Antihypertensive effects of Korean wild simulated ginseng (Sanyangsam) extracts in spontaneously hypertensive rats

문재남,김종국,이슬,권중호 한국식품과학회 2019 Food Science and Biotechnology Vol.28 No.5

Ginseng possesses a wide spectrum of medicinal effects and has widely been used in traditional medicine for thousands of years. In this study, the antihypertensive effect of Korean wild simulated ginseng in spontaneously hypertensive rats was investigated. Three groups of hypertensive rats—a group without wild simulated ginseng treatment; another group treated with 100 mg of wild simulated ginseng extract/kg of body weight; and the other group treated with 200 mg of wild simulated ginseng extract/kg of body weight were tested over 8 weeks. The two wild simulated ginseng-treated groups showed significantly (p < 0.05) reduced systolic blood pressure at 4 and 6 weeks of wild simulated ginseng treatment. However, the wild simulated ginseng treatment did not adversely affect the food intake, serum electrolytes, osmolality, heart weight, heart rate, and the cross-section of the aorta as well as enzyme activities. The results suggested that Korean wild simulated ginseng is effectively used for reducing high systolic blood pressure in hypertensive patients without causing adverse health effects.

Kinetic Changes and Antihypertensive Effect of Aqueous Extract of Danggui (Angelica sinensis Radix) after Stir-fry Processing

Gui-Fen Zhou,Xiao-Yan Dai,Chen-Huan Yu,Jie Fang 한국식품과학회 2013 Food Science and Biotechnology Vol.22 No.3

Danggui (Angelica sinensis Radix) in East Asia for its unique pleasant flavor is usually cooked before utilizing to enhance its tonic effect. To evaluate the quality and bioactivity changes, heat treatments were carried out at 250oC for 0-45 min. 5-Hydroxymaltol, 5-hydroxymethylfurfural,Z-ligustilide, and ferulic acid in aqueous extract of processed danggui (APD) were determined by HPLC while antihypertensive effects were studied after oral administration of APD (50 and 100 mg/kg) for 3 days in spontaneously hypertensive rats (SHR). Compared with aqueous extract of danggui (AD), contents of ferulic acid and Z-ligustilide in APD were significantly decreased but 5-hydroxymaltol and 5-hydroxymethylfurfural were increased. APD could lower blood pressures, plasma renin activities, and angiotensin II levels of SHR, but AD failed to do those. APD exhibited hypotensive effects by regulating renin-angiotensin system and may warrant further evaluation as a potential antihypertensive agent.

새로운 Dihydropyridine 유도체, KR-30006과 KR-1008의 심장순환계 약리작용

이병호(Byung Ho Lee),정이숙(Yee Sook Jung),권광일(Kwang Il Kwon),지옥표(Ok Pyo Zee) 대한약학회 1989 약학회지 Vol.33 No.3

KR-1008 and KR-30006 are 1,4-dihydropyridine derivatives, new vasodilatory calcium antagonists from KRICT. Calcium antagonistic properties of the compounds were studied in the isolated heart (Langendorff preparation), pulmonary artery (vasodilation), and in the papillary muscle (negative inotropic effect) of the guinea pig. Antihypertensive effect were also investigated after i.v. or oral administration in the SHR (spontaneously hypertensive rat). They produced a sigificant inhibition of Ca-induced contraction in the guinea pig pulmonary artery at the concentrations of above 10-8M. The negative inotropic effect of the electrically stimulated papillary muscle appeared from the concentration of 10-6M, which is about hundred times higer than the concentration of vasodilation effect. Left ventricular pressure also decreased from the concentration of 3 X 10-6M,in KR-1008 and KR-30006 in the Langendorff heart preparations. Coronary flow rate increased from 10-6M in KR-1008 and nicardipine and appeared no change in KR-30006. The antihypertensive effect of KR-1008 (EC 20 : 2.9mcg/kg) was potent more than nicardipine (EC 20 : 3.4mcg/kg) and than KR-30006 (EC 20 : 6.8mcg/kg) was, after i.v. bolus injection in the anesthetized SHR. The antihypertensive effect in the conscious SHR appeared 30 minutes after oral administration of 10mg/kg and persisted 4 hrs in KR-1008 and 12 hrs in KR-30006. Heart rate tended to increase for 0.5-1 hr after oral administration of the test compounds.

