Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (9): 1009-1017.doi: 10.3736/jcim20120910

Previous Articles     Next Articles

Effects of extracts of Radix Scrophulariae on blood pressure in spontaneously hypertensive rats and the underlying mechanisms

Chan Chen1(), Chang-xun Chen1, Xi-min Wu2, Rui Wang2, Yi-ming Li2   

  1. 1. Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    2. Department of Natural Product Chemistry, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2012-02-09 Accepted:2012-02-28 Online:2012-09-20 Published:2018-10-15
  • Contact: Chan Chen E-mail:chenchantwins@hotmail.com

Objective: To explore the effects of extracts of Radix Scrophulariae (ERS) on blood pressure, vasoconstrictors and morphology of artery in spontaneously hypertensive rats (SHRs).

Methods: Fifty SHRs were randomly divided into SHR, SHR plus 40 mg/kg of captopril, SHR plus 70 mg/kg of ERS, SHR plus 140 mg/kg of ERS and SHR plus 280 mg/kg of ERS groups. Wistar-Kyoto (WKY) rats were randomly divided into two groups, namely, WKY and WKY plus 140 mg/kg of ERS groups. The rats were orally administered with the corresponding drugs or drinking water once a day for 20 weeks. The blood pressure was determined every three weeks. At the 21st week, the concentrations of noradrenaline (NA), angiotensin Ⅱ (AngⅡ), thromboxane B2 (TXB2) and 6-keto-prostaglandin F in serum and endothelin-1 (ET-1) were detected by enzyme-linked immunosorbent assay. The morphological changes in abdominal aorta were observed under an optical microscope with hematoxylin and eosin staining. The ratio of intima-media thickness/lumen radius of abdominal aorta was calculated.

Results: ERS significantly lowered the blood pressure of SHRs from the 3rd to the 21st week; ERS also reduced the levels of NA, AngⅡ, ET-1 and TXB2, decreased the intima-media thickness of abdominal aortal wall and improved the morphological changes in abdominal aorta in SHRs. In addition, ERS did not significantly change blood pressure and vasoactive substances in WKY rats.

Conclusion: ERS possesses beneficial effects in inhibiting hypertension and attenuating arteriosclerosis. The underlying mechanism may be associated with restraining the release of vasoconstrictors, such as NA, AngⅡ, ET-1 and TXB2.

Key words: plant extracts, hypertension, antihypertensive agents, endothelin 1, angiotensin Ⅱ, thromboxane A2, arachidonic acids, rats, inbred SHR

Figure 1

The trend of systolic blood pressure of each group during 21 weeks"

Table 1

Effects of ERS on systolic blood pressure in SHRs ($\overline{x}$±s)"

Group Dose (mg/kg) n Systolic blood pressure (mmHg)
Before administration 3 weeks 6 weeks 9 weeks
WKY 10 156.0±12.2 148.3±14.2 147.4±16.1 149.5±8.7
SHR 10 177.7±6.4** 186.5±7.2** 188.8±8.5** 195.9±5.0**
Captopril 40 10 178.2±8.2 171.0±12.2△△ 170.8±9.4△△ 166.2±11.7△△
SHR plus low-dose ERS 70 10 180.4±7.1 180.0±8.4 172.5±13.0△△ 172.2±17.7△△
SHR plus medium-dose ERS 140 10 178.3±10.5 174.4±10.8△△ 162.1±14.6△△ 169.6±8.4△△
SHR plus high-dose ERS 280 10 179.0±7.2 176.4±5.4△△ 165.5±7.9△△ 165.1±17.5△△
Group Dose (mg/kg) n Systolic blood pressure (mmHg)
12 weeks 15 weeks 18 weeks 21 weeks
WKY 10 148.8±16.1 161.7±7.5 162.9±13.7 160.5±11.3
SHR 10 196.8±5.5** 197.6±3.4** 197.5±6.8** 191.6±15.3**
Captopril 40 10 156.0±29.8△△ 173.0±17.7△△ 176.2±11.3△△ 177.8±6.0
Low-dose ERS 70 10 159.9±23.0△△ 177.5±11.8△△ 175.1±16.5△△ 178.0±10.3
Medium-dose ERS 140 10 163.5±21.4△△ 166.4±15.1△△ 174.8±10.9△△ 173.3±18.9
High-dose ERS 280 10 154.7±24.2△△ 168.1±21.5△△ 172.5±15.1△△ 172.2±12.6△△

Table 2

Effects of ERS on serum TXB2 and 6-keto-PGF1α contents and ratio of TXB2/6-keto-PGF1α in SHRs and WKY rats ($\overline{x}$±s)"

