Spatholobi Caulis extracts promote angiogenesis in HUVECs in vitro and in zebrafish embryos in vivo via up-regulation of VEGFRs

Zhou, Zhong-Yan; Huan, Liyun; Zhao, Wai-Rong; Tang, Nuo; Jin, Yu; Tang, Jingyi

doi:10.1016/j.jep.2016.10.075

Cited by 47 publications

(32 citation statements)

References 37 publications

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“…Zebrafish disease models have the advantages of low cost, ease of observation, and genetic similarity with humans, which facilitates drug discovery ( Dooley and Zon, 2000 ; Kari et al, 2007 ; Delvecchio et al, 2011 ). In our group, we have established various zebrafish disease models, including neuroprotection ( Chong et al, 2013 ; Chong et al, 2014 ), angiogenesis ( Zhou et al, 2017 ; Zhou et al, 2019b ; Zhou et al, 2020 ), cerebral hemorrhage ( Huang et al, 2018 ; Zhou et al, 2019c ), etc., for bioactive constitutes discovery from natural products and underlying mechanisms studies. Thus, zebrafish-based cerebral hemorrhage model attracted our attention for high-throughput screening of drugs for hemorrhage stroke ( Hung et al, 2012 ; Crilly et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, KEGG pathway enrichment analysis suggested that the PI3K/Akt, mTOR, and MAPK signaling pathways might regulate the HIF-1 signaling cascade involved in the protective effect of STS against cerebral hemorrhage ( Figure S1 ). PI3K/Akt, mTOR, and MAPK signaling pathways could also trigger normoxic HIF activation ( Agani and Jiang, 2013 ) and regulate cell proliferation and survival, which are essential for maintaining vascular relaxation, angiogenesis, and vascular integrity ( Zhou et al, 2017 ; Liang et al, 2018 ; Zhou et al, 2019a ). The previous study revealed that the activation of Akt and ERK up-regulated the mRNA expression of HIF-1α in brain microvascular endothelial cells ( Liang et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

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Mechanism Study of the Protective Effects of Sodium Tanshinone IIA Sulfonate Against Atorvastatin-Induced Cerebral Hemorrhage in Zebrafish: Transcriptome Analysis

et al. 2020

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Hemorrhage stroke is a severe vascular disease of the brain with a high mortality rate in humans. Salvia miltiorrhiza Bunge (Danshen) is a well-known Chinese Materia Medica for treating cerebral vascular and cardiovascular diseases in traditional Chinese medicine. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, which is the main active ingredient of Danshen. In our previous study, we established a zebrafish model of cerebral hemorrhage and found that STS dramatically decreased both the hemorrhage rate and hemorrhage area, although the underlying mechanism was not fully elucidated. We conducted a transcriptome analysis of the protective effect of STS against atorvastatin (Ator)-induced cerebral hemorrhage in zebrafish using RNA-seq technology. RNA-seq revealed 207 DEGs between the Ator-treated group and control group; the expression levels of 53 DEGs between the Ator-treated group and control group were reversed between the STS + Ator-treated group and Ator-treated group. GO enrichment analysis indicated that these 53 DEGs encode proteins with roles in hemoglobin complexes, oxygen carrier activity and oxygen binding, etc. KEGG analysis suggested that these 53 DEGs were most enriched in three items, namely, porphyrin and chlorophyll metabolism, ferroptosis, and the HIF-1 signaling pathway. The PPI network analysis identified 12 hub genes, and we further verified that Ator elevated the mRNA expression levels of hemoglobin ( hbae1.3 , hbae3 , hbae5, hbbe2 , and hbbe3 ), carbonic anhydrase ( cahz) , HIF-1 ( hif1al2 ) and Na+/H+ exchanger ( slc4a1a and slc9a1 ) genes, while STS significantly suppressed these genes. In addition, we found that pharmacological inhibition of PI3K/Akt, MAPKs, and mTOR signaling pathways by specific inhibitors partially attenuated the protective effect of STS against Ator-induced cerebral hemorrhage in zebrafish, regardless of mTOR inhibition. We concluded that hemoglobin, carbonic anhydrase, Na+/H+ exchanger and HIF-1 genes might be potential biomarkers of Ator-induced cerebral hemorrhage in zebrafish, as well as pharmacological targets of STS. Moreover, HIF-1 and its regulators, i.e., the PI3K/Akt and MAPK signaling pathways, were involved in the protective effect of STS against Ator-induced cerebral hemorrhage. This study also provided evidence of biomarkers involved in hemorrhage stroke and improved understanding of the effects of HMG-COA reductase inhibition on vascular permeability and cerebral hemorrhage.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mechanism Study of the Protective Effects of Sodium Tanshinone IIA Sulfonate Against Atorvastatin-Induced Cerebral Hemorrhage in Zebrafish: Transcriptome Analysis

et al. 2020

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“…Cell migration plays a vital role in the process of angiogenesis, and it is the basis for assessing angiogenesis at the cellular level [ 32 ]. This dynamic process of angiogenesis is induced by cytokines, chemical substances, and external stimuli [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Long‐Zhi Decoction Medicated Serum Promotes Angiogenesis in Human Umbilical Vein Endothelial Cells Based on Autophagy