새로운 Dihydropyridine 유도체, KR-30006과 KR-1008의 심장순환계 약리작용

이병호,정이숙,권광일,지옥표 충남대학교 약학대학 의약품개발연구소 1989 藥學論文集 Vol.5 No.-

KR-1008 and KR-30006 are 1,4-dihydropyridine derivatives, new vasodilatory calcium antagonists from KRICT. Calcium antagonistic properties of the compounds were studied in the isolated heart (Langendorff preparation), pulmonary artery (vasodilation), and in the papillary muscle (negative inotropic effect) of the guinea pig. Antihypertensive effect were also investigated after i.v. or oral administration in the SHR (spontaneously hypertensive rat). They produced a sigificant inhibition of Ca-induced contraction in the guinea pig pulmonary artery at the concentrations of above 10^-8M. The negative inotropic effect of the electrically stimulated papillary muscle appeared from the concentration of 10^-6M, which is about hundred times higer than the concentration of vasodilation effect. Left ventricular pressure also decreased from the concentration of 3×10^-6M in KR-1008 and KR-3006 in the Langendorff heart preparations. Coronary flow rate increased from 10^-6M in KR-1008 and nicardipine and appeared no change in KR-30006. The antihypertensive effect of KR-1008 (EC 20:2.9 ㎍/㎏) was potent more than nicardipine (EC 20:3.4 ㎍/㎏) and than Kr-30006 (EC 20:6.8 ㎍/㎏) was, after i.v. bolus injection in the anesthetized SHR. The antihypertensive effect in the conscious SHR appeared 30 minutes after oral administration of 10 ㎎/㎏ and persisted 4 hrs in KR-1008 and 12 hrs in KR-30006. Heart rate tended to increase for 0.5-1 hr after oral administration of the test compounds.

Vasorelaxing Mechanism of Crude Saponin of Korea Red Ginseng in the Resistance-sized Mesenteric Artery of Rat

Kim, Shin-Hye,Park, Hyung-Seo,Lee, Mee-Young,Oh, Young-Sun,Kim, Se-Hoon The Korean Society of Ginseng 2002 Journal of Ginseng Research Vol.26 No.1

고려홍삼은 혈압강하효과가 있음이 잘 알려져 있다. 이에 백서장간막이 동맥의 저항혈관에서 고려홍삼 사포닌 성분의 혈관 이완기전을 규명하고자 내경이 150$\mu\textrm{m}$이하의 작은 혈관을 이요하여 여러 실험 조건에서 장력의 변화를 측정하여 다음과 같은 결과를 얻었다. 고려홍삼 사포닌 성분은 농도 의존적으로 (0.01mg/$m\ell$~1mg/$m\ell$) 혈관 평활근을 이완시켰으며 내피세포를 제거한 상태에서도 혈관의 이완효과는 지속되었다. A23187 이나 phorbol 12, 13-dibutyrate 에 의한 수축에서는 고려홍삼 사포닌에 의한 혈관의 이완효과가 나타나지 않았다. 고려홍삼 사포닌에 의한 혈관이완효과는 실험용액의 $K^{+}$ 농도를 증가시키면 감소되었으며 각종 $K^{+}$이 온통로 억제제인 tetaethylammonium, glybenclamide, 4-aminopyridine 및 BaCl$_2$를 전처치한 결과 BaCl$_2$에 의해서만 농도에 의존적으로 고려홍삼 사포닌에 의한 혈관이완작용이 억제되었다. 이상의 실험결과로부터 고려홍삼 사포닌은 장간막 동맥의 저항혈관에서 $K^{+}$의 유출을 증가시켜 혈관평활근을 이완시키며 $Ba^{2+}$에 의하여 차단되는 $K^{+}$ 이온통로가 고려홍삼 사포닌에 의한 혈관이완작용에 관여함을 알 수 있었다. It has been well known that Korea red ginseng has an antihypertensive effect. The antihypertensive effect may be due to its ability to change the peripheral resistance. Change of vascular tone in the resistance-sized artery contribute to the peripheral resistance, thereby regulate the blood pressure. Therefore, we investigated to clarify the vasorelaxing mechanism induced by crude saponin of Korea red ginseng in the resistance-sized mesenteric artery of rats. The resistance-sized mesenteric artery was isolated and cut into a ring. The ring segment was immersed in HEPES-buffered solution and its isometric tension was measured using myograph force-displacement transducer. Crude saponin of ginseng relaxed the mesenmetric arterial rings precontracted with norepinephrine (3$\mu$M) in dose-dependent manner (0.01 mg/㎖ -1 mg/㎖. The relaxation by crude saponin was smaller in endothelium-intact preparation than that in endothelium-denuded preparation. The contraction induced by A23187 or phorbol 12,13-dibutyrate was not affected by crude saponin of ginseng. The vasorelaxing effect of crude saponin of ginseng was significantly attenuated by the increase of the extracellular K$\^$+/ concentration. Crude saponin-induced vasorelaxation was not affected by tetraethylammonium (1 mM), glybenclamide (10$\mu$M), and 4-aminopyridine (0.1 mM) in these preparations. Ba$\^$2+/(10$\mu$M ∼100$\mu$M) markedly reduced the crude saponin-induced vasorelakation dose-dependently. From the above results, we suggest that crude saponin of ginseng may stimulate K$\^$+/ efflux and hyperpolarize the membrane, thereby cause the vasorelaxation in the resistance-sized mesenteric artery of rats.

