Baoyuan Jiedu decoction alleviating cancer cachexia-Induced muscle atrophy by regulating muscle mitochondrial function in Apc Min/+ mice

Abstract

Cancer cachexia is a complex syndrome that leads to an ongoing loss of skeletal muscle mass in many malignant tumors. Our previous studies have evaluated the effectiveness of Baoyuan Jiedu decoction (BJD) in alleviating cancer-induced muscle atrophy. However, the mechanisms of BJD regulating muscle atrophy could not be fully understood. Therefore, we further investigated the mechanisms of BJD mitigating muscle atrophy both in an Apc ^Min/+ mouse model and the Lewis-conditioned medium-induced C2C12 myotube atrophy model. We confirmed the quality of BJD extracts by HPLC. In an In vivo study, body weight loss and muscle atrophy were alleviated with BJD treatment. GO analysis suggested that ATP metabolism and mitochondria were involved. The results of the electron microscope show that BJD treatment may have a healing effect on mitochondrial structure. Moreover, ATP content and mitochondrial numbers were improved with BJD treatment. Furthermore, both in vivo and in vitro, we demonstrated that the BJD treatment could improve mitochondrial function owing to the increased number of mitochondria, balanced dynamic, and regulation of the electron transport chain according to the protein and mRNA expressions. In addition, oxidative stress caused by mitochondrial dysfunction was ameliorated by BJD treatment in Apc ^Min/+ mice. Consequently, our study provides proof for BJD treatment alleviating cancer cachexia-induced muscle atrophy by modulating mitochondrial function in Apc ^Min/+ mice.

Keywords: APCMin/+ mice; Baoyuan Jiedu decoction; cancer cachexia; mitochondrial function; muscle atrophy.