First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, BJ 100029, China.
Andrology Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, BJ 100700, China.
Comb Chem High Throughput Screen. 2022;25(9):1474-1487. doi: 10.2174/1386207324666210628105233.
Achyranthis Bidentatae Radix plus Semen Vaccariae are traditional Chinese medicines, which have been widely applied in the treatment of migraine and Erectile Dysfunction (ED) for many years. This study verified the effect of Achyranthis Bidentatae Radix plus Semen Vaccariae in improving migraine-induced ED and explored its potential mechanism.
Key targets and signaling pathways of Achyranthis Bidentatae Radix plus Semen Vaccariae in migraine-induced erectile dysfunction treatment were predicted by network pharmacology. A rat model of migraine was established by nitroglycerin injection. Apomorphine was injected into rats to screen the migraine-induced erectile dysfunction model, Achyranthis Bidentatae Radix-Semen Vaccariae granule suspension administered, and erectile function evaluated. Hematoxylin and eosin staining was used to compare the histological structure of the penile tissue, while RT-qPCR and Western blotting were used to determine mRNA and protein levels, respectively.
Screening allowed us to identify common targets for migraine and ED; the signaling pathway exhibiting the greatest change was the Myosin light chain kinase- Calcium (MLCK-CaM) signal pathway. From Western blotting and RT-qPCR, we found that the levels of MLCK mRNA and protein in rats from Group B rats were significantly higher (P <0.05) than those in Groups A and C. Furthermore, the mRNA and protein levels of CaM were significantly higher in Group B (P <0.05) than in Groups A and C.
Data indicate that the regulatory effects of Achyranthis Bidentatae Radix plus Semen Vaccariae on migraine-induced ED in a rat model are mediated by the MLCK-CaM signaling pathway.
牛膝和蒺藜是传统中药,多年来广泛应用于偏头痛和勃起功能障碍(ED)的治疗。本研究验证了牛膝和蒺藜在改善偏头痛引起的 ED 中的作用,并探讨了其潜在机制。
通过网络药理学预测牛膝和蒺藜治疗偏头痛引起的勃起功能障碍的关键靶点和信号通路。采用硝酸甘油注射建立偏头痛大鼠模型,注射阿扑吗啡筛选偏头痛引起的勃起功能障碍模型,给予牛膝和蒺藜颗粒混悬液,评价勃起功能。苏木精-伊红染色比较阴茎组织的组织学结构,同时采用 RT-qPCR 和 Western blot 分别测定 mRNA 和蛋白水平。
筛选发现了偏头痛和 ED 的共同靶点;变化最大的信号通路是肌球蛋白轻链激酶-钙(MLCK-CaM)信号通路。从 Western blot 和 RT-qPCR 结果来看,B 组大鼠 MLCK mRNA 和蛋白水平明显高于 A 组和 C 组(P<0.05)。此外,B 组 CaM 的 mRNA 和蛋白水平明显高于 A 组和 C 组(P<0.05)。
数据表明,牛膝和蒺藜对偏头痛诱导的 ED 大鼠模型的调节作用是通过 MLCK-CaM 信号通路介导的。