Discussions
Ginseng’s quality mostly depends on elements including its wild kind,
cultivation, age, and technique of processing. CG and MCG are grown in
gardens for 4-6 years and mountainous forests for over 20 years,
respectively. However, it is still unclear how MCG reduces the
dysfunction of the skeletal myoblast and cardiomyocyte. The activation
of the AKT, PI3K, and mTOR signaling pathway is an approach for the
treatment of skeletal muscle atrophy in people with diabetes, according
to clinical and experimental evidence. Therefore, it is important to
look into how T2DM circumstances affect the functional alterations that
occur in cardiomyocytes and skeletal myoblasts.
This work, revealed the unreported property of APMCG-1 as an AKT
activator in the protection against oxidant stress not only in
cardiomyocytes but also in skeletal myoblasts under T2DM conditions.
Importantly, on the basis of these findings, we proposed a model of
biological adaptation in which cardiomyocytes and skeletal myoblasts
pretreated with APMCG-1 can induce the enhancement of glucose uptake, ER
metabolism and mitochondrial biosynthesis and consequently protect
oxidant stimulated injury through regulation of the PI3K/AKT signaling
pathway.
TCM industries produce large amounts of herbal extraction residues,
which amount to approximately millions of tons of solid waste annually
(Meng et al., 2017). The residues without well-designed management
indirectly or directly contaminate groundwater and soil. These ”waste
residues” contain certain amounts of bio-resources, and have great
potential as feedstock to generate various valuable and useful products.
Researchers believe that the quality and price of MCG are considerably
higher than those of CG (Lu & Li, 2021). In recent years, report
focused that industrial herbal waste should advance management, but a
strategy for recycling MCG is unclear (Huang et al., 2021). We designed
and performed a systematic extraction protocol for three kinds of
ginsengs, and explored their ethanol- and water-soluble compounds. The
ethanol-extracted MCG residue was extracted again by water to obtain
water-soluble compounds. APMCG-1 was first obtained from the
ethanol-extracted MCG residue. Meanwhile, APMCG-1 was found to contain
polysaccharide and proteins, which are connected by O-linked
glycopeptide bonds. Seven indicated monosaccharides and seven amino
acids were found in APMCG-1. Hence, the novel extraction method for
APMCG-1 was performed and the potential biological properties of APMCG-1
are highly expected.
Importantly, we have confirmed the activation of AKT by APMCG-1 in
cardiac and skeletal muscle cells and zebrafish models under type 2
diabetic conditions. AKT has been proposed to inhibit ER stress and
apoptosis by activating PI3K, which is important for the regulation of
ER biogenesis, particularly in rat cardiomyocytes (Liang et al., 2008).
Previous reports revealed that PA reduced insulin-induced
phosphorylation of AKT, and stimulated ER stress and mitochondrial
dysfunction in myoblasts (Peng et al., 2011; Yen et al., 2012).
Moreover, insulin regulates heart metabolism through the regulation of
insulin-induced glucose uptake, leading to mitochondrial fusion via the
AKT-mTOR-nuclear factor-κB-Opa-1 pathway (Parra et al., 2014).
Consistent with these results, our study demonstrated that APMCG-1
enhanced glucose uptake through the downregulation of CK-MB and cTnI in
cardiomyocytes and neurons. Moreover, the Western blotting analysis
demonstrated that APMCG-1 evidently increased expressions of IRS1, PI3K,
AKT and GLUT4, which suggest that APMCG-1 caused the increases in
cardiac and skeletal muscle glucose uptake.
Overexpression or activation of the PI3K/AKT/mTOR signaling pathway
suppresses ER stress, apoptosis, and autophagy in diabetic
cardiomyopathy (G. Zhao et al., 2020). In our study, consistent with the
data on cell viability and ROS, APMCG-1 decreased PA-induced
intracellular Ca2+ levels in PA-induced H9c2 cells,
attenuating ER-dependent cell apoptosis. Moreover, calcium ion regulates
non-gene transcription and is involved in cell growth, differentiation
and proliferation. Stored Ca2+ plays an essential role
in apoptosis-associated Bcl2 activation by regulating the two-way
cross-talk between the mitochondria and ER (Wu et al., 2015). Previous
disconcerting reports regarding an approach to increasing skeletal
myoblast viability after transplantation in the ischemic heart have
reached minimal success, with approximately 20% of the live skeletal
myoblasts left within 72h (Niagara et al., 2007). Intriguingly, the
evidence showed that APMCG-1 both protects skeletal myoblasts and
cardiomyocytes from oxidant-induced damage, which suggests that APMCG-1
can serve as a complementary agent in the strategies. Collectively, we
observed that APMCG-1 pretreatment restored ER and mitochondrial
function under normal circumstances to resist diabetic injury with the
reduction of ROS production and mitochondrial apoptosis based on thein vitro and in vivo observations.