Key Laboratory of Standardization of Chinese Herbal Medicines of the Ministry of Education, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611173, PR China.
TCM Qi&Blood Functional Laboratory, College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611173, PR China.
J Ethnopharmacol. 2018 Jun 28;220:188-196. doi: 10.1016/j.jep.2017.09.036. Epub 2017 Sep 28.
The aerial parts of Pogostemon cablin (Blanco) Benth. for the treatment of cardiodynia have been documented in Mingyi Bielu of late Han Dynasty, in addition to that the Ca antagonized activities of P. cablin and its critically pharmacological ingredient patchouli alcohol (PA) were reported previously.
To investigate the relaxant effects of PA on rat isolated thoracic aortas and further explore its potential mechanisms of actions.
The aortas with endothelium and without endothelium were prepared and suspended in the organ bath for isometric tension recordings. The responses to accumulative concentrations of PA in endothelium-intact (E + ) aortas with basal tension and in different treated aortas pre-contracted with potassium chloride (KCl) or phenylephrine (PHE) were observed; the effects of L-NAME and indomethacin in aortas with intact endothelium, and of L-NAME, propranolol, tetraethtylamine (TEA), 4-aminopyridine (4-AP), barium chloride (BaCl), glyburide in aortas with endothelial denudation on PA-produced vasorelaxation were assessed; the influences of PA on extracellular Ca influx and intracellular Ca release were measured in Ca-free medium. Finally, the abilities of PA to inhibit KCl- and PHE-induced contractions were compared to that of verapamil in E- aortas.
PA produced vasorelaxant effects in KCl- and PHE-precontracted E + aortas in a concentration-dependent manner, which had no statistically different from that in KCl- and PHE-precontracted E- aortas. PA (10 μM) significantly reduced KCl-induced contractions while PHE-induced contractions were significantly reduced by 100 μM of PA instead of 10 μM and 30 μM in aortas with endothelium. Pre-incubation of E + aortas with L-NAME as well as indomethacin and of E- aortas with L-NAME, propranolol, TEA, 4-AP, BaCl and glyburide had no obvious effects on vasorelaxation of PA. In endothelium-removed aortas around Ca-free solution, PA remarkably lowered the contractions stimulated with Ca and PHE, and application of ruthenium red and heparin further enhanced the abilities of PA to reduce PHE-caused contractions. In aortas without endothelium, 100 μM of PA markedly attenuated KCl-induced contractions but not affect PHE-induced contractions. Verapamil at the equal dose markedly attenuated KCl- and PHE-induced contractions, and the inhibitory effects on KCl-induced contractions were more forceful than that on PHE-induced contractions. In combined usage, the inhibitory effects on the contractions elicited by KCl were evidently weaker than that of verapamil alone and indifferently stronger than that of PA alone, and the inhibitory effects on the contractions elicited by PHE were evidently weaker than that of single verapamil but stronger than that of single PA.
PA may act as a Ca antagonist to exert an intensively vasorelaxant effects through endothelium-independent pathway, and its mechanisms underlying the vasoactivities seem to be associated with the blockade of extracellular Ca influx through VDCCs and ROCCs in vascular smooth muscle cells (VSMCs) membrane and intracellular Ca releases through IPR- and RYR-mediated Ca channels in sarcolemma.
在汉代末期的《名医别录》中，就有记载将唇形科植物普济（白花丹）的地上部分用于治疗心痛。此外，先前曾报道过，钙离子拮抗剂可拮抗普济及其关键药效成分广藿香醇（PA）的作用。
研究 PA 对大鼠离体胸主动脉的舒张作用，并进一步探讨其潜在的作用机制。
制备有内皮和无内皮的主动脉，并将其悬挂在器官浴中进行等长张力记录。观察累积浓度的 PA 对基础张力状态下有内皮完整（E+）主动脉和不同浓度氯化钾（KCl）或苯肾上腺素（PHE）预收缩主动脉的舒张作用；观察 L-NAME 和吲哚美辛对内皮完整主动脉的作用，以及 L-NAME、心得安、四乙铵（TEA）、4-氨基吡啶（4-AP）、氯化钡（BaCl）、格列本脲对内皮去极化主动脉中 PA 引起的血管舒张作用；测量 PA 在无钙介质中对细胞外钙内流和细胞内钙释放的影响。最后，比较 PA 抑制 KCl 和 PHE 诱导收缩的能力与维拉帕米在 E 主动脉中的作用。
PA 以浓度依赖性方式对 KCl 和 PHE 预收缩的 E+主动脉产生舒张作用，其作用与 KCl 和 PHE 预收缩的 E-主动脉无统计学差异。PA（10 μM）显著降低 KCl 诱导的收缩，而 100 μM 的 PA 可显著降低 PHE 诱导的收缩，而非 10 μM 和 30 μM 的 PA 则可降低 E 主动脉的收缩。E+主动脉预先孵育 L-NAME 以及吲哚美辛，E-主动脉预先孵育 L-NAME、心得安、TEA、4-AP、BaCl 和格列本脲，对 PA 引起的血管舒张均无明显影响。在去除内皮的主动脉中，PA 明显降低了由 Ca 和 PHE 刺激引起的收缩，而钌红和肝素的应用进一步增强了 PA 降低 PHE 引起的收缩的能力。在没有内皮的主动脉中，100 μM 的 PA 显著减弱了 KCl 诱导的收缩，但不影响 PHE 诱导的收缩。等剂量的维拉帕米明显减弱了 KCl 和 PHE 诱导的收缩，对 KCl 诱导的收缩的抑制作用比 PHE 诱导的收缩更强。联合使用时，KCl 诱导的收缩的抑制作用明显弱于单独使用维拉帕米，与单独使用 PA 的抑制作用无差异，且强于单独使用 PA。
PA 可能作为一种钙拮抗剂，通过非内皮依赖途径发挥强烈的血管舒张作用，其血管活性的机制似乎与 VDCCs 和 ROCCs 介导的细胞外钙内流以及肌浆网内钙释放通过 IPR 和 RYR 介导的钙通道有关。
