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.