Wild Cordyceps proteins reinforce intestinal epithelial barrier through MAPK/NF-κB pathway in MRL/lpr mice

J Pharm Pharmacol. 2024 Mar 23:rgad118. doi: 10.1093/jpp/rgad118. Online ahead of print.

Abstract

Objectives: The effects of wild Cordyceps proteins (WCPs) on the gut microbiota and the immune system of MRL/lpr mice were studied.

Methods: The effects of WCP on serum metabolic indexes (total triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) content was measured by a biochemical analyzer. CD4+, CD8+ cells, intestinal inflammation, and intestinal barrier function in MRL/lpr mice were measured by flow cytometry, 16S ribosomal RNA, western blot, and quantitative real-time polymerase chain reaction RT-PCR.

Key findings: The results showed that after the intervention of WCP, the content of CD4+ cells in lupus mice increased, and the levels of proinflammatory cytokines were down-regulated, such as tumor necrosis factor-α and interleukin-6. Secondly, WCP up-regulated the proteins and mRNA levels of ZO-1, Claudin-1, and Occludin. Thirdly, it also increased the Firmicutes/Bacteroidetes ratio and the abundance of Oscillospirales, Lachnospirales, Lachnospiraceae, and Clostridia, as well as negatively regulated the MAPK/NF-кB signaling pathway in lupus nephritis (LN) mice.

Conclusions: These findings suggested that WCP may improve the symptoms of LN by altering immune factors and the intestinal barrier.

Keywords: gut microbiota; inflammatory; lupus nephritis; mechanism; wild Cordyceps protein.