Group Dose (mg/kg) n TXB2 (ng/L) 6-keto-PGF (mg/L) TXB2/6-keto-PGF (×10–6)
WKY 7 295.42±37.83 24.14±19.40 16.79±8.72
WKY plus ERS 140 7 340.74±48.62 17.15±15.77 29.45±14.71
SHR 7 376.17±63.82* 49.70±32.68 10.24±6.32
SHR plus captopril 40 7 309.42±47.18 33.68±18.11 11.70±6.05
SHR plus ERS 70 7 362.31±43.33 39.75±21.16 10.91±4.12
SHR plus ERS 140 7 294.52±38.98 53.91±20.09 5.94±1.70
SHR plus ERS 280 7 279.63±30.43△△ 41.77±22.02 9.08±6.02

Table 3

Effects of ERS on serum NA and AngⅡ and ET-1 contents in SHRs and WKY rats ($\overline{x}$±s)"

Group Dose (mg/kg) n NA (μg/L) AngⅡ (μg/L) ET-1 (ng/L)
WKY 7 1.227±1.281 2.13±1.37 7.61±1.75
WKY plus ERS 140 7 0.413±0.177 1.73±0.32 7.59±2.85
SHR 7 3.025±1.699* 5.71±2.54** 16.91±7.51*
SHR plus captopril 40 7 0.659±0.292△△ 3.14±0.91 9.87±1.53
SHR plus ERS 70 7 0.651±0.190△△ 5.70±2.80 15.95±8.87
SHR plus ERS 140 7 0.567±0.302△△ 5.31±1.46 13.60±6.38
SHR plus ERS 280 7 1.403±0.971 3.27±1.39 9.75±2.59

Figure 2

Effects of ERS on morphological changes in abdominal aorta in SHRs and WKY rats (Hematoxylin-eosin staining, light microscopy, ×40) A: WKY group; B: WKY plus 140 mg/kg ERS group; C: SHR group; D: SHR plus captopril group; E: SHR plus 70 mg/kg of ERS group; F: SHR plus 140 mg/kg of ERS group; G: SHR plus 280 mg/kg of ERS group. WKY: Wistar Kyoto; SHR: spontaneously hypertensive rat; ERS: extracts of Radix Scrophulariae."

Figure 3

Effects of ERS on morphological changes in intima-media structure of abdominal aorta in SHRs and WKY rats (Hematoxylin-eosin staining, light microscopy, ×200) A: WKY group; B: WKY plus 140 mg/kg of ERS group; C: SHR group; D: SHR plus captopril group; E: SHR plus 70 mg/kg of ERS group; F: SHR plus 140 mg/kg of ERS group; G: SHR plus 280 mg/kg of ERS group. WKY: Wistar Kyoto; SHR: spontaneously hypertensive rat; ERS: extracts of Radix Scrophulariae."

Figure 4

Effects of ERS on ratio of intima-media thickness/lumen radius of abdominal aorta in SHRs and WKY rats*P<0.05, vs WKY group; △P<0.05, vs SHR group. WKY: Wistar Kyoto; SHR: spontaneously hypertensive rat; ERS: extracts of Radix Scrophulariae; IMT: intima-media thickness; LR: lumen radius. Data are expressed as $\overline{x}$±s; n=8."

