(2R,3S,2″R,3″R)‑Manniflavanone Protects Proliferating Skeletal Muscle Cells against Oxidative Stress and Stimulates Myotube Formation

• Published in: Journal of agricultural and food chemistry Vol. 65; no. 18; pp. 3636 - 3646
• Main Authors: Acharya, Suresh, Stark, Timo D, Oh, Seung Tack, Jeon, Songhee, Pak, Sok Cheon, Kim, Mina, Hur, Jinyoung, Matsutomo, Toshiaki, Hofmann, Thomas, Hill, Rodney A, Balemba, Onesmo B
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10.05.2017
• Subjects: Animals; Cell Differentiation - drug effects; Cell Line; Cell Proliferation - drug effects; Flavones - chemistry; Flavones - pharmacology; Garcinia - chemistry; Hydrogen Peroxide - toxicity; Mice; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Muscle, Skeletal - cytology; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Myogenin - genetics; Myogenin - metabolism; Oxidative Stress - drug effects; Plant Bark - chemistry; Plant Extracts - chemistry; Plant Extracts - pharmacology; Protective Agents - chemistry; Protective Agents - pharmacology; Up-Regulation - drug effects; antioxidant; flavonoid; Garcinia; myogenesis; reactive oxygen species
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.6b05161

We investigated the antioxidative properties of (2R,3S,2″R,3″R)-manniflavanone (MF) using in vitro assays and examined its effects on myogenesis and lactate-induced oxidative stress in C2C12 cells. MF was purified from Garcinia buchananii stem bark. H2O2 and oxygen radical absorbance capacity assays demonstrated that MF is a powerful antioxidant. This finding was supported by diphenylpicrylhydrazine radical scavenging activity of MF. MF was less cytotoxic to C2C12 cells compared to ascorbic acid and myricetin. Moreover, MF accelerated myotube formation in the differentiated C2C12 cells by up-regulating myogenic proteins such as MyoG and myosin heavy chain. Furthermore, MF rescued late differentiation of myoblast suppressed by lactate treatment and up-regulated the expression levels of Nrf2 in lactate-induced oxidative stress, indicating that MF stimulates antioxidative activity inside C2C12 cells. Collectively, MF is a potent antioxidant with a higher safety profile than ascorbic acid and myricetin. It reduces oxidative stress-induced delaying of skeletal muscle differentiation by scavenging reactive oxygen species and regulating myogenic proteins factors.