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Dendrobium officinale polysaccharides ameliorate radiation-induced premature ovarian insufficiency through coordinated modulation involving the gut microbiota-PI3K/AKT-glycolysis axis

Year: 2026

Type: article

Abstract: Radiotherapy-induced premature ovarian insufficiency (POI) remains a clinical challenge with limited preventative strategies. Dendrobium officinale polysaccharides (DOP) exhibit beneficial bioactivities, but their efficacy and mechanism against radiation-induced POI are unknown. In this study, a mouse model of POI was established by single-dose whole-body X-ray irradiation (5 Gy). Mice were pretreated with a partially purified DOP preparation (500 mg/kg/day) for 7 days prior to and 14 days post-irradiation. Ovarian function was assessed via estrous cyclicity, hormone assays, histomorphology, and follicle counting. Mechanisms were investigated through analysis of apoptosis (TUNEL, IHC, flow cytometry), PI3K/AKT signaling and glycolysis-related marker expression (qPCR, IF, Western blot), and gut microbiota (16S rRNA sequencing), with in vitro validation using irradiated human granulosa cells (KGN). DOP pretreatment significantly attenuated POI phenotypes, restoring estrous cyclicity, improving serum sex hormone profiles (increased E2 and AMH; decreased FSH and LH), and preserving ovarian/uterine morphology and follicle pool. Mechanistically, DOP inhibited ovarian granulosa cell apoptosis in vivo and in vitro , concomitant with reduced ROS levels. Immunofluorescence and qPCR analyses revealed that DOP modulated the PI3K/AKT pathway in growing follicles while suppressing its overactivation in primordial follicles, as evidenced by modulated expression and localization of FOXO3a and rps6 and increased phosphorylation of AKT, mTOR, FOXO3a, and rps6. Concurrently, DOP upregulated the expression of glycolysis-related markers including GLUT4, HK1, PKM2, and LDHA at both mRNA and protein levels. Furthermore, DOP restored gut microbiota diversity and composition altered by irradiation, increasing the abundance of beneficial taxa such as Muribaculum. Collectively, these findings suggest that DOP exerts a protective effect against radiation-induced POI through a multi-targeted mechanism involving anti-apoptosis, modulation of PI3K/AKT signaling and glycolysis-related marker expression in growing follicles, inhibition of primordial follicle overactivation, and remediation of gut dysbiosis. These findings position DOP as a promising natural candidate for improving ovarian injury-related parameters, warranting further investigation.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1891795