Inhibitory effects of Centella asiatica (L.) Urban on enlarged prostate through androgen receptor and PI3K/Akt signaling pathways.

Centella asiatica (L.) Urban (C. asiatica) is a traditional herbal medicine that has been used for wound healing and anti-inflammation since ancient times. Various biological effects of C. asiatica ethanolic extract (CAE) were previously reported. However, in our previous study, C. asiatica aqueous extract (CAA) exhibited higher inhibitory activity on benign prostatic hyperplasia (BPH) than CAE. Therefore, the aim of this study was to investigate the effect of CAA on BPH, and elucidate the inhibitory mechanism through in vitro and in vivo experiments as well as metabolite analysis of CAA. A BPH rat model was induced by daily subcutaneous injection of testosterone propionate (TP, 3 mg kg-1) dissolved in corn oil for 4 weeks after castration. The experimental group, the CAA treatment group, was orally administered CAA (100 mg kg-1) for 4 weeks while inducing prostatic hyperplasia. Saw palmetto extract (Saw, 100 mg kg-1) and Finasteride (Fi, 1 mg kg-1) were used as positive controls and were administered orally for 4 weeks. CAA significantly inhibited androgen receptor signaling related factors overexpressed by dihydrotestosterone (DHT) treatment in prostate cell lines. Afterwards, the testosterone-induced BPH model was used to verify the alleviation efficacy of CAA in prostatic hyperplasia. Prostate size and the thickness of the prostate tissue epithelium were significantly decreased in the group treated with CAA compared to those in the BPH group. The results of protein expression in the prostate tissue confirmed that CAA inhibited androgen receptor signaling in BPH and decreased the expression of growth factors. Moreover, CAA suppressed the expression of the PI3K/Akt pathway and cell proliferation-related factors compared to the BPH group. Taken together, these results indicate that CAA improves the inhibitory efficacy of BPH by inhibiting the androgen receptor and PI3K/Akt pathways, suggesting that CAA may be a promising candidate for biopharmaceutical formulations of BPH.

Efficacy and Mechanism of Polymerized Anthocyanin from Grape-Skin Extract on High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease.

We investigated the therapeutic potential of polymerized anthocyanin (PA) on a nonalcoholic fatty liver disease (NAFLD) model in mice. C57BL/6 mice were fed a high-fat diet (HFD) for 8 weeks to establish the NAFLD mouse model and randomly divided into four groups: control diet (con), NAFLD mice treated with saline (NAFLD), NAFLD mice treated with PA (PA), and NAFLD mice treated with orlistat (Orlistat) for four weeks. Mice were euthanized at the end of the four weeks. Total cholesterol (TC) and triglyceride (TG) levels were estimated, and pathological changes in the liver, white adipose tissue, and signaling pathways related to lipid metabolism were evaluated. Results revealed that the body, liver, and white fat weight of the NAFLD group was significantly increased compared to that of the con group, while that of the PA group showed significant reduction. NAFLD led to an increase in blood lipids in mice (except for HDL). Conversely, PA effectively reduced TC and LDL-C. Compared to the control group, the degree of steatosis in the mice of PA group was decreased. Moreover, PA also regulated the NAFLD signaling pathway. In agreement with improved lipid deposition, PA supplementation inhibited the activation of inflammatory pathways, depressing oxidative stress through increased antioxidant levels, and increasing ß-oxidation to inhibit mitochondrial dysfunction. Taken together, our results demonstrate that PA can improve the liver function of NAFLD mice, regulating blood lipids, reducing liver-fat accumulation, and regulating lipid metabolism.