title: Compatibility of Tanshinone IIA and Astragaloside IV in attenuating hypoxia-induced cardiomyocytes injury.
abstract: BACKGROUND
  Herbal medicines including Tanshinone IIA (TanIIA) and Astragaloside IV (AsIV) are widely used in Asia as therapeutic agents for cardiovascular diseases, due to their complementary roles and shared properties based on the theory of traditional Chinese medicine and pharmacological researches. However, the underlying pathological mechanisms for their efficacy are still unclear. In addition, the compatibility or incompatibility of the herbal medicines when administered with other herbal remedies or with prescription drugs is unknown.
  
  
  OBJECTIVE
  We aimed to investigate the compatibility of TanIIA and AsIV in protecting cardiomyocytes against hypoxia-induced injury.
  
  
  METHODS
  Cultured cardiomyocytes were stimulated in hypoxia condition, in the absence or presence of the two herbal compounds, TanIIA and AsIV. Indicators were determined by cytotoxicity assay, quantitative PCR, ELISA, flow cytometry assay, immunofluorescence staining and western blot.
  
  
  RESULTS
  Either TanIIA alone or the combined herbal compounds inhibited hypoxia-triggered chemokines production including CCL2/5/19, CXCL2 and Transwell assay-indicated monocyte/macrophage recruitment, cytokines production including TNF-α and IL-6. While AsIV alone or the combined herbal compounds attenuated hypoxia-induced cell apoptosis indicated by decreased Annexin V+cells and the ratio of Bax/Bcl-2, but no significant effect of the herbal compounds was observed in modulating cell apoptosis following both hypoxia and TNF-α stimulation. As an anti-apoptotic factor, stress granule formation was further enhanced by AsIV alone or the combined herbal compounds in hypoxia or heat shock stress. Moreover, immunoblotting analysis indicated that stress-responsive mitogen-activated protein kinases (MAPK) pathways including the phosphorylation of ERK1/2, p38 and JNK were inhibited while the phosphorylation of Akt in phosphatidylinositol 3-kinase (PI3K) -Akt pathway for cell survival was restored by the herbal compounds. Among these results, the combination of TanIIA and AsIV comprised most of the beneficial properties tested, although their combination did not improve the maximal effects achieved by any of the compounds alone.
  
  
  CONCLUSIONS
  Taken together, these data suggest a compatibility of TanIIA and AsIV in protecting cardiomyocyte against hypoxia-induced injury.
authors.affiliation: The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Emergency Department, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China; Guangdong Provincial Key Laboratory of Research on Emergency in TCM, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Wang
authors.affiliation: The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Emergency Department, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China; Guangdong Provincial Key Laboratory of Research on Emergency in TCM, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Guofu
authors.initials: G
authors.lastname: Zhong
authors.affiliation: The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Yan
authors.affiliation: The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. Electronic address: 851757626@qq.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics; D000860:Hypoxia / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D045784:Abietanes; D018925:Chemokines; D012333:RNA, Messenger; D012503:Saponins; D014315:Triterpenes; C021751:tanshinone; C052064:astragaloside A; D007770:L-Lactate Dehydrogenase; D020928:Mitogen-Activated Protein Kinases
keywords: Astragaloside IV; Cardiovascular disease; Compatibility; Hypoxia; Tanshinone IIA