Anthocyanins Prevent AAPH-Induced Steroidogenesis Disorder in Leydig Cells by Counteracting Oxidative Stress and StAR Abnormal Expression in a Structure-Dependent Manner

Abstract

Testosterone deficiency may increase the risk of sexual dysfunction and the failure of spermatogenesis. Oxidative stress that is derived from the destruction of homeostasis, disease, and exposure to contaminants can damage the steroidogenicity process in Leydig cells, resulting in a reduction in testosterone synthesis. Anthocyanins are a group of innoxious antioxidants widely recognized in food sources, and are an ideal candidate to relieve oxidative stress-related steroidogenesis disorder. However, there is still a major gap in our knowledge of the structure–function relationship of anthocyanin on the activity mentioned above. In the present study, four anthocyanins including cyanidin-3-glucoside (Cy-3-glu), delphinidin-3-glucoside (Dp-3-glu), pelargonidin-3-glucoside (Pg-3-glu), and cyanidin-3,5-diglucoside (Cy-3,5-diglu) were applied to reverse testosterone generation after employing 2,2′-Azobis(2-amidinopropane)-dihydrochloride (AAPH) as the inducer of oxidative stress in R2C cells. The results demonstrated that all four kinds of anthocyanins can inhibit ROS generation, alleviate mitochondrial membrane potential damage, and contribute to increased testosterone. Among them, Cy-3,5-diglu with diglycoside performed best on antioxidative ability and improved cell dysfunction and upregulated the expression of the steroidogenic acute regulatory protein (StAR). The molecular docking further revealed the direct combination between anthocyanins and StAR, suggesting that anthocyanins with monosaccharide were more likely to interact with StAR than with diglycoside. Taken together, these data indicate that recipient R2C cells under oxidative stress submitted to anthocyanins exhibited improved steroidogenesis in a structure-dependent manner. Anthocyanins could be considered the ideal ingredients against oxidative stress-induced testosterone deficiency.

Protective effect of bioactive components from Rubi fructus against oxidative damage in human ovarian granulosa cells induced by 2,2‐azobis (2‐methylpropionamidine) dihydrochloride

“…16 Rubi fructus protects ovarian health, but the effective components and corresponding mechanisms remain to be elucidated. 42 Researchers have commonly used AAPH to induce cellular senescence, 43 impaired steroidogenesis, 44 and erythrocyte hemolysis 45 brought about by oxidative stress. It is a common generator of free radicals, decomposed into nitrogen and two R˙radicals under heat around 37 °C, producing ROO˙, ROOR radicals, or R-R products by diffusion or reaction with oxygen.…”

Sea cucumber peptides positively regulate sexual hormones in male mice with acute exhaustive swimming: possibly through the Ca2+/PKA signaling pathway

“…Hu et al indicated that anthocyanins prevented 2,2′-azobis(2-amidinopropane)-dihydrochloride (AAPH)-induced steroidogenesis disorder in the Leydig cells by counteracting oxidative stress and StAR abnormal expression. 36 Furthermore, cholesterol will be converted into pregnenolone by cholesterol side chain lyase in the mitochondria, and pregnenolone further enters the endoplasmic reticulum and is converted into steroid dehydrogenation epiandrosterone or androstenedione by Cyp17a1. Thus, Cyp17a1 deficiency will affect the synthesis of gonadal sex steroids such as cortisol, androgen, and estrogen.…”

Advancements in Genetic Biomarkers and Exogenous Antioxidant Supplementation for Safeguarding Mammalian Cells against Heat-Induced Oxidative Stress and Apoptosis

“…Anthocyanins are a group of natural flavonoids widely distributed in various plant sources, including fruits, vegetables, grains, and other botanicals [ 159 ]. Multiple research studies have elucidated the antioxidative properties of anthocyanins and their correlation with enhancements in spermatogenesis processes [ 160 , 161 , 162 , 163 , 164 ]. Notably, cyanidin-3-O-glucoside (C3G) and protocatechuic acid (PCA) have emerged as prominent anthocyanins found in dietary sources, recognized for their robust antioxidant capabilities in supporting male reproductive health [ 159 , 162 , 165 ] and uterine epithelial cells [ 166 ].…”