Liu

Chen

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Ischemic stroke (IS) is a fatal subtype of stroke that lacks effective treatments. Angiogenesis following IS is an effective response that mediates brain recovery and repair. Our previous study demonstrated that long-zhi decoction (LZD), a Chinese herbal formula, promoted angiogenesis in rats of IS model. To further investigate the association between the proangiogenic mechanism of an LZD-medicated serum and cellular autophagy, we evaluated its promotional effect on angiogenesis in human umbilical vein endothelial cells (HUVECs) in vitro. We used HUVECs subjected to H2O2 to induce injury and observed the effects of the LZD-medicated serum treatment. Cell-based assays included proliferation, migration, and tube formation. To assess the extent of autophagy, transmission electron microscopy was used to measure the number of autophagosomes. Immunofluorescence and Western blotting were performed to evaluate the autophagy-related protein of LC3-II and Beclin-1. The LZD-medicated serum promoted proliferation, migration, and tube formation in HUVECs. The LZD-medicated serum also increased the autophagosomes and the autophagic protein expressions of LC3-II and Beclin-1. The proangiogenic and autophagic activity of LZD provides new cogitations to its clinical application and may lead to potential drug development for treating various vascular diseases, especially in the elderly, in the future.

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“…Spatholobi caulis is a traditional blood-activating and stasis-dispelling herb medicine, which has been used to treat diseases related to blood stasis syndrome by inhibiting platelet aggregation and stimulating hematopoiesis. A recent study further revealed that the FSC presented proangiogenic activity in human umbilical vein endothelial cells (HUVECs) as well as in zebrafish [ 49 ]. With an LPS-activated Raw264.7 cells model, the Spatholobi caulis MeOH extract (containing flavonoids) inhibited the expressions of iNOS and COX-2 and suppressed the production of proinflammatory cytokines, such as IL-1beta and IL-6 [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

The Vasodilatory Effects of Anti‐Inflammatory Herb Medications: A Comparison Study of Four Botanical Extracts

Zhang

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Inflammation plays a pivotal role in the development and progression of cardiovascular diseases, in which, the endothelium dysfunction has been a key element. The current study was designed to explore the vasodilatory effect of anti-inflammatory herbs which have been traditionally used in different clinical applications. The total saponins from Actinidia arguta radix (SAA), total flavonoids from Glycyrrhizae radix et rhizoma (FGR), total coumarins from Peucedani radix (CPR), and total flavonoids from Spatholobi caulis (FSC) were extracted. The isometric measurement of vasoactivity was used to observe the effects of herbal elements on the isolated aortic rings with or without endothelium. To understand endothelium-independent vasodilation, the effects of herb elements on agonists-induced vasocontractility and on the contraction of endothelium-free aortic rings exposed to a Ca2+-free medium were examined. Furthermore, the role of nitric oxide signaling in endothelium-dependent vasodilation was also evaluated. In summary, FGR and FSC exhibit potent anti-inflammatory effects compared to CPR and SAA. FGR exerts the strongest vasodilatory effect, while CPR shows the least. The relaxation induced by SAA and FSC required intact endothelia. The mechanism of this vasodilation might involve eNOS. CPR-mediated vasorelaxation appears to involve interference with intracellular calcium homeostasis, blocking Ca2+ influx or releasing intracellular Ca2+.

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Spatholobi Caulis extracts promote angiogenesis in HUVECs in vitro and in zebrafish embryos in vivo via up-regulation of VEGFRs

Cited by 47 publications

References 37 publications

Mechanism Study of the Protective Effects of Sodium Tanshinone IIA Sulfonate Against Atorvastatin-Induced Cerebral Hemorrhage in Zebrafish: Transcriptome Analysis

Mechanism Study of the Protective Effects of Sodium Tanshinone IIA Sulfonate Against Atorvastatin-Induced Cerebral Hemorrhage in Zebrafish: Transcriptome Analysis

Long‐Zhi Decoction Medicated Serum Promotes Angiogenesis in Human Umbilical Vein Endothelial Cells Based on Autophagy

The Vasodilatory Effects of Anti‐Inflammatory Herb Medications: A Comparison Study of Four Botanical Extracts

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