特殊製備之高麗紅參萃取物透過組織接受器拮抗作用舒張離體大白兔陰莖海綿組織並有效提升海綿體內壓

Special Processed Panax Ginseng (SPPG) Relaxes Isolated Rabbit Corpus Cavernosum through Histamine Antagonized Property and with a Beneficial Effect in Raising Intracavernous Pressure

特殊製備之高麗紅參萃取物（SPPG）呈現濃度相關性地舒張phenylephrine 預收縮的大白兔陰莖海綿組織（一半有效劑量 = 0.39 ± 0.06 mg/ml），而且活性大於人參總皂　（一半有效劑量=1.33 ± 0.09 mg/ml）。以高效能層析儀分析並配合市售之七種皂　標準品檢定，發現SPPG 主要含Rg1、Rf、及Rc（約分別佔65、20、及2.5%），但並不含已知的Rb1、Rb2、Rd 及Re 四種主要皂　。進一步衣上述比例製備Rg1 + Rf + Rc 的混合物重新評估海綿體舒張活性，發現並無法引發與SPPG 相等、且有效的舒張反應，暗示參與SPPG 舒張陰莖海綿體的作用可能並不是上述七種主要的人參皂　。此外，不論是去除海綿體血管內膜或是處理一氧化氮合成　抑制劑，皆不影響SPPG 的舒張活性。另一方面，組織　（histamine）可以收縮陰莖海綿組織，而且此收縮反應可同時被H1-接受器拮抗劑triprolidine 及SPPG 所抑制。注射不同劑量SPPG （0.5, 1, 2, 及4毫克/公斤）至麻醉大白兔，可有效使海綿體內壓由基準值（13.7 ± 4.3 毫米汞柱）分別上升至19.2± 5.4, 34.6 ± 4.2，以及46.7 ± 8.2 毫米汞柱的最高值，且陰莖腫脹期間也可持續20~90 分鐘。以上結果顯示由非主要人參皂　參與SPPG 的海綿體舒張作用，並透過內膜非依賴性、以及一部份的組織　H1-接受器拮抗作用來產生舒張活性。而SPPG 可升高海綿體內壓的活性暗示其可能可以應用在治療勃起功能障礙。The in vitro and in vivo effects of special processed Panax ginseng (SPPG) in rabbit corpus cavernosum were investigated. SPPG induced a concentration-dependent relaxation in phenylephrine-precontracted cavernosal strips with an EC50 of 0.39 ± 0.06 mg/ml and turned out to be more potent than total ginsenosides (1.33 ± 0.09 mg/ml). Comparison the HPLC profile of SPPG with 7 major ginsenoside standards indicated that Rg1, Rf and Rc, with a percentage of 65, 20, and 2.5%, respectively, were the predominant component and pre-cluding the involvement of Rb1, Rb2, Rd, and Re. The corporal relaxation of SPPG may be mediated by component(s) in addition to Rg1/Rf/Rc because a reconstituted mixture did not mimic the potent relaxant effect of SPPG. Neither endothelial removal nor L-NAME treatment affect SPPG-induced relaxation. Histamine (10-8-10-4 M) produced concentration-dependent contraction of cavernosal strips. The contractile response to histamine was progressively suppressed both by H1-receptor antagonist triprolidine and by SPPG (1, 2 and 4 mg/ml). On the other hand, SPPG-induced relaxation of phenylephrine-precontracted cavernosal strips was not attenuated by H2 receptor antagonist cimetidine. Intracavernous (IC) injection of SPPG (0.5, 1, 2 and 4 mg/ml) to anesthetized rabbits, rose the IC pressure from basal (13.7 ± 4.2 mmHg) to19.2 ± 5.4, 34.6 ± 4.2, and 46.7 ± 8.2 mmHg, respectively and prolonged the duration of tumescence ranged from 20 to 90 min. These finding indicate that non-major ginsenosides contribute to the beneficial corporal relaxant effect of SPPG, which is attributable to an endothelium-independent properties possibly link to antagonizing the H1 receptor in the cavernosal smooth muscle. Furthermore, the in vivo effects of SPPG may implicate a potential for the treatment of erectile dysfunction.