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15.11.2024 | Note

Dendrobium nobile Lindl. alkaloids protect CCl₄-induced acute liver injury via upregulating LAMP1 expression and activating autophagy flux

verfasst von: Nan Nan, Yonggang Yang, Xiaolong Fu, Siting Xian, Qin Wu, Jingshan Shi, Shaoyu Zhou

Erschienen in: Journal of Natural Medicines | Ausgabe 1/2025

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Abstract

Dendrobium nobile Lindl. alkaloids (DNLA) are considered important active ingredients of Dendrobium, which have a variety of pharmacological functions. Recent studies indicate that DNLA has beneficial activity in acute liver injury. However, the specific mechanism by which DNLA produces liver protective effects is stills unclear. This study was designed to determine whether regulation of autophagy is involved in the mode of action of DNLA in liver protection. Using CCl₄-induced acute liver injury (ALI) and cell culture models, the molecular mechanism of DNLA-mediated autophagy regulation was studied. The results showed that DNLA significantly improved CCl₄-induced liver damage and oxidative stress, which was confirmed in AML-12 cells. DNLA promoted autophagy in cells treated with CCl₄, manifested by reduced protein expressions of p62 and LC3-II. Fluorescence imaging showed a decrease in the number of autophagosomes in AML-12 cells transfected with mCherry-GFP-LC3B. In addition, DNLA inhibited lysosomal membrane permeabilization by upregulating lysosomal associated membrane protein-1 (LAMP1), thereby promoting autophagy, preventing CCl₄-induced mitochondrial dysfunction, and reducing the production of mitochondrial reactive oxygen species (ROS). While pretreatment of cells with lysosomal inhibitor chloroquine weakened mitochondrial protection elicited by DNLA, overexpression of mitochondrial-targeted SOD2 in AML-12 cells significantly blocked CCl₄ induced downregulation of LAMP1, thereby improving lysosome integrity and promoting lysosome dependent autophagy, suggesting that there may exist a bidirectional regulation between mitochondrial ROS and lysosome-autophagy activation. Collectively, these results demonstrated that DNLA can protect the liver injury mediated by dysregulation of lysosome-autophagy process through promoting ROS-lysosome-autophagy axis and improving mitochondrial damage.

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Titel: Dendrobium nobile Lindl. alkaloids protect CCl4-induced acute liver injury via upregulating LAMP1 expression and activating autophagy flux
verfasst von: Nan Nan
Yonggang Yang
Xiaolong Fu
Siting Xian
Qin Wu
Jingshan Shi
Shaoyu Zhou
Publikationsdatum: 15.11.2024
Verlag: Springer Nature Singapore
Erschienen in: Journal of Natural Medicines / Ausgabe 1/2025
Print ISSN: 1340-3443
Elektronische ISSN: 1861-0293
DOI: https://doi.org/10.1007/s11418-024-01852-9

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