SIRT1 overexpression by melatonin and resveratrol combined treatment attenuates premature ovarian failure through activation of SIRT1/FOXO3a/BCL2 pathway.
Level 5 - mechanism / opinion, no new human data
Controlled animal experiment
PubMed 38224665 · doi:10.1016/j.bbrc.2024.149506
What was done
Female Sprague Dawley rats were assigned to seven experimental groups: control, cisplatin-induced premature ovarian failure (CIS/POF), melatonin alone (MEL), resveratrol alone (RES), POF + MEL, POF + RES, and POF + MEL + RES. Investigators evaluated histological parameters (follicular degeneration, vascular congestion, inflammation, zona pellucida integrity, connective tissue) using H&E, PAS, and Masson trichrome staining. Immunofluorescence and RT-PCR measured protein and mRNA expression of DNA damage marker pH2Ax, SIRT1, FOXO3a, and BCL2. Serum estrogen was measured by ELISA. Statistical significance was defined as p < 0.002 after Bonferroni correction.
What was found
The POF group differed significantly from controls in all parameters except tertiary follicle count and hemorrhage. Combined treatment (POF + MEL + RES) significantly decreased atretic follicle count compared to POF + MEL and POF + RES single-treatment groups. The combination group also showed significant differences in protein expression of pH2Ax, SIRT1, FOXO3a, and BCL2 and mRNA expression of SIRT1 and BCL2 compared to untreated POF, with significantly higher SIRT1 mRNA expression than either single treatment. No absolute numerical values, group sizes, or effect sizes were provided in the abstract.
Why it matters
This study demonstrates a synergistic protective effect of melatonin and resveratrol against cisplatin-induced ovarian damage in a rodent model, mediated through SIRT1 pathway activation.
Limits
The study is confined to an animal model; results cannot be directly extrapolated to human clinical efficacy or dosing. The abstract does not report the total animal sample size (n), group numbers, or quantitative values (means and standard deviations) for hormone levels and follicle counts.
Cited by
- supports Research shows a synergistic activation effect between melatonin, resveratrol, and SIRT1.