Aqueous extract of Astragali Radix induces human natriuresis through enhancement of renal response to atrial natriuretic peptide

The diuretic effect of Astragali Radix (AR) in humans was described in ancient books, but its mechanism has not been identified. To evaluate its diuretic/natriuretic effect, we conducted a double-blind, randomized, crossover study in 12 healthy men. They were randomized to receive either placebo (n=6) or a single oral dosage of 0.3g/kg body weight of aqueous extract of AR (ARE) (n=6). Compared with placebo, ARE treatment markedly increased urinary sodium excretion (U(Na)V), fractional sodium excretion, and urinary excretion of chloride during the first 4h. No significant changes of these parameters were observed during 12h or 24h. ARE elevated plasma ANP (pANP), urinary excretion of cGMP (U(cGMP)V) and U(cGMP)V/pANP ratio without affecting plasma level of rennin-angiotensin-aldosterone system, mean arterial blood pressure and glomerular filtration rate. The change in U(Na)V was closely correlated with pANP, U(cGMP)V, and U(cGMP)V/pANP ratio. In addition, the seven volunteers who presented marked natriuresis did not show higher level of plasma Astragaloside IV than the other five volunteers. We first demonstrate that ARE induces a marked natriuresis in healthy men, which is attributed to enhanced renal responses to endogenous ANP. The Astragaloside IV in the ARE is not the active component for natriuresis.     

Euphorbia hirta leaf extracts increase urine output and electrolytes in rats.

Euphorbia hirta is locally used in Africa and Australia to treat numerous diseases, including hypertension and edema. The diuretic effect of the E. hirta leaf extracts were assessed in rats using acetazolamide and furosemide as standard diuretic drugs. The water and ethanol extracts (50 and 100 mg/kg) of the plant produced time-dependent increase in urine output. Electrolyte excretion was also significantly affected by the plant extracts. The water extract increased the urine excretion of Na+, K+ and HCO3-. In contrast, the ethanol extract increased the excretion of HCO3- decreased the loss of K+ and had little effect on renal removal of Na+. Acetazolamide, like the water extract, increased urine output and enhanced the excretion of Na+, K+ and HCO3-. The high-ceiling diuretic, furosemide, increased the renal excretion of Na+ and Cl-; but had no effect on K+ and HCO3- loss. This study suggests that the active component(s) in the water extract of E. hirta leaf had similar diuretic spectrum to that of acetazolamide. These results validate the traditional use of E. hirta as a diuretic agent by the Swahilis and Sukumas.     

Long-term reno-cardiovascular effects of orally administered aconiti tuber in humans

The reno-cardiovascular effects of Aconiti Tuber were studied. In a controlled, double-blind, and randomized clinical trial, it was found that in 9 months, Aconiti Tuber, after preparation (120 degrees C, 40 min), (1) had no apparent adverse effects, (2) showed positive inotropic, positive chronotropic, and vasodilator effects, (3) increased renal blood flow, and glomerular filtration rate, Na+/Cl-/K+ excretions. The renal function test results could be interpreted as secondary to hemodynamic changes. We conclude that specially prepared Aconiti Tuber may be a promising cardiotonic agent.     

Effects of moxibusting Point Kuan-Yuan on cardiovascular and renal responses to histamine-induced shock

Moxibustion of the Point Kuan-Yuan is said by some Chinese herb doctors to have "anti-shock" effect. Using histamine-induced shock in anesthetized dogs, we studied the cardiovascular and renal effects of moxibusting Point Kuan-Yuan. We found that it significantly increased cardiac output, total peripheral resistance, and mean blood pressure but it did not significantly increase heart rate. Moxibustion also significantly increased renal plasma flow, glomerular filtration rate, urine flow, and Na+ Cl-K+ excretions. Whether moxibusting Kuan-Yuan may be useful as an adjunct in treating clinical shocks deserves more extensive studies in well-controlled clinical situations. It may also be helpful in clinical situations in which elevation of the sympathetic activity may be beneficial.     

