Taraxasterol(TS)is a naturally occurring pentacyclic triterpenoid extracted from the traditional Chinese herb Taraxacum mongolicum.Previous studies have highlighted its significant roles in exhibiting anti-inflammator...Taraxasterol(TS)is a naturally occurring pentacyclic triterpenoid extracted from the traditional Chinese herb Taraxacum mongolicum.Previous studies have highlighted its significant roles in exhibiting anti-inflammatory,anti-oxidant,and liver protective effects.In the present study,the anti-cancer potential of TS against cervical cancer was investigated,employing network pharmacology techniques,molecular docking,and in vitro experimental validation.TS exhibits its anticancer properties by modulating multiple targets,pathways,and biological processes.In vitro experiments demonstrated the potent inhibitory effects of TS on cancer cell growth and migration,while no significant impact on apoptosis was observed.The primary objective was to elucidate the anti-cancer potential of TS,which is a crucial lead compound in the treatment of cervical cancer.The findings may serve as a basis for the development of novel anticancer therapeutics and medicine-based interventions for cervical cancer.展开更多
Idiopathic pulmonary fibrosis(IPF)is a chronic and fatal lung disease characterized by pulmonary inflam-mation,oxidative stress,and excessive extracellular matrix(ECM)deposition.Current anti-fibrotic drugs for IPF tre...Idiopathic pulmonary fibrosis(IPF)is a chronic and fatal lung disease characterized by pulmonary inflam-mation,oxidative stress,and excessive extracellular matrix(ECM)deposition.Current anti-fibrotic drugs for IPF treatment in the clinic lack selectivity and demonstrate unsatisfactory efficacy,highlighting the urgent necessity for a novel therapeutic strategy.Taraxasterol(TA),which has biological activities against lung injury induced by various factors,is a potential anti-IPF drug due to its anti-inflammatory,antiox-idant and lung-protective effects.However,the protective effect of TA on IPF has not been confirmed,and its clinical application is limited due to its poor aqueous solubility.In this study,we demonstrated that TA could inhibit epithelial-mesenchymal transition(EMT)and migration of A549 cells by inhibiting the transforming growth factor-β1(TGF-β1)/Smad signaling pathway.To improve the aqueous solubility and pulmonary administration performance of TA,we prepared TA loaded methoxy poly(ethylene glycol)-poly(d,l-lactide)(mPEG-PLA)/d-α-tocopheryl polyethylene glycol succinate(TPGS)mixed polymeric mi-celles(TA-PM).Then a MicroSprayer^(R) Aerosolizer was used to deliver TA-PM once every two days for three weeks to evaluate their therapeutic effects on bleomycin(BLM)-induced IPF mice.Our results demonstrated that inhaled TA-PM significantly inhibited BLM-induced inflammation,oxidative stress and fibrosis in lung tissue.Furthermore,TA-PM exhibited high pulmonary deposition and retention by pul-monary administration,along with a favorable safety profile.Overall,this study emphasizes the potential of inhaled TA-PM as a promising treatment for IPF,providing a new opportunity for their clinical appli-cation.展开更多
目的以传统中药蒲公英的主要成分蒲公英甾醇为研究对象,探讨蒲公英甾醇的体外抗炎作用及其作用机制。方法培养小鼠腹腔巨噬细胞RAW264.7进行试验分组,检测RAW264.7细胞COX-2和i NOS m RNA和蛋白的表达,并检测ERK 1/2、JNK和p38 MAPK及...目的以传统中药蒲公英的主要成分蒲公英甾醇为研究对象,探讨蒲公英甾醇的体外抗炎作用及其作用机制。方法培养小鼠腹腔巨噬细胞RAW264.7进行试验分组,检测RAW264.7细胞COX-2和i NOS m RNA和蛋白的表达,并检测ERK 1/2、JNK和p38 MAPK及其磷酸化水平的表达。结果蒲公英甾醇分别不同程度的抑制了i NOS和COX-2 m RNA和蛋白的表达,且呈一定的剂量依赖关系;显著抑制了LPS诱导的RAW 264.7细胞p38和ERK 1/2激酶的磷酸化,并呈剂量依赖关系;但对JNK激酶磷酸化的抑制作用不显著。结论蒲公英甾醇通过调节p38和ERK 1/2 MAPKs的磷酸化水平抑制i NOS和COX-2的表达,从而发挥体外抗炎作用。展开更多
基金This study was supported by local special projects in major health of Hubei Provincial Science and Technology Department(2022BCE054)key scientific research projects of Hubei polytechnic University(23xjz08A).
文摘Taraxasterol(TS)is a naturally occurring pentacyclic triterpenoid extracted from the traditional Chinese herb Taraxacum mongolicum.Previous studies have highlighted its significant roles in exhibiting anti-inflammatory,anti-oxidant,and liver protective effects.In the present study,the anti-cancer potential of TS against cervical cancer was investigated,employing network pharmacology techniques,molecular docking,and in vitro experimental validation.TS exhibits its anticancer properties by modulating multiple targets,pathways,and biological processes.In vitro experiments demonstrated the potent inhibitory effects of TS on cancer cell growth and migration,while no significant impact on apoptosis was observed.The primary objective was to elucidate the anti-cancer potential of TS,which is a crucial lead compound in the treatment of cervical cancer.The findings may serve as a basis for the development of novel anticancer therapeutics and medicine-based interventions for cervical cancer.
