Taehyun Bae1, Jaewoong Jang2, Hyunji Lee3, Jaewon Song4, Seyeon Chae5, Minwoo Park6, Chang-Gue Son7, Seokmin Yoon8, Yoosik Yoon9. 1. Department of Microbiology, Chung-Ang University College of Medicine, Seoul, 06974, Republic of Korea. Electronic address: bthyun92@naver.com. 2. Department of Microbiology, Chung-Ang University College of Medicine, Seoul, 06974, Republic of Korea. Electronic address: jjw4207@naver.com. 3. Department of Microbiology, Chung-Ang University College of Medicine, Seoul, 06974, Republic of Korea. Electronic address: happy1004303@naver.com. 4. Department of Microbiology, Chung-Ang University College of Medicine, Seoul, 06974, Republic of Korea. Electronic address: s536142@naver.com. 5. Department of Microbiology, Chung-Ang University College of Medicine, Seoul, 06974, Republic of Korea. Electronic address: tpdus618@naver.com. 6. Research Center, EBIOGEN Inc, Seoul, 07282, Republic of Korea. Electronic address: mwpark@e-biogen.com. 7. Liver and Immunology Research Center, Dunsan Oriental Hospital of Daejeon University, Daejeon, 35353, Republic of Korea. Electronic address: ckson@dju.ac.kr. 8. Research Center, ADM Korea Inc, Seoul, 03173, Republic of Korea. Electronic address: smyoon@admkorea.co.kr. 9. Department of Microbiology, Chung-Ang University College of Medicine, Seoul, 06974, Republic of Korea. Electronic address: thanks@cau.ac.kr.
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.
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 cancerpatients, 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.