The In Vitro and In Vivo Inhibitory Effect of Combined Extracts of Cervus elaphus Antler, Glycyrrhiza uralensis, and Angelica gigas on Benign Prostatic Hyperplasia

Abstract

Combinations of natural products have a number of benefits. We investigated the inhibitory effect of a combination of 50% ethanol extracts of Cervus elaphus antler (CEE), Glycyrrhiza uralensis (GUE), and Angelica gigas (AGE) on benign prostatic hyperplasia (BPH) using BPH-1 cells and testosterone propionate (TP)-induced BPH rats. The combination, called CGA113, inhibited cell proliferation by decreasing the cell viability of BPH-1 cells up to 72.03% more than the individual extracts. In addition, CGA113 significantly reduced the mRNA expressions of AR and SRD5A2 in BPH-1 cells. Sprague-Dawley rats were subjected to castration surgery to remove endogenous testosterone, and 3 mg/kg testosterone propionate was subcutaneously injected to induce BPH. Subsequently, CGA113 (50 and 200 mg/kg BW/day) was orally administered to the TP-induced BPH rats for 8 weeks. In the CGA113-H group (200 mg/kg of CGA113), the prostate ratio, serum DHT, prostate DHT, and prostate 5α-reductase2 were significantly decreased compared to the BPH group. Histology with H&E staining of the prostate tissue, revealed a reduction in the thickening of the prostate epithelial cells and enlargement of the lumen compared to the BPH group. The mRNA levels of the Bax/Bcl2 ratio in prostate tissue of the CGA113-H group were significantly increased. Overall, the combined extract of CEE, GUE, and AGE, was determined to exert synergistic effects, indicating the potential of the three natural materials as therapeutic agents for alleviation of BPH symptoms.

Cervi Parvum Cornu complex for men with lower urinary tract symptoms: a multicenter, randomized, double-blind, placebo-controlled trial

“…A previous study has confirmed the mechanism and effect of CAG used in this clinical trial through in vitro and in vivo experiments. 13 Cell experiments proved that CAG could decrease the proliferation of human prostatic hyperplasia epithelial cells significantly. On the other hand, in animal experiments, prostatic hyperplasia could be suppressed by increased Bax protein mRNA expression level and Bax/Bcl-2 ratio in prostate tissues induced by CAG.…”

“…17 In a recent animal study, the mRNA expression of Bax protein and the Bax/Bcl2 ratio in the prostate tissue were significantly increased in the Cervi Parvum Cornu complex treatment group used in this study than in the BPH group, suggesting the possible use of Cervi Parvum Cornu complex as a treatment for LUTS caused by BPH. 13 …”

“…The product was manufactured according to Korean Traditional Medicine Standardization Project guidelines on pharmacopuncture. 14 In order to apply the validated efficacy dose from animal experiment 13 to humans, the Human Equivalent Dose conversion factor (rat 0.16) recommended by the FDA was applied. As a result, the optimal effective dosage of 200 mg/kg was converted to 1,920 mg when applied to an adult weighing 60 kg.…”

“…A previous in vitro and in vivo experiment has shown that mRNA expression level of Bax protein in prostate tissue and Bax/Bcl2 ratio are significantly increased in a group treated with CAG ( Cervi Parvum Cornu, Angelicae gigas Nakai, and Glycyrrhizae Uralensis Fischer ) complex compared to those in the placebo group and that the CAG complex could reduce prostate epithelial cell thickening and enlarge lumen, showing its potential for LUTS treatment due to benign prostate hyperplasia (BPH). 13 …”