Manshor Nurul Maizan, Razali Nadiah, Jusoh Rusdiah Ruzanna, Asmawi Mohd Zaini, Mohamed Nornisah, Zainol Syafinaz, Altaf Rabia, Dewa Aidiahmad
Department of Physiology and Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia.
Department of Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia.
Int J Cardiol Hypertens. 2020 Jan 11;4:100024. doi: 10.1016/j.ijchy.2020.100024. eCollection 2020 Mar.
has been reported to possess activities including antioxidant, anti-aging and anti-cancer but there is no report on its vasorelaxant effects.
This study aims to fractionate water extract of , identify the compound(s) involved and elucidate the possible mechanism(s) of its vasorelaxant effects.
Water extract of was subjected to liquid-liquid extraction to obtain ethyl acetate, n-butanol and water fractions. In SHR aortic ring preparations, water fraction (WF-LPWE) was established as the most potent fraction for vasorelaxation. The pharmacological mechanisms of the vasorelaxant effect of WF-LPWE were investigated with and without the presence of various inhibitors. The cumulative dose-response curves of potassium chloride (KCl)-induced contractions were conducted to study the possible mechanisms of WF-LPWE in reducing vasoconstriction.
WF-LPWE produced dose-dependent vasorelaxant effect in endothelium-denuded aortic ring and showed non-competitive inhibition of dose-response curves of PE-induced contraction, and at its higher concentrations reduced KCl-induced contraction. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) significantly inhibited vasorelaxant effect of WF-LPWE. WF-LPWE significantly reduced the release of intracellular calcium ion (Ca) from the intracellular stores and suppressed the calcium chloride (CaCal)-induced contraction. N-nitro-L-arginine methyl ester (L-NAME), methylene blue, indomethacin and atropine did not influence the vasorelaxant effects of WF-LPWE.
WF-LPWE exerts its vasorelaxant effect independently of endothelium and possibly by inhibiting the release of calcium from intracellular calcium stores, receptor-operated calcium channels and formation of inositol 1,4,5- triphosphate. WF-LPWE vasorelaxant effect may also mediated via nitric oxide-independent direct involvement of soluble guanylate cyclase (sGC)/ cyclic guanosine monophosphate (cGMP) pathways.
据报道，[提取物名称未给出]具有抗氧化、抗衰老和抗癌等活性，但尚无关于其血管舒张作用的报道。
本研究旨在对[提取物名称未给出]的水提取物进行分离，鉴定其中的化合物，并阐明其血管舒张作用的可能机制。
对[提取物名称未给出]的水提取物进行液-液萃取，得到乙酸乙酯、正丁醇和水相部分。在自发性高血压大鼠（SHR）主动脉环标本中，水相部分（WF-LPWE）被确定为血管舒张作用最强的部分。在有无各种抑制剂存在的情况下，研究WF-LPWE血管舒张作用的药理机制。进行氯化钾（KCl）诱导收缩的累积剂量-反应曲线实验，以研究WF-LPWE减轻血管收缩的可能机制。
WF-LPWE在去内皮的主动脉环中产生剂量依赖性血管舒张作用，对苯肾上腺素（PE）诱导收缩的剂量-反应曲线表现为非竞争性抑制，且在较高浓度下可降低KCl诱导的收缩。1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ）显著抑制WF-LPWE的血管舒张作用。WF-LPWE显著减少细胞内钙库中细胞内钙离子（Ca）的释放，并抑制氯化钙（CaCal）诱导的收缩。N-硝基-L-精氨酸甲酯（L-NAME）、亚甲蓝、吲哚美辛和阿托品均不影响WF-LPWE的血管舒张作用。
WF-LPWE的血管舒张作用不依赖于内皮，可能是通过抑制细胞内钙库中钙的释放、受体操纵性钙通道以及肌醇1,4,5-三磷酸的形成来实现的。WF-LPWE的血管舒张作用也可能通过可溶性鸟苷酸环化酶（sGC）/环磷酸鸟苷（cGMP）途径的一氧化氮非依赖性直接参与来介导。