고혈압의 최신 약물치료

박창규 대한의사협회 2010 대한의사협회지 Vol.53 No.8

The majority of hypertensive patients do not achieve target blood pressure for a variety of reasons, including insufficient medication, drug resistance, and noncompliance. There remains a significant need to develop new agents to better control hypertension. Nebivolol is a thirdgeneration β-adrenergic receptor blocker which is very highly cardioselective and has direct vasodilator properties via stimulation of endothelial nitric oxide synthase activity. Aliskiren is the first orally active inhibitor of renin as an antihypertensive agent. It is associated with dose-related falls in blood pressure comparable to other major classes of antihypertensive drugs with a placebo level of side effects. Endothelin is a powerful vasoconstrictor peptide. An endothelin-receptor antagonist such as bosentan significantly lowered blood pressure in patients with essential hypertension. Vasopeptidase inhibitors inhibit neutral endopeptidase and angiotensin converting enzymes, but side-effects such as angio-oedema and cough remain to be overcome. AngQb vaccine in hypertensive patients showed a marked reduction in early morning blood pressure without serious adverse events.

Antihypertensive and Cardiovascular Effects of the New Calcium Antagonist YH334

Lee, Jong-Wook,Han, Byung-Hee,Lee, Jeong-Won,Seok, Ji-Hee,Kim, Su-Chang,Hong, You-Hwa,HongSuh, Jung-Jin,Hong, Soon-Uk The Pharmaceutical Society of Korea 1991 Archives of Pharmacal Research Vol.14 No.3

Antihypertensive effect of YH 334 was examined in various experimental hypertension rat models and the systemic and regional hymohynamic profiles of the compound were investigated in conscious spontaneously hypertensive rats (SHR). The antiypertensive potensive potency of YH 334 is found to be more than 10 times stronger than that of nitrendipine in the all hypertensive models. The effective doses to lower the initial blood pressure by 20% $(ED_{20})$ of YH334 were 1.4 mg/kg in normotensive rats (NR), 0.7 mglkg in SHR. 0.1 mg/kg in DOCA salt hypertensive rats (DHR) and 0.4 mg/kg in renal hypertensive rats (RHR), and the $ED_{20}$ values of nitrendipine were 15.8 mg/kg in NR, 7.1 mg/kg in SHR, 1.7 mg/kg in DHR and 4.8 mg/kg in RHR. The primary hemodynamic effect hemodynamic profile is similar to that of nitrendipine. Both compounds seem to produce potent antihypertensive effects by lowering peripheral resistance in the skeletal muscles. In the organ bath study using isolated rabbit aorta, YH 334 was found to be a potent voltage dependent calcium channel blocker without significant inhibitory effect on the receptor operated calcium channels like the most of other dihydropyridine type calcium antagonists. Furthermore, YH334 showed acute diuretic and natriuretic effects in conscious SHR, which may render the unnecessary restriction of sodium in the diet of those patients on long term hypertension therapy. This effect would provide an additional benefit to its potent antihypertensive activity.

