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Plant‑derived natural products alleviate dexamethasone‑induced skeletal muscle atrophy by modulating FoxO (Review)
Wei Dai1, Jiabin Wu1, Xiaotong Ma2
1Shanghai Key Laboratory of Human Performance (Shanghai University of Sport), Shanghai University of Sport, Shanghai 200438, P.R. China.
Abstract:
Muscle atrophy (MA) is a major global health issue, and systematic strategies for its prevention and treatment are lacking. Diverse factors contribute to MA, amongst which the exogenous over‑supplementation and endogenous pathological elevation of glucocorticoids (GCs) are key causes. The present study summarizes MA induced by the GC dexamethasone (DEX) and its molecular mechanisms, including protein metabolism imbalance, mitochondrial dysfunction and abnormalities in epigenetic regulatory proteins, to explore potential therapeutic approaches for MA. FoxO transcription factor serves a central regulatory role in DEX‑induced MA by modulating the ubiquitin‑proteasome system, autophagy‑lysosomal system and energy metabolism pathways. Therefore, FoxO may serve as a critical therapeutic target for DEX‑induced MA. Plant‑derived natural products are promising candidates for the development of clinical drugs for tumors, myocardial infarction and diabetic nephropathy. These products protect against MA by regulating FoxO activity through multiple signaling pathways, including Akt, AMPK, and SIRT. Plant monomer compounds, such as flavonoids, polyphenols and terpenes, exert therapeutic effects and may provide new strategies for the precise prevention and treatment of MA induced by elevated GC levels.
Insights
Glucocorticoids (GCs) cause muscle atrophy (MA) by affecting protein metabolism and energy pathways via the FoxO transcription factor. Natural compounds targeting FoxO show promise for preventing and treating GC-induced MA.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Muscle atrophy (MA) is a significant global health concern with limited therapeutic strategies.
- Elevated glucocorticoids (GCs) are a primary cause of MA, impacting protein metabolism, mitochondrial function, and epigenetic regulation.
- The FoxO transcription factor plays a crucial role in mediating GC-induced MA.
Purpose of the Study:
- To summarize the molecular mechanisms of dexamethasone (DEX)-induced MA.
- To explore potential therapeutic targets for MA.
- To investigate the role of plant-derived natural products in preventing and treating MA.
Main Methods:
- Review of literature on GC-induced MA and its molecular pathways.
- Analysis of the role of FoxO transcription factor in DEX-induced MA.
- Examination of signaling pathways (Akt, AMPK, SIRT) modulated by plant-derived compounds.
Main Results:
- DEX-induced MA involves protein metabolism imbalance, mitochondrial dysfunction, and epigenetic alterations.
- FoxO transcription factor is a key regulator of DEX-induced MA through ubiquitin-proteasome and autophagy-lysosomal systems.
- Plant-derived natural products, including flavonoids, polyphenols, and terpenes, can regulate FoxO activity and show therapeutic potential.
Conclusions:
- FoxO transcription factor is a critical therapeutic target for GC-induced muscle atrophy.
- Plant-derived natural products offer promising strategies for the prevention and treatment of MA.
- Targeting FoxO signaling pathways with natural compounds may provide precise therapeutic approaches for elevated GC levels.
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