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HEP14 treatment improves ovarian function in aged mice through mitophagy enhancement and oxidative stress reduction
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HEP14 treatment improves ovarian function in aged mice through mitophagy enhancement and oxidative stress reduction
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Journal Article
HEP14 treatment improves ovarian function in aged mice through mitophagy enhancement and oxidative stress reduction
2025
Overview
Ovarian aging profoundly impacts reproductive health and accelerates the overall aging process, yet the development of effective therapeutic strategies remains a formidable challenge. In this study, we report the rejuvenating effects of HEP14, a natural activator of protein kinase C (PKC) pathway, on aged ovarian function by inducing mitophagy and effectively clearing reactive oxygen species. To ensure controlled and sustained delivery of HEP14 in vivo, we develop HEP14-loaded PLGA microspheres. Transcriptomic analysis reveals a significant overlap between the transcriptional profiles of HEP14-treated aged ovaries and those of adult ovaries, suggesting molecular rejuvenation process closely associated to HEP14-induced mitophagy. Histopathological evaluations further substantiate these findings, showing that HEP14 enhances mitophagy, exhibits antioxidative properties and promotes follicular regeneration. Consequently, ovarian endocrine function in aged mice is substantially restored. Using transmission electron microscopy, confocal microscopy, and western blot analysis alongside pharmocological inhibitors and PKC-specific siRNA, in vitro studies further demonstrate the restorative effect of HEP14 on mitophagy, leading to improved mitochondrial function and subsequent alleviation of oxidative stress in senescent ovarian granulosa cells. This effect is mediated through the activation of the PKC-ERK1/2 pathway, which plays an pivotal role in the action mechanism in HEP14. These discoveries offer new therapeutic hope for ovarian aging.
PLGA microspheres ensure controlled delivery of HEP14, which restores ovarian function in aged mice by inducing mitophagy and clearing reactive oxygen species via molecular rejuvenation.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/100
/ 14/28
/ 38
/ 38/91
/ 82
/ 82/80
/ 96/34
/ Aging
/ Animals
/ Biomedical and Life Sciences
/ Extracellular signal-regulated kinase
/ Female
/ Genes
/ Genomes
/ Kinases
/ Mice
/ Ontology
/ Ovaries
/ Oxidative Stress - drug effects
/ Protein Kinase C - metabolism
/ Proteins
/ Reactive Oxygen Species - metabolism
/ siRNA
/ Steroids