[1] Xu CB . Hypertension, hyperlipidemia and atherosclerosis — vascular lesion[J]. Gao Xue Ya Za Zhi, 2003,11(z1):32-34
徐成斌 . 高血压及高脂血症与动脉粥样硬化——血管损害[J]. 高血压杂志, 2003,11(z1):32-34
[2] Lim JS, Kwon HM . Risk of “silent stroke” in patients older than 60 years: risk assessment and clinical perspectives[J]. Clin Interv Aging, 2010, 5239-251
[3] Lee SJ, Cho SJ, Moon HS, Shon YM, Lee KH, Kim DI, Lee BB, Byun HS, Han SH, Chung CS . Combined extracranial and intracranial atherosclerosis in Korean patients[J]. Arch Neurol, 2003,60(11):1561-1564
doi: 10.1001/archneur.60.11.1561
[4] Iso H . Lifestyle and cardiovascular disease in Japan[J]. J Atheroscler Thromb, 2011,18(2):83-88
doi: 10.5551/jat.6866
[5] Hu YY, Huang Z . Advances in research of chemical constituents and pharmacological effects of Scrophularia ningpoensis Hemsl[J]. Zhejiang Zhong Yi Yao Da Xue Xue Bao, 2008,32(2):268-270
胡瑛瑛, 黄真 . 玄参的化学成分及药理作用研究进展[J]. 浙江中医药大学学报, 2008,32(2):268-270
[6] Chen L, Gao M , Lu Y . The experimental research on the effect of total glucoside of Radix Scrophulariae on experimental rat model of focal cerebral ischemia caused by electrocoagulation. Nanjing Zhong Yi Yao Da Xue Xue Bao. 2009; 25(3):230-232 Chinese.
陈磊, 郜明, 陆茵 . 玄参总苷对电凝法致实验性大鼠局灶性脑缺血模型的实验研究[J]. 南京中医药大学学报, 2009,25(3):230-232
[7] Li YM, Han ZH, Jiang SH, Jiang Y, Yao SD, Zhu DY . Fast repairing of oxidized OH radical adducts of dAMP and dGMP by phenylpropanoid glycosides from Scrophularia ningpoensis Hemsl[J]. Acta Pharmacol Sin, 2000,21(12):1125-1128
[8] Li J, Chen CX, Gao Y, Jiao YB, Wu XM, Wang R, Wu YC , Li YM . Research on the anti-inflammation and anti-atherosclerosis of extracts from Radix Scrophulariae . Shizhen Guo Yi Guo Yao. 2010; 21(3):532-534. Chinese with abstract in English.
李静, 陈长勋, 高阳, 焦亚斌, 吴喜民, 王瑞, 吴银春, 李医明 . 玄参提取物抗炎与抗动脉硬化作用的探索[J]. 时珍国医国药, 2010,21(3):532-534
[9] Huang XY, Chen CX, Zhang XM, Liu Y, Wu XM, Li YM . Effects of ethanolic extract from Radix Scrophulariae on ventricular remodeling in rats[J]. Phytomedicine, 2012,19(3-4):193-205
doi: 10.1016/j.phymed.2011.09.079
[10] Limas C, Westrum B, Limas CJ . The evolution of vascular changes in the spontaneously hypertensive rat[J]. Am J Pathol, 1980,98(2):357-384
[11] Wang XZ, Jiang JY, Lu JF, Luo SS, Wang X.Bian K, Ke Y . Study in the damage of endothelial function and administration recovery among different arteries during the developing progress of SHR[J]. Zhongguo Yao Li Xue Tong Bao, 2010,26(2):163-168
王现珍, 蒋嘉烨, 陆家凤, 罗珊珊, 王勋, 卞卡, 可燕 . SHR高血压进程中不同类型血管内皮功能损伤及药物修复[J]. 中国药理学通报, 2010,26(2):163-168
[12] Kanda Y, Watanabe Y . Adrenaline increases glucose transport via a Rap1-p38MAPK pathway in rat vascular smooth muscle cells[J]. Br J Pharmacol, 2007,151(4):476-482
[13] Ulu N, Gurdal H, Landheer SW, Duin M, Guc MO, Buikema H, Henning RH . α1-Adrenoceptor-mediated contraction of rat aorta is partly mediated via transactivation of the epidermal growth factor receptor[J]. Br J Pharmacol, 2010,161(6):1301-1310
doi: 10.1111/j.1476-5381.2010.00829.x
[14] Pang X, Sun NL . Calcineurin-NFAT signaling is involved in phenylephrine-induced vascular smooth muscle cell proliferation[J]. Acta Pharmacol Sin, 2009,30(5):537-544
doi: 10.1038/aps.2009.28
[15] Iwai M, Chen R, Li Z, Shiuchi T, Suzuki J, Ide A, Tsuda M, Okumura M, Min LJ, Mogi M, Horiuchi M . Deletion of angiotensin Ⅱ type 2 receptor exaggerated atherosclerosis in apolipoprotein E-null mice[J]. Circulation, 2005,112(11):1636-1643
doi: 10.1161/CIRCULATIONAHA.104.525550
[16] Jung HO, Uhm JS, Seo SM, Kim JH, Youn HJ, Baek SH, Chung WS, Seung KB . Angiotensin Ⅱ-induced smooth muscle cell migration is mediated by LDL receptor-related protein 1 via regulation of matrix metalloproteinase 2 expression[J]. Biochem Biophys Res Commun, 2010,402(4):577-582
doi: 10.1016/j.bbrc.2010.10.019
[17] Simeone SM, Li MW, Paradis P, Schiffrin EL . Vascular gene expression in mice overexpressing human endothelin-1 targeted to the endothelium[J]. Physiol Genomics, 2011,43(3):148-160
