Syed Anees A, Lahiri Shibani, Mohan Divya, Valicherla Guru R, Gupta Anand P, Riyazuddin Mohammed, Kumar Sudhir, Maurya Rakesh, Hanif Kashif, Gayen Jiaur R
Division of Pharmacokinetics & Metabolism, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226031, India.
Division of Pharmacology, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226031, India.
J Ethnopharmacol. 2016 Dec 4;193:555-565. doi: 10.1016/j.jep.2016.10.008. Epub 2016 Oct 5.
Ulmus wallichiana Planchon (Himalayan Elm), a traditional medicinal plant, used in fracture healing in folk tradition of Uttarakhand, Himalaya, India. It is also used as diuretic. U. rhynchophylla, native to China, known as Gou Teng in Chinese medicine, is used for hypertension (WHO). U. macrocarpa has antihypertensive and vasorelaxant activity. However, no detailed studies related to hypertension have been reported previously, so we have explored the antihypertensive activity of U. wallichiana.
To investigate the pharmacological effect of ethanolic extract (EE) and butanolic fraction (BF) of U. wallichiana in hypertensive rats.
SHR, DOCA-salt- and L-NAME-induced hypertension models were used. Treatment was performed by oral administration of EE and BF of U. wallichiana (500mg/kg/day and 50mg/kg/day) for 14 days. Then blood pressure was measured by non-invasive blood pressure (NIBP) measurement technique. Invasive blood pressure (IBP) was also reported to support the NIBP data. Concentrations of plasma renin, angiotensin II (Ang II), nitrate/nitrite (NO), cGMP were estimated. Angiotensin-converting enzyme (ACE) activity and ROS activity were also estimated.
Blood pressure was significantly higher in SHR as compared to normotensive wistar group (170.59±0.83mmHg vs 121.54±1.24mmHg, respectively). SBP was increased in DOCA-salt induced group compared to their control (132.77±3.90mmHg vs 107.85±5.95mmHg, respectively) and L-NAME-induced group compared to their control (168.55±5.07mmHg vs 113.03±4.13mmHg, respectively). The treatment of extract and fraction of U. wallichiana significantly decreased the blood pressure in SHR+EE (151.26±1.85mmHg, p<0.001), SHR+BF (140.44±1.16mmHg, p<0.001); DOCA+EE (113.43±5.44mmHg, p<0.05), DOCA+BF (105.09±5.12mmHg, p<0.05) and L-NAME+EE (119.76±4.39mmHg, p<0.001), L-NAME+BF (117.50±7.27mmHg, p<0.001) compared to their respective diseased control groups. The plasma renin, Ang II and ACE activity were also significantly decreased and augmented the NO and cGMP levels. It also down regulated the expression of Renin, ACE, NOS3 and TGF-β1 at mRNA levels.
The EE and BF probably reducing the BP via Renin-angiotensin-aldosterone system and NO/cGMP signaling pathway. The decrease in blood pressure may be due to presence of quercetin analogue flavonoids (2S,3S)-(+)-3',4',5,7-tetrahydroxydihydroflavonol-6-C-β-D-glucopyranoside; 6-Glucopyranosyl-3,3',4',5,7-pentahydroxyflavone; 6-Glucopyranosyl-4',5,7-trihydroxyflavanone and (2S,3S)-(+)-4',5,7-trihydroxydihydroflavonol-6-C-β-D-glucopyranoside, may be due to its antioxidant activity. Thus EE and BF of U. wallichiana found to have the potential ability to be used as herbal medicament to treat hypertension.
印度喜马拉雅地区北阿坎德邦民间传统中用于促进骨折愈合的传统药用植物喜马拉雅榆（Ulmus wallichiana Planchon），也用作利尿剂。原产于中国的钩藤（U. rhynchophylla），在中药中称为钩藤，用于治疗高血压（世界卫生组织）。大果榆（U. macrocarpa）具有抗高血压和血管舒张活性。然而，此前尚未有与高血压相关的详细研究报道，因此我们对喜马拉雅榆的抗高血压活性进行了探索。
研究喜马拉雅榆乙醇提取物（EE）和正丁醇部位（BF）对高血压大鼠的药理作用。
使用自发性高血压大鼠（SHR）、去氧皮质酮盐（DOCA）-盐和左旋硝基精氨酸甲酯（L-NAME）诱导的高血压模型。通过口服给予喜马拉雅榆的EE和BF（500mg/kg/天和50mg/kg/天）进行治疗，持续14天。然后采用无创血压（NIBP）测量技术测量血压。还报告了有创血压（IBP）以支持NIBP数据。测定血浆肾素、血管紧张素II（Ang II）、硝酸盐/亚硝酸盐（NO）、环磷酸鸟苷（cGMP）的浓度。还测定了血管紧张素转换酶（ACE）活性和活性氧（ROS）活性。
与正常血压的Wistar组相比，SHR的血压显著更高（分别为170.59±0.83mmHg和121.54±1.24mmHg）。与各自的对照组相比，DOCA-盐诱导组的收缩压升高（分别为132.77±3.90mmHg和107.85±5.95mmHg），L-NAME诱导组的收缩压升高（分别为168.55±5.07mmHg和113.03±4.13mmHg）。喜马拉雅榆提取物和部位的治疗显著降低了SHR+EE组（151.26±1.85mmHg，p<0.001）、SHR+BF组（140.44±1.16mmHg，p<0.001）；DOCA+EE组（113.43±5.44mmHg，p<0.05）、DOCA+BF组（105.09±5.12mmHg，p<0.05）以及L-NAME+EE组（119.76±4.39mmHg，p<0.001）、L-NAME+BF组（117.50±7.27mmHg，p<0.001）相对于各自疾病对照组的血压。血浆肾素、Ang II和ACE活性也显著降低，NO和cGMP水平升高。它还在mRNA水平下调了肾素、ACE、一氧化氮合酶3（NOS3）和转化生长因子-β1（TGF-β1）的表达。
EE和BF可能通过肾素-血管紧张素-醛固酮系统和NO/cGMP信号通路降低血压。血压降低可能归因于槲皮素类似物黄酮类化合物（2S,3S）-(+)-3',4',5,7-四羟基二氢黄酮醇-6-C-β-D-葡萄糖苷；6-葡萄糖吡喃糖基-3,3',4',5,7-五羟基黄酮；6-葡萄糖吡喃糖基-4',5,7-三羟基黄烷酮和（2S,3S）-(+)-4',5,7-三羟基二氢黄酮醇-6-C-β-D-葡萄糖苷的存在，可能是由于其抗氧化活性。因此，喜马拉雅榆的EE和BF被发现具有用作治疗高血压草药药物的潜在能力。
