Dendrobium officinale Polysaccharide Alleviates Intestinal Inflammation by Promoting Small Extracellular Vesicle Packaging of miR-433-3p

Abstract

Dendrobium officinale polysaccharide (DOP) attenuates inflammatory bowel disease (IBD), but its role in regulating cross-talk between intestinal epithelial cells (IEC) and macrophages against IBD is unclear. This study aimed to investigate DOP protective effects on the intestinal inflammatory response through regulation by miRNA in small extracellular vesicles (sEVs). Our results show that DOP interfered with the secretion of small extracellular vesicles (DIEs) by IEC, which reduced the levels of inflammatory mediators. Increased miR-433-3p expression in DIEs was identified as an important protector against intestinal inflammation. DOP regulated the loading of miR-433-3p by hnRNPA2B1 into the intestinal sEV to increase the abundance of miR-433-3p. DIEs delivered miR-433-3p to lipopolysaccharide-induced macrophages and targeted the MAPK8 gene, leading to inhibition of the MAPK signaling pathway and reduced production of inflammatory cytokines. One protective mechanism of DOP is mediated by intestinal sEV containing miR-433-3p, which is a potential therapeutic agent for the prevention of inflammatory factor accumulation from excessive intestinal macrophage activity and for restoring homeostasis in the intestinal microenvironment.

Bioactivities and Mechanism of Actions of Dendrobium officinale: A Comprehensive Review

“…On the other hand, the polysaccharides could ameliorate inflammatory bowel disease by increasing miR-433-3p in the intestinal small extracellular vesicle. The increased delivery of miR-433-3p reduced the inflammation from excessive macrophage activity in the intestine by inhibiting the MAPK signaling pathway, which was beneficial for maintaining the intestinal microenvironment [78]. Besides, the O-acetyl-glucomannan extracted from Dendrobium officinale was found to improve the colonic microenvironment and benefit colon health in mice, which increased the content of SCFAs, colonic length, and fecal moisture and reduced the colonic pH and defecation time [79].…”

Impact of the Exposome on the Epigenome in Inflammatory Bowel Disease Patients and Animal Models

“…Antibiotics [ 268 , 269 , 270 ] and probiotics [ 271 , 272 , 273 , 274 , 275 , 276 ] can also reduce gut inflammation through various epigenetic mechanisms. Finally, a range of Chinese herbs have been shown to have an epigenetically mediated anti-inflammatory action in the gut [ 277 , 278 , 279 , 280 , 281 , 282 , 283 , 284 , 285 , 286 , 287 ].…”

Tripeptide Leu-Ser-Trp Regulates the Vascular Endothelial Cells Phenotype Switching by Mediating the Vascular Smooth Muscle Cells-Derived Small Extracellular Vesicles Packaging of miR-145

“…The Paeonol from the radix of Cortex Moutan was proved to improve the inflammatory response of endothelial cells by mediating the miRNA-223 packaging in the monocytes-derived EVs [ 12 ]. Liu et al reported that the polysaccharide of Dendrobium officinale could attenuate the inflammatory bowel disease by mediating intestinal EVs with miRNA-433-5p delivering [ 31 ]. Consequently, two different EVs from VSMCs with or without peptide LSW incubation were prepared ( Figure 2 ), and the appropriate concentration of LSW was selected not to cause adverse effects on VSMCs and HVUECs ( Figure 1 ).…”