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  3. Echinacoside modulates PARP14-GLUD1 axis to mediate energy metabolism reprogramming and mitochondrial function in diminished ovarian reserve

Echinacoside modulates PARP14-GLUD1 axis to mediate energy metabolism reprogramming and mitochondrial function in diminished ovarian reserve

  • Phytomedicine. 2026 Jun:155:158100. doi: 10.1016/j.phymed.2026.158100.
Huizhen Liang 1,  Chuqiang Shu 2,  Zhizhen Huang 3,  Sisi Yuan 3,  Qi Yang 3,  Shu Chen 3,  Xiaoyi Zhou 4,  Ninglian Yang 4,  Xinyu Xiang 4,  Qiong Xia 4
Affiliations

Affiliations

  • 1 Department of Integrated Chinese and Western Medicine, NHC Key Laboratory of Birth Defect for Research and Prevention (Hunan Provincial Maternal and Child Health Care Hospital), Changsha 410028, China. Electronic address: [email protected].
  • 2 Department of Obstetrics and Gynecology, NHC Key Laboratory of Birth Defect for Research and Prevention (Hunan Provincial Maternal and Child Health Care Hospital), Changsha 410028, China. Electronic address: [email protected].
  • 3 Department of Integrated Chinese and Western Medicine, NHC Key Laboratory of Birth Defect for Research and Prevention (Hunan Provincial Maternal and Child Health Care Hospital), Changsha 410028, China.
  • 4 The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410119, China.
PMID: 41895093 DOI: 10.1016/j.phymed.2026.158100
Abstract

Objective: Diminished ovarian reserve (DOR) is a primary cause of female infertility. With urbanization and lifestyle changes, its incidence is rising annually, necessitating new therapeutic strategies. This study investigates the efficacy and molecular mechanisms of echinacoside (ECH) in treating DOR.

Methods: A DOR rat model was established using tripterygium glycosides (TG), followed by ECH intervention. ECH's effects on DOR were evaluated from multiple aspects such as body weight and estrous cycles, combined with various assays including ELISA, HE, TUNEL stainings, WB, and IHC. Transcriptomic Sequencing and bioinformatics identified core genes and targets of ECH in DOR treatment. Energy metabolism, oxidative stress, and mitochondrial function in ovarian tissue were assessed via colorimetry, WB, DHE staining, flow cytometry, and TEM. In SVOG cells, ECH's regulation of poly(ADP-ribose) polymerase 14 (PARP14) and glutamate dehydrogenase 1 (GLUD1), and its effects on cell Apoptosis, energy metabolism, oxidative stress, and mitochondrial function were measured using CCK-8, WB, Annexin V-FITC/PI staining, colorimetry, biochemical analysis, JC-1 staining, DCFH-DA staining, TEM, IP, and etc. RESULTS: ECH treatment significantly restored estrous cycles, attenuated DOR, inhibited ovarian cell Apoptosis, and normalized hormone levels in DOR rats. Transcriptomic and bioinformatics analyses identified PARP14 as a core target gene of ECH in DOR treatment, with GLUD1 as a potential downstream target. Mechanistic studies revealed that PARP14 inhibited GLUD1 activity via mono-ADP-ribosylation (MARylation), reducing alpha-ketoglutarate (α-KG) production and suppressing energy metabolism. ECH downregulated PARP14 expression, reversing TG-induced energy metabolism suppression, mitigating oxidative stress, and restoring mitochondrial function, thereby reducing granulosa cell Apoptosis.

Conclusion: ECH restores energy metabolism by inhibiting the PARP14-GLUD1-α-KG axis, which suppresses oxidative stress and improves mitochondrial function, inhibiting ovarian cell Apoptosis and ultimately treating DOR.

Keywords

Diminished ovarian reserve; Echinacoside; Energy metabolism; Mitochondrial function; PARP14-GLUD1-α-KG axis.

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