Brassinin alleviates cancer cachexia by suppressing diverse inflammatory mechanisms in mice

Cancer cachexia is a multifactorial condition that contributes to the death of about 20% of cancer patients. It has the potential to cause weight loss, reduction in muscle mass, and loss of fat tissue, significantly lowering the quality of life. Currently, there are no approved drugs for cancer cachexia. Here, we have explored the possible impact of brassinin (BSN) on cancer cachexia under in vitro and in vivo settings. After differentiation, C2C12 and 3T3‐L1 cells were incubated with colorectal carcinoma cells conditioned media or BSN. For preclinical studies, mice were injected with HT‐29 cells followed by intraperitoneal administration of BSN, and muscle and adipose tissues were evaluated by Western blotting and hematoxylin and eosin staining. BSN effectively suppressed muscle atrophy by down‐regulating the levels of Muscle RING‐finger protein‐1 and Atrogin‐1, while also increasing the expression of myosin heavy chain in cachexia‐induced‐C2C12 myotubes. The induction of adipogenesis by BSN prevented adipocyte atrophy in cachexia‐induced 3T3‐L1 adipocytes. We also noted that BSN disrupted the interaction between COX‐2 and signaling transducer and activator of transcription 3 (STAT3) promoter, leading to down‐regulation of STAT3 activation. Moreover, it was found that BSN inhibited weight loss in mice and demonstrated anti‐cachexic effects. Overall, our observations indicate that BSN can attenuate cancer cachexia through diverse mechanisms. Cancer cachexia is a multifactorial syndrome that is responsible for the death of approximately 20% of cancer patients. It can effectively cause weight loss, skeletal muscle atrophy, and adipose tissue atrophy which can adversely affect the quality of life. However, effective drugs for cancer cachexia are still lacking. In this study, we have investigated whether brassinin (BSN) can affect cancer cachexia under in vitro and in vivo settings. We found that BSN effectively suppressed muscle atrophy by down‐regulating the levels of Muscle RING‐finger protein‐1 and Atrogin‐1, accompanied by increased expression of myosin heavy chain in cachexia‐induced‐C2C12 myotubes. BSN inhibited adipocyte atrophy by inducing adipogenesis in cachexia‐induced 3T3‐L1 adipocytes. We also noted that BSN can down‐regulate signaling transducer and activator of transcription 3 activation. Moreover, it was found that BSN inhibited weight loss in mice and exerted anti‐cachexic actions. Overall, our observations indicate that BSN can attenuate can