基金supported by National Natural Science Foundation of China(No.31872754)Fundamental Research Funds for the Central Universities(No.201964018).
文摘Idiopathic pulmonary fibrosis(IPF)is a chronic and fatal lung disease characterized by pulmonary inflam-mation,oxidative stress,and excessive extracellular matrix(ECM)deposition.Current anti-fibrotic drugs for IPF treatment in the clinic lack selectivity and demonstrate unsatisfactory efficacy,highlighting the urgent necessity for a novel therapeutic strategy.Taraxasterol(TA),which has biological activities against lung injury induced by various factors,is a potential anti-IPF drug due to its anti-inflammatory,antiox-idant and lung-protective effects.However,the protective effect of TA on IPF has not been confirmed,and its clinical application is limited due to its poor aqueous solubility.In this study,we demonstrated that TA could inhibit epithelial-mesenchymal transition(EMT)and migration of A549 cells by inhibiting the transforming growth factor-β1(TGF-β1)/Smad signaling pathway.To improve the aqueous solubility and pulmonary administration performance of TA,we prepared TA loaded methoxy poly(ethylene glycol)-poly(d,l-lactide)(mPEG-PLA)/d-α-tocopheryl polyethylene glycol succinate(TPGS)mixed polymeric mi-celles(TA-PM).Then a MicroSprayer^(R) Aerosolizer was used to deliver TA-PM once every two days for three weeks to evaluate their therapeutic effects on bleomycin(BLM)-induced IPF mice.Our results demonstrated that inhaled TA-PM significantly inhibited BLM-induced inflammation,oxidative stress and fibrosis in lung tissue.Furthermore,TA-PM exhibited high pulmonary deposition and retention by pul-monary administration,along with a favorable safety profile.Overall,this study emphasizes the potential of inhaled TA-PM as a promising treatment for IPF,providing a new opportunity for their clinical appli-cation.
文摘【目的】探究蒲公英甾醇对黄曲霉毒素B 1(AFB_(1))诱导鸡原代肝细胞凋亡、自噬的影响及其作用机制。【方法】采用MTT法测定蒲公英甾醇对鸡原代肝细胞的毒性,确定蒲公英甾醇安全作用浓度。将鸡原代肝细胞分为空白组(Normal)、模型组(AFB_(1),0.05μg/mL)、水飞蓟宾阳性组(Sil,2μg/mL)以及蒲公英甾醇低(L-dose,5μg/mL)、中(M-dose,10μg/mL)、高(H-dose,20μg/mL)剂量组。各试验组经相应浓度药物处理后收集细胞,利用流式细胞术和CYTO-ID法检测鸡原代肝细胞凋亡和自噬情况。采用实时荧光定量PCR检测鸡原代肝细胞中细胞色素酶、凋亡和自噬相关基因mRNA表达量。【结果】蒲公英甾醇浓度为5~25μg/mL时对鸡原代肝细胞无明显毒性,因此后续选用蒲公英甾醇低、中、高剂量组给药浓度分别为5、10、20μg/mL。流式细胞术和CYTO-ID检测结果显示,与空白组相比,模型组鸡原代肝细胞中绿色荧光标记的自噬滤泡数量明显增多。与模型组相比,水飞蓟宾组、蒲公英甾醇各剂量组鸡原代肝细胞中绿色荧光标记的自噬滤泡数量明显减少。实时荧光定量PCR结果显示,与空白组相比,模型组鸡原代肝细胞中细胞色素酶P4501A5(CYP1A5)、CYP 3 A 37 A、半胱氨酸蛋白水解酶3(Caspase-3)、Caspase-9、苄氯素1(Beclin-1)、自噬蛋白5(ATG-5)、微管相关蛋白轻链3Ⅰ(LC3-Ⅰ)和LC 3-Ⅱ基因mRNA表达量均极显著升高(P<0.01)。与模型组相比,水飞蓟宾和蒲公英甾醇各剂量组鸡原代肝细胞中CYP 1 A 5、CYP 3 A 37、Caspase-3、Caspase-9、Beclin-1、ATG-5、LC 3-Ⅰ、LC 3-Ⅱ基因mRNA表达量均极显著减低(P<0.01)。【结论】蒲公英甾醇通过影响细胞色素酶、凋亡和自噬相关基因的表达,进而对AFB_(1)所致鸡原代肝细胞损伤起到保护作用。
文摘目的以传统中药蒲公英的主要成分蒲公英甾醇为研究对象,探讨蒲公英甾醇的体外抗炎作用及其作用机制。方法培养小鼠腹腔巨噬细胞RAW264.7进行试验分组,检测RAW264.7细胞COX-2和i NOS m RNA和蛋白的表达,并检测ERK 1/2、JNK和p38 MAPK及其磷酸化水平的表达。结果蒲公英甾醇分别不同程度的抑制了i NOS和COX-2 m RNA和蛋白的表达,且呈一定的剂量依赖关系;显著抑制了LPS诱导的RAW 264.7细胞p38和ERK 1/2激酶的磷酸化,并呈剂量依赖关系;但对JNK激酶磷酸化的抑制作用不显著。结论蒲公英甾醇通过调节p38和ERK 1/2 MAPKs的磷酸化水平抑制i NOS和COX-2的表达,从而发挥体外抗炎作用。