Diuretic effect and mechanism of action of parsley

This work provides substantial evidence for the advocated diuretic effect of parsley in folk medicine and determines the mechanism of action of the herb. Rats offered an aqueous parsley seed extract to drink, eliminated a significantly larger volume of urine per 24 h as compared to when they were drinking water. These findings were supported by the results of other experiments using an in situ kidney perfusion technique which demonstrated also a significant increase in urine flow rate with parsley seed extract. This effect was still apparent in presence of amiloride, furosemide and in the absence of sodium, but not in the absence of potassium, suggesting that the diuretic effect of the herb is mediated through an increase in K+ retention in the lumen. Parsley extract, was shown on the other hand, to reduce the activity of the Na+-K+ ATPase in both cortex and medulla homogenates. Such an inhibition would decrease apical cellular Na+ reabsorption, lower K+ secretion, increase K+ concentration in the intercellular space and consequently would inhibit passive K+ influx across the tight junctions. The mechanism of action of parsley seems to be mediated through an inhibition of the Na+-K+ pump that would lead to a reduction in Na+ and K+ reabsorption leading thus to an osmotic water flow into the lumen, and diuresis.     

白术利尿作用研究

目的:研究白术及其拆分组分对大鼠的利尿作用。方法:采用多模式联用的方法对白术化学组分进行拆分;通过预先胃水负荷模型,以6 h尿量为指标考察白术及其拆分组分对水负荷大鼠利尿作用;进一步测定红细胞和肾髓中Na~+-K~+-ATP酶活力、血尿素氮浓度、肾髓中碳酸酐酶水平和Na~+、K~+、Cl-排出量,研究其相关机理。结果:高剂量白术水煎液和白术挥发油组分对大鼠有一定的抗利尿作用;与空白组相比,白术水煎液及其拆分组分组红细胞中Na~+-K~+-ATP酶活力、肾髓中Na~+-K~+-ATP酶和碳酸酐酶水平无显著变化。结论:白术对正常动物无利尿作用,相反表现出一定的抗利尿作用,且首次研究发现白术挥发油有一定的抗利尿作用。     

基于NaCl重吸收抑制作用的石韦利尿活性成分筛选

目的建立基于抑制NaCl重吸收作用的利尿药物体外筛选模型,研究21个从石韦中分离的化合物的利尿活性,并通过体内实验进行验证。方法采用犬肾小管上皮细胞MDCK对石韦中21个化合物进行体外利尿活性筛选,确定NaCl体外转运实验的最佳NaCl剂量;将MDCK细胞接种于Transwell小室内,设置对照组、石韦化合物(100μmol/L)组、氢氯噻嗪(100μmol/L)组,给药孵育24 h后,加入NaCl溶液(15 mg/mL),于30 min、2 h、4 h分别取Transwell下室培养液,检测Cl-和Na+吸光度。昆明小鼠随机分为对照组、绿原酸甲酯(10 mg/kg)组、山柰酚(10 mg/kg)组、氢氯噻嗪(10 mg/kg)组,给予药物干预5 d后,检测各组小鼠5 h内的尿量。结果与对照组比较,加入NaCl 30 min,氢氯噻嗪组MDCK细胞Cl-和Na+水平显著降低(P<0.05),绿原酸甲酯组MDCK细胞Na+水平显著降低(P<0.05);加入NaCl 2h,绿原酸甲酯组MDCK细胞Cl-水平显著降低(P<0.05)。与对照组比较,绿原酸甲酯组和氢氯噻嗪组小鼠给药后5 h内的总尿量显著增加(P<0.05);氢氯噻嗪组和绿原酸甲酯组小鼠尿量峰值分别为给药后1.5、2.5h,随后尿量均呈下降趋势。结论绿原酸甲酯可抑制肾小管氯化钠转运,对小鼠具有利尿作用,是石韦中的利尿活性成分。     

