AAP-C1

Anemarrhena asphodeloides is a traditional herbal medicine for treating respiratory disorders. Cigarette smoke (CS) exposure is closely associated with increased risk of skeletal muscle atrophy.

We isolated a bioactive polysaccharide from Anemarrhena asphodeloides and investigated its efficacy in attenuating CS-induced sarcopenia and the underlying mechanisms.

Bioactivity-guided isolation approach was used to purify AAP-C1, a bioactive polysaccharide from Anemarrhena asphodeloides. Spectroscopic and chromatographic analyses were performed to characterize its structural details. CS-exposed C2C12 myoblasts and model mice were used to evaluate the therapeutic effects of AAP-C1 on skeletal muscle atrophy and elucidate the underlying molecular mechanisms.

Structural analysis identified AAP-C1 as a heteropolysaccharide (Molecular weight: 3.2 kDa) with fructose and glucose residues in a molar ratio of 18.6:1. AAP-C1 consists of a backbone with →1)-β-D-Fruf-(2→, →6)-β-D-Fruf-(2→, and →6)-α-D-Glcp-(1→ units and β-D-Fruf-(2→ side chains at O-6 positions. AAP-C1 enhanced myoblast proliferation by upregulating myogenic regulators (MyoD1 and MHC) and suppressing muscle proteolysis markers (MuRF-1 and Atrogin1) in the CS-exposed C2C12 cells. AAP-C1 treatment improved muscle function in the CS-exposed mice, as evidenced by increased grip strength, climbing endurance, and wheel-running activity. Mechanistically, AAP-C1 promoted MyoD1-mediated myogenesis by activating the Akt/mTOR signaling pathway. Concurrently, AAP-C1 inhibited the ubiquitin-proteasome pathway by reducing the expression levels of muscle atrophy-related ubiquitin ligases.

AAP-C1 ameliorates CS-induced sarcopenia by inducing myogenic differentiation and inhibiting ubiquitin-proteasome-mediated proteolysis through activation of the Akt/mTOR signaling pathway. Therefore, AAP-C1 demonstrates immense therapeutic potential in alleviating CS-related muscle atrophy.