丹参酮IIA,也称为TanIIA,在生物体内代谢过程中扮演着多重角色,其产物能够影响多种生物化学反应。这些反应中,TanIIA有时作为辅酶参与,有时则可能促进或干扰这些反应过程,从而展现出多样的药理特性。尽管在脊髓损伤等神经系统疾病的治疗...丹参酮IIA,也称为TanIIA,在生物体内代谢过程中扮演着多重角色,其产物能够影响多种生物化学反应。这些反应中,TanIIA有时作为辅酶参与,有时则可能促进或干扰这些反应过程,从而展现出多样的药理特性。尽管在脊髓损伤等神经系统疾病的治疗中,TanIIA已经显示出了一定的疗效,但其具体的作用机制尚未完全阐明。基于现有的研究成果,我们推测TanIIA可能通过多种药理途径,包括抗炎、抗氧化、抗细胞凋亡以及保护血管,来促进脊髓损伤后的神经细胞存活和修复。Tanshinone IIA, also known as TanIIA, plays multiple roles in the metabolic process of living organisms, and its products can affect a variety of biochemical reactions. In these reactions, TanIIA is sometimes involved as a coenzyme, and sometimes it may facilitate or interfere with these reaction processes, thus exhibiting diverse pharmacological properties. Although TanIIA has shown some efficacy in the treatment of neurological diseases such as spinal cord injury, its specific mechanism of action has not been fully elucidated. Based on the existing research results, we speculate that TanIIA may promote the survival and repair of nerve cells after spinal cord injury through multiple pharmacological pathways, including anti-inflammatory, antioxidant, anti-apoptosis, and vascular protection.展开更多
丹参酮IIA (Tanshinone IIA, TanIIA)是从中药丹参中提取的主要有效成分之一,研究表明其在抗炎、抗氧化、抗肿瘤、心脏保护及神经系统保护方面具有显著的药理活性。本文采用文献计量学的方法,对国内外有关丹参酮IIA的研究进行分析,发现...丹参酮IIA (Tanshinone IIA, TanIIA)是从中药丹参中提取的主要有效成分之一,研究表明其在抗炎、抗氧化、抗肿瘤、心脏保护及神经系统保护方面具有显著的药理活性。本文采用文献计量学的方法,对国内外有关丹参酮IIA的研究进行分析,发现丹参酮IIA的研究是基于2000年至2024年间发表的13,681篇有关丹参酮IIA的文献的计量学分析;该领域发表研究论文最多的国家是中国,美国和澳大利亚,而发表论文最多的机构为中国医科大学,中国科学院和中山大学。丹参酮IIA在心血管疾病和神经系统疾病中的研究文献占比最高,研究类型主要以应用基础研究,临床研究和技术开发为主,出现频率最多的关键词为凋亡,表达,激活,氧化应激,炎症反应等,体现了其在这些领域的研究热度和临床应用价值。丹参酮IIA作为一种具有多重药理活性的中药成分,显示出广泛的临床应用前景,而当前研究的局限性和挑战需要我们在未来的研究中予以重视,通过多学科合作和创新研究方法,共同推动丹参酮IIA在疾病治疗中的进一步应用与发展。Tanshinone IIA (TanIIA) is one of the main active ingredients extracted from the traditional Chinese medicine Danshen, and studies have shown that it has significant pharmacological activities in anti-inflammatory, antioxidant, anti-tumor, cardioprotective and nervous system protection. In this paper, bibliometric methods were used to analyze the studies on tanshinone IIA at home and abroad, and found that the research on tanshinone IIA was based on quantitative analysis of 13,681 articles on tanshinone IIA published between 2000 and 2024. The countries with the most published research papers in this field are China, United States and Australia, while the institutions with the most published papers are China Medical University, Chinese Academy of Sciences and Sun Yat-sen University. Tanshinone IIA has the highest proportion of research literature in cardiovascular diseases and nervous system diseases, and the research types are mainly applied basic research, clinical research and technology development, and the most frequent keywords are apoptosis, expression, activation, oxidative stress, inflammatory response, etc., reflecting its research enthusiasm and clinical application value in these fields. As a traditional Chinese medicine ingredient with multiple pharmacological activities, tanshinone IIA has shown a wide range of clinical application prospects, but the limitations and challenges of current research need to be paid attention to in future research, and jointly promote the further application and development of tanshinone IIA in disease treatment through multidisciplinary cooperation and innovative research methods.展开更多
Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis (PF). It is considered as a promising therapeutic targe...Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis (PF). It is considered as a promising therapeutic target anti-PF. The well-documented against PF properties of Tanshinone IIA (Tan IIA) have been primarily attributed to its antioxidant and anti-inflammatory potency. Emerging evidence suggests that Tan IIA may target energy metabolism pathways, including glycolysis and tricarboxylic acid (TCA) cycle. However, the detailed and advanced mechanisms underlying the anti-PF activities remain obscure. In this study, we applied [U-13C]-glucose metabolic flux analysis (MFA) to examine metabolism flux disruption and modulation nodes of Tan IIA in PF. We identified that Tan IIA inhibited the glycolysis and TCA flux, thereby suppressing the production of transforming growth factor-β1 (TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro. We further revealed that Tan IIA inhibited the expression of key metabolic enzyme hexokinase 2 (HK2) by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1α (HIF-1α) pathway activities, which decreased the accumulation of abnormal metabolites. Notably, we demonstrated that Tan IIA inhibited ATP citrate lyase (ACLY) activity, which reduced the collagen synthesis pathway caused by cytosol citrate consumption. Further, these results were validated in a mouse model of bleomycin-induced PF. This study was novel in exploring the mechanism of the occurrence and development of Tan IIA in treating PF using 13C-MFA technology. It provided a novel understanding of the mechanism of Tan IIA against PF from the perspective of metabolic reprogramming.展开更多
Background:Inflammatory bowel disease(IBD)is a chronic inflammatory disease of the gastrointestinal tract.The destruction of the intestinal epithelial barrier is one of the major pathological processes in IBD patholog...Background:Inflammatory bowel disease(IBD)is a chronic inflammatory disease of the gastrointestinal tract.The destruction of the intestinal epithelial barrier is one of the major pathological processes in IBD pathology.Growing evidence indicated that epithelial cell ferroptosis is linked to IBD and is considered a target process.Methods:RAS-selective lethal 3(RSL3)was used to induce ferroptosis in intestinal epithelial cell line No.6(IEC-6)cells,and cell ferroptosis and the effects of tanshinone IIA(Tan IIA)were determined by cell counting kit-8(CCK-8),reactive oxygen species(ROS)staining,Giemsa staining and transmission electron microscope(TEM).The cell viability of natural product library compounds was determined by CCK-8.The expression of ferroptosis-related genes were detected by real-time quantitative polymerase chain reaction(RT-qPCR)and western blot.Results:Treatment of IEC-6 cells results in the accumulation of ROS and typical morphological characteristics of ferroptosis.RSL3 treatment caused rapid cellular cytotoxicity which could be reversed by ferrostatin-1(Fer-1)in IEC-6 cells.Natural product library screening revealed that Tan IIA is a potent inhibitor of IEC-6 cell ferroptosis.Tan IIA could significantly protect the RSL3-induced ferroptosis of IEC-6 cells.Furthermore,the ferroptosis suppressors,glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and miR-17-92 were found to be early response genes in RSL3-treated cells.Treatment of IEC-6 cells with Tan IIA resulted in upregulation of GPX4,SLC7A11,and miR-17-92.Conclusion:Our study demonstrated that Tan IIA protects IEC-6 cells from ferroptosis through the upregulation of GPX4,SLC7A11,and miR-17-92.The findings might provide a theoretical grounding for the future application of Tan IIA to treat or prevent IBD.展开更多
Tanshinone IIA,one of the main ingredients of Danshen,is used to treat hepatocellular carcinoma(HCC).However,potential targets of the molecule in the therapy of HCC are unknown.Methods:In this study,we collected the t...Tanshinone IIA,one of the main ingredients of Danshen,is used to treat hepatocellular carcinoma(HCC).However,potential targets of the molecule in the therapy of HCC are unknown.Methods:In this study,we collected the tanshinone IIA targets from public databases for investigation.We screened differentially expressed genes(DEGs)across HCC and normal tissues using mRNA expression profiles from The Cancer Genome Atlas(TCGA).Univariate Cox regression analysis and least absolute shrinkage and selection operator(LASSO)Cox regression models were used to identify and construct the prognostic gene signature.Results:Finally,we discovered common genes across tanshinone IIA targets and HCC DEGs.We reported Fatty acid binding protein-6(FABP6),Polo-like Kinase 1(PLK1),deoxythymidylate kinase(DTYMK),Uridine