Ameliorative Role of β-Caryophyllene on Antioxidant Biomarkers in a Paroxetine-Induced Model of Male Sexual Dysfunction

Abstract

Male sexual dysfunction, characterised by reduced libido, ejaculatory issues and erectile dysfunction, often results from oxidative stress and enzymatic imbalance, notably involving phosphodiesterase type 5 (PDE5) and nitric oxide synthase (NOS). This study explores the therapeutic potential of β-caryophyllene (β-CBP), a sesquiterpene with antioxidant and anti-inflammatory properties, in mitigating paroxetine-induced sexual dysfunction in rats. Male Wistar rats were divided into nine treatment groups: control, paroxetine (20 mg/kg/day), sildenafil (20 mg/kg/day), β-CBP (10 mg/kg/day), β-CBP (20 mg/kg/day), paroxetine with β-CBP (10 mg/kg), paroxetine with β-CBP (20 mg/kg), paroxetine with sildenafil and β-CBP with sildenafil. Sexual behavioural assays were evaluated, along with oxidative stress markers, including superoxide dismutase (SOD) and catalase (CAT) activity in penile tissue, assessed using spectrophotometric analysis. CB2 receptor expression was significantly increased in β-CBP-treated groups, suggesting enhanced cannabinoid receptor-mediated signalling, which may be linked to improved erectile function. The effects were dose-dependent, with the 20 mg/kg β-CBP group displaying the most significant improvements. Additionally, β-CBP restored antioxidant enzyme activities, including SOD, CAT and reduced glutathione (GSH) levels in penile tissue, effectively reducing oxidative stress. β-CBP shows promise as a therapeutic agent for male sexual dysfunction by enhancing antioxidative capacity and modulating enzymatic balance.

Keywords: CB2; erectile dysfunction; oxidative stress; paroxetine; β‐caryophyllene.

FIGURE 1

In vitro antioxidant activity of β‐caryophyllene. (a) Ferric reducing antioxidant scavenging ability, (b) ABTS radical scavenging ability of β‐caryophyllene, (c) OH radical scavenging ability, (d) % TBARS, (e) DPPH radical scavenging ability, (f) iron chelation scavenging ability. BCP, β‐caryophyllene. Values represent mean ± standard deviation of triplicate readings. Error bar was constructed using 1 standard deviation from mean. The result in Figure 1 shows the antioxidant activity of β‐caryophyllene and sildenafil citrate. Their antioxidant activity was compared to each other across different assays invitro, as no animals were used.

FIGURE 2

Effect of β‐caryophyllene on antioxidant liver biomarkers of paroxetine‐induced rats. (a) SOD activity, (b) catalase activity, (c) glutathione‐S‐transferase (GST) activity, (d) glutathione peroxidase (GPx) activity, (e) lipid peroxidation activity. Values represent means ± standard deviation of replicate readings (n = 8). Number sign and asterisk indicate significant difference when compared to NC and PD, respectively. p < 0.05 is considered significant.

FIGURE 3

CB2 receptor expression levels in different experimental groups. Values are expressed relative to the normal control group. Error bars represent the standard deviation of the mean (n = 6). Statistical significance was determined at p < 0.05.