Ameliorative effects of elderberry (Sambucus nigra L.) extract and extract-derived monosaccharide-amino acid on H₂O₂-induced decrease in testosterone-deficiency syndrome in a TM3 Leydig cell

With aging, men develop testosterone-deficiency syndrome (TDS).The development is closely associated with age-related mitochondrial dysfunction of Leydig cell and oxidative stress-induced reactive oxygen species (ROS).Testosterone-replacement therapy (TRT) is used to improve the symptoms of TDS.However, due to its various side effects, research on functional ingredients derived from natural products that do not have side effects is urgently needed.In this study, using the mitochondrial dysfunction TM3 (mouse Leydig) cells, in which testosterone biosynthesis is reduced by H₂O₂, we evaluated the effects of elderberry extract and monosaccharide-amino acid (fructose-leucine; FL) on mRNA and protein levels related to steroidogenesis-related enzymes steroidogenic acute regulatory protein (StAR), cytochrome P450 11A1(CYP11A1, cytochrome P450 17A1(CYP17A1), cytochrome P450 19A1(CYP19A1, aromatase), 3β-hydroxysteroid dehydrogenase (3β-HSD), and 17β-hydro-xysteroid dehydrogenase(17β-HSD).We analyzed elderberry extract and extract-derived FL for changes in ROS scavenging activity and testosterone secretion.Elderberry extract and FL significantly reduced H₂O₂-induced intracellular ROS levels, improved testosterone secretion, and increased the mRNA and protein expression levels of steroidogenesis-related enzymes (StAR, 3b-HSD, 17b-HSD, CYP11A1, CYp17A1).However, the conversion of testosterone to estradiol was inhibited by elderberry extract and extract-derived FL, which reduced the mRNA and protein expression of CYP19A1.In conclusion, elderberry extract and FL are predicted to have value as novel functional ingredients that may contribute to the prevention of TDS by ameliorating reduced steroidogenesis.