Paeonia lactiflora root extract suppresses cancer cachexia by down-regulating muscular NF-κB signalling and muscle-specific E3 ubiquitin ligases in cancer-bearing mice

Abstract

Ethnopharmacological relevance: The dried root of Paeonia lactiflora Pall. (Radix Paeoniae) has been traditionally used to treat various inflammatory diseases in many Asian countries.

Aim of the study: Cancer cachexia is a catabolic syndrome driven by inflammation and characterised by a loss of skeletal muscle. This study aimed to assess the effects of an ethanolic extract of Radix Paeoniae (RP) on cancer cachexia and elucidate its mechanism of action.

Material and methods: The anti-cachexic effect and mechanism of RP were examined in mouse models of cancer cachexia established in C57BL/6 mice by subcutaneously injecting Lewis lung carcinoma or MC38 colon carcinoma cells. Skeletal muscle tissues were analysed by RNAseq, real-time quantitative reverse transcription PCR, western blotting, and immunofluorescence microscopy. Megestrol acetate, which is recommended for the treatment of cachexia in cancer patients, was used as the comparator treatment in this study.

Results: In lung and colon cancer-bearing mice, RP significantly restored food intake and muscle mass, along with muscle function measured by grip strength and treadmill running time. In the skeletal muscle tissue of the cancer-bearing mice, RP suppressed NF-κB signalling and reduced inflammatory cytokines, including TNF-α, IL-6, and IL-1β; it also down-regulated the muscle-specific E3 ubiquitin ligases MuRF1 and MAFbx.

Conclusion: RP restored skeletal muscle function and mass in cancer-bearing mice by down-regulating the muscular NF-κB signalling pathway and muscle-specific E3 ubiquitin ligases. Our study indicates that RP is a potential candidate for development as a therapeutic agent against cancer cachexia.

Keywords: Cancer; Gene expression; Inflammation; Signal transduction; Transcriptomics.