Quercetin and Kaempferol Mitigate Endotoxin‐Induced Skeletal Muscle Wasting by Inhibiting KLF15 Expression and Restoring the Antioxidant System
Abstract
The loss of muscle mass or muscle atrophy is a significant health concern associated with aging, diabetes, cardiovascular diseases, environmental toxicity, and inflammation, and it is becoming a significant issue requiring effective therapeutic strategies. Sepsis is caused by bacterial infection leading to inflammation and has a plethora of consequences, one of which is loss of muscle mass commonly observed for intensive care unit patients with a high morbidity rate. Flavonoids are well‐known natural compounds for restoring muscle wasting. Our study investigates the efficacy of two flavonoids, quercetin and kaempferol, in mitigating lipopolysaccharide (LPS)‐induced muscle atrophy. LPS treatment was followed by increased ROS production, upregulated inflammation (NF‐Kβ, TLR4, MyD88, IL‐6), and disruption of mitochondrial homeostasis in C2C12 myoblasts. The KLF15 knockdown cellular model also revealed a negligible effect of LPS in C2C12. Furthermore, the antioxidant properties of quercetin and kaempferol, individually and in combination, were evidenced to attenuate LPS‐induced cellular oxidative stress and promote myogenesis by downregulating inflammatory regulators and atrophy‐related genes triggered by LPS. Hence, this study illuminates the status of quercetin's and kaempferol's cytoprotective effect, individually and in combination, on muscle cells affected by sepsis‐induced atrophy.
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