Antihypertensive Effect of Amlodipine Adipate, a Novel Salt of Amlodipine, in Hypertensive Rat Models

( Byung Ho Lee ),( Ho Won Seo ),( Myeong Yun Chae ),( Kyu Jeong Yeon ) 한국응용약물학회 2004 Biomolecules & Therapeutics(구 응용약물학회지) Vol.12 No.1

N/A The vascular relaxant effect of amlodipine adipate, a new salt of amlodipine, was evaluated in isolated rat aorta, and compared with that of amlodipine besylate. Furthermore, antihypertensive effects were measured in hypertensive rat models, such as spontaneously hypertensive rats(SHR) and renal hypertensive rats(RHR). Amlodipine adipate concentration-dependently inhibited Ca^(2+)-induced contraction of rat aorta with a very slow onset of action (reached its maximum at 3.5h; IC_(50): 3.76 nM), having a pattern and a potency similar to those of amlodipine besylate (IC_(50): 4.01 nM). In SHR and RHR, orally administered amlodipine adipate produced at dose-dependent and long-lasting(>10-24 h) antihypertensive effect(ED,,,:2.48 and 1.57 mg/kg, respectively). with a pattern and a potency similar to those of amlodipine besylate(ED_(20):2.50 and 1.90mg/kg in SHR and RHR, respectively). These results suggest that amlodipine adipate is a potent and long-lasting antihypertensive agent and that its antihypertensive effect is not significantly different to that of amlodipine besylate.

Adverse effects and non-adherence to antihypertensive medications in University of Gondar Comprehensive Specialized Hospital

Eyob Alemayehu Gebreyohannes,Akshaya Srikanth Bhagavathula,Tamrat Befekadu Abebe,Yonas Getaye Tefera,Tadesse Melaku Abegaz 대한고혈압학회 2019 Clinical Hypertension Vol.25 No.2

Background: A considerable proportion of cardiovascular events could be attributed to poor adherence to antihypertensive medications. Adverse effects can be severe enough to affect adherence to antihypertensive medications. This study aimed to measure the contribution of adverse effects on antihypertensive medications adherence. Methods: The study was conducted from May 1 to June 30, 2017, at the ambulatory clinic of University of Gondar Comprehensive Specialized Hospital (UOGCSH) in Gondar town. A binary logistic regression was performed to determine the significance of the association between adverse effects and adherence to antihypertensive medications. An institution-based cross-sectional study was conducted by administering a questionnaire to hypertensive patients who came for follow-up at the ambulatory clinic of UOGCSH. Level of adherence to antihypertensive medications was used as outcome measure. Results: A total of 249 patients were included in the final analysis with a mean age of 56.51 years and a female majority (53%). The following variables were identified as predictors of poor adherence: tiredness [AOR (95% CI): 3.802 (1.723–8.391), p = 0.001], muscle pain [AOR (95% CI): 5.199 (1.407–19.214), p = 0.013], poor sleep [AOR (95% CI): 4.891 (1.578–15.160), p = 0.006] and, believing that the symptoms were caused by antihypertensive medications [AOR (95% CI): 3.249 (1.248–8.456), p = 0.016]. Conclusion: Adverse effect significantly contributes to antihypertensive medication non-adherence among hypertensive patients

Structure Characterization and Antihypertensive Effect of an Antioxidant Peptide Purified from Alcalase Hydrolysate of Velvet Antler

임승태,이승홍 한국축산식품학회 2023 한국축산식품학회지 Vol.43 No.1

Recently, interest in food-derived bioactive peptides as promising ingredients for the prevention and improvement of hypertension is increasing. The purpose of this study was to determine the structure and antihypertensive effect of an antioxidant peptide purified from velvet antler in a previous study and evaluate its potential as a various bioactive peptide. Molecular weight (MW) and amino acid sequences of the purified peptide were determined by quadrupole time-of-flight electrospray ionization mass spectroscopy. The angiotensin I-converting enzyme (ACE) inhibition activity of the purified peptide was assessed by enzyme reaction methods and in silico molecular docking analysis to determine the interaction between the purified peptide and ACE. Also, antihypertensive effect of the purified peptide in spontaneously hypertensive rats (SHRs) was investigated. The purified antioxidant peptide was identified to be a pentapeptide Asp-Asn-Arg-Tyr-Tyr with a MW of 730.31 Da. This pentapeptide showed potent inhibition activity against ACE (IC50 value, 3.72 μM). Molecular docking studies revealed a good and stable binding affinity between purified peptide and ACE and indicated that the purified peptide could interact with HOH2570, ARG522, ARG124, GLU143, HIS387, TRP357, and GLU403 residues of ACE. Furthermore, oral administration of the pentapeptide significantly reduced blood pressure in SHRs. The pentapeptide derived from enzymatic hydrolysate of velvet antler is an excellent ACE inhibitor. It might be effectively applied as an animal-based functional food ingredient.