Muscle wasting — whether from aging, corticosteroid therapy, or chronic disease — remains one of the most under-addressed threats to healthspan. A compound already present in Ginkgo biloba extracts may offer a targeted molecular strategy to counter it, and the mechanistic evidence presented here is unusually multi-layered for a phytochemical study.
Amentoflavone (AMF), a biflavonoid compound, was investigated as a direct inhibitor of myostatin (MSTN), the endogenous brake on skeletal muscle growth. Computational docking revealed high-affinity binding between AMF and MSTN, which was then confirmed through 100-nanosecond molecular dynamics simulations and a cellular thermal shift assay — a more rigorous target engagement validation than most plant-compound studies provide. In C2C12 mouse myoblasts and human muscle satellite cells, AMF upregulated myosin heavy chain (MYH) and myogenin (MYOG) — key markers of myogenic differentiation — while concurrently suppressing MSTN expression and reducing phosphorylated SMAD signaling, the downstream pathway through which myostatin exerts its growth-inhibiting effects. Critically, these benefits held in a dexamethasone-induced atrophy model, both in cell culture and in living mice, where AMF prevented muscle mass and body weight loss.
Myostatin inhibition has attracted intense pharmaceutical interest for decades, yet no small-molecule inhibitor has reached clinical use. Most candidates have been biologics — antibodies or propeptides — with complex manufacturing and delivery constraints. A bioavailable dietary biflavonoid that engages the same target represents a conceptually different approach. AMF is already detectable in standardized Ginkgo biloba extracts and in plants like Hypericum and Selaginella, meaning a translational path exists. However, important caveats apply: the in vivo data are from a pharmacologically induced, short-term atrophy model in mice, not a chronic sarcopenia model or aging cohort. Human bioavailability of AMF is poorly characterized, and effective tissue concentrations in skeletal muscle after oral dosing remain unknown. This study is best read as a strong mechanistic foundation warranting pharmacokinetic optimization and eventual human trials, rather than actionable supplementation guidance.
