2. Academic Validation
  3. Anemarrhena asphodeloides fructan attenuates cigarette smoke-induced muscle atrophy by activating the Akt/mTOR pathway and inhibiting the ubiquitin-proteasome pathway

Anemarrhena asphodeloides fructan attenuates cigarette smoke-induced muscle atrophy by activating the Akt/mTOR pathway and inhibiting the ubiquitin-proteasome pathway

  • J Ethnopharmacol. 2025 Jul 24:351:120116. doi: 10.1016/j.jep.2025.120116.
Leqian Wang 1,  Yuqin Pan 2,  Bingfeng Lin 3,  Fanxuan Zhang 4,  Lu Xu 5,  Feihua Huang 6,  Nani Wang 7
Affiliations

Affiliations

  • 1 College of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China. Electronic address: wlq20221217@163.com.
  • 2 College of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China. Electronic address: 15258340803@163.com.
  • 3 Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, 310007, China; Tongde hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310000, China. Electronic address: bingfengl1995@163.com.
  • 4 Tongde hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310000, China. Electronic address: 17794527838@163.com.
  • 5 College of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China. Electronic address: 18350267058@163.com.
  • 6 College of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China; Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, 310007, China; Tongde hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310000, China. Electronic address: hfhua238@sohu.com.
  • 7 College of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China; Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, 310007, China; Tongde hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310000, China. Electronic address: wnn8511@163.com.
PMID: 40484257 DOI: 10.1016/j.jep.2025.120116
Abstract

Ethnopharmacological relevance: 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.

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

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Keywords

Anemarrhena asphodeloides; Fructan; Myoblasts; Sarcopenia.

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