Chronic diuretic effect of the water extract of Spergularia purpurea in normal rats

The purpose of this study was to examine the chronic diuretic effect of the water extract of the whole plant of Spergularia purpurea (SP) at different doses (100, 200 and 400 mg/kg) in normal rats. Daily oral administration of the water extract was tested for 4 weeks. Urinary water and electrolytes excretion were determined weekly. Oral administration of the water extract at different doses produced a significant and dose-dependent diuresis and increase in electrolytes excretion. The highest dose (400 mg/kg) of the water extract of SP enhanced urine output from 7.15 +/- 0.42 ml/24 h at the start to 23.01 +/- 0.75 ml/24 h after 4 weeks (p < 0.001). It also produced significant increase in urinary excretion of Na+ (P < 0.01), K+ (P < 0.01) and Cl(-) (P < 0.01). Chronic treatment with SP decreased significantly urine osmolality (P < 0.01 vs. control), while a slight increase in glomerular filtration rate was also observed (P < 0.05) for both doses of water extract (100 and 400 mg/kg). It is concluded that the water extract of whole plant of SP has a significant diuretic effect in rats.     

Renal excretion of stevioside in rats.

The renal excretion of stevioside, a glycoside extracted from the leaves of Stevia rebaudiana, and its effect on renal excretion of several substances, was studied through clearance techniques in Wistar rats. After a control period, stevioside was infused iv at four concentrations (4, 8, 12, and 16 mg/kg). During all the experiments no significant changes in inulin clearance (CIn) were observed. The stevioside infusion induced a significant increase in the p-aminohippuric acid clearance (CPAH), fractional sodium excretion (FeNa+), urinary flow as percent of glomerular filtration rate (V/GFR), and glucose clearance (CG) when compared to controls, but these effects were absent with the dose of 4 mg/kg. The stevioside clearance (CS) was higher than the CIn and lower than the CPAH at all the doses employed in this study. These results indicate that the stevioside is secreted by renal tubular epithelium and induces diuresis and natriuresis and a fall in renal tubular reabsorption of glucose.     

Cardiovascular and diuretic activity of kaurene derivatives of Xylopia aethiopica and Alepidea amatymbica

The extractives, crude and pure, of Alepidea amatymbica (AA) and Xylopia aethiopica (XA) were subjected to bioassay-directed phytochemical examination for potential cardiovascular and diuretic activity. All extractives and derivatives (XA/O, AA/1, xylopic acid, AA/3, AA/4, AA/5, AA/6, XA/1, XA/2, XA/3) displayed low toxicity, with LC(50) 0.5-5.0 ng/ml. For the first time, diterpene kaurenoids were reported to have significant systemic hypotensive and coronary vasodilatory effect accompanied with bradycardia. These effects were attributed to calcium antagonistic mechanism. The diuretic and natriuretic effects found were similar to the effects of chlorothiazide, suggesting inhibition of Na+ and K+ reabsorption in the early portion of the distal tubule. Further experiments are needed to elaborate the exact mechanisms of the hypotensive and diuretic effects of diterpene kaurenoids.     

Cordyceps sobolifera extract ameliorates lipopolysaccharide-induced renal dysfunction in the rat

