Extraction, Characterization, and Biological Evaluation of Atranorin Against Diabetes-Induced Reproductive Dysfunction Through Modulation of Oxidative Stress, Inflammatory Pathways and Key Reproductive Enzymes

TL;DR

Atranorin, a natural compound, protects against diabetes-induced male reproductive damage by reducing inflammation and oxidative stress.

Contribution

Atranorin's efficacy in reversing diabetes-induced reproductive dysfunction in rats is demonstrated through multiple biological parameters.

Findings

Atranorin reduced hyperglycemia by 66% and decreased inflammation in seminal plasma.

Oxidative stress markers like TBARS and TOS were reduced by 73% and 70%, respectively.

Sperm motility and viability improved by 189% and 69%, with a 90% recovery in testosterone levels.

Abstract

Male fertility is declining worldwide, with notable reductions in sperm counts, emphasizing the need for new therapeutic interventions. Atranorin (ATR), a lichen-derived secondary metabolite, exhibits strong antioxidant and anti-inflammatory activities. This study assessed the protective effects of ATR on type 1 diabetes (T1D)-induced reproductive dysfunction in rats. T1D was induced in male Wistar rats via a single intraperitoneal injection of alloxan at 150 mg/kg body weight (bw). ATR significantly ameliorated T1D-related reproductive damage. At 170 mg/kg bw, ATR reduced hyperglycemia by 66% and attenuated seminal inflammation, decreasing leukocyte infiltration (−51%) and myeloperoxidase (MPO) activity (−68%). Oxidative balance improved, as evidenced by increased total antioxidant status (TAS) (+203%) and decreased thiobarbituric acid reactive substances (TBARS) (−73%), hydrogen peroxide (H2O2) (−45%), and total oxidant status (TOS) (−70%). Steroidogenesis was restored through enhanced 3β-hydroxysteroid dehydrogenase (3β-HSD) (+65%) and 17β-hydroxysteroid dehydrogenase (17β-HSD) (+102%) activities, resulting in a 90% recovery of testosterone levels. Seminal plasma function improved, with increased fructose levels (+71%), normalized pH (7.4), and enhanced hyaluronidase (HYAL) (+71%), adenosine triphosphatase (ATPase) (+71%), and prostatic acid phosphatase (PAP) (+79%) activities. Fertility biomarkers, such as adenosine deaminase (ADA) (+148%) and lactate dehydrogenase-C4 (LDH-C4) (+62%), increased, and essential minerals Zn2+ (+72%), Ca2+ (+96%), Mg2+ (+84%), and Se (+57%) were restored. Consequently, sperm density (+87%), viability (+69%), and motility (+189%) improved, while abnormalities declined (−46%). Histological findings confirmed the restoration of spermatogenesis and epididymal maturation. ATR effectively counteracts diabetes-induced reproductive dysfunction by reducing oxidative and inflammatory stress while improving hormonal and seminal parameters.

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