Aucubin prevents steroid‐induced osteoblast apoptosis by enhancing autophagy via AMPK activation

Chen, Yue; Jin, Hongting; Zhang, Xue; Li, Wuyin; Wang, Deli; Tong, Peijian; Liu, Youwen; Tan, Zhen

doi:10.1111/jcmm.16954

Cited by 24 publications

(19 citation statements)

References 43 publications

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“…Autophagy has many physiological and pathophysiological roles in a variety of diseases ( Mizushima, 2007 ). For example, increasing autophagy can reduce steroid-induced apoptosis of bone cells ( Yue et al, 2021 ) and protect cells from premature aging ( Rossiter et al, 2021 ). In addition, activation of FUNDC1-dependent mitophagy protects neurons against cerebral I/R injury ( Cai et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps

et al. 2022

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The multiterritory perforator flap is one of the widest flap patterns used to repair tissue defects. However, flap necrosis of the distal part is still a challenging issue for plastic surgeons. Diallyl trisulfide (DATS) is an efficient ingredient extracted from garlic, exerting many important effects on different diseases. Our experiment aims to reveal whether DATS has a beneficial effect on the survival of perforator flaps and to explore its mechanism of action. The results showed that DATS enhanced angiogenesis and autophagy and reduced cell apoptosis and oxidative stress, thereby improving the survival rate of skin flaps. After co-administration with autophagy inhibitor 3-methyladenine (3MA), perforator flap survival was further improved. Mechanistically, we showed that PI3K/Akt and AMPK-HIF-1α signaling pathways in flap were activated under DATS treatment. All in all, DATS promoted the survival of multiterritory perforator flaps via the synergistic regulation of PI3K/Akt and AMPK-HIF-1α signaling pathways, and inhibition of DATS-induced autophagy further improves flap survival.

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Section: Introductionmentioning

confidence: 99%

Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps

et al. 2022

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“…Network analysis showed that aucubin, geniposide, reptoside and ajugoside were the core compounds of IGEUs against OP. Aucubin had strong anti-OP activity, which can not only increased the differentiation of osteoblasts, promote the increase of cortical bone thickness and bone density, but also prevented the apoptosis of osteoclasts 71 , 72 . Moreover, we have also reported that the total glycosides in Eucommia ulmoides seeds contain high content of aucubin, which could enhance bone mineral density and bone strength, suggesting that it may be a potential alternative drug for the treatment of OP 73 .…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology of iridoid glycosides from Eucommia ulmoides Oliver against osteoporosis

Wang

Fan

Feng

et al. 2022

Sci Rep

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Eucommia ulmoides Oliver is one of the commonly used traditional Chinese medicines for the treatment of osteoporosis, and iridoid glycosides are considered to be its active ingredients against osteoporosis. This study aims to clarify the chemical components and molecular mechanism of iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis by integrating network pharmacology and molecular simulations. The active iridoid glycosides and their potential targets were retrieved from text mining as well as Swiss Target Prediction, TargetNet database, and STITCH databases. At the same time, DisGeNET, GeneCards, and Therapeutic Target Database were used to search for the targets associated with osteoporosis. A protein–protein interaction network was built to analyze the interactions between targets. Then, DAVID bioinformatics resources and R 3.6.3 project were used to carry out Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Moreover, interactions between active compounds and potential targets were investigated through molecular docking, molecular dynamic simulation, and binding free energy analysis. The results showed that a total of 12 iridoid glycosides were identified as the active iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis. Among them, aucubin, reptoside, geniposide and ajugoside were the core compounds. The enrichment analysis suggested iridoid glycosides of Eucommia ulmoides Oliver prevented osteoporosis mainly through PI3K-Akt signaling pathway, MAPK signaling pathway and Estrogen signaling pathway. Molecular docking results indicated that the 12 iridoid glycosides had good binding ability with 25 hub target proteins, which played a critical role in the treatment of osteoporosis. Molecular dynamic and molecular mechanics Poisson–Boltzmann surface area results revealed these compounds showed stable binding to the active sites of the target proteins during the simulations. In conclusion, our research demonstrated that iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis involved a multi-component, multi-target and multi-pathway mechanism, which provided new suggestions and theoretical support for treating osteoporosis.

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“…In addition, aucubin prevents apoptosis in osteoblasts via the AMPK-regulated autophagy pathway. 39 Therefore, we selected autophagy as a downstream signalling pathway of AMPK to resolve palmitate-induced apoptosis in tenocytes. DEL-1 treatment upregulates autophagy markers and autophagosome biogenesis.…”

Section: Discussionmentioning

confidence: 99%

Developmental endothelial locus-1 attenuates palmitate-induced apoptosis in tenocytes through the AMPK/autophagy-mediated suppression of inflammation and endoplasmic reticulum stress

Park

Cho

et al. 2022

Bone & Joint Research

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Aims Myokine developmental endothelial locus-1 (DEL-1) has been documented to alleviate inflammation and endoplasmic reticulum (ER) stress in various cell types. However, the effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes remain unclear. Methods Human primary tenocytes were cultured in palmitate (400 μM) and palmitate plus DEL-1 (0 to 2 μg/ml) conditions for 24 hours. The expression levels of ER stress markers and cleaved caspase 3, as well as phosphorylated 5' adenosine monophosphate-activated protein kinase (AMPK) and autophagy markers, were assessed by Western blotting. Autophagosome formation was measured by staining with monodansylcadaverine, and apoptosis was determined by cell viability assay and caspase 3 activity assay. Results We found that treatment with DEL-1 suppressed palmitate-induced inflammation, ER stress, and apoptosis in human primary tenocytes. DEL-1 treatment augmented LC3 conversion and p62 degradation as well as AMPK phosphorylation. Moreover, small interfering RNA for AMPK or 3-methyladenine (3-MA), an autophagy inhibitor, abolished the suppressive effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes. Similar to DEL-1, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, also attenuated palmitate-induced inflammation, ER stress, and apoptosis in tenocytes, which 3-MA reversed. Conclusion These results revealed that DEL-1 suppresses inflammation and ER stress, thereby attenuating tenocyte apoptosis through AMPK/autophagy-mediated signalling. Thus, regular exercise or administration of DEL-1 may directly contribute to improving tendinitis exacerbated by obesity and insulin resistance. Cite this article: Bone Joint Res 2022;11(12):854–861.

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Aucubin prevents steroid‐induced osteoblast apoptosis by enhancing autophagy via AMPK activation

Cited by 24 publications

References 43 publications

Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps

Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps

Network pharmacology of iridoid glycosides from Eucommia ulmoides Oliver against osteoporosis

Developmental endothelial locus-1 attenuates palmitate-induced apoptosis in tenocytes through the AMPK/autophagy-mediated suppression of inflammation and endoplasmic reticulum stress

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