Objective：To investigate the role of 5-HT7 receptor in the pathogenesis of irritable bowel syndrome（IBS）. Methods：Rat model of D-IBS was established by intracolonic instillation of acetic acid and restraint stress...Objective：To investigate the role of 5-HT7 receptor in the pathogenesis of irritable bowel syndrome（IBS）. Methods：Rat model of D-IBS was established by intracolonic instillation of acetic acid and restraint stress; Rat model of C-IBS was established by stomach irrigated with 0-4℃ cool water daily for 14 d. The content and distribution of 5-HT7 receptor at the brain and bowel was examined by immunohistochemistry and the expression of 5-HT7 receptor mRNA was detected by fluorescence quantitative RT-PCR（Real-time PCR）. Results：Immunocytochemistry result showed the 5-HT7 rceptor positive staining at hippocampus and hypothalamus of both C-IBS and D-IBS group was stronger than that of control group（P 〈 0.01）. The 5-HT7R expression at ileum, proximate colon, distal colon of C-IBS group was significantly stronger than that of control group（P 〈 0.05）. Realtime-PCR analysis results showed the expression level of 5-HT7 receptor at hippocampus and hypothalamus of both C-IBS and D-IBS group was increased than that of control group（P〈 0.05）. At proximal and distal colon of C-IBS group, the 5-HT7 receptor mRNA expression was increased compared with control group（P〈 0.05）. Conclusion：The up-regulated expression of 5-HT7 receptor at brain and colon may play an important role in the pathogenesis of C-IBS.展开更多
Dihydrotestosterone (DHT) is implicated in the development of benign prostate hyperplasia (BPH). We investigated if Uromedic? pumpkin (variety of Cucurbita pepo L. convar. citrullinina GREB. var. styriaca GREB) seed s...Dihydrotestosterone (DHT) is implicated in the development of benign prostate hyperplasia (BPH). We investigated if Uromedic? pumpkin (variety of Cucurbita pepo L. convar. citrullinina GREB. var. styriaca GREB) seed soft extract (active ingredients of GRANUFINK? Prosta forte 500 mg), seed oil and isolated Δ7-sterols could inhibit the conversion of [1,2,6,7-3H(N)]-testosterone to DHT by 5α-reductases. Also, we tested competition with [3H]-DHT for binding to the androgen receptor (AR). Pumpkin seed oil and pumpkin seed soft extract were identified as moderately active inhibitors of 5α-R1 and 5α-R2, with almost similar inhibitory capacities (IC50 5 mg/ml for 5α-R1 and about IC50 = 6 mg/ml for 5α-R2). The isolated Δ7-sterols were more active inhibitors (IC50 = 0.3 mg/ml for 5α-R1, IC50 = 1.0 mg/ml for 5α-R2). All three test compounds bound to the AR dose-dependently, with strong binding by Δ7-sterols (IC50 = 0.2 mg/ml) and weaker binding by pumpkin seed oil (IC50 = 0.4 mg/ml) and pumpkin seed soft extract (IC50 = 1.1 mg/ml). We propose that inhibition of 5α-reductases and competitive binding to the AR are mechanisms of action, by which the Uromedic? pumpkin seed derived test compounds, most specifically Δ7-sterols, counteract DHT and thereby exert clinically positive effects on the prostate, as well as bladder-strengthening effects.展开更多
基金This study was supported by grants from the the National Natural Science Foundation of China(No.30170414)
文摘Objective：To investigate the role of 5-HT7 receptor in the pathogenesis of irritable bowel syndrome（IBS）. Methods：Rat model of D-IBS was established by intracolonic instillation of acetic acid and restraint stress; Rat model of C-IBS was established by stomach irrigated with 0-4℃ cool water daily for 14 d. The content and distribution of 5-HT7 receptor at the brain and bowel was examined by immunohistochemistry and the expression of 5-HT7 receptor mRNA was detected by fluorescence quantitative RT-PCR（Real-time PCR）. Results：Immunocytochemistry result showed the 5-HT7 rceptor positive staining at hippocampus and hypothalamus of both C-IBS and D-IBS group was stronger than that of control group（P 〈 0.01）. The 5-HT7R expression at ileum, proximate colon, distal colon of C-IBS group was significantly stronger than that of control group（P 〈 0.05）. Realtime-PCR analysis results showed the expression level of 5-HT7 receptor at hippocampus and hypothalamus of both C-IBS and D-IBS group was increased than that of control group（P〈 0.05）. At proximal and distal colon of C-IBS group, the 5-HT7 receptor mRNA expression was increased compared with control group（P〈 0.05）. Conclusion：The up-regulated expression of 5-HT7 receptor at brain and colon may play an important role in the pathogenesis of C-IBS.
文摘Dihydrotestosterone (DHT) is implicated in the development of benign prostate hyperplasia (BPH). We investigated if Uromedic? pumpkin (variety of Cucurbita pepo L. convar. citrullinina GREB. var. styriaca GREB) seed soft extract (active ingredients of GRANUFINK? Prosta forte 500 mg), seed oil and isolated Δ7-sterols could inhibit the conversion of [1,2,6,7-3H(N)]-testosterone to DHT by 5α-reductases. Also, we tested competition with [3H]-DHT for binding to the androgen receptor (AR). Pumpkin seed oil and pumpkin seed soft extract were identified as moderately active inhibitors of 5α-R1 and 5α-R2, with almost similar inhibitory capacities (IC50 5 mg/ml for 5α-R1 and about IC50 = 6 mg/ml for 5α-R2). The isolated Δ7-sterols were more active inhibitors (IC50 = 0.3 mg/ml for 5α-R1, IC50 = 1.0 mg/ml for 5α-R2). All three test compounds bound to the AR dose-dependently, with strong binding by Δ7-sterols (IC50 = 0.2 mg/ml) and weaker binding by pumpkin seed oil (IC50 = 0.4 mg/ml) and pumpkin seed soft extract (IC50 = 1.1 mg/ml). We propose that inhibition of 5α-reductases and competitive binding to the AR are mechanisms of action, by which the Uromedic? pumpkin seed derived test compounds, most specifically Δ7-sterols, counteract DHT and thereby exert clinically positive effects on the prostate, as well as bladder-strengthening effects.