doi: 10.1152/physiolgenomics.00218.2009
[18] Wang C, Liu J, Guo F, Ji Y, Liu N . Endothelin-1 induces the expression of C-reactive protein in rat vascular smooth muscle cells[J]. Biochem Biophys Res Commun, 2009,389(3):537-542
doi: 10.1016/j.bbrc.2009.09.023
[19] Gomez Sandoval YH, Anand-Srivastava MB . Enhanced levels of endogenous endothelin-1 contribute to the over expression of Giα protein in vascular smooth muscle cells from SHR: role of growth factor receptor activation[J]. Cell Signal, 2011,23(2):354-362
doi: 10.1016/j.cellsig.2010.10.005
[20] Li Y, Lévesque LO, Anand-Srivastava MB . Epidermal growth factor receptor transactivation by endogenous vasoactive peptides contributes to hyperproliferation of vascular smooth muscle cells of SHR[J]. Am J Physiol Heart Circ Physiol, 2010,299(6):H1959-H1967
doi: 10.1152/ajpheart.00526.2010
[21] Bouallegue A, Vardatsikos G, Srivastava AK . Involvement of insulin-like growth factor 1 receptor transactivation in endothelin-1-induced signaling in vascular smooth muscle cells[J]. Can J Physiol Pharmacol, 2010,88(5):501-509
doi: 10.1139/Y10-030
[22] Li JM, Liu CY, Zhao SX . Relationship between carotid atherosclerotic plaque, blood lipid and thromboxane[J]. Hebei Yi Ke Da Xue Xue Bao, 2010,31(9):1045-1047
李嘉民, 刘春燕, 赵素霞 . 颈动脉粥样硬化斑块与血脂和血栓素相关性研究[J]. 河北医科大学学报, 2010,31(9):1045-1047
[23] Francois H, Makhanova N, Ruiz P, Ellison J, Mao L, Rockman HA, Coffman TM . A role for the thromboxane receptor in L-NAME hypertension[J]. Am J Physiol Renal Physiol, 2008,295(4):F1096-F1102
doi: 10.1152/ajprenal.00369.2007
[24] Liu F, Zhu YK . A case report of syncope caused by captopril[J]. Zhongguo Min Kang Yi Xue, 2008,20(12):1376
刘凡, 朱玉昆 . 卡托普利致晕厥1例[J]. 中国民康医学, 2008,20(12):1376
[25] Zhan MM . Brief introduction of cardiovascular adverse reactions of captopril in clinical application[J]. Yi Xue Li Lun Yu Shi Jian, 2011,24(10):1155
詹苗苗 . 简述卡托普利心血管临床不良反应[J]. 医学理论与实践, 2011,24(10):1155
[1] Pranay Soni, Rajesh Choudhary, Surendra H. Bodakhe. Effects of a novel isoflavonoid from the stem bark of Alstonia scholaris against fructose-induced experimental cataract. Journal of Integrative Medicine, 2019, 17(5): 374-382.
[2] Stefania Lamponi, Anna Maria Aloisi, Claudia Bonechi, Marco Consumi, Alessandro Donati, Gemma Leone, Claudio Rossi, Gabriella Tamasi, Luana Ghiandai, Ersilia Ferrini, Paolo Fiorenzani, Ilaria Ceccarelli, Agnese Magnani. Evaluation of in vitro cell and blood compatibility and in vivo analgesic activity of plant-derived dietary supplements. Journal of Integrative Medicine, 2019, 17(3): 213-220.
[3] Sonia Chew Wen Phang, Uma Devi Palanisamy, Khalid Abdul Kadir. Effects of geraniin (rambutan rind extract) on blood pressure and metabolic parameters in rats fed high-fat diet. Journal of Integrative Medicine, 2019, 17(2): 100-106.
[4] Rohitash Jamwal. Bioavailable curcumin formulations: A review of pharmacokinetic studies in healthy volunteers. Journal of Integrative Medicine, 2018, 16(6): 367-374.
[5] Supakanya Kumkarnjana, Rutt Suttisri, Ubonthip Nimmannit, Thongchai Koobkokkruad, Chutichot Pattamadilok, Nontima Vardhanabhuti . Anti-adipogenic effect of flavonoids from Chromolaena odorata leaves in 3T3-L1 adipocytes. Journal of Integrative Medicine, 2018, 16(6): 427-434.
[6] Morufu Eyitayo Balogun, Elizabeth Enohnyaket Besong, Jacinta Nkechi Obimma, Ogochukwu Sophia Mbamalu, Fankou Serges Athanase Djobissie. Protective roles of Vigna subterranea (Bambara nut) in rats with aspirin-induced gastric mucosal injury. Journal of Integrative Medicine, 2018, 16(5): 342-349.
[7] Shohini Chakraborty, Nashra Afaq, Neelam Singh, Sukanta Majumdar. Antimicrobial activity of Cannabis sativaThuja orientalis and Psidium guajava leaf extracts against methicillin-resistant Staphylococcus aureus. Journal of Integrative Medicine, 2018, 16(5): 350-357.
