Shenfu Injection Promotes Vasodilation by Enhancing eNOS Activity Through the PI3K/Akt Signaling Pathway In Vitro

Zhu, Junquan; Song, Wook; Xu, Shixin; Ma, Yan; Wei, Baoyu; Wang, Hongwu; Hua, Shan

doi:10.3389/fphar.2020.00121

Cited by 25 publications

(20 citation statements)

References 40 publications

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“…In the endothelium, phosphorylation of PI3K and Akt promotes eNOS activity, further enhancing NO production [ 23 ]. Thus, to verify the NO production pathway induced by ECE and DK in endothelial cells, the protein levels of p-PI3K, p-Akt, and p-eNOS were investigated.…”

Section: Resultsmentioning

confidence: 99%

Ecklonia cava Extract and Its Derivative Dieckol Promote Vasodilation by Modulating Calcium Signaling and PI3K/AKT/eNOS Pathway in In Vitro and In Vivo Models

Hwang

et al. 2021

Biomedicines

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Nitric oxide (NO), an endothelial-derived relaxing factor synthesized by endothelial nitric oxide synthase (eNOS) in endothelial cells, enhances vasodilation by modulating vascular tone. The calcium concentration critically influences eNOS activation in endothelial cells. Thus, modulation of calcium-dependent signaling pathways may be a potential therapeutic strategy to enhance vasodilation. Marine algae reportedly possess protective effects against cardiovascular disorders, including hypertension and vascular dysfunction; however, the underlying molecular signaling pathways remain elusive. In the present study, we extracted and isolated dieckol from Ecklonia cava and investigated calcium transit-enhanced vasodilation. Calcium modulation via the well-known M3 muscarinic acetylcholine receptor (AchM3R), which is linked to NO formation, was investigated and the vasodilatory effect of dieckol was verified. Our results indicated that dieckol effectively promoted NO generation via the PI3K/Akt/eNOS axis and calcium transients influenced by AchM3R. We also treated Tg(flk: EGFP) transgenic zebrafish with dieckol to assess its vasodilatory effect. Dieckol promoted vasodilation by enlarging the dorsal aorta diameter, thus regulating blood flow velocity. In conclusion, our findings suggest that dieckol modulates calcium transit through AchM3R, increases endothelial-dependent NO production, and efficiently enhances vasodilation. Thus, E. cava and its derivative, dieckol, can be considered as potential natural vasodilators.

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Section: Resultsmentioning

confidence: 99%

Ecklonia cava Extract and Its Derivative Dieckol Promote Vasodilation by Modulating Calcium Signaling and PI3K/AKT/eNOS Pathway in In Vitro and In Vivo Models

Hwang

et al. 2021

Biomedicines

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“…The treatment with SBT or Stig did not affect the pH values of the culture medium ( Supplementary Figure S2 ), indicating that there were no changes in conditions of the culture medium or stable conditions of the SBT or Stig-added medium. Furthermore, several reports have suggested that SBT and Stig exert beneficial effects in various long-term experiments [ 22 , 78 , 79 , 80 , 81 , 82 , 83 ]. Thus, we presuppose that SBT or Stig may be stably maintained in the culture medium.…”

Section: Discussionmentioning

confidence: 99%

SBT (Composed of Panax ginseng and Aconitum carmichaeli) and Stigmasterol Enhances Nitric Oxide Production and Exerts Curative Properties as a Potential Anti-Oxidant and Immunity-Enhancing Agent

