Rutin Prevents Dexamethasone-Induced Muscle Loss in C2C12 Myotube and Mouse Model by Controlling FOXO3-Dependent Signaling

Abstract

One of the causes of sarcopenia is that homeostasis between anabolism and catabolism breaks down due to muscle metabolism changes. Rutin has shown antioxidant and anti-inflammatory effects in various diseases, but there are few studies on the effect on muscle loss with aging. The effect of rutin on muscle loss was evaluated using dexamethasone-induced muscle loss C2C12 myoblast and mouse model. In the group treated with dexamethasone, the muscle weight of gastrocnemius (GA), tibialis anterior (TA), and extensor digitorum longus (EDL) in the mouse model were significantly decreased (p < 0.0001 in GA, p < 0.0001 in TA, and p < 0.001 in EDL) but recovered (p < 0.01 in GA, p < 0.0001 in TA, and p < 0.01 in EDL) when treated with rutin. MAFbx, MuRF1, and FOXO3 protein expression of C2C12 myoblast were significantly increased (p < 0.01 in MAFbx, p < 0.01 in MuRF1, and p < 0.01 in FOXO3) when treated with dexamethasone, but it was recovered (p < 0.01 in MAFbx, p < 0.01 in MuRF1, and p < 0.01 in FOXO3) when rutin was treated. In addition, MAFbx and FOXO3 protein expression in GA of mouse model was significantly increased (p < 0.0001 in MAFbx and p < 0.001 in FOXO3) when treated with dexamethasone, but it was also recovered (p < 0.01 in MAFbx and p < 0.001 in FOXO3) when rutin was treated. The present study shows that rutin blocks the FOXO3/MAFbx and FOXO3/MuRf1 pathways to prevent protein catabolism. Therefore, rutin could be a potential agent for muscle loss such as sarcopenia through the blocking ubiquitin-proteasome pathway associated with catabolic protein degradation.

The Anti-Muscle Atrophy Effects of Ishige sinicola in LPS-Induced C2C12 Myotubes through Its Antioxidant and Anti-Inflammatory Actions

“…Polyphenols, such as catechin and quercetin, have been shown to prevent clinorotation-induced expression of MAFbx and MuRF1 in C2C12 myotubes [23]. Rutin, one of the flavonoids, prevented dexamethasone-induced muscle loss in C2C12 myotubes and mouse models by controlling FOXO3-dependent signaling [24]. Didrovaltrate, an active compound of Valeriana fauriei, has ROS scavenging activity and has inhibited dexamethasone-induced muscle atrophy in C2C12 myotubes and C57BL/6 mice [25].…”

Accounting Gut Microbiota as the Mediator of Beneficial Effects of Dietary (Poly)phenols on Skeletal Muscle in Aging

“…The major source of rutin is buckwheat, but it is also present in apples, citrus fruits, asparagus, onions and tea [ 164 ]. Experimental mouse studies have shown that rutin is associated with increased protein synthesis and mitochondrial biogenesis, and reduced apoptosis, in skeletal muscle cells [ 165 , 166 ]. Rutin has also shown antinflammatory properties in vitro [ 167 ], confirming its potential beneficial effect against muscle wasting.…”

The Effects of Flavonoids on Skeletal Muscle Mass, Muscle Function, and Physical Performance in Individuals with Sarcopenia: A Systematic Review of Randomized Controlled Trials

“…Depending on the chemical structure, flavonoids are divided into flavonols, flavan-3-ols, anthocyanidins, isoflavones, flavanones, and flavones [ 15 ]. Current evidence shows various flavonoids, such as rutin, nobiletin, luteolin, and quercetin have a favorable impact on skeletal muscle health by regulating protein homeostasis in vitro and in mouse models [ 16 , 17 , 18 , 19 ].…”