Effect of Baicalein on Experimental Prostatic Hyperplasia in Rats and Mice

March 2004 Biol. Pharm. Bull. 27(3) 333—337 (2004) 333 Effect of Baicalein on Experimental Prostatic Hyperplasia in Rats and Mice 1) Qing-Long GUO,* Qi-Long DING, and Zhao-Qiu WU Department of Physiology, No. 24 Tong Jia Xiang, China Pharmaceutical University; Nanjing 210009, China. Received August 27, 2003; accepted November 14, 2003 We determined the effect of baicalein on prostatic hyperplasia in experimental animal models. Prostatic hyperplasia was induced by testosterone propionate in mice and castrated rats and by transplantation of homologous strain fetal mice urogenital sinus in mice. With the histopathological examination, the efficacy of baicalein on prostate hyperplasia in experimental animals was evaluated by the activity of serum acid phosphatase (ACP) and the following norm of the prostate gland: the volume, wet weight, wet weight index, dry weight index, DNA contents and prostatic epithelial height and cavity diameter. Results showed that baicalein at doses of 260 and 130 mg/kg administrated intragastrically (i.g.) significantly inhibited prostatic hyperplasia in castrated rats induced by testosterone propionate compared with the negative control group (p,0.01). Baicalein at doses of 520 and 260 mg/kg (i.g.) also significantly inhibited prostatic hyperplasia in mice induced by transplantation of homologous strain fetal mouse urogenital sinus and by testosterone propionate (p,0.01). These results suggested that baicalein has an inhibitory effect on prostatic hyperplasia in experimental animals. Key words Scutellaria baicalensis; baicalein; testosterone propionate; prostatic hyperplasia; animal model Scutellaria baicalensis GEORGI is a traditional Chinese University. The animals were raised in an air-conditioned medicine. Recently there have been broad studies on its room under controlled lighting (12 h lighting/d) and provided chemical components, pharmacological activity, and clinical with food and water at discretion. Animal care and surgery effects on anti-inflammation, anti-allergy, antihypotension, protocols were approved by the Animal Care Committees of diuresis, antibacteria and other bioactivities.2—9) Baicalein is China Pharmaceutical University, and all animals were ap- extracted from Scutellaria baicalensis GEORGI and purified propriately appropriately housed and used in a valid and eth- with a new preparation method. The main components of nically scientific manner. baicalein are flavonoid glycosides-baicalein and wogonin, Effect of Medicine on Prostatic Hyperplasia of Cas- and contents of these two components are more than 50%. trated Rat Induced by Testosterone Propionate Accord- There is no related report about the effect of baicalein on ing to the method of the reference document,10) 60 of a total anti-proliferation of the prostate gland. The present study of 70 male SD rats were castrated. The scrota of the other ten was on the effect of baicalein on treatment of prostatic hyper- rats were just cut open and then sewed up without cutting off plasia in experimental animals. the testicles as the control group. A week after the operation, the 60 rats with their testicles removed were equally divided MATERIALS AND METHODS into the following groups at random: a model group, which was given 0.5% CMC–Na; 3 baicalein groups, which were Reagents Baicalein provided by the Department of Phar- administered (i.g.) 260, 130, and 65 mg/kg, respectively; pos- macology of China Pharmaceutical University was mixed itive control group 1 (Qian Lie Kang, 1000 mg/kg, i.g.); and with 0.5% CMC–Na before use, and the lot number was positive control group 2 (Finasteride, 5 mg/kg, i.g.). The in- 20001010. The extraction technics for baicalein were differ- jection of edible oil was subcutaneously given to rats of the ent from the pre-technics, which applied the extraction and control group, and testosterone propionate was subcuta- then precipitation for the mixed solvent of contain con- neously given to the castrated rats (0.5 mg/0.1 ml per rat) stituents. An application for a patent for the technic is con- each day. The medicines were administered daily for 3 weeks vently pending in P.R. China. Qian Lie Kang (0.5g/tablet) at a dose of 1 ml per 100 g of body weight. Twenty-four was purchased from Kang En Bei Pharmaceutical Co. (Zhe- hours after the last administration, rats were bled to death jiang, China), and had lot numbers of 000921-2 and 020920. from the carotid and the prostate was taken out and weighed. Finasteride (5 mg/tablet) was purchased from Merck Pharma- The volume was measured (by the formula: 1/2(a3b2), ceutical Co. (Hangzhou, China), and had a lot number of where a and b refer to longer and shorter dimension, respec- 205317. Estradiol benzoate (2 mg/ml) was provided by tively) and