Rgl-exomiR-7972, a novel plant exosomal microRNA derived from fresh Rehmanniae Radix, ameliorated lipopolysaccharide-induced acute lung injury and gut dysbiosis

• Published in: Biomedicine & pharmacotherapy 2023-09, Vol.165, p.115007-115007, Article 115007
• Main Authors: Qiu, Fen-Sheng, Wang, Jia-Feng, Guo, Mei-Ying, Li, Xue-Jian, Shi, Chang-Yi, Wu, Fang, Zhang, Huan-Huan, Ying, Hua-Zhong, Yu, Chen-Huan
• Format: Article
• Language: English
• Subjects: Biofilm form; GPR161; Gut microbiota; Hedgehog pathway; MicroRNA; Virulence gene
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.115007

Plant-derived exosome-like nanoparticles (ELNs) have been proposed as a novel therapeutic tool for preventing human diseases. However, the number of well-verified plant ELNs remains limited. In this study, the microRNAs in ELNs derived from fresh Rehmanniae Radix, a well-known traditional Chinese herb for treating inflammatory and metabolic diseases, were determined by using microRNA sequencing to investigate the active components in the ELNs and the protection against lipopolysaccharide (LPS)-induced acute lung inflammation in vivo and in vitro. The results showed that rgl-miR-7972 (miR-7972) was the main ingredient in ELNs. It exerted stronger protective activities against LPS-induced acute lung inflammation than catalpol and acteoside, which are two well-known chemical markers in this herb. Moreover, miR-7972 decreased the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), reactive oxygen species (ROS) and nitric oxide (NO) in LPS-exposed RAW264.7 cells, thereby facilitating M2 macrophage polarization. Mechanically, miR-7972 downregulated the expression of G protein-coupled receptor 161 (GPR161), activating the Hedgehog pathway, and inhibited the biofilm form of Escherichia coli via targeting virulence gene sxt2. Therefore, miR-7972 derived from fresh R. Radix alleviated LPS-induced lung inflammation by targeting the GPR161-mediated Hedgehog pathway, recovering gut microbiota dysbiosis. It also provided a new direction for gaining novel bioactivity nucleic acid drugs and broadening the knowledge on cross-kingdom physiological regulation through miRNAs. [Display omitted] •Rgl-miR-7972 was the main ingredient in ELNs derived from fresh Rehmanniae Radix.•Rgl-miR-7972 improved LPS-induced inflammation via inhibiting GPR161.•Rgl-miR-7972 inhibited the biofilm form of Escherichia coli via inhibiting sxt2.•ELNs act as novel drug deliver for cross-kingdom physiological regulation.