[Jiedu Huoxue Decoction improves mitochondrial damage of the prostate in rats with chronic nonbacterial prostatitis].

OBJECTIVE: To explore the possible pathogenesis of chronic nonbacterial prostatitis (CNP) in rats from the perspective of mitochondria, and the interventional effect of Jiedu Huoxue Decoction (JHD) on CNP. METHODS: Forty clean-grade SD male rats were randomly divided into 4 groups of an equal number, sham control, CNP model control, Qianliekang Tablets intervention (QLK) and JHD intervention, those in the former two groups treated intragastrically with normal saline, and those in the latter two with QLK and JHD, respectively, at 2g/kg qd for 30 successive days. Then serum and prostate tissue samples were collected from the rats for calculation of the organ coefficients, HE staining, extraction of mitochondria in the prostate tissue, measurement of the levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-PX) and Na+-K+-ATPase by colorimetric assay, and observation of the ultrastructural changes of the prostatic epithelial cells under the transmission electron microscope (TEM). RESULTS: The organ coefficient of the prostate was significantly higher in the CNP model controls (ï¼»1.95 ± 0.39ï¼½%) than in the sham control (ï¼»1.50 ± 0.42ï¼½%, P < 0.05), QLK (ï¼»1.54 ± 0.32ï¼½%, P < 0.05) and JHD groups (ï¼»1.47 ± 0.53ï¼½%, P < 0.05). TEM showed significant hyperplasia of the interstitial fibrous tissue, glandular structural disorder and inflammatory cell immersion in the CNP model controls, decreased inflammatory cells and reduced hyperplasia of epithelial cells in the acinar and interstitial fibrous tissues in the QLK and JHD groups, but no significant changes in the sham controls. The CNP model controls, compared with the QLK and JHD groups, exhibited remarkably lower levels of SOD (ï¼»17.42 ± 2.91ï¼½ vs ï¼»23.47 ± 5.79ï¼½ and ï¼»22.52 ± 3.88ï¼½ U/mg prot, P < 0.05), GSH-PX (ï¼»38.35 ± 6.98ï¼½ vs ï¼»47.68 ± 10.37ï¼½ and ï¼»89.95 ± 7.65ï¼½ U/mg prot, P < 0.05 or P < 0.01), and Na+-K+-ATPase in the prostatic mitochondria (ï¼»0.98 ± 0.40ï¼½ vs ï¼»1.37 ± 0.29ï¼½ and ï¼»1.85 ± 0.32ï¼½ µmol Pi/mg prot/h, P < 0.05 or P < 0.01), but a higher level of MDA (ï¼»1.70 ± 0.22ï¼½ vs ï¼»0.54 ± 0.14ï¼½ and ï¼»0.59 ± 0.17ï¼½ nmol/mg prot, P < 0.01). Significant mitochondrial damage was observed in the prostate tissue of the CNP model controls, and markedly enhanced mitochondrial autophagy was seen in the JHD group. CONCLUSIONS: Chronic nonbacterial prostatitis induces mitochondrial dysfunction in the prostate of rats, and Jiedu Huoxue Decoction can promote the recovery of mitochondrial function, which may be related to mitochondrial autophagy.

Inhibition potential of UDP-glucuronosyltransferases (Ugts) 1A isoforms by the analogue of resveratrol, bakuchiol.

Bakuchiol is a promising anti-tumor candidate with resveratrol-like structure. The present study aims to evaluate the inhibition potential of bakuchiol towards UDP-glucuronosyltransferases (UGT) 1A isoforms. An in vitro incubation system using 4-methylumbelliferone (4-MU) glucuronidation was used to evaluate the inhibition capability of bakuchiol towards UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9 and 1A10. The glucuronidation of trifluoperazine (TFP) was employed as the probe reaction to determine bakuchiol's inhibition towards UGT1A4. At 1 microM and 10 microM of bakuchiol, no or weak inhibition was observed for all the tested UGT1A isoforms. At 100 microM of bakuchiol, the activity of UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9 and 1A10 was inhibited by -46.2%, 74.7%, 17.8%, 98.7%, 70.4%, 99.2%, 75.8%, and 93.3%, respectively. Further inhibition kinetic behaviour was determined for UGT1A6, 1A8, and 1A10. Both Dixon plot and Lineweaver-Burk plot showed the noncompetitive inhibition of bakuchiol towards all these three UGT isoforms. The inhibition kinetic parameters (Ki) were calculated to be 5.3, 1.8, and 92.6 microM for UGT1A6, 1A8, and 1A10, respectively. In combination with the in vivo exposure of bakuchiol, the high possibility of in vivo inhibition of UGT1A6 and 1A8 was predicted. However, relatively low possibility of in vivo inhibition towards UGT1A10 was predicted due to lower in vivo concentration of bakuchiol than its inhibition parameter (Ki). All these information will be helpful for the R&D of bakuchiol as a promising anti-tumor drug.