Introduction
Diabetes mellitus raises the risk of heart failure and skeletal muscle dysfunction, which is responsible for reduced exercise capacity commonly observed in heart failure (Cui et al., 2022). In cardiomyocytes, excess lipid droplets occurring in diabetes cause mitochondrial dysfunction in diabetic cardiomyopathy (Abel, 2018). Lipid overload in the endoplasmic reticulum (ER) led to ER stress and increased levels of reactive oxygen species (ROS), causing mitochondrial dysfunction and further promoting the progression of heart failure and muscle wasting (Frontera & Ochala, 2015; Ohsaki et al., 2017). Fatty acids maintain contractile function in cardiac and skeletal muscles. The uptake and β-oxidation of fatty acids are coordinately regulated to meet a sufficient supply for mitochondrial β-oxidation (Zhang et al., 2010). Mitochondrial dysfunction and inhibition of myoblast differentiation are mainly observed in diabetes (Jung & Mun, 2019), and they cause the failure of the skeletal myoblast to maintain normal function resulting in a weak exercise ability (Phielix & Mensink, 2008). The impaired function of the skeletal myoblast affects glucose metabolism, leading to diabetic myopathy (Sinacore & Gulve, 1993). Clinical and experimental evidence supports that activation of phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) /mammalian target of rapamycin (mTOR) (Xu et al., 2016) signaling pathway is a strategy for the treatment of skeletal muscle atrophy in individuals with diabetes (Jiao et al., 2022). Thus, the functional changes of cardiomyocytes and skeletal myoblasts under type 2 diabetes mellitus (T2DM) conditions should be investigated.
More than 1500 traditional Chinese medicine (TCM) manufacturers yield up to 35 million tons of herbal solid wastes annually, and most of these waters are managed through landfills and incineration rather than considered as recyclable biomass (Tao et al., 2021). For ginseng extraction, water-insoluble ginsenosides are generally extracted by ethanol, and water-soluble ginsenosides polysaccharides/proteins are extracted by water (Sun et al., 2022). The extraction method applied by of TCM manufacturers uses either water or ethanol, resulting in a considerable amount of ethanol (or water)-insoluble active ingredients in herbal residues. Especially for the expensive mountain cultivated ginseng (MCG), functional substances make ginseng residues an attractive material in the field of active compounds. Recently, in China, the evident functional effect of Panax ginseng in attenuating the inflammatory response for the alleviation of COVID-19 has been reported, and it elicited great confidence and interest in the world (Yi, 2022). However, the mechanism of how MCG attenuates the cardiomyocyte and skeletal myoblast dysfunction is still unknown. Herein, three types of ginsengs were selected for screening and discovery of their protective effect on the heart and skeletal muscles under diabetic conditions. A total of 53 water or ethanol extracts were obtained from the ginsengs, and the sample with strongest properties was selected and for further characterized by analytical technologies.