Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung County 90741, Taiwan.
Am J Chin Med. 2009;37(6):1045-58. doi: 10.1142/S0192415X0900748X.
We previously reported that the leaf extract of Muntingia calabura L. (Tiliaceae) exerts a potent hypotensive effect in the normotensive rats. The antihypertensive activity of this plant extract, however, is currently unknown. In the present study, we investigated the antihypertensive effects of the n-butanol soluble fraction (BSF) from methanol leaf extract of M. calabura in spontaneously hypertensive rats (SHR), and delineated is underlying mechanisms. The intravenous bolus administration of the BSF (10-100 mg/kg) of M. calabura produced biphasic dose-related antihypertensive and bradycardiac effects in SHR. The BSF-induced initial cardiovascular depressive effects lasted for 10 min, and the delayed effects commenced 40 min and lasted for at least 120 min postinjection. These cardiovascular depressive effects of BSF treatments were greater in SHR than in normotensive Wistar-Kyoto (WKY) rats. Both the initial and delayed antihypertensive and bradycardiac effects of BSF (25 mg/kg, i.v.) in SHR, were significantly blocked by pretreatment with a nonselective nitric oxide (NO) synthase (NOS) inhibitor, a soluble guanylyl cyclase (sGC) inhibitor, or a protein kinase G (PKG) inhibitor. Moreover, the initial effects of BSF in SHR were inhibited by pretreatment with a selective endothelial NOS (eNOS) inhibitor; whereas the delayed effects were attenuated by a selective inducible NOS (iNOS) inhibitor. These results indicate that the BSF from the leaf of M. calabura elicited both transient and delayed antihypertensive and bradycardiac actions in SHR, which might be mediated through NO generated respectively by eNOS and iNOS. Furthermore, activation of sGC/cGMP/PKG signaling pathway may participate in the M. calabura-induced biphasic cardiovascular effects.
我们之前报道过山芝麻（锦葵科）叶提取物对正常血压大鼠具有显著的降压作用。然而，该植物提取物的降压活性目前尚不清楚。在本研究中，我们研究了山芝麻甲醇叶提取物正丁醇可溶部分（BSF）在自发性高血压大鼠（SHR）中的降压作用，并阐明了其潜在机制。BSF（10-100mg/kg，静脉内推注）呈双相剂量依赖性降低 SHR 的血压和心率。BSF 引起的初始心血管抑制作用持续 10 分钟，延迟作用于给药后 40 分钟开始，并持续至少 120 分钟。BSF 处理对 SHR 的心血管抑制作用强于对正常血压 Wistar-Kyoto（WKY）大鼠的抑制作用。BSF（25mg/kg，静脉内）对 SHR 的初始和延迟降压及心率减慢作用均被非选择性一氧化氮合酶（NOS）抑制剂、可溶性鸟苷酸环化酶（sGC）抑制剂或蛋白激酶 G（PKG）抑制剂预处理所阻断。此外，BSF 对 SHR 的初始作用被选择性内皮型 NOS（eNOS）抑制剂所抑制；而延迟作用则被选择性诱导型 NOS（iNOS）抑制剂减弱。这些结果表明，山芝麻叶的 BSF 诱发了 SHR 的短暂和延迟降压及心率减慢作用，这可能是由 eNOS 和 iNOS 分别产生的 NO 介导的。此外，sGC/cGMP/PKG 信号通路的激活可能参与了山芝麻引起的双相心血管作用。
