Astragalus mongholicus (Fisch.) Bge Improves Peripheral Treg Cell Immunity Imbalance in the Children With Viral Myocarditis by Reducing the Levels of miR-146b and miR-155

Abstract

Viral myocarditis (VMC) is a common cardiac disease, however, there still lacks an effective therapeutic strategy for VMC. Astragalus mongholicus (Fisch.) Bge (AB), a Chinese herb with some functional metabolites, may have some pharmacological effects on VMC. AB ingredients were measured by a full-scan LCQ mass spectrum. We aimed to explore the effects of AB on the VMC children by investigating peripheral Treg cell homeostasis. A total of 68 VMC children were random and evenly assigned into an AG group (received 10-mL AB oral liquid daily), and a CG group (received placebo daily). Peripheral blood mononuclear cells (PBMC) were obtained from peripheral blood and Treg cells were isolated. The levels of miR-146b, miR-155, Treg immunity activity and myocarditis biomarkers were measured in Treg cells. There were four main components (sucrose, calycosin, Astragaloside IV and calycosin-7-glucoside) in AB. The cases sinus tachycardia, frequent premature ventricular contractions, and supraventricular tachycardia were significantly reduced in the AG group (P < 0.05). Meanwhile, the myocardial enzymes and cardiac function indexes were improved in the AG group when compared with the CG group (P < 0.05). The time of electrocardiogram recovery, symptom duration and hospital stay was shorter in the AG group than in the CG group (P < 0.05). The levels of miR-146b and miR-155 were higher in the CG group than in the AG group (P < 0.05). The levels of ROR-γt (retinoic acid receptor-related orphan nuclear receptor gamma), FoxP3 (forkhead transcription factor), IL-10 (interleukin-11) and TGF-β (transforming growth factor beta) were lower in the CG group than in the AG group (P < 0.05). In contrast, the levels of IL-17, IL-21, CK-MB (creatine kinase-MB), cTnI (cardiac troponin I), GrB (granzyme B), sFasL (soluble fas ligand) and caspase-3 were higher in the CG group than in the AG group (P < 0.05). Furthermore, the levels of ROR-γt, FoxP3, IL-10, and TGF-β were positively, whereas the levels of IL-17, IL-21, CK-MB, cTnI, GrB, sFasL and caspase-3 were negatively, associated with the levels of miR-146b and miR-155 (P < 0.05). AB treatment improved cardiac functions, peripheral Treg cell immunity imbalance in the children with VMC by reducing the levels of miR-146b and miR-155.

Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway

“…In our previous study, As-IV exerts cognitive benefits and promotes hippocampal neurogenesis and synaptic plasticity in stroke mice via Wnt pathway. IL-17 expression is downregulated by administering As-IV 29 , which is consistent with the results in other acute diseases [30][31][32] . Therefore, it seems that As IV could be a promising strategy in the therapeutic arsenal against ischemic cortex after stroke for its effect on activating proliferation and promoting neurogenesis.…”

“…6a). Previous studies have suggested that As-IV inhibits IL-17 expression 30,32 and pro-apoptotic protein Caspase 3 expression 35 in other animal models. In this study, we first observed how As-IV made effect on IL-17 and Caspase 3.…”

Astragaloside IV Exerts Cognitive Benefits and Promotes Hippocampal Neurogenesis in Stroke Mice by Downregulating Interleukin-17 Expression via Wnt Pathway

“…We found that the expression of IL-17 in the ischemic cortex and hippocampus of stroke mice treated with As IV was decreased remarkably by both immunohistochemistry and Western blot analysis (Figures 3A, B) and the expression of IL-17 increased gradually and slowly after stroke as time went on and lagged far behind the appearance of apoptosis ( Figure 3C). Consistently, previous results also suggest that the over expression of IL-17 indicates a poorer treatment effect and prognosis for ischemic stroke (He et al, 2019;Tian et al, 2019;Zhou et al, 2019), which always abolishes some neuroprotective effect (Ma et al, 2018;Sun et al, 2018;Zhao et al, 2019) and it can be reduced by As IV (Jin et al, 2017;Zhang et al, 2018). So, IL-17 expression is upregulated remarkably by ischemic stroke, which can be reversed by As IV, indicating IL-17 is a key regulation factor for As IV's neuroprotective effect on ischemic stroke.…”

“…Some results have suggested that As IV can reduce IL-4, IL-5, and IL-17 levels to inhibit asthmatic effects (Jin et al, 2017) and improve cardiac functions in children with viral myocarditis by reducing the levels of IL-17, IL-21, and caspase-3 (Zhang et al, 2018). We consistently found that the overexpression of IL-17 induced by stroke was downregulated significantly by giving As IV in both the ischemic cortex ( Figure 3A) and ipsilateral hippocampus ( Figure 3B).…”

“…Wnt signaling pathway exists widely in invertebrates and vertebrates and it plays an important role in early embryonic development, organ formation, tissue regeneration, and other physiological processes. Interestingly, As IV can not only activate Wnt signaling pathway (Cheng et al, 2016;Bao et al, 2019), but also downregulate IL-17 (Jin et al, 2017;Zhang et al, 2018).…”