Cordyceps Sobolifera (CS), an economic traditional Chinese herb, may ameliorate nephrotoxicity-induced renal dysfunction in the rat via antioxidant, anti-apoptosis, and anti-autophagy mechanisms. We investigated the water extract of fermented whole broth of CS on lipopolysaccharide (LPS)-induced renal cell injury in vitro and in vivo. CS effect on LPS-induced epithelial Lilly pork kidney (PK1) and Madin-Darby canine kidney epithelial (MDCK) cell death was detected with MTT assay. Two-month treatment of CS effects on renal blood flow (RBF), glomerular filtration rate (GFR), plasma blood urea nitrogen, creatinine level and leukocytes (WBC) count were determined in the LPS-treated rats. We further examined the effects of CS supplement on renal tubular oxidative stress, endoplasmic reticulum stress, apoptosis and autophagy by Western blot analysis. LPS dose-dependently induced PK1 and MDCK cell death, which can be ameliorated by CS treatment. LPS significantly decreased RBF and GFR and increased blood leukocyte counts, plasma blood urea nitrogen and creatinine level in the rat after 24 hours of injury. LPS enhanced renal tubular ER stress, autophagy and apoptosis via by increase protein expressions of GRP78, caspase 12, Beclin-1 and Bax/Bcl-2 ratio. These findings are associated with the significant staining in renal proximal and distal tubular ED-1, GRP78, Beclin-1 autophagy, and TUNEL apoptosis in the LPS-treated kidneys. Two months of CS supplement significantly improved RBF, GFR and WBC values and reduced ED-1, GRP78, Beclin-1 autophagy and TUNEL apoptosis in the LPS-treated kidneys. Long-term CS treatment reduced LPS-induced stress responses and tissue damage possibly via blocking LPS-triggered signaling pathways.     

Pharmacological studies on hypotensive, diuretic and vasodilator activities of chrysin glucoside from Calycotome villosa in rats

The present study was undertaken in normotensive anaesthetized male rats that received a continuous perfusion of a chrysin glucoside isolated from the flowers and leaves of Calycotome villosa subsp intermedia at a dose of 2.5 mg/kg, or furosemide (control diuretic) at a dose of 0.5 mg/kg. Compared with the control rats receiving NaCl (0.9%), the urine flow, glomerular filtration and electrolyte excretion (Na+, K+) increased significantly in rats treated with chrysin glucoside (p < 0.001). A similar effect was observed in the rats perfused with furosemide. Intravenous injections of bolus doses (1-3 mg/kg) of the chrysin glucoside to anaesthetized rats elicited an immediate and dose-dependent decrease in mean arterial blood pressure (MABP). Pretreatment of the rats with the nitric oxide synthase inhibitor, l-NOArg (10 mg/kg), reduced partially, but significantly (p < 0.01), the maximal decrease in MABP elicited by chrysin glucoside. In the rat isolated aorta preparation, chrysin glucoside (10-100 microm) inhibited in a concentration-dependent manner the noradrenaline (1 microm) induced contractions (IC(50) = 52 microm). This relaxant activity of chrysin glucoside was significantly reduced by incubation of the endothelium-intact rings with l-NOArg (100 microm), (80 +/- 4.7% vs 48 +/- 5.06% in the absence of L-NOArg). In conclusion, these results demonstrate a diuretic and hypotensive action of a chrysin glucoside from Calycotome villosa in anaesthetized rats and indicating an action on renal function, and an active vascular relaxation mediated partially through nitric oxide release.     

Acute diuretic effect of aqueous extract of Retama raetam in normal rats

The purpose of this study was to examine the acute diuretic effect of the water extract of the aerial parts of Retama raetam (RR) at a dose of 5 mg/kg/h in normal rats. The aqueous extract was administered intravenously and the diuresis was followed within 4 h after starting the treatment. Intravenous administration of the aqueous RR extract produced a significant increment on diuresis from the second hour (p<0.01) to the fourth hour (p<0.001). Furosemide at a dose of 0.1 mg/kg/h had a similar effect when compared to RR administration. Parallel, the noticed increase of diuresis was associated with an elevation of glomerular filtration rate (p<0.05) and a significant decrease of urinary osmolarity (p<0.001). However, RR extract did not affect plasma urea levels, urine pH, plasma osmolarity and hematocrite. It is then concluded that the water extract of the aerial parts of RR exhibited a significant diuretic effect in normal rat.     

尿毒清片对正常大鼠利尿及血瘀大鼠血液流