Marine-Derived Quinolinone CHNQD-00603 Triggers Autophagy via Suppressing the AKT/ERK/mTOR Pathway to Reverse Senescence and Restore Osteogenic Potential in Bone Marrow Mesenchymal Stem Cells

Apr 5, 2026Current protein & peptide science

Marine Compound CHNQD-00603 May Reverse Aging and Restore Bone-Building Ability in Stem Cells by Activating Cell Recycling Pathways

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Abstract

CHNQD-00603 significantly reduced the proportion of SA-β-gal-positive cells (P < 0.001).

The compound downregulated senescence markers p16 (P < 0.05) and p21 (P < 0.001).
CHNQD-00603 restored osteogenic potential by increasing RUNX2 (P < 0.001), ALP (P < 0.01), OPN (P < 0.001), and OCN (P < 0.001).
It activated autophagy by inhibiting the AKT/ERK/mTOR pathway, indicated by an increased LC3-II/LC3-I ratio and decreased p62 levels.
Autophagosome accumulation was observed, suggesting enhanced autophagic flux.
These findings suggest that CHNQD-00603 may act as a dual regulator of senescence and osteogenesis.

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INTRODUCTION: Cellular senescence of Bone Marrow Mesenchymal Stem Cells (BMSCs) acts as a primary driver of age-related bone loss. This study aimed to investigate the anti-senescence potential of CHNQD-00603, a marine-derived quinolone derivative, and its underlying molecular mechanism in BMSCs.

METHODS: BMSCs isolated from Sprague-Dawley rats were induced to senesce using D-galactose and treated with CHNQD-00603. The study employed SA-β-gal staining, qRT-PCR, Western blotting, and transmission electron microscopy to evaluate cellular senescence, osteogenic differentiation, and autophagic flux. Key signaling pathways were analyzed through the phosphorylation status of AKT, ERK, and mTOR.

RESULTS: CHNQD-00603 significantly reduced the proportion of SA-β-gal-positive cells (P < 0.001) and downregulated senescence markers p16 (P< 0.05) and p21 (P < 0.001). Concurrently, it restored osteogenic potential, increasing the expression of RUNX2 (P < 0.001), ALP (P < 0.01), OPN (P < 0.001), and OCN (P < 0.001). Mechanistically, CHNQD-00603 activated autophagy by inhibiting the AKT/ERK/mTOR pathway, as manifested by an increased LC3-II/LC3-I ratio, decreased p62 levels, and autophagosome accumulation.

DISCUSSION: These findings highlight CHNQD-00603 as a dual regulator that suppresses senescence while promoting osteogenesis. Although the study is limited by a lack of in vivo validation, it effectively positions this marine-derived compound as a specific modulator of autophagy-dependent signaling.

CONCLUSION: CHNQD-00603 mitigates BMSC senescence and restores osteogenic capacity by activating AKT/ERK/mTOR-mediated autophagy, making it a promising therapeutic candidate for the treatment of age-related skeletal disorders.

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Marine-Derived Quinolinone CHNQD-00603 Triggers Autophagy via Suppressing the AKT/ERK/mTOR Pathway to Reverse Senescence and Restore Osteogenic Potential in Bone Marrow Mesenchymal Stem Cells

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