金森病患者的运动状态,对参与者进行分层,以探索舞蹈疗法对帕金森病初期、中期和复杂期症状的具体影响。如果试验成功,将首次证明以芭蕾为基础的舞蹈干预对帕金森病症状的临床疗效,并以稳健、严格的方式进行评估。NCT04719468。
{"title":"The PD-Ballet study: study protocol for a randomised controlled single-blind hybrid type 2 clinical trial evaluating the effects of ballet dancing on motor and non-motor symptoms in Parkinson’s disease","authors":"Aleksandra M. Podlewska, Lucia Batzu, Tayana Soukup, Nick Sevdalis, Ioannis Bakolis, Fleur Derbyshire-Fox, Alison Hartley, Andy Healey, Anthony Woods, Nikki Crane, Carmine Pariante, K Ray Chaudhuri","doi":"10.1186/s12906-023-04296-y","DOIUrl":"https://doi.org/10.1186/s12906-023-04296-y","url":null,"abstract":"To date, beneficial effects of multimodal exercise programmes on Parkinson’s disease (PD) have focused on motor symptoms and little attention has been paid to the potential effects of such programmes on the non-motor symptoms of PD, which are now universally known as one of the key drivers of quality of life and a key unmet need. We aim to explore clinical effectiveness of a ballet-based dance programme in addressing non-motor and motor symptoms of Parkinson’s disease across all stages of progression. A randomised, single-blind, controlled trial of 160 people with Parkinson’s across all motor stages (Participants will be stratified into three groups of motor advancement: Hoehn and Yahr (HY) stages I and II being Mild Group, HY Stage III being Moderate Group and HY Stages IV and V being Severe Group) will be randomly allocated to either an intervention or a control group using an independent randomisation body. The primary outcome is an improvement in non-motor symptoms as measured by the Movement Disorders Society Non-Motor Scale (MDS-NMS). The intervention protocol consists of 12 one-weekly dance sessions led by English National Ballet. Each session is followed by a ‘tea and biscuit’ social time. Control group follows standard clinical pathway and joins the ‘tea and biscuit’ to control for any positive effects of social interactions. All participants are assessed at baseline, immediately after completion of the intervention and 3–6 months later to explore any potential longitudinal effects. To our knowledge, no adequately powered study has explored the effects of a dance-based intervention on non-motor symptoms of Parkinson’s disease, assessing these on both holistic and granular levels. We also aim to stratify participants in accordance with their motor state as assessed by. HY staging to explore specific effects on the symptoms at the initial, moderate and complex stages of the disease. If successful, this trial provides first evidence on clinical effectiveness of a ballet-based dance intervention for symptoms of Parkinson’s disease, assessed in a robust, rigorous manner. NCT04719468.","PeriodicalId":9132,"journal":{"name":"BMC Complementary and Alternative Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139483514","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
Comparison of the protective effects of CS/TPP and CS/HPMCP nanoparticles containing berberine in ethanol-induced hepatotoxicity in rat 比较含有小檗碱的 CS/TPP 和 CS/HPMCP 纳米颗粒对乙醇诱导的大鼠肝毒性的保护作用
2区 医学 Q1 Medicine Pub Date : 2024-01-15 DOI: 10.1186/s12906-023-04318-9
Maral Mahboubi Kancha, Morteza Alizadeh, Mohsen Mehrabi
Alcoholic liver disease (ALD) is a globally critical condition with no available efficient treatments. Herein, we generated chitosan (CS) nanoparticles cross-linked with two different agents, hydroxypropyl methylcellulose phthalate (HPMCP; termed as CS/HPMCP) and tripolyphosphate (TPP; termed as CS/TPP), and loaded them with berberine (BBr; referred to as CS/HPMCP/BBr and CS/TPP/BBr, respectively). Alongside the encapsulation efficiency (EE) and loading capacity (LC), the releasing activity of the nanoparticles was also measured in stimulated gastric fluid (SGF) and stimulated intestinal fluid (SIF) conditions. The effects of the prepared nanoparticles on the viability of mesenchymal stem cells (MSCs) were also evaluated. Ultimately, the protective effects of the nanoparticles were investigated in ALD mouse models. SEM images demonstrated that CS/HPMCP and CS/TPP nanoparticles had an average size of 235.5 ± 42 and 172 ± 21 nm, respectively. The LC and EE for CS/HPMCP/BBr were calculated as 79.78% and 75.79%, respectively; while the LC and EE for CS/TPP/BBr were 84.26% and 80.05%, respectively. pH was a determining factor for releasing BBr from CS/HPMCP nanoparticles as a higher cargo-releasing rate was observed in a less acidic environment. Both the BBr-loaded nanoparticles increased the viability of MSCs in comparison with their BBr-free counterparts. In vivo results demonstrated CS/HPMCP/BBr and CS/TPP/BBr nanoparticles protected enzymatic liver functionality against ethanol-induced damage. They also prevented histopathological ethanol-induced damage. Crosslinking CS nanoparticles with HPMCP can mediate controlled drug release in the intestine improving the bioavailability of BBr.
