Jae-Kwan Hwang

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.

Jiyeon Lee, Mi-Bo Kim, Changhee Kim, Chae Young Moon, Hyunju Kang, and Jae-Kwan Hwang. J. Microbiol. Biotechnol. 2026;36:1-10. https://doi.org/10.4014/jmb.2604.04033

5,7-Dimethoxyflavone (DMF), a bioactive flavone derived from Kaempferia parviflora Wall. ex Baker, has been reported to exhibit anti-obesity and muscle-protective potential; however, its effects on obesity-related muscle dysfunction and the underlying mechanisms in a leptin-deficient model remain to be fully elucidated. This study investigated the dual effects of DMF, on obesity and muscle atrophy in ob/ob mice. Male ob/ob mice were randomly assigned to vehicle- or DMF (20 or 50 mg/kg/day)–treated groups and orally administered DMF for 8 weeks, with age-matched wild-type mice serving as controls. Adiposity, skeletal muscle mass, grip strength, treadmill exercise endurance, and related molecular signaling pathways were evaluated. DMF significantly decreased body weight, fat volume, and fat mass without affecting appetite, suggesting a potential shift in energy partitioning. Mechanistically, DMF was associated with reduced expression of adipogenic transcription factors and lipogenic enzymes by upregulating AMP-activated protein kinase in epididymal fat. Conversely, DMF markedly increased muscle fiber size and muscle mass, which resulted in enhanced muscle function, such as exercise endurance and grip strength. At the molecular level, DMF activated the phosphatidylinositol 3-kinase / protein kinase B pathway, subsequently stimulating the mammalian target of rapamycin pathway and the concomitant phosphorylation of forkhead box O3a. Mitochondrial biogenesis-related markers were also upregulated by DMF. Overall, DMF may serve as a potential functional agent to mitigate obesity-induced muscle loss by modulating metabolic and atrophic signaling pathways.

Background/Objectives: Cancer cachexia involves progressive skeletal muscle and adipose tissue loss, which is further aggravated by cisplatin chemotherapy via increased systemic inflammation, tissue catabolism, and renal toxicity. The present study aimed to evaluate whether a combination of amaranth protein hydrolysate and Agastache rugosa extract (AKE) could attenuate cisplatin-associated cachexia and nephrotoxicity in CT26 tumor-bearing mice. Methods: Cancer cachexia was induced by subcutaneous CT26 cell inoculation in 6-week-old male BALB/c mice, followed by a 7-day tumor establishment period. Cisplatin was then administered intraperitoneally, and AKE (125 or 250 mg/kg/day) was given daily by oral gavage for 14 days. Results: AKE administration significantly alleviated cisplatin-induced body weight loss and systemic inflammation, accompanied by preservation of skeletal muscle and adipose tissue mass, as well as increased myofiber cross-sectional area and adipocyte size. AKE markedly reduced serum inflammatory cytokines, blood urea nitrogen, and creatinine levels, indicating protection against cisplatin-induced renal injury. Mechanistically, AKE suppressed renal apoptosis through inhibition of mitogen-activated protein kinase signaling. In skeletal muscle, AKE attenuated muscle atrophy by modulating protein turnover pathways, including downregulation of muscle-specific ubiquitin ligases and restoration of Akt/mTOR and FoxO3a signaling. Furthermore, AKE mitigated adipose tissue wasting by suppressing AMP-activated protein kinase-dependent browning and restoring adipogenic signaling involved in lipid storage and differentiation. Conclusions: These findings demonstrate that AKE confers comprehensive protection against cisplatin-induced cachexia and nephrotoxicity by coordinately preserving muscle and adipose tissue and attenuating renal injury, suggesting its potential as a functional nutritional strategy to alleviate chemotherapy-associated tissue wasting.

Squalene, a polyunsaturated triterpene and sterol precursor present in shark liver oil, was evaluated for its protective effects against skeletal muscle atrophy. This study examined its effects in both tumor necrosis factor-alpha (TNF-α)-treated C2C12 myotubes and in a mouse model of immobilization-induced muscle atrophy. After 7 days of immobilization, C57BL/6J mice received daily oral squalene (100 or 200 mg/kg) or saline for 7 days. Squalene alleviated muscle atrophy, as evidenced by increases in grip strength, muscle mass, and muscle fiber cross-sectional area. Mechanistically, squalene activated the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway to promote protein synthesis and suppressed forkhead box O3a-mediated protein degradation by downregulating muscle-specific E3 ubiquitin ligases. Furthermore, squalene enhanced antioxidant enzyme and reduced pro-inflammatory cytokines via inhibition of nuclear factor kappa B phosphorylation. These findings suggest that squalene attenuates muscle atrophy and improves muscle function primarily through modulation of the PI3K/Akt signaling pathway.