Beta-caryophyllene mitigates high fat diet-induced testicular dysfunctions by targeting JNK/ERK-1 and JAK-1/STAT-3 pathways in rats

Obesity exacerbates metabolic alterations, increasingly linked to male reproductive dysfunction through oxidative stress and inflammatory signaling. β-caryophyllene (BCP) has shown several biological activities due to its antioxidant potential. This study addressed the efficacy of BCP treatment in ameliorating testicular dysfunctionality in obese male rats. Forty male rats were used as follows: G1 as a negative control, fed on a balanced diet; Gps2-5 were fed on a high-fat diet (HFD) for 12 weeks. G2 acted as a positive control. Subsequently, Gps3-5 were administered intraperitoneally (i.p.) with BCP at doses of 25, 50, and 75 mg/kg, respectively for 8 weeks following 12 weeks of HFD induction. After 20 weeks, spermatological parameters, hormone profiles, oxidative stress markers, inflammatory cytokines, expression of JNK/ERK-1 and JAK-1/ STAT-3 pathway components, and testicular histopatholog were assessed. The HFD significantly impaired reproductive parameters, with decreased sperm count, motility, and testosterone levels and increased oxidative stress markers, including malondialdehyde (MDA), and pro-inflammatory cytokines. BCP treatment dose-dependently ameliorated these alterations, with the highest dose restoring sperm count and motility and significantly elevating testosterone levels. BCP downregulated the overexpression of JNK/ERK-1 and JAK-1/STAT-3 signaling pathways. Histopathological examination confirmed marked improvement in testicular architecture in BCP-treated groups. Collectively, BCP treatment effectively mitigates HFD-induced testicular dysfunction via antioxidant, anti-inflammatory, and targeted testicular JNK/ERK-1 and JAK-1/ STAT-3 pathways in obese rats. These findings highlight its potential as a therapeutic candidate for obesity-associated male reproductive impairment.