Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a...Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a persistent gap between preclinical evidence and practical application.This review aims to assess the readiness of cardamonin to progress from laboratory research to clinical application as an anticancer agent by examining both scientific evidence and translational challenges.Preclinical pharmacokinetic and pharmacodynamic data suggest that cardamonin’s therapeutic potential as an anticancer agent is hindered by its poor oral bioavailability.Although its molecular targets remain undefined,evidence indicates that cardamonin can inhibit various signaling pathways,including nuclear factor kappa-light-chain-enhancer of activated B cells,mammalian target of rapamycin,signal transducer and activator of transcription 3,and Wnt/β-catenin.The lack of in vivo toxicity studies creates uncertainty regarding the balance between its therapeutic benefits and potential adverse effects when moving from laboratory research to human trials.Despite these limitations,cardamonin has,however,demonstrated antiproliferative,anti-metastatic,and chemosensitizing effects,mainly against breast,colorectal,and ovarian cancers.Nevertheless,exploring its combination with standard chemotherapeutic agents may offer a promising foundation for advancing cardamonin into clinical trials.展开更多
Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to ident...Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin(CDN), the major active ingredient of the traditional Chinese medicinal herb Alpinia katsumadai, has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-κB-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner.Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1βproduction induced by LPS in vivo, which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases.展开更多
小豆蔻明(cardamonin,CAR)的化学结构为2’,4’-二甲基-6’-甲氧基查尔酮,是一种主要存在于姜科山姜属植物草豆蔻种子中的黄酮类单体,生物活性广泛。由于其具有抗肿瘤作用,近年来倍受关注,并已有系列衍生物被合成。研究表明,CAR对多形...小豆蔻明(cardamonin,CAR)的化学结构为2’,4’-二甲基-6’-甲氧基查尔酮,是一种主要存在于姜科山姜属植物草豆蔻种子中的黄酮类单体,生物活性广泛。由于其具有抗肿瘤作用,近年来倍受关注,并已有系列衍生物被合成。研究表明,CAR对多形性胶质母细胞瘤、Lewis肺癌、乳腺癌、结肠癌和前列腺癌等肿瘤细胞的生长均有抑制作用,其作用机制涉及哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)通路、核因子κB(nuclear factor kappa B,NF-κB)信号通路、谷氨酰胺转氨酶2、内源性凋亡途径、信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)、E-钙黏蛋白(E-cadherin)、细胞自噬、β-catenin和细胞周期调控等。本文主要对CAR及其衍生物的抗肿瘤作用及其机制进行综述。展开更多
目的:探讨小豆蔻明抑制C3H10T1/2细胞成脂分化的作用机制。方法:观察C3H10T1/2细胞成脂过程形态学变化,采用MTS法、油红O染色法、GAP-PAP酶法检测小豆蔻明对C3H10T1/2细胞增殖、成脂分化以及胞内甘油三酯含量的影响,采用RT-PCR与Western...目的:探讨小豆蔻明抑制C3H10T1/2细胞成脂分化的作用机制。方法:观察C3H10T1/2细胞成脂过程形态学变化,采用MTS法、油红O染色法、GAP-PAP酶法检测小豆蔻明对C3H10T1/2细胞增殖、成脂分化以及胞内甘油三酯含量的影响,采用RT-PCR与Western Blot技术检测小豆蔻明对C3H10T1/2细胞PPARγ、C/EBPα和FABP4 m RNA以及蛋白表达的影响。结果:60、80、100μmol/L小豆蔻明能够显著抑制C3H10T1/2细胞存活率(P<0.01);5、10、30μmol/L小豆蔻明能够抑制C3H10T1/2细胞脂滴的形成,从而抑制成脂分化;5、10、30μmol/L小豆蔻明能够显著降低细胞中甘油三酯的含量(P<0.05,P<0.01);10、30μmol/L小豆蔻明能够显著下调PPARγ、C/EBPα和FABP4 m RNA的表达(P<0.05,P<0.01);5、10、30μmol/L小豆蔻明能够显著降低成脂关键转录因子PPARγ、C/EBPα和成脂分化标志因子FABP4蛋白的表达(P<0.05,P<0.01)。结论:小豆蔻明通过下调PPARγ、C/EBPα、FABP4 m RNA以及蛋白表达抑制细胞成脂分化并降低胞内甘油三酯含量。展开更多
基金Supported by Malaysian Ministry of Higher Education through the Fundamental Research Grant Scheme,No.FP103-2019.
文摘Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a persistent gap between preclinical evidence and practical application.This review aims to assess the readiness of cardamonin to progress from laboratory research to clinical application as an anticancer agent by examining both scientific evidence and translational challenges.Preclinical pharmacokinetic and pharmacodynamic data suggest that cardamonin’s therapeutic potential as an anticancer agent is hindered by its poor oral bioavailability.Although its molecular targets remain undefined,evidence indicates that cardamonin can inhibit various signaling pathways,including nuclear factor kappa-light-chain-enhancer of activated B cells,mammalian target of rapamycin,signal transducer and activator of transcription 3,and Wnt/β-catenin.The lack of in vivo toxicity studies creates uncertainty regarding the balance between its therapeutic benefits and potential adverse effects when moving from laboratory research to human trials.Despite these limitations,cardamonin has,however,demonstrated antiproliferative,anti-metastatic,and chemosensitizing effects,mainly against breast,colorectal,and ovarian cancers.Nevertheless,exploring its combination with standard chemotherapeutic agents may offer a promising foundation for advancing cardamonin into clinical trials.
