Beta-caryophyllene mitigates high fat diet-induced testicular dysfunctions by targeting JNK/ERK-1 and JAK-1/STAT-3
Alaa Muqbil Alsirhani1, Othman R Alzahrani2, Amal S Abu-Almakarem3
1Department of Chemistry, College of Science, Jouf University, 72341, Sakaka, Al-Jouf, Saudi Arabia.
Abstract:
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.
Insights
Obesity impairs male fertility through oxidative stress. Beta-caryophyllene (BCP) treatment improved sperm parameters and testosterone levels in obese rats by reducing inflammation and oxidative damage.
Area of Science:
- Reproductive Biology
- Endocrinology
- Toxicology
Background:
- Obesity is linked to male reproductive dysfunction via oxidative stress and inflammation.
- Beta-caryophyllene (BCP) possesses antioxidant properties with potential therapeutic benefits.
Purpose of the Study:
- To investigate the efficacy of BCP in ameliorating testicular dysfunction in diet-induced obese male rats.
- To assess BCP's effects on spermatological parameters, hormone profiles, oxidative stress, and inflammatory markers.
Main Methods:
- Male rats were fed a high-fat diet (HFD) for 12 weeks, followed by 8 weeks of BCP treatment (25, 50, 75 mg/kg).
- Evaluated sperm count, motility, testosterone, oxidative stress markers (MDA), inflammatory cytokines, JNK/ERK-1 and JAK-1/STAT-3 pathways, and testicular histology.
Main Results:
- HFD induced decreased sperm count/motility, lower testosterone, increased MDA, and elevated pro-inflammatory cytokines.
- BCP treatment dose-dependently improved reproductive parameters, restored testosterone levels, and reduced oxidative/inflammatory markers.
- BCP downregulated JNK/ERK-1 and JAK-1/STAT-3 signaling pathways, with improved testicular histology.
Conclusions:
- BCP effectively mitigates HFD-induced testicular dysfunction in obese rats.
- The therapeutic effects are attributed to BCP's antioxidant, anti-inflammatory actions, and modulation of specific signaling pathways.
- BCP shows potential as a therapeutic agent for obesity-associated male reproductive impairment.
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