[8] Bruno José Martins Da Silva, Amanda Anastácia Pinto Hage, Edilene Oliveira Silva, Ana Paula Drummond Rodrigues. Medicinal plants from the Brazilian Amazonian region and their antileishmanial activity: A review. Journal of Integrative Medicine, 2018, 16(4): 211-222.
[9] Lucky Legbosi Nwidu, Raphael Ellis Teme. Hot aqueous leaf extract of Lasianthera africana (Icacinaceae) attenuates rifampicin-isoniazid-induced hepatotoxicity. Journal of Integrative Medicine, 2018, 16(4): 263-272.
[10] Nisha Panth, Keshav Raj Paudel, Rajendra Karki. Phytochemical profile and biological activity of Juglans regia. Journal of Integrative Medicine, 2016, 14(5): 359-373.
[11] Musa Toyin Yakubu, Abdulquadri Funmbi Olutoye. Aphrodisiac activity of aqueous extract of Anthonotha macrophylla P. Beauv. leaves in female Wistar rats. Journal of Integrative Medicine, 2016, 14(5): 400-408.
[12] JiaXia, Li-qunHe, XiaoSu. Interventional mechanisms of herbs or herbal extracts on renal interstitial fibrosis. Journal of Integrative Medicine, 2016, 14(3): 165-173.
[13] Nathalia Gomes Ribeiro de Moura, Ivan Cordovil, Arthurde Sá Ferreira. Traditional Chinese medicine wrist pulse-taking is associated with pulse waveform analysis and hemodynamics in hypertension. Journal of Integrative Medicine, 2016, 14(2): 100-113.
[14] Wei Chiang Chan Eric, Kuin Wong Siu. Phytochemistry and pharmacology of ornamental gingers, Hedychium coronarium and Alpinia purpurata: A review. Journal of Integrative Medicine, 2015, 13(6): 368-379.
[15] Nouran A. Aleyeidi, Khaled S. Aseri, Shadia M. Matbouli, Albaraa A. Sulaiamani, Sumayyah A. Kobeisy. Effects of wet-cupping on blood pressure in hypertensive patients: A randomized controlled trial. Journal of Integrative Medicine, 2015, 13(6): 391-399.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] Jun Cai, Hua Wang, Sheng Zhou, Bin Wu, Hua-rong Song, Zheng-rong Xuan. Effect of Sijunzi Decoction and enteral nutrition on T-cell subsets and nutritional status in patients with gastric cancer after operation: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2008, 6(1): 37-40
[2] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[3] Zhi-chun Jin. Problems in establishing clinical guideline for integrated traditional Chinese and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 5-8
[4] Min Cheng, Qiong Feng, Shu-wen Qian, Hui Gao, Cui-qing Zhu. Preliminary assay of p-amyloid binding elements in heart-beneficial recipe. Journal of Chinese Integrative Medicine, 2008, 6(1): 68-72
[5] A-gao Zhou, Yong Zhang, Gang Kui, De-Yun Kong, Hai-liang Ge, Qiu-hua Ren, Jia-rong Dong, Sheng Hong, Xu-ming Mao, Yin Wang, Hui-zheng Zhang, Shu-jun Wang. Influence of traditional Chinese compound recipes with different efficacy on body weight, tumor weight and immune function in H22 cancer-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 77-82
[6] Guo-hong Yuan, Xiao-jing Pang, He-chao Ma. Synergic effects of Danggui Buxue Decoction in reducing toxicity of cytoxan in tumor-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 83-88
[7] Li Zhou, Hong-xing Zhang, Ling-guang Liu, Wen-jun Wan. Effect of electro-acupuncture at Fenglong (GV 16) on nitric oxide and endothelin in rats with hyperlipidemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 89-92
[8] . Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing for biomedical publication (Chinese version, part two). Journal of Chinese Integrative Medicine, 2010, 8(11): 1001-1005
[9] Daniel Weber, Janelle M Wheat, Geoffrey M Currie. Inflammation and cancer: Tumor initiation, progression and metastasis,and Chinese botanical medicines. Journal of Chinese Integrative Medicine, 2010, 8(11): 1006-1013
[10] Bo Wang , Wei Yan , Li-hui Hou, Xiao-ke Wu. Disorder of Tiangui (kidney essence) and reproductive dysfunction in patients with polycystic ovary syndrome. Journal of Chinese Integrative Medicine, 2010, 8(11): 1018-1022