Cytidine Kinase 2(UCK2),Enhancer of Zeste Homolog 2(EZH2),and Cytochrome P4502C9(CYP2C9)as components of a gene signature.The six-gene signature’s prognostic ability was evaluated using the Kaplan-Meier curve,time-dependent receiver operating characteristic(ROC),multivariate Cox regression analysis,and the nomogram.The mRNA level and protein expression of UCK2 were experimentally validated after treatment with different concentrations of tanshinone IIA in HEPG2 cells.CIBERSORTx,TIMER2.0,and GEPIA2 tools were employed to explore the relationship between the prognostic signature and immune cell infiltration.Conclusion:We established a six-gene signature as a reliable model with significant therapeutic possibility for prognosis and overall survival estimation in HCC patients,which might also benefit medical decision-making for appropriate treatment.展开更多
文摘丹参酮IIA,也称为TanIIA,在生物体内代谢过程中扮演着多重角色,其产物能够影响多种生物化学反应。这些反应中,TanIIA有时作为辅酶参与,有时则可能促进或干扰这些反应过程,从而展现出多样的药理特性。尽管在脊髓损伤等神经系统疾病的治疗中,TanIIA已经显示出了一定的疗效,但其具体的作用机制尚未完全阐明。基于现有的研究成果,我们推测TanIIA可能通过多种药理途径,包括抗炎、抗氧化、抗细胞凋亡以及保护血管,来促进脊髓损伤后的神经细胞存活和修复。Tanshinone IIA, also known as TanIIA, plays multiple roles in the metabolic process of living organisms, and its products can affect a variety of biochemical reactions. In these reactions, TanIIA is sometimes involved as a coenzyme, and sometimes it may facilitate or interfere with these reaction processes, thus exhibiting diverse pharmacological properties. Although TanIIA has shown some efficacy in the treatment of neurological diseases such as spinal cord injury, its specific mechanism of action has not been fully elucidated. Based on the existing research results, we speculate that TanIIA may promote the survival and repair of nerve cells after spinal cord injury through multiple pharmacological pathways, including anti-inflammatory, antioxidant, anti-apoptosis, and vascular protection.
文摘丹参酮IIA (Tanshinone IIA, TanIIA)是从中药丹参中提取的主要有效成分之一,研究表明其在抗炎、抗氧化、抗肿瘤、心脏保护及神经系统保护方面具有显著的药理活性。本文采用文献计量学的方法,对国内外有关丹参酮IIA的研究进行分析,发现丹参酮IIA的研究是基于2000年至2024年间发表的13,681篇有关丹参酮IIA的文献的计量学分析;该领域发表研究论文最多的国家是中国,美国和澳大利亚,而发表论文最多的机构为中国医科大学,中国科学院和中山大学。丹参酮IIA在心血管疾病和神经系统疾病中的研究文献占比最高,研究类型主要以应用基础研究,临床研究和技术开发为主,出现频率最多的关键词为凋亡,表达,激活,氧化应激,炎症反应等,体现了其在这些领域的研究热度和临床应用价值。丹参酮IIA作为一种具有多重药理活性的中药成分,显示出广泛的临床应用前景,而当前研究的局限性和挑战需要我们在未来的研究中予以重视,通过多学科合作和创新研究方法,共同推动丹参酮IIA在疾病治疗中的进一步应用与发展。Tanshinone IIA (TanIIA) is one of the main active ingredients extracted from the traditional Chinese medicine Danshen, and studies have shown that it has significant pharmacological activities in anti-inflammatory, antioxidant, anti-tumor, cardioprotective and nervous system protection. In this paper, bibliometric methods were used to analyze the studies on tanshinone IIA at home and abroad, and found that the research on tanshinone IIA was based on quantitative analysis of 13,681 articles on tanshinone IIA published between 2000 and 2024. The countries with the most published research papers in this field are China, United States and Australia, while the institutions with the most published papers are China Medical University, Chinese Academy of Sciences and Sun Yat-sen University. Tanshinone IIA has the highest proportion of research literature in cardiovascular diseases and nervous system diseases, and the research types are mainly applied basic research, clinical research and technology development, and the most frequent keywords are apoptosis, expression, activation, oxidative stress, inflammatory response, etc., reflecting its research enthusiasm and clinical application value in these fields. As a traditional Chinese medicine ingredient with multiple pharmacological activities, tanshinone IIA has shown a wide range of clinical application prospects, but the limitations and challenges of current research need to be paid attention to in future research, and jointly promote the further application and development of tanshinone IIA in disease treatment through multidisciplinary cooperation and innovative research methods.
基金supported by the National Natural Science Foundation of China(Grant No.:82174100).
