Mogroside V (MV), a natural sweetener extracted from edible plant Momordica grosvenori, which possess anti-inflammatory bioactivity. It has been reported that miRNAs acted as an important role in inflammation response suppressed by natural agents. However, whether the anti-inflammation effect of Mogroside V is related with miRNAs and the underlying mechanism remains unclear. Our study aimed to find the key miRNAs which is important for the anti-inflammation effect of MV, and reveal its underlying mechanisms. Our results showed that MV effectively alleviated lung inflammation in OVA-induced asthmatic mice. miRNA-seq and mRNA-seq combined analysis screened miR-21-5p was the important miRNAs for the inflammation inhibition effect of MV and predicted SPRY1 was the target gene of miR-21-5p. We found that MV significantly inhibited the production of TNF-α, IL-1β, IL-2, IL-6 and NO and the protein expression of p-P65/P65, COX-2 and iNOS in OVA-induced asthmatic mice and LPS-treated RAW 264.7 cells. Moreover, the release of ROS increased in LPS-stimulated RAW 264.7 cells was mitigated by MV pretreatment. At the meantime, the expression of miR-21-5p was decreased by MV, which increased the expression of SPRY1 in RAW 264.7 cells. Furthermore, miR-21-5p overexpressed or SPRY1 knockdown reversed MV’s protective effect on inflammatory responses, and miR-21-5p inhibitor or SPRY1 overexpressed enhanced MV’s effect on inflammatory responses in LPS-exposed RAW 264.7 cells. Therefore, the significant protective effect of mogroside V on inflammation response is related with the downregulation of miR-21-5p and upregulation of SPRY1 in vitro and in vivo, MiR-21-5p/ SPRY1 may be a novel therapeutic targets of MV for anti-inflammation treatment.
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