Han

Kim

et al. 2022

Antioxidants

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Immune dysregulation is a risk factor for several diseases, including infectious diseases. Immunostimulatory agents have been used for the treatment of immune dysregulation, but deleterious adverse effects have been reported. The present study aims to establish the anti-oxidant and immunity-enhancing effects of Sambu-Tang (SBT), composed of Panax ginseng and Aconitum carmichaeli, and stigmasterol (Stig), an active compound of SBT. Immune-related factors were analyzed in RAW264.7 macrophage cells, mouse primary splenocytes, and the serum and spleen of cyclophosphamide-induced immunosuppressed mice. Results showed that the production levels of nitric oxide (NO) and expression levels of inducible NO synthase and heme oxygenase-1 were increased following SBT or Stig treatment in RAW264.7 cells. SBT or Stig increased the production levels of G-CSF, IFN-γ, IL-12, IL-2, IL-6, and TNF-α and induced the activation of NF-κB in RAW264.7 cells. SBT or Stig promoted splenic lymphocyte proliferation and increased splenic NK cell cytotoxic activity. In addition, SBT or Stig enhanced the levels of IFN-γ, IL-12, IL-2, IL-6, or TNF-α in the serum and spleen of the immunosuppressed mice. SBT or Stig increased the superoxide dismutase activity in the spleen. Collectively, SBT and Stig possess anti-oxidant and immunomodulatory activities, so they may be considered effective natural compounds for the treatment of various symptoms caused by immune dysregulation.

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“…These results (Figure 3B) indicated that the protective effects of SFD against myocardial injury involve seven signaling pathways. Previous studies demonstrated that SFD exerted cardiotonic effects by regulating the TNF signaling pathway (32), apoptosis (33), the PI3K-Akt signaling pathway (34), TGF-β/Smads signaling pathway (35), and Akt/eNOS signaling pathway (36). Ubiquitination (37) and neddylation (38) were also shown to play a role in myocardial injury; however, the relationships between SFD and these pathways need to be confirmed in further studies.…”

Section: Wwwddtjournalcommentioning

confidence: 98%

Clarifying the pharmacological mechanisms of action of Shenfu Decoction on cardiovascular diseases using a network pharmacology approach

Zhao

Tohda

2021

DD&T

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Since the molecular mechanisms underlying in the pathogenesis of cardiovascular diseases (CVD) are extremely complex and have not yet been elucidated in detail, CVD remain the leading cause of death worldwide. Traditional Chinese medicine involves the treatment of disease from an overall perspective, and its therapeutic effects on CVD have been demonstrated. However, the mechanisms contributing to the multiscale treatment of cardiovascular diseases at the systematic level remain unclear. Network pharmacology methods and a gene chip data analysis were integrated and applied in the present study, which was conducted to investigate the potential target genes and related pathways of Shenfu Decoction (SFD) for the treatment of myocardial injury. The gene chip analysis was initially performed, followed by network pharmacology to identify differentially expressed genes (DEG) and a functional enrichment analysis. Protein-protein networks were constructed and a module analysis was conducted. A network analysis was used to identify the target genes of SFD. Regarding the results obtained, 1134 DEG were identified using the STRING website. The module analysis revealed that nine hub genes exhibited ubiquitin-protein ligase activity. Therefore, SFD significantly alters the expression of ubiquitination-related genes and, thus, plays an important therapeutic role in the treatment of heart failure. In conclusion, hub genes may provide a more detailed understanding of the molecular mechanisms of action of as well as candidate targets for SFD therapy.

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Shenfu Injection Promotes Vasodilation by Enhancing eNOS Activity Through the PI3K/Akt Signaling Pathway In Vitro

Cited by 25 publications

References 40 publications

Ecklonia cava Extract and Its Derivative Dieckol Promote Vasodilation by Modulating Calcium Signaling and PI3K/AKT/eNOS Pathway in In Vitro and In Vivo Models

Ecklonia cava Extract and Its Derivative Dieckol Promote Vasodilation by Modulating Calcium Signaling and PI3K/AKT/eNOS Pathway in In Vitro and In Vivo Models

SBT (Composed of Panax ginseng and Aconitum carmichaeli) and Stigmasterol Enhances Nitric Oxide Production and Exerts Curative Properties as a Potential Anti-Oxidant and Immunity-Enhancing Agent

Clarifying the pharmacological mechanisms of action of Shenfu Decoction on cardiovascular diseases using a network pharmacology approach

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