文摘Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis (PF). It is considered as a promising therapeutic target anti-PF. The well-documented against PF properties of Tanshinone IIA (Tan IIA) have been primarily attributed to its antioxidant and anti-inflammatory potency. Emerging evidence suggests that Tan IIA may target energy metabolism pathways, including glycolysis and tricarboxylic acid (TCA) cycle. However, the detailed and advanced mechanisms underlying the anti-PF activities remain obscure. In this study, we applied [U-13C]-glucose metabolic flux analysis (MFA) to examine metabolism flux disruption and modulation nodes of Tan IIA in PF. We identified that Tan IIA inhibited the glycolysis and TCA flux, thereby suppressing the production of transforming growth factor-β1 (TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro. We further revealed that Tan IIA inhibited the expression of key metabolic enzyme hexokinase 2 (HK2) by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1α (HIF-1α) pathway activities, which decreased the accumulation of abnormal metabolites. Notably, we demonstrated that Tan IIA inhibited ATP citrate lyase (ACLY) activity, which reduced the collagen synthesis pathway caused by cytosol citrate consumption. Further, these results were validated in a mouse model of bleomycin-induced PF. This study was novel in exploring the mechanism of the occurrence and development of Tan IIA in treating PF using 13C-MFA technology. It provided a novel understanding of the mechanism of Tan IIA against PF from the perspective of metabolic reprogramming.
基金supported by the National Key Research and Development Program(Grant Number:2017YFA0105303)the Natural Science Foundation of Shandong Province(Grant Number:ZR2020MH327).
文摘Background:Inflammatory bowel disease(IBD)is a chronic inflammatory disease of the gastrointestinal tract.The destruction of the intestinal epithelial barrier is one of the major pathological processes in IBD pathology.Growing evidence indicated that epithelial cell ferroptosis is linked to IBD and is considered a target process.Methods:RAS-selective lethal 3(RSL3)was used to induce ferroptosis in intestinal epithelial cell line No.6(IEC-6)cells,and cell ferroptosis and the effects of tanshinone IIA(Tan IIA)were determined by cell counting kit-8(CCK-8),reactive oxygen species(ROS)staining,Giemsa staining and transmission electron microscope(TEM).The cell viability of natural product library compounds was determined by CCK-8.The expression of ferroptosis-related genes were detected by real-time quantitative polymerase chain reaction(RT-qPCR)and western blot.Results:Treatment of IEC-6 cells results in the accumulation of ROS and typical morphological characteristics of ferroptosis.RSL3 treatment caused rapid cellular cytotoxicity which could be reversed by ferrostatin-1(Fer-1)in IEC-6 cells.Natural product library screening revealed that Tan IIA is a potent inhibitor of IEC-6 cell ferroptosis.Tan IIA could significantly protect the RSL3-induced ferroptosis of IEC-6 cells.Furthermore,the ferroptosis suppressors,glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and miR-17-92 were found to be early response genes in RSL3-treated cells.Treatment of IEC-6 cells with Tan IIA resulted in upregulation of GPX4,SLC7A11,and miR-17-92.Conclusion:Our study demonstrated that Tan IIA protects IEC-6 cells from ferroptosis through the upregulation of GPX4,SLC7A11,and miR-17-92.The findings might provide a theoretical grounding for the future application of Tan IIA to treat or prevent IBD.
基金funded by the Sichuan Natural Science Foundation(No.2022NSFSCO654)the Radiation Oncology Key Laboratory of Sichuan Province Open Fund(No.2020FSZLX-03)the UESTC-Sichuan Cancer Hospital 2021 Medical-Engineering Oncology Innovation Fund(No.ZYGX2021YGCX013).
文摘Tanshinone IIA,one of the main ingredients of Danshen,is used to treat hepatocellular carcinoma(HCC).However,potential targets of the molecule in the therapy of HCC are unknown.Methods:In this study,we collected the tanshinone IIA targets from public databases for investigation.We screened differentially expressed genes(DEGs)across HCC and normal tissues using mRNA expression profiles from The Cancer Genome Atlas(TCGA).Univariate Cox regression analysis and least absolute shrinkage and selection operator(LASSO)Cox regression models were used to identify and construct the prognostic gene signature.Results:Finally,we discovered common genes across tanshinone IIA targets and HCC DEGs.We reported Fatty acid binding protein-6(FABP6),Polo-like Kinase 1(PLK1),deoxythymidylate kinase(DTYMK),Uridine Cytidine Kinase 2(UCK2),Enhancer of Zeste Homolog 2(EZH2),and Cytochrome P4502C9(CYP2C9)as components of a gene signature.The six-gene signature’s prognostic ability was evaluated using the Kaplan-Meier curve,time-dependent receiver operating characteristic(ROC),multivariate Cox regression analysis,and the nomogram.The mRNA level and protein expression of UCK2 were experimentally validated after treatment with different concentrations of tanshinone IIA in HEPG2 cells.CIBERSORTx,TIMER2.0,and GEPIA2 tools were employed to explore the relationship between the prognostic signature and immune cell infiltration.Conclusion:We established a six-gene signature as a reliable model with significant therapeutic possibility for prognosis and overall survival estimation in HCC patients,which might also benefit medical decision-making for appropriate treatment.
