Sanggenon C is isolated from Morus alba, a plant that has been used for anti‑inflammatory purposes in
Oriental medicine. Little is known about the effect of Sanggenon C on cardiomyocyte
hypoxia injury. This study, using H9c2 rat cardiomyoblasts, was designed to determine the effects of Sanggenon C on cardiomyocyte
hypoxia injury. Inflammatory
cytokine levels were measured by reverse transcription‑polymerase chain reaction,
reactive oxygen species were measured by 2',7'‑dichlorofluorescin diacetate
fluorescent probe, autophagy was detected using the LC3II/I ratio and cell apoptosis was detected by TUNEL staining. The molecular mechanisms underlying Sanggenon C‑induced cyto‑protection were also determined by western blotting, especially the possible involvement of autophagy and AMP‑activated
protein kinase (AMPK). Results indicated that samples pretreated with different concentrations of Sanggenon C (1, 10 and 100 µM) reduced the expression levels of pro‑inflammatory
cytokines, including
tumor necrosis factor α,
interleukin (IL)‑1 and IL‑6, under
hypoxia. The beneficial effects of Sanggenon C were also associated with reduced levels of
reactive oxygen species generation and increased levels of
antioxidant nitric oxide and
superoxide dismutase. Sanggenon C enhanced hypoxia‑induced autophagy as evidenced by the increased expression levels of autophagy‑associated
proteins Beclin and autophagy related 5 as well as the decreased the accumulation of p62, and increased the LC3II/I ratio. Sanggenon C also reduced hypoxia‑induced apoptosis as detected by TUNEL staining and the expression of Bcl‑2
proteins. The beneficial effects of Sanggenon C were associated with enhanced activation level of AMPKα and suppressed hypoxia‑induced mechanistic target of
rapamycin (mTOR) and forkhead box O3a (FOXO3a) phosphorylation. The
AMPK inhibitor Compound C (
CpC) was used, and the anti‑apoptotic and pro‑autophagy effects of Sanggenon C in response to
hypoxia were abolished by
CpC. In conclusion, the current study demonstrated that Sanggenon C possessed direct cytoprotective effects against
hypoxia injury in cardiac cells via signaling mechanisms involving the activation of AMPK and concomitant inhibition of mTOR and FOXO3a.