酒精性肝病(ALD)是一种全球性的严重疾病,目前尚无有效的治疗方法。在此,我们制备了与两种不同制剂(邻苯二甲酸羟丙基甲基纤维素(HPMCP,简称 CS/HPMCP)和三聚磷酸钠(TPP,简称 CS/TPP))交联的壳聚糖(CS)纳米颗粒,并在其中负载小檗碱(BBr,分别简称 CS/HPMCP/BBr 和 CS/TPP/BBr)。在测定封装效率(EE)和负载能力(LC)的同时,还测定了纳米颗粒在刺激胃液(SGF)和刺激肠液(SIF)条件下的释放活性。此外,还评估了制备的纳米颗粒对间充质干细胞活力的影响。最后,在 ALD 小鼠模型中研究了纳米颗粒的保护作用。SEM 图像显示,CS/HPMCP 和 CS/TPP 纳米粒子的平均尺寸分别为 235.5 ± 42 nm 和 172 ± 21 nm。根据计算,CS/HPMCP/BBr 的 LC 和 EE 分别为 79.78% 和 75.79%;而 CS/TPP/BBr 的 LC 和 EE 分别为 84.26% 和 80.05%。pH 值是 CS/HPMCP 纳米粒子释放 BBr 的决定性因素,因为在酸性较低的环境中观察到较高的货物释放率。与不含BBr的纳米颗粒相比,负载BBr的纳米颗粒都能提高间充质干细胞的存活率。体内研究结果表明,CS/HPMCP/BBr 和 CS/TPP/BBr 纳米颗粒能保护酶肝功能免受乙醇引起的损伤。它们还能防止乙醇诱导的组织病理学损伤。用 HPMCP 交联 CS 纳米粒子可以在肠道中介导药物的可控释放,从而提高 BBr 的生物利用率。
{"title":"Comparison of the protective effects of CS/TPP and CS/HPMCP nanoparticles containing berberine in ethanol-induced hepatotoxicity in rat","authors":"Maral Mahboubi Kancha, Morteza Alizadeh, Mohsen Mehrabi","doi":"10.1186/s12906-023-04318-9","DOIUrl":"https://doi.org/10.1186/s12906-023-04318-9","url":null,"abstract":"Alcoholic liver disease (ALD) is a globally critical condition with no available efficient treatments. Herein, we generated chitosan (CS) nanoparticles cross-linked with two different agents, hydroxypropyl methylcellulose phthalate (HPMCP; termed as CS/HPMCP) and tripolyphosphate (TPP; termed as CS/TPP), and loaded them with berberine (BBr; referred to as CS/HPMCP/BBr and CS/TPP/BBr, respectively). Alongside the encapsulation efficiency (EE) and loading capacity (LC), the releasing activity of the nanoparticles was also measured in stimulated gastric fluid (SGF) and stimulated intestinal fluid (SIF) conditions. The effects of the prepared nanoparticles on the viability of mesenchymal stem cells (MSCs) were also evaluated. Ultimately, the protective effects of the nanoparticles were investigated in ALD mouse models. SEM images demonstrated that CS/HPMCP and CS/TPP nanoparticles had an average size of 235.5 ± 42 and 172 ± 21 nm, respectively. The LC and EE for CS/HPMCP/BBr were calculated as 79.78% and 75.79%, respectively; while the LC and EE for CS/TPP/BBr were 84.26% and 80.05%, respectively. pH was a determining factor for releasing BBr from CS/HPMCP nanoparticles as a higher cargo-releasing rate was observed in a less acidic environment. Both the BBr-loaded nanoparticles increased the viability of MSCs in comparison with their BBr-free counterparts. In vivo results demonstrated CS/HPMCP/BBr and CS/TPP/BBr nanoparticles protected enzymatic liver functionality against ethanol-induced damage. They also prevented histopathological ethanol-induced damage. Crosslinking CS nanoparticles with HPMCP can mediate controlled drug release in the intestine improving the bioavailability of BBr.","PeriodicalId":9132,"journal":{"name":"BMC Complementary and Alternative Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139470614","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
Biochanin A abrogates osteoclastogenesis in type 2 diabetic osteoporosis via regulating ROS/MAPK signaling pathway based on integrating molecular docking and experimental validation 基于分子对接和实验验证的生物变色素 A 通过调节 ROS/MAPK 信号通路抑制 2 型糖尿病骨质疏松症的破骨细胞生成
2区 医学 Q1 Medicine Pub Date : 2024-01-08 DOI: 10.1186/s12906-023-04332-x
Qi He, Junzheng Yang, Weijian Chen, Zhaofeng Pan, Baihao Chen, Jiaxu Zeng, Nenling Zhang, Yuewei Lin, Chuyi Chen, Jiacong Xiao, Miao Li, Shaocong Li, Haibin Wang, Peng Chen
There are accumulating type 2 diabetes patients who have osteoporosis simultaneously. More effective therapeutic strategies should be discovered. Biochanin A (BCA) has been indicated that can play a role in improving metabolic disorders of type 2 diabetes and preventing osteoporosis. But whether BCA can treat type 2 diabetic osteoporosis has not been studied. To investigate if the BCA can protect against type 2 diabetic osteoporosis and clarify the mechanism. Micro-CT and histology assays were performed to detect the trabecular bone and analyze the bone histomorphology effect of BCA. CCK-8 assay was performed to detect the toxicity of BCA. TRAcP staining, immunofluorescence and hydroxyapatite resorption assay were used to observe osteoclasts differentiation and resorptive activity. Molecular docking provided evidence about BCA regulating the MAPK axis via prediction by the algorithm. QRT-PCR and Western Blotting were utilized to detect the expression of osteoclastogenesis-related markers and MAPK signaling pathway. Accumulation of bone volume after BCA treatment could be found based on the 3D reconstruction. Besides, there were fewer osteoclasts in db/db mice treated with BCA than db/db mice treated with saline. In vitro, we found that BCA hadn’t toxicity in osteoclasts precursor, but also inhibited differentiation of osteoclasts. Further, we found that BCA suppresses osteoclastogenesis via ROS/MAPK signaling pathway. BCA can prevent type 2 diabetic osteoporosis by restricting osteoclast differentiation via ROS/MAPK signaling pathway.
越来越多的 2 型糖尿病患者同时患有骨质疏松症。因此,需要找到更有效的治疗策略。有研究表明,生物茶素 A(BCA)可在改善 2 型糖尿病代谢紊乱和预防骨质疏松症方面发挥作用。但BCA是否能治疗2型糖尿病骨质疏松症还没有研究。为了研究 BCA 是否能预防 2 型糖尿病骨质疏松症并阐明其机制。通过显微CT和组织学检测检测骨小梁,分析BCA对骨组织形态学的影响。CCK-8试验检测BCA的毒性。TRAcP染色、免疫荧光和羟基磷灰石吸收试验用于观察破骨细胞的分化和吸收活性。分子对接通过算法预测提供了BCA调控MAPK轴的证据。利用QRT-PCR和Western Blotting检测破骨细胞生成相关标记物和MAPK信号通路的表达。根据三维重建可以发现,BCA治疗后骨量增加。此外,使用BCA治疗的db/db小鼠的破骨细胞数量少于使用生理盐水治疗的db/db小鼠。在体外,我们发现 BCA 对破骨细胞前体没有毒性,但也抑制了破骨细胞的分化。此外,我们还发现 BCA 通过 ROS/MAPK 信号通路抑制破骨细胞的生成。BCA可通过ROS/MAPK信号通路限制破骨细胞分化,从而预防2型糖尿病骨质疏松症。
{"title":"Biochanin A abrogates osteoclastogenesis in type 2 diabetic osteoporosis via regulating ROS/MAPK signaling pathway based on integrating molecular docking and experimental validation","authors":"Qi He, Junzheng Yang, Weijian Chen, Zhaofeng Pan, Baihao Chen, Jiaxu Zeng, Nenling Zhang, Yuewei Lin, Chuyi Chen, Jiacong Xiao, Miao Li, Shaocong Li, Haibin Wang, Peng Chen","doi":"10.1186/s12906-023-04332-x","DOIUrl":"https://doi.org/10.1186/s12906-023-04332-x","url":null,"abstract":"There are accumulating type 2 diabetes patients who have osteoporosis simultaneously. More effective therapeutic strategies should be discovered. Biochanin A (BCA) has been indicated that can play a role in improving metabolic disorders of type 2 diabetes and preventing osteoporosis. But whether BCA can treat type 2 diabetic osteoporosis has not been studied. To investigate if the BCA can protect against type 2 diabetic osteoporosis and clarify the mechanism. Micro-CT and histology assays were performed to detect the trabecular bone and analyze the bone histomorphology effect of BCA. CCK-8 assay was performed to detect the toxicity of BCA. TRAcP staining, immunofluorescence and hydroxyapatite resorption assay were used to observe osteoclasts differentiation and resorptive activity. Molecular docking provided evidence about BCA regulating the MAPK axis via prediction by the algorithm. QRT-PCR and Western Blotting were utilized to detect the expression of osteoclastogenesis-related markers and MAPK signaling pathway. Accumulation of bone volume after BCA treatment could be found based on the 3D reconstruction. Besides, there were fewer osteoclasts in db/db mice treated with BCA than db/db mice treated with saline. In vitro, we found that BCA hadn’t toxicity in osteoclasts precursor, but also inhibited differentiation of osteoclasts. Further, we found that BCA suppresses osteoclastogenesis via ROS/MAPK signaling pathway. BCA can prevent type 2 diabetic osteoporosis by restricting osteoclast differentiation via ROS/MAPK signaling pathway.","PeriodicalId":9132,"journal":{"name":"BMC Complementary and Alternative Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139397291","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
Effect of YuPingFeng granules on clinical symptoms of stable COPD: study protocol for a multicenter, double-blind, and randomized controlled trial 玉屏风颗粒对慢性阻塞性肺病稳定期临床症状的影响:多中心、双盲、随机对照试验研究方案
2区 医学 Q1 Medicine Pub Date : 2024-01-08 DOI: 10.1186/s12906-023-04271-7
Ruifeng Chen, Yangqing Zhan, Zhengshi Lin, Xiao Wu, Jinchao Zhou, Zifeng Yang, Jinping Zheng
Reducing current clinical symptoms and the risks of future exacerbations is the main goal of stable COPD management. Traditional Chinese medicine has unique advantages in chronic disease management. YuPingFeng (YPF), as a classical prescription, has been proven to reduce the risk of exacerbations, but there is a lack of high-quality evidence for the assessment of clinical symptoms and quality of life, particularly for the assessment of treatment response of microecology and immunity. This is a prospective, multicentre, randomized, double-blind, placebo-controlled clinical trial. A total of 316 eligible subjects with moderate to severe COPD will be randomized 1:1 to receive YPF or placebo. Participants will receive either YPF or a placebo at 5 g three times daily for 52 weeks. The primary outcome will be the change in the COPD Assessment Test (CAT) score after 52 weeks of treatment. Secondary outcomes will include changes in the St George's Respiratory Questionnaire (SGRQ) score and clinical symptom score, among others. Outcomes will be measured at each visit. The study will continue for 52 weeks and will include six visits to each subject (at day 0 and weeks 4,12,24,36 and 52). In the event of exacerbations, subjects will be required to go back to the hospital once on the first day of exacerbation or when their condition permits. This trial will provide research methods to evaluate the clinical efficacy, safety, and the possible mechanism of YPF in the treatment of stable moderate-to-severe COPD patients. In addition, we hope to provide more possibilities for TCM to participate in the management of stable COPD. The trial was registered at the Chinese Clinical Trials Registry on 3 June 2022 (ChiCTR2200060476; date recorded: 3/6/2022, https://www.chictr.org.cn/ ).
减少目前的临床症状和未来病情加重的风险是慢性阻塞性肺病稳定期管理的主要目标。中医药在慢性病管理方面具有独特的优势。玉屏风散(YuPingFeng,YPF)作为一种经典处方,已被证实可降低病情恶化的风险,但在临床症状和生活质量的评估方面,尤其是在微生态和免疫的治疗反应评估方面,还缺乏高质量的证据。这是一项前瞻性、多中心、随机、双盲、安慰剂对照临床试验。共有 316 名符合条件的中度至重度慢性阻塞性肺病患者将按 1:1 的比例随机接受 YPF 或安慰剂治疗。受试者将接受 YPF 或安慰剂治疗,每次 5 克,每天三次,持续 52 周。主要结果是治疗 52 周后慢性阻塞性肺病评估测试 (CAT) 分数的变化。次要结果包括圣乔治呼吸问卷 (SGRQ) 评分和临床症状评分等的变化。结果将在每次就诊时进行测量。研究将持续 52 周,对每位受试者进行六次访视(第 0 天、第 4、12、24、36 和 52 周)。如果病情恶化,受试者需要在病情恶化的第一天或病情允许时返回医院一次。这项试验将为评估 YPF 治疗稳定期中重度慢性阻塞性肺病患者的临床疗效、安全性和可能的机制提供研究方法。此外,我们还希望为中医药参与稳定期慢性阻塞性肺病的治疗提供更多的可能性。该试验于2022年6月3日在中国临床试验注册中心注册(ChiCTR2200060476;注册日期:2022年6月3日,https://www.chictr.org.cn/ )。
{"title":"Effect of YuPingFeng granules on clinical symptoms of stable COPD: study protocol for a multicenter, double-blind, and randomized controlled trial","authors":"Ruifeng Chen, Yangqing Zhan, Zhengshi Lin, Xiao Wu, Jinchao Zhou, Zifeng Yang, Jinping Zheng","doi":"10.1186/s12906-023-04271-7","DOIUrl":"https://doi.org/10.1186/s12906-023-04271-7","url":null,"abstract":"Reducing current clinical symptoms and the risks of future exacerbations is the main goal of stable COPD management. Traditional Chinese medicine has unique advantages in chronic disease management. YuPingFeng (YPF), as a classical prescription, has been proven to reduce the risk of exacerbations, but there is a lack of high-quality evidence for the assessment of clinical symptoms and quality of life, particularly for the assessment of treatment response of microecology and immunity. This is a prospective, multicentre, randomized, double-blind, placebo-controlled clinical trial. A total of 316 eligible subjects with moderate to severe COPD will be randomized 1:1 to receive YPF or placebo. Participants will receive either YPF or a placebo at 5 g three times daily for 52 weeks. The primary outcome will be the change in the COPD Assessment Test (CAT) score after 52 weeks of treatment. Secondary outcomes will include changes in the St George's Respiratory Questionnaire (SGRQ) score and clinical symptom score, among others. Outcomes will be measured at each visit. The study will continue for 52 weeks and will include six visits to each subject (at day 0 and weeks 4,12,24,36 and 52). In the event of exacerbations, subjects will be required to go back to the hospital once on the first day of exacerbation or when their condition permits. This trial will provide research methods to evaluate the clinical efficacy, safety, and the possible mechanism of YPF in the treatment of stable moderate-to-severe COPD patients. In addition, we hope to provide more possibilities for TCM to participate in the management of stable COPD. The trial was registered at the Chinese Clinical Trials Registry on 3 June 2022 (ChiCTR2200060476; date recorded: 3/6/2022, https://www.chictr.org.cn/ ).","PeriodicalId":9132,"journal":{"name":"BMC Complementary and Alternative Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139397288","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
Supplementation of papaya leaf juice has beneficial effects on glucose homeostasis in high fat/high sugar-induced obese and prediabetic adult mice 补充木瓜叶汁对高脂/高糖诱导的肥胖和糖尿病前期成年小鼠的葡萄糖稳态具有有益影响
2区 医学 Q1 Medicine Pub Date : 2024-01-03 DOI: 10.1186/s12906-023-04320-1
Benard B. Nyakundi, Marisa M. Wall, Jinzeng Yang
Prediabetes is characterized by a cluster of glycemic parameters higher than normal but below the threshold of type 2 diabetes mellitus (T2DM). In recent years, phytochemical-rich plant extracts have gained popularity as therapeutic agents for metabolic disorders. This study investigated the effects of papaya leaf (PL) juice supplementation on blood glucose levels in diet-induced obese and prediabetic adult mice. B65JL F1 mice (n = 20) at 12–14 months old were fed a high fat/sugar diet (HFHS) for 120 days. Mice were switched to restricted rodent chow of 3 g feed/30 g body weight/day, supplemented with 3 g/100 mL PL juice for 30 days. HFHS diet remarkably increased fasting plasma glucose levels from 114 ± 6.54 mg/dL to 192.7 ± 10.1 mg/dL and body weight from 32.5 ± 1.6 to 50.3 ± 4.1 g. HFHS diet results in hyperglycemia, insulin resistance, hyperlipidemia, and liver steatosis. The combination of PL juice and restricted diet significantly reduced body weight and fasting blood glucose levels to 43.75 ± 1.4 g and 126.25 ± 3.2 mg/dl, respectively. Moreover, PL juice with a restricted diet significantly improved lipid profile: cholesterol from 204 to 150 mg/dL, LDL-c from 110.4 to 50 mg/dL, and triglyceride from 93.7 to 60 mg/dL. Additionally, PL juice combined with a restricted diet significantly reduced adiposity, reversed fatty liver, and restored skeletal muscle Glut4 and phosphorylated (p-AKT (ser473). This study demonstrated that supplementation of PL juice with a restricted diet was more effective than a restricted diet alone in reversing major symptoms related to prediabetic and obesity conditions.
糖尿病前期的特征是一组血糖参数高于正常值,但低于 2 型糖尿病(T2DM)的临界值。近年来,富含植物化学成分的植物提取物作为代谢紊乱的治疗药物越来越受欢迎。本研究调查了补充木瓜叶(PL)汁对饮食诱导的肥胖和糖尿病前期成年小鼠血糖水平的影响。对 12-14 个月大的 B65JL F1 小鼠(n = 20)喂食高脂肪/糖饮食(HFHS)120 天。小鼠改用限制性啮齿动物饲料(3 克饲料/30 克体重/天),并补充 3 克/100 毫升 PL 果汁 30 天。HFHS饮食显著增加了空腹血浆葡萄糖水平,从114±6.54毫克/分升增加到192.7±10.1毫克/分升,体重从32.5±1.6克增加到50.3±4.1克。将聚乳酸果汁与限制性饮食相结合,可显著降低体重和空腹血糖水平,分别降至 43.75 ± 1.4 克和 126.25 ± 3.2 毫克/分升。此外,聚乳酸果汁与限制性饮食相结合可明显改善血脂状况:胆固醇从 204 毫克/分升降至 150 毫克/分升,低密度脂蛋白胆固醇从 110.4 毫克/分升降至 50 毫克/分升,甘油三酯从 93.7 毫克/分升降至 60 毫克/分升。此外,PL果汁与限制性饮食相结合可显著减少脂肪含量,逆转脂肪肝,恢复骨骼肌Glut4和磷酸化p-AKT(ser473)。这项研究表明,在逆转与糖尿病前期和肥胖症有关的主要症状方面,在限制饮食的同时补充聚乳酸汁比单独限制饮食更有效。
{"title":"Supplementation of papaya leaf juice has beneficial effects on glucose homeostasis in high fat/high sugar-induced obese and prediabetic adult mice","authors":"Benard B. Nyakundi, Marisa M. Wall, Jinzeng Yang","doi":"10.1186/s12906-023-04320-1","DOIUrl":"https://doi.org/10.1186/s12906-023-04320-1","url":null,"abstract":"Prediabetes is characterized by a cluster of glycemic parameters higher than normal but below the threshold of type 2 diabetes mellitus (T2DM). In recent years, phytochemical-rich plant extracts have gained popularity as therapeutic agents for metabolic disorders. This study investigated the effects of papaya leaf (PL) juice supplementation on blood glucose levels in diet-induced obese and prediabetic adult mice. B65JL F1 mice (n = 20) at 12–14 months old were fed a high fat/sugar diet (HFHS) for 120 days. Mice were switched to restricted rodent chow of 3 g feed/30 g body weight/day, supplemented with 3 g/100 mL PL juice for 30 days. HFHS diet remarkably increased fasting plasma glucose levels from 114 ± 6.54 mg/dL to 192.7 ± 10.1 mg/dL and body weight from 32.5 ± 1.6 to 50.3 ± 4.1 g. HFHS diet results in hyperglycemia, insulin resistance, hyperlipidemia, and liver steatosis. The combination of PL juice and restricted diet significantly reduced body weight and fasting blood glucose levels to 43.75 ± 1.4 g and 126.25 ± 3.2 mg/dl, respectively. Moreover, PL juice with a restricted diet significantly improved lipid profile: cholesterol from 204 to 150 mg/dL, LDL-c from 110.4 to 50 mg/dL, and triglyceride from 93.7 to 60 mg/dL. Additionally, PL juice combined with a restricted diet significantly reduced adiposity, reversed fatty liver, and restored skeletal muscle Glut4 and phosphorylated (p-AKT (ser473). This study demonstrated that supplementation of PL juice with a restricted diet was more effective than a restricted diet alone in reversing major symptoms related to prediabetic and obesity conditions.","PeriodicalId":9132,"journal":{"name":"BMC Complementary and Alternative Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139083706","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
Effects of aromatherapy with Matricaria chamomile essential oil on anxiety and hemodynamic indices in patients with acute coronary syndrome, 2021: a randomized controlled trial 母菊洋甘菊精油芳香疗法对急性冠状动脉综合征患者焦虑和血液动力学指标的影响(2021 年):随机对照试验
2区 医学 Q1 Medicine Pub Date : 2024-01-03 DOI: 10.1186/s12906-023-04326-9
Majid Pourshaikhian, Mohammad Taghi Moghadamnia, Ehsan Kazemnezhad Leyli, Zahra Shafiei Kisomi
Patients with Acute Coronary Syndrome (ACS) experience high levels of anxiety that may cause instability of hemodynamic indices, increased risk of ischemia, myocardial infarction and poor quality of life. Aromatherapy can affect patients’ anxiety levels and improve hemodynamic indices. This study aimed to evaluate the efficacy of aromatherapy on anxiety and hemodynamic indices in ACS patients. This study was a double-blind, randomized clinical trial conducted on 154 ACS patients. The participants were classified into two equal groups of intervention and placebo through the block randomization method. The data collection tools consisted of demographic information, a shortened 6-item version of the Spielberger questionnaire and a form of hemodynamic indices. For two consecutive nights, the intervention group inhaled 7 drops of the chamomile essential oil (%10) and the placebo group inhaled 7 drops of the sesame oil poured on a sterile cotton ball. The hemodynamic indices were collected half an hour before, one and four hours after the intervention until the next morning. The Spielberger questionnaire was completed once before the intervention and once after the end of the intervention, by the researcher through an interview. The number of heart rate (HR) was counted for a full minute. Also, the blood pressure (BP) of all the samples was measured by the researcher. Data analysis was done using Chi-square, paired t-test, and analysis of variance (ANOVA) in SPSS22. The mean and standard deviation of the age of patients were 58/2 ± 11.6 and 59.7% of them were female. The results of ANOVA showed a significantly lower anxiety score as well as systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR in the intervention group compared to those of the placebo group (P < 0.001). The decrease in anxiety score after the intervention, in the intervention and placebo groups was (5.2 ± 1.9) and (1 ± 1. 18) respectively. In the intervention group, the SBP and DBP after the intervention, was significant (P < 0.05). Also, the HR was significant (P < 0.001) after the intervention. Aromatherapy could reduce anxiety and improve hemodynamic indices in ACS patients. IRCT20080825001083N11.
急性冠状动脉综合征(ACS)患者会感到高度焦虑,这可能会导致血液动力学指标不稳定、缺血风险增加、心肌梗死和生活质量下降。芳香疗法可影响患者的焦虑水平,改善血液动力学指标。本研究旨在评估芳香疗法对 ACS 患者焦虑和血液动力学指标的疗效。本研究是一项双盲、随机临床试验,对象为 154 名 ACS 患者。通过分块随机法将参与者分为干预组和安慰剂组。数据收集工具包括人口统计学信息、斯皮尔伯格6项问卷的简短版本和血液动力学指数表。连续两个晚上,干预组吸入 7 滴洋甘菊精油(10%),安慰剂组吸入 7 滴倒在消毒棉球上的芝麻油。在干预前半小时、干预后一小时和四小时至次日早晨收集血液动力学指数。研究人员在干预前和干预结束后通过访谈完成了一次斯皮尔伯格问卷调查。对心率(HR)进行了整分钟的计数。此外,研究人员还测量了所有样本的血压(BP)。数据分析采用 SPSS22 中的卡方检验、配对 t 检验和方差分析(ANOVA)。患者年龄的平均值和标准差为(58/2 ± 11.6),其中 59.7% 为女性。方差分析结果显示,与安慰剂组相比,干预组的焦虑评分、收缩压(SBP)、舒张压(DBP)和心率均明显降低(P < 0.001)。干预后,干预组和安慰剂组的焦虑评分降幅分别为(5.2 ± 1.9)和(1 ± 1.18)。干预后,干预组的 SBP 和 DBP 显著降低(P < 0.05)。此外,干预后的心率也明显下降(P < 0.001)。芳香疗法可以减轻 ACS 患者的焦虑并改善血液动力学指标。IRCT20080825001083N11.
{"title":"Effects of aromatherapy with Matricaria chamomile essential oil on anxiety and hemodynamic indices in patients with acute coronary syndrome, 2021: a randomized controlled trial","authors":"Majid Pourshaikhian, Mohammad Taghi Moghadamnia, Ehsan Kazemnezhad Leyli, Zahra Shafiei Kisomi","doi":"10.1186/s12906-023-04326-9","DOIUrl":"https://doi.org/10.1186/s12906-023-04326-9","url":null,"abstract":"Patients with Acute Coronary Syndrome (ACS) experience high levels of anxiety that may cause instability of hemodynamic indices, increased risk of ischemia, myocardial infarction and poor quality of life. Aromatherapy can affect patients’ anxiety levels and improve hemodynamic indices. This study aimed to evaluate the efficacy of aromatherapy on anxiety and hemodynamic indices in ACS patients. This study was a double-blind, randomized clinical trial conducted on 154 ACS patients. The participants were classified into two equal groups of intervention and placebo through the block randomization method. The data collection tools consisted of demographic information, a shortened 6-item version of the Spielberger questionnaire and a form of hemodynamic indices. For two consecutive nights, the intervention group inhaled 7 drops of the chamomile essential oil (%10) and the placebo group inhaled 7 drops of the sesame oil poured on a sterile cotton ball. The hemodynamic indices were collected half an hour before, one and four hours after the intervention until the next morning. The Spielberger questionnaire was completed once before the intervention and once after the end of the intervention, by the researcher through an interview. The number of heart rate (HR) was counted for a full minute. Also, the blood pressure (BP) of all the samples was measured by the researcher. Data analysis was done using Chi-square, paired t-test, and analysis of variance (ANOVA) in SPSS22. The mean and standard deviation of the age of patients were 58/2 ± 11.6 and 59.7% of them were female. The results of ANOVA showed a significantly lower anxiety score as well as systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR in the intervention group compared to those of the placebo group (P < 0.001). The decrease in anxiety score after the intervention, in the intervention and placebo groups was (5.2 ± 1.9) and (1 ± 1. 18) respectively. In the intervention group, the SBP and DBP after the intervention, was significant (P < 0.05). Also, the HR was significant (P < 0.001) after the intervention. Aromatherapy could reduce anxiety and improve hemodynamic indices in ACS patients. IRCT20080825001083N11.","PeriodicalId":9132,"journal":{"name":"BMC Complementary and Alternative Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139083919","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
Ammidin ameliorates myocardial hypoxia/reoxygenation injury by inhibiting the ACSL4/AMPK/mTOR-mediated ferroptosis pathway 氨酰胺通过抑制 ACSL4/AMPK/mTOR 介导的铁氧化途径改善心肌缺氧/复氧损伤
2区 医学 Q1 Medicine Pub Date : 2023-12-15 DOI: 10.1186/s12906-023-04289-x
Yue Han, Hui Yuan, Fengxiang Li, Yueying Yuan, Xuezhi Zheng, Xudong Zhang, Jian Sun
The aim of the present study was to investigate the therapeutic effect of ammidin on hypoxia/reoxygenation (H/R) injury in primary neonatal rat cardiomyocytes by observing the role of ferroptosis in the process of H/R injury, and to verify its target and regulatory signaling pathways. The network pharmacology analysis was used to predict the biological processes, core targets and related signaling pathways of Angelica dahurica in the treatment of ferroptosis. Cell viability was assessed using live cell imaging and cell counting kit-8. Lactate dehydrogenase (LDH), reactive oxygen species (ROS) production, and malondialdehyde (MDA), superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) content were determined to assess the level of ferroptosis. Western blotting was performed to measure protein expression. Network pharmacology predicted that Acyl-CoA synthetase long chain family member 4 (ACSL4) was highly associated with myocardial H/R injury in the intersection of Angelica dahurica and ferroptosis. The top three active components of Angelica dahurica were found to be mandenol, alloisoimperatorin and ammidin, among which ammidin was found to have the strongest binding to the target proteins of the ACSL4/AMPK/mTOR pathway. H/R reduced the viability of cardiomyocytes, while the inhibition of ferroptosis by ferrostatin-1 alleviated the H/R-induced inhibition of cardiomyocyte viability. This was evidenced by the increased cell viability, SOD release, MMP level and glutathione peroxidase 4 (GPX4) protein expression, as well as the decreased LDH and MDA release and ROS production and ACSL4 protein expression (P < 0.05). To verify the existence of ferroptosis in myocardial hypoxia/reoxygenation injury. In addition, ammidin increased cell viability and GPX4 protein expression (P < 0.05), decreased ROS generation, and MDA and MTT expression (P < 0.05), then inhibited ferroptosis, and finally alleviated myocardial H/R injury by regulating the ACSL4/AMPK signaling pathway. Network pharmacology was used to predict the correlation between ammidin and ferroptosis following myocardial H/R injury. It was demonstrated that ammidin may regulate ferroptosis by inhibiting the ACSL4/AMPK/mTOR signaling pathway and reduce H/R injury in cardiomyocytes.
本研究旨在通过观察白芷在新生大鼠心肌细胞缺氧/再氧合(H/R)损伤过程中的作用,验证其靶点和调控信号通路,从而研究白芷对新生大鼠心肌细胞缺氧/再氧合(H/R)损伤的治疗效果。利用网络药理学分析预测了白芷治疗高铁血症的生物学过程、核心靶点及相关信号通路。使用活细胞成像和细胞计数试剂盒-8评估细胞活力。测定乳酸脱氢酶(LDH)、活性氧(ROS)产生量、丙二醛(MDA)、超氧化物歧化酶(SOD)和线粒体膜电位(MMP)含量,以评估铁中毒程度。还进行了 Western 印迹以测定蛋白质表达。网络药理学预测,在白芷和铁变态反应的交叉点上,酰基-CoA合成酶长链家族成员4(ACSL4)与心肌H/R损伤高度相关。研究发现,白芷的前三大活性成分为曼陀罗醇、异橙皮苷和氨酰胺,其中氨酰胺与ACSL4/AMPK/mTOR通路的靶蛋白结合力最强。H/R降低了心肌细胞的活力,而铁前列素-1抑制铁凋亡则减轻了H/R引起的心肌细胞活力抑制。这表现在细胞活力、SOD释放、MMP水平和谷胱甘肽过氧化物酶4(GPX4)蛋白表达的增加,以及LDH和MDA释放、ROS产生和ACSL4蛋白表达的减少(P<0.05)。为了验证心肌缺氧/复氧损伤中是否存在铁变态反应。此外,氨酰胺可提高细胞活力和GPX4蛋白表达(P<0.05),减少ROS生成、MDA和MTT表达(P<0.05),进而抑制铁变态反应,最终通过调节ACSL4/AMPK信号通路缓解心肌H/R损伤。研究人员利用网络药理学预测了氨酰胺与心肌H/R损伤后铁细胞减少之间的相关性。结果表明,氨酰胺可通过抑制ACSL4/AMPK/mTOR信号通路来调节铁突变,减轻心肌细胞的H/R损伤。
{"title":"Ammidin ameliorates myocardial hypoxia/reoxygenation injury by inhibiting the ACSL4/AMPK/mTOR-mediated ferroptosis pathway","authors":"Yue Han, Hui Yuan, Fengxiang Li, Yueying Yuan, Xuezhi Zheng, Xudong Zhang, Jian Sun","doi":"10.1186/s12906-023-04289-x","DOIUrl":"https://doi.org/10.1186/s12906-023-04289-x","url":null,"abstract":"The aim of the present study was to investigate the therapeutic effect of ammidin on hypoxia/reoxygenation (H/R) injury in primary neonatal rat cardiomyocytes by observing the role of ferroptosis in the process of H/R injury, and to verify its target and regulatory signaling pathways. The network pharmacology analysis was used to predict the biological processes, core targets and related signaling pathways of Angelica dahurica in the treatment of ferroptosis. Cell viability was assessed using live cell imaging and cell counting kit-8. Lactate dehydrogenase (LDH), reactive oxygen species (ROS) production, and malondialdehyde (MDA), superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) content were determined to assess the level of ferroptosis. Western blotting was performed to measure protein expression. Network pharmacology predicted that Acyl-CoA synthetase long chain family member 4 (ACSL4) was highly associated with myocardial H/R injury in the intersection of Angelica dahurica and ferroptosis. The top three active components of Angelica dahurica were found to be mandenol, alloisoimperatorin and ammidin, among which ammidin was found to have the strongest binding to the target proteins of the ACSL4/AMPK/mTOR pathway. H/R reduced the viability of cardiomyocytes, while the inhibition of ferroptosis by ferrostatin-1 alleviated the H/R-induced inhibition of cardiomyocyte viability. This was evidenced by the increased cell viability, SOD release, MMP level and glutathione peroxidase 4 (GPX4) protein expression, as well as the decreased LDH and MDA release and ROS production and ACSL4 protein expression (P < 0.05). To verify the existence of ferroptosis in myocardial hypoxia/reoxygenation injury. In addition, ammidin increased cell viability and GPX4 protein expression (P < 0.05), decreased ROS generation, and MDA and MTT expression (P < 0.05), then inhibited ferroptosis, and finally alleviated myocardial H/R injury by regulating the ACSL4/AMPK signaling pathway. Network pharmacology was used to predict the correlation between ammidin and ferroptosis following myocardial H/R injury. It was demonstrated that ammidin may regulate ferroptosis by inhibiting the ACSL4/AMPK/mTOR signaling pathway and reduce H/R injury in cardiomyocytes.","PeriodicalId":9132,"journal":{"name":"BMC Complementary and Alternative Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138681449","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
Antimicrobial, antioxidant and cytotoxic activities of the leaf and stem extracts of Carissa bispinosa used for dental health care 用于牙齿保健的双子荠叶和茎提取物的抗菌、抗氧化和细胞毒性活性
2区 医学 Q1 Medicine Pub Date : 2023-12-15 DOI: 10.1186/s12906-023-04308-x
Wanda Shekwa, Tsolanku Sidney Maliehe, Peter Masoko
Carissa bispinosa (L.) Desf. ex Brenan is one of the plants used traditionally to treat oral infections. However, there is limited data validating its therapeutic properties and photochemistry. The aim of this study was to investigate the protective efficacy of the leaf and stem extracts of C. bispinosa against oral infections. The phenolic and tannin contents were measured using Folin-Ciocalteau method after extracting with different solvents. The minimum inhibitory concentrations (MIC) of the extracts were assessed using the microdilution method against fungal (Candida albicans and Candida glabrata) and bacterial (Streptococcus pyogenes, Staphylococcus aureus and Enterococcus faecalis) strains. The 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing power (FRP) models were utilised to assess the antioxidant potential of the extracts. Cytotoxicity of the leaf acetone extract was evaluated using the methylthiazol tetrazolium assay. The methanol leaf extract had the highest phenolic content (113.20 mg TAE/g), whereas hexane extract displayed the highest tannin composition of 22.98 mg GAE/g. The acetone stem extract had the highest phenolic content (338 mg TAE/g) and the stem extract yielded the highest total tannin content (49.87 mg GAE/g). The methanol leaf extract demonstrated the lowest MIC value (0.31 mg/mL), whereas the stem ethanol extract had the least MIC value of 0.31 mg/mL. The stem methanol extract had the best DPPH free radical scavenging activity (IC50, 72 µg/mL) whereas the stem ethanol extract displayed maximum FRP with absorbance of 1.916. The leaf acetone extract had minimum cytotoxicity with the lethal concentration (LC50) of 0.63 mg/mL. The results obtained in this study validated the protective effect of C. bispinosa against oral infections.
Carissa bispinosa (L.) Desf. ex Brenan 是传统上用于治疗口腔感染的植物之一。然而,证实其治疗特性和光化学作用的数据有限。本研究的目的是调查 C. bispinosa 的叶和茎提取物对口腔感染的保护功效。用不同溶剂萃取后,采用 Folin-Ciocalteau 法测量了酚和单宁的含量。采用微量稀释法评估了提取物对真菌(白色念珠菌和光滑念珠菌)和细菌(化脓性链球菌、金黄色葡萄球菌和粪肠球菌)菌株的最低抑菌浓度(MIC)。利用 2-二苯基-1-苦基肼(DPPH)和铁还原力(FRP)模型来评估提取物的抗氧化潜力。使用甲基噻唑四氮唑测定法评估了叶片丙酮提取物的细胞毒性。甲醇叶提取物的酚含量最高(113.20 毫克 TAE/克),而正己烷提取物的单宁含量最高,为 22.98 毫克 GAE/克。丙酮茎提取物的酚含量最高(338 毫克 TAE/克),茎提取物的总单宁含量最高(49.87 毫克 GAE/克)。甲醇叶提取物的 MIC 值最低(0.31 毫克/毫升),而茎乙醇提取物的 MIC 值最低,为 0.31 毫克/毫升。茎甲醇提取物的 DPPH 自由基清除活性最高(IC50,72 µg/mL),而茎乙醇提取物的 FRP 最高,吸光度为 1.916。叶丙酮提取物的细胞毒性最小,致死浓度(LC50)为 0.63 毫克/毫升。这项研究的结果验证了双孢蘑菇对口腔感染的保护作用。
{"title":"Antimicrobial, antioxidant and cytotoxic activities of the leaf and stem extracts of Carissa bispinosa used for dental health care","authors":"Wanda Shekwa, Tsolanku Sidney Maliehe, Peter Masoko","doi":"10.1186/s12906-023-04308-x","DOIUrl":"https://doi.org/10.1186/s12906-023-04308-x","url":null,"abstract":"Carissa bispinosa (L.) Desf. ex Brenan is one of the plants used traditionally to treat oral infections. However, there is limited data validating its therapeutic properties and photochemistry. The aim of this study was to investigate the protective efficacy of the leaf and stem extracts of C. bispinosa against oral infections. The phenolic and tannin contents were measured using Folin-Ciocalteau method after extracting with different solvents. The minimum inhibitory concentrations (MIC) of the extracts were assessed using the microdilution method against fungal (Candida albicans and Candida glabrata) and bacterial (Streptococcus pyogenes, Staphylococcus aureus and Enterococcus faecalis) strains. The 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing power (FRP) models were utilised to assess the antioxidant potential of the extracts. Cytotoxicity of the leaf acetone extract was evaluated using the methylthiazol tetrazolium assay. The methanol leaf extract had the highest phenolic content (113.20 mg TAE/g), whereas hexane extract displayed the highest tannin composition of 22.98 mg GAE/g. The acetone stem extract had the highest phenolic content (338 mg TAE/g) and the stem extract yielded the highest total tannin content (49.87 mg GAE/g). The methanol leaf extract demonstrated the lowest MIC value (0.31 mg/mL), whereas the stem ethanol extract had the least MIC value of 0.31 mg/mL. The stem methanol extract had the best DPPH free radical scavenging activity (IC50, 72 µg/mL) whereas the stem ethanol extract displayed maximum FRP with absorbance of 1.916. The leaf acetone extract had minimum cytotoxicity with the lethal concentration (LC50) of 0.63 mg/mL. The results obtained in this study validated the protective effect of C. bispinosa against oral infections.","PeriodicalId":9132,"journal":{"name":"BMC Complementary and Alternative Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138693308","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
Artichoke (Cynara scolymus L.) water extract alleviates palmitate-induced insulin resistance in HepG2 hepatocytes via the activation of IRS1/PI3K/AKT/FoxO1 and GSK-3β signaling pathway 朝鲜蓟(Cynara scolymus L.)水提取物通过激活 IRS1/PI3K/AKT/FoxO1 和 GSK-3β 信号通路减轻棕榈酸酯诱导的 HepG2 肝细胞胰岛素抵抗
2区 医学 Q1 Medicine Pub Date : 2023-12-15 DOI: 10.1186/s12906-023-04275-3
Aihua Deng, Yun Wang, Kerui Huang, Peng Xie, Ping Mo, Fengying Liu, Jun Chen, Kaiyi Chen, Yun Wang, Bing Xiao
Artichoke (Cynara scolymus L.) is a typical element of a traditional Mediterranean diet and has potential health advantages for insulin resistance (IR) and type 2 diabetes mellitus (T2DM). This study aims to evaluate the effect and underlying mechanism of artichoke water extract (AWE) on palmitate (PA)-induced IR in human hepatocellular carcinoma (HepG2) cells. The effect of AWE on cell viability was determined using CCK8 assay. Cellular glucose uptake, glucose consumption, glucose production, and glycogen content were assessed after AWE treatment. The gene expression and protein levels were examined by real-time polymerase chain reaction (qRT-PCR) and western blotting. The results showed that AWE dose-dependently increased cell viability in IR HepG2 cells (P < 0.01). AWE treatment significantly promoted glucose uptake and consumption, decreased glucose production, and increased the cellular glycogen content in IR HepG2 cells (P < 0.01). Mechanistically, AWE elevated the phosphorylation and total protein levels of major insulin signaling molecules in IR HepG2 cells, which resulted in a decrease in the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and the inhibition of glycogen synthase (GS) phosphorylation in IR HepG2 cells. Furthermore, the protective effect of AWE on IR HepG2 cells might be ascribed to the inhibition of the endoplasmic reticulum (ER) stress. We conclude that AWE may improve glucose metabolism by regulating IRS1/PI3K/AKT/FoxO1 and GSK-3β signaling associated with the inhibition of ER stress in IR HepG2 cells induced by PA.
朝鲜蓟(Cynara scolymus L.)是传统地中海饮食的典型成分,对胰岛素抵抗(IR)和 2 型糖尿病(T2DM)具有潜在的健康优势。本研究旨在评估朝鲜蓟水提取物(AWE)对棕榈酸酯(PA)诱导的人肝细胞癌(HepG2)细胞 IR 的影响及其内在机制。使用 CCK8 检测法确定 AWE 对细胞活力的影响。评估了 AWE 处理后细胞的葡萄糖摄取、葡萄糖消耗、葡萄糖生成和糖原含量。基因表达和蛋白质水平通过实时聚合酶链反应(qRT-PCR)和免疫印迹法进行检测。结果表明,AWE 剂量依赖性地提高了 IR HepG2 细胞的存活率(P < 0.01)。AWE 处理可明显促进 IR HepG2 细胞对葡萄糖的摄取和消耗,减少葡萄糖的产生,并增加细胞糖原含量(P < 0.01)。从机理上讲,AWE 提高了 IR HepG2 细胞中主要胰岛素信号分子的磷酸化水平和总蛋白水平,导致 IR HepG2 细胞中磷酸烯醇丙酮酸羧激酶(PEPCK)和葡萄糖-6-磷酸酶(G6Pase)的表达减少,糖原合成酶(GS)的磷酸化受到抑制。此外,AWE 对 IR HepG2 细胞的保护作用可能是由于抑制了内质网(ER)应激。我们得出的结论是,AWE 可通过调节 IRS1/PI3K/AKT/FoxO1 和 GSK-3β 信号传导来改善葡萄糖代谢,这与 PA 诱导的 IR HepG2 细胞的 ER 应激抑制有关。
{"title":"Artichoke (Cynara scolymus L.) water extract alleviates palmitate-induced insulin resistance in HepG2 hepatocytes via the activation of IRS1/PI3K/AKT/FoxO1 and GSK-3β signaling pathway","authors":"Aihua Deng, Yun Wang, Kerui Huang, Peng Xie, Ping Mo, Fengying Liu, Jun Chen, Kaiyi Chen, Yun Wang, Bing Xiao","doi":"10.1186/s12906-023-04275-3","DOIUrl":"https://doi.org/10.1186/s12906-023-04275-3","url":null,"abstract":"Artichoke (Cynara scolymus L.) is a typical element of a traditional Mediterranean diet and has potential health advantages for insulin resistance (IR) and type 2 diabetes mellitus (T2DM). This study aims to evaluate the effect and underlying mechanism of artichoke water extract (AWE) on palmitate (PA)-induced IR in human hepatocellular carcinoma (HepG2) cells. The effect of AWE on cell viability was determined using CCK8 assay. Cellular glucose uptake, glucose consumption, glucose production, and glycogen content were assessed after AWE treatment. The gene expression and protein levels were examined by real-time polymerase chain reaction (qRT-PCR) and western blotting. The results showed that AWE dose-dependently increased cell viability in IR HepG2 cells (P < 0.01). AWE treatment significantly promoted glucose uptake and consumption, decreased glucose production, and increased the cellular glycogen content in IR HepG2 cells (P < 0.01). Mechanistically, AWE elevated the phosphorylation and total protein levels of major insulin signaling molecules in IR HepG2 cells, which resulted in a decrease in the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and the inhibition of glycogen synthase (GS) phosphorylation in IR HepG2 cells. Furthermore, the protective effect of AWE on IR HepG2 cells might be ascribed to the inhibition of the endoplasmic reticulum (ER) stress. We conclude that AWE may improve glucose metabolism by regulating IRS1/PI3K/AKT/FoxO1 and GSK-3β signaling associated with the inhibition of ER stress in IR HepG2 cells induced by PA.","PeriodicalId":9132,"journal":{"name":"BMC Complementary and Alternative Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138681329","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
期刊
BMC Complementary and Alternative Medicine
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1