Endogenous Sphingolipid Signaling Pathway Implicated in the Action of Croton membranaceus on the Prostate Gland in BPH Patients.

Background: Croton membranaceus extract has apoptotic effects on BPH-1 cells. This study determined if the apoptotic effects were created through the ceramide pathway. Methods: The study was a follow-up to a previous observational study of 30 histologically confirmed patients with benign prostatic hyperplasia (BPH) who were on C. membranaceus ethanolic extract at 20 mg t.i.d orally for 3 mo. Thereafter, total and free prostate-specific antigen (PSA), lipid profile plus Apo lipoprotein A and B, ceramide/Sphingophospho-kinase 1 (SphK1) and 2 (SphK2), sphingosine lyase (SPL), the cytotoxic adducts of oxidative stress 4-hydroxy-2-nonenal (4HNE) and malondialdehyde (MDA), were determined. Results: Total and free PSA were significantly (p < 0.05) different after treatment. Apo lipoprotein A was significantly different (p = 0.024). The SphK1/SphK2 ratio reduced significantly (p = 0.049). Furthermore, SPL, ceramide, and MDA increased significantly after treatment (p = 0.05, p = 0.004, and p = 0.007, respectively). A weak positive correlation was found between high-density lipoprotein (HDL) cholesterol and SphK1, and HDL and ceramide before treatment (p = 0.036, r = 0.3826; p = 0.018, r = 0.4286, respectively. Conclusions:C. membranaceus uses the ceramide pathway by modulating the SphK1/SphK2 ratio and increasing SPL to generate oxidative stress and consequently apoptosis.

The role of sex steroid hormones in benign prostatic hyperplasia.

INTRODUCTION: The etiology of benign prostatic hyperplasia (BPH) remains a mystery to scientists; estrogen/androgen imbalance in aged men has been implicated. METHODS: Thirty (30) apparently healthy men and newly diagnosed BPH patients were recruited from the Ghana Police Hospital. Lower urinary tract syndrome (LUTS) and prostate volume were assessed via the prostate symptom score sheet (IPSS) and abdominopelvic scan, respectively. Laboratory assays for total prostate specific antigen (tPSA) and hormones [androstenedione (AED), testosterone (T), dihydrotestosterone (DHT), androstanedioladiol (3α-adiol), androstanediol (3ß-diol), estrone (E1) and estradiol (E2)] were performed via ELISA techniques. Non-parametric analyses were employed. p < 0.05 was considered significant. RESULTS: AED was significantly higher in controls compared to the BPH patients. AKRIC2 (3α-diol/DHT) was significantly higher in the BPH group (p < 0.001) whiles AKRIC1 (3ß-diol/DHT) was significantly lower. Estradiol was significantly higher in BPH (p= 0.029). Age correlated negatively with T, while a negative correlation was observed between TIPSS and 3ß-diol and AKRIC1. Also, prostate volume correlated negatively with fT.tPSA correlated positively with E2 and aromatase activity (E2/T) and negatively with fT. On multiple linear regression, DHT and 3ß-diol remained independent predictors for TIPSS and fT for tPSA. CONCLUSION: Estrogens and androstanediols seem to play a role in BPH development.

Shrinkage of Prostate and Improved Quality of Life: Management of BPH Patients with Croton membranaceus Ethanolic Root Extract.

Benign prostatic hyperplasia (BPH) is an enlargement of the prostate. The study aimed at validating the use of freeze-dried Croton membranaceus ethanolic root extract for BPH management. Thirty-three patients were observed before and after 3-month administration of 20 mg t.i.d orally. The International Prostate Symptom Score (IPSS), and the International Index of Erectile Function (IIEF) questionnaires were used. Total/free PSA (tPSA, fPSA), renal, liver function, lipid tests, and ultrasonographic imaging were performed. Thirty (30) patients (66 ± 11 years) completed the study. IPSS results showed 37% had severe, 40% moderate, and 23% mild symptoms before; 57% and 43% had moderate and mild symptoms, respectively, after treatment. IIED of patients' results showed 30% with severe, 40% moderate, 24% mild-moderate, 3% mild, and 3% no erectile dysfunction before treatment and 20% severe, 43% moderate, and 37% mild-moderate dysfunction, after treatment. Quality of life (QoL) improved (P = 0.001). Significant but non-pathological increases in total and indirect bilirubin as well as apolipoprotein A occurred. Mean tPSA reduced from 27.9 ± 19.0 to 16.2 ± 11.8 ng/mL (P = 0.002); fPSA from 6.1 ± 4.8 to 3.9 ± 2.9 ng/mL (P = 0.045); and prostate volume from 101.8 ± 41.3 to 54.5 ± 24.8 cm(3) (P = 0.023). C. membranaceus shrinks the prostate and improves QoL.