Cordycepin Attenuates Testosterone-Induced Benign Prostatic Hyperplasia in Rats via Modulation of AMPK and AKT Activation.
Abdulmohsen J AlamoudiSami A AlessiWaleed Yousof RizgAbdulmajeed M JaliAwaji Y SafhiFahad Y SabeiSameer AlshehriKhaled M HosnyAshraf B Abdel-NaimPublished in: Pharmaceutics (2022)
Benign prostatic hyperplasia (BPH) is a disease that commonly affects elderly men. Cordycepin is an adenosine analog with a wide range of pharmacological activities including antiproliferative and prostatic smooth muscle relaxant effects. This study was designed to assess the actions of cordycepin in testosterone-induced BPH in rats. Animals were divided into six treatment groups: control, cordycepin-alone (10 mg/kg), testosterone-alone (3 mg/kg), cordycepin (5 mg/kg) + testosterone, cordycepin (10 mg/kg) + testosterone, and finasteride (0.5 mg/kg) + testosterone. Treatments were continued daily, 5 days a week, for 4 weeks. Cordycepin significantly prevented the increase in prostate weight and prostate index induced by testosterone. This was confirmed by histopathological examinations. Cordycepin antiproliferative activity was further defined by its ability to inhibit cyclin-D1 and proliferating cell nuclear antigen (PCNA) expression. In addition, cordycepin exhibited significant antioxidant properties as proven by the prevention of lipid peroxidation, reduced glutathione diminution, and superoxide dismutase exhaustion. This was paralleled by anti-inflammatory activity as shown by the inhibition of interleukin-6, tumor necrosis factor-α, and nuclear factor-κB expression in prostatic tissues. It also enhanced apoptosis as demonstrated by its ability to enhance and inhibit mRNA expression of Bax and Bcl2, respectively. Western blot analysis indicated that cordycepin augmented phospho-AMP-activated protein kinase (p-AMPK) and inhibited p-AKT expression. Collectively, cordycepin has the ability to prevent testosterone-induced BPH in rats. This is mediated, at least partially, by its antiproliferative, antioxidant, anti-inflammatory, and pro-apoptotic actions in addition to its modulation of AMPK and AKT activation.
Keyphrases
- benign prostatic hyperplasia
- lower urinary tract symptoms
- replacement therapy
- protein kinase
- anti inflammatory
- poor prognosis
- oxidative stress
- smooth muscle
- signaling pathway
- nuclear factor
- diabetic rats
- cell proliferation
- prostate cancer
- rheumatoid arthritis
- skeletal muscle
- randomized controlled trial
- clinical trial
- body mass index
- nitric oxide
- toll like receptor
- weight loss
- endoplasmic reticulum stress
- weight gain
- south africa
- middle aged
- immune response
- hydrogen peroxide
- cell cycle
- single cell
- body weight
- drug induced
- long non coding rna
- community dwelling
- study protocol
- pi k akt