Standardized Korean Mint (Agastache rugosa) Extract Attenuates Cancer-induced Cachexia by Ameliorating Anorexia, Muscle Atrophy, and Adipose Tissue Wasting in BALB/c Mice

Background Agastache rugosa (Korean mint) has been used traditionally in Korea to alleviate nausea, poor appetite, and inflammatory symptoms, suggesting its potential for treating cancer cachexia, which involves anorexia, systemic inflammation, and the loss of skeletal muscle and adipose tissue. In this study, we evaluated the therapeutic effects of a standardized hot water extract of A. rugosa (ARE) in BALB/c mice with cancer-induced cachexia, focusing on improvements in anorexia, inflammation, muscle atrophy, and fat wasting. Methods Cachexia was induced by subcutaneously injecting CT26 colon carcinoma cells. Subsequently, ARE (100 or 250 mg/kg) was administered daily for 18 days. Losses in muscle and fat mass and alterations in anorexia-related hormone levels were evaluated, and the molecular mechanisms involved in ARE’s action were explored. Results ARE administration significantly prevented body weight loss, restored muscle and fat mass, enhanced grip strength, and improved food intake, without altering tumor growth. The serum levels of pro-inflammatory cytokines and appetite-related hormones, including leptin and ghrelin, were modulated in ARE-treated mice. At molecular level, ARE inhibited activation of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway, a key mediator of inflammation-induced catabolism. Consequently, ARE downregulated E3 ubiquitin ligases involved in proteolysis within skeletal muscle and inhibited lipolysis and thermogenesis in adipose tissue. Conclusion ARE mitigates cancer cachexia by reducing systemic inflammation, anorexia, and JAK/STAT3-mediated catabolic responses in skeletal muscle and adipose tissue, which indicates its potential as a plant-based therapeutic candidate for treating cancer-induced cachexia.