Amelioration of Cancer Cachexia-Induced Muscle Atrophy and Adipose Tissue Wasting by a Combination of Amaranth (Amaranthus caudatus L.) Hydrolysate and Korean Mint (Agastache rugosa) Extract in BALB/c Mice.

Cancer cachexia (CC) is a multifactorial metabolic syndrome characterized by systemic inflammation, muscle wasting, and adipose tissue depletion. Amaranth (Amaranthus caudatus L.), a pseudocereal rich in proteins, squalene, and tocotrienols, exhibits strong antioxidant and anti-inflammatory activities. Enzymatic hydrolysis of amaranth proteins enhances bioavailability and physiological potency. Korean mint (Agastache rugosa) extract, abundant in flavonoids such as tilianin and acacetin, has been reported to suppress inflammatory and oxidative pathways. However, the combined effect of amaranth hydrolysate and Korean mint extract (AKE) on cancer cachexia has not been elucidated. CT26 tumor-bearing mice (six-week-old male BALB/c) were orally administered AKE (125 or 250 mg/kg/day) for 14 days. AKE attenuated cachexia-induced weight loss (3.6%-10.3%, p < 0.01) and preserved muscle (13.6%-15.8%, p < 0.01) and fat mass (36.0%-40.8%, p < 0.01). Grip strength was significantly improved. AKE suppressed serum pro-inflammatory cytokines and inhibited muscle protein degradation by downregulating muscle RING-finger protein-1 and muscle atrophy F-box expression. It also enhanced protein synthesis by activating the protein kinase B/mammalian target of rapamycin pathway. In adipose tissue, AKE reduced AMP-activated protein kinase browning while promoting adipogenesis via proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, and Sterol regulatory element-binding protein 1 upregulation. These findings demonstrate that AKE mitigates cancer-induced muscle and fat loss by modulating inflammation, proteolysis, and metabolic remodeling, highlighting its potential as a multi-targeted nutritional strategy for managing cancer cachexia.