基金supported by the National Key Technology R&D Program(No.2017ZX09301022)the National Key Technology R&D Program(No.2015ZX09501-004-001-008)+1 种基金the BeijingNova program(No.Z181100006218001)the National Natural Science Foundation of China(No.81630100)
文摘Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin(CDN), the major active ingredient of the traditional Chinese medicinal herb Alpinia katsumadai, has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-κB-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner.Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1βproduction induced by LPS in vivo, which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases.
文摘目的观察豆蔻明(Cardamonin,CDN)对肺纤维化小鼠的作用,并探究其对转化生长因子-β1(transforming growth factor-β1,TGF-β1)/smad信号通路的影响。方法将小鼠随机分为生理盐水(Sham)组、博莱霉素(Bleomycin,BLM)组、豆蔻明低剂量(low dose of Cardamonin,CDN-L)组、豆蔻明中剂量(medium dose of Cardamonin,CDN-M)组、豆蔻明高剂量(high dose of Cardamonin,CDN-H)组、地塞米松(dexamethasone,DXM)组;单次气管注射BLM诱导肺纤维化,计算肺指数;酶联免疫吸附法测血清肿瘤坏死因子(tumor necrosis factor-α,TNF-α)水平;试剂盒测肺组织羟脯氨酸(hydroxyproline,HYP)含量,苏木精-伊红、马松染色观察肺炎症程度及纤维化情况,RT-PCR法检测肺组织TGF-β1/smad信号通路相关基因表达情况。结果与Sham组相比,BLM组小鼠肺指数、Szapiel评分、Ashcroft评分明显升高(P<0.05),肺部炎症程度和纤维化程度严重。血清中TNF-α含量升高(P<0.05)、肺组织HYP水平升高(P<0.05),TGF-β1[(1.02±0.21)vs.(3.25±0.14)]、smad2[(1.00±0.05)vs.(1.63±0.09)]、smad3[(1.00±0.06)vs.(1.82±0.07)]、α-平滑肌肌动蛋白(α-smoothmuscleactin,α-SMA)[(1.00±0.10)vs.(2.15±0.10)]mRNA表达升高(P<0.05),上皮-钙黏蛋白(E-Cadherin)[(1.01±0.16)vs.(0.57±0.09)]mRNA水平降低(P<0.05)。CDN-M、CDN-H干预可减低小鼠肺指数,减轻炎性和肺纤维化,降低TNF-α、HYP水平(P<0.05),同时下调肺纤维小鼠肺组织中TGF-β1、smad2、smad3、α-SMA表达,上调E-Cadherin表达。CDN-L无明显治疗效果,CDN-H治疗作用与DXM相似。结论CDN可能通过TGF-β1/Smad通路介导上皮-间充质转化而发挥抗纤维化作用。
文摘小豆蔻明(cardamonin,CAR)的化学结构为2’,4’-二甲基-6’-甲氧基查尔酮,是一种主要存在于姜科山姜属植物草豆蔻种子中的黄酮类单体,生物活性广泛。由于其具有抗肿瘤作用,近年来倍受关注,并已有系列衍生物被合成。研究表明,CAR对多形性胶质母细胞瘤、Lewis肺癌、乳腺癌、结肠癌和前列腺癌等肿瘤细胞的生长均有抑制作用,其作用机制涉及哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)通路、核因子κB(nuclear factor kappa B,NF-κB)信号通路、谷氨酰胺转氨酶2、内源性凋亡途径、信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)、E-钙黏蛋白(E-cadherin)、细胞自噬、β-catenin和细胞周期调控等。本文主要对CAR及其衍生物的抗肿瘤作用及其机制进行综述。
文摘目的:探讨小豆蔻明抑制C3H10T1/2细胞成脂分化的作用机制。方法:观察C3H10T1/2细胞成脂过程形态学变化,采用MTS法、油红O染色法、GAP-PAP酶法检测小豆蔻明对C3H10T1/2细胞增殖、成脂分化以及胞内甘油三酯含量的影响,采用RT-PCR与Western Blot技术检测小豆蔻明对C3H10T1/2细胞PPARγ、C/EBPα和FABP4 m RNA以及蛋白表达的影响。结果:60、80、100μmol/L小豆蔻明能够显著抑制C3H10T1/2细胞存活率(P<0.01);5、10、30μmol/L小豆蔻明能够抑制C3H10T1/2细胞脂滴的形成,从而抑制成脂分化;5、10、30μmol/L小豆蔻明能够显著降低细胞中甘油三酯的含量(P<0.05,P<0.01);10、30μmol/L小豆蔻明能够显著下调PPARγ、C/EBPα和FABP4 m RNA的表达(P<0.05,P<0.01);5、10、30μmol/L小豆蔻明能够显著降低成脂关键转录因子PPARγ、C/EBPα和成脂分化标志因子FABP4蛋白的表达(P<0.05,P<0.01)。结论:小豆蔻明通过下调PPARγ、C/EBPα、FABP4 m RNA以及蛋白表达抑制细胞成脂分化并降低胞内甘油三酯含量。