the weight index obtained. About half of the Shanghai No. 9 Pharmaceutical Factory (Shanghai, China), gland tissue of each rat was fixed in 10% formalin solution and the lot number was 00100105. Testosterone propionate for histopathological examination and measurement of pro- (25 mg/ml) was provided by Shanghai No. 7 Pharmaceutical static epithelial height and cavity diameter (3100). The other Factory with a lot number of 991002773. Contents of the half of the glands was baked in an oven for 24 h to obtain the DNA determining kit and ACP activity determining kit were dry weight index. purchased from Roche. Effect of Medicine on Prostatic Hyperplasia of Mice In- Animals Male SD rats (weighing 150—200 g) and male duced by Transplantation of Homologous Strain Fetal Kunming strains of mice (weighing 25—30 g) were supplied Mouse Urogenital Sinus According to the method re- by the Laboratory Animal Centre of China Pharmaceutical ported previously,11) 100 male mice of the Kunming strain, ∗ To whom correspondence should be addressed. e-mail: [email protected] © 2004 Pharmaceutical Society of Japan 334 Vol. 27, No. 3 weighing 25—30 g, were anaesthetized and aseptically oper- thymus as internal control. ated to implant 3 urogenital sinuses of 16-d embryonic mice Statistical Analysis Data were expressed as mean6S.D. into each side of the prostate gland. Another 20 male mice and statistically compared by double-tail Student’s t test; were sham operated as a control group. The mice were ob- p,0.05 was taken as statistically significant. served for 3 d after operation. Then the 100 mice were equally divided into the following groups at random (20 mice RESULTS per group): the model group, which was given (i.g.) 0.5% CMC–Na; baicalein group 1, 2 and 3, which were adminis- The Effect of Baicalein on Prostatic Hyperplasia of tered (i.g.) 520, 260, 130 mg/kg, respectively; and the posi- Castrated Rat Induced by Testosterone Propionate The tive control group (estradiol benzoate, 15 mg per mouse, 2 result of baicalein on the volume and weight index of times per week, s.c.). The medicines were given i.g. daily for prostate gland showed that when constantly i.g. for 21 d, the 3weeks. Twenty-four hours after the last administration, the volume and weight index of this gland were reduced in cas- mice were killed; the prostate glands of ten mice of each trated prostatic hyperplasia rats in baicalein groups 1 and 2 group were taken out and weighed. The volume was mea- (which were given 260 and 130 mg/kg, respectively), positive sured (by the formulas: 1/2(a3b2), where a and b refer to longer and shorter dimension, respectively) and the weight index was obtained. Then the gland tissues were fixed in a 10% formalin solution for histopathological examination and to measure prostatic epithelial height and cavity diameter (3100). In the measurement, eighty prostatic acinus were se- lected at random. Prostate glands of the other 10 mice were dried in an oven for 24 h to determine the dry weight index. Effect of Medicine on Prostatic Hyperplasia of Mice Induced by Testosterone Propionate According to the method of the reference document,10) 80 male mice weighing 25—30 g were divided into a control group and model groups. Animals of the model groups were s.c. injected with testosterone propionate (0.5 mg per mouse), once a day for 14 d. On day15, 10 of the control and 10 of the model mice were killed, and then volume, weight and DNA content in the prostate glands and the activity of ACP were measured. Ac- cording to the index of the prostate glands and the activity of ACP, testosterone propionate was stopped when the model was successfully set up. Then the 60 mice were equally divided into 6 groups at random: a negative group, which was given 0.5% CMC–Na; baicalein groups 1, 2 and 3, which were given (i.g.) 520, 260 and 130 mg/kg, respectively; positive control group 1 (Qian Lie Kang, 2000 mg/kg, i.g.); and positive control group 2 (Finasteride, 10 mg/kg, i.g.). The medicines were given once a day for 2 weeks. Twenty-four hours after the last i.g., the eyeball blood of mice was extracted to measure the activity of ACP and then the animals were killed instantly by dislocation and prostate glands were taken out and weighed. The volume was measured (by the Fig. 1. The Effect of Baicalein on Prostatic Epithelial Height and Cavity formula: 1/2(a3b2), where a and b refer longer and shorter Diameter in Castrated Prostatic Hyperplasia Rat dimension, respectively) and the wet weight index was deter- A: control group; B: negative model group (0.5% CMC–Na); C: baicalein group (260 mg/kg); D: baicalein (130 mg/kg); E: baicalein (65 mg/kg); F: finasteride group mined. DNA contents of prostate glands were determined by (5 mg/kg); G: Qian Lie Kang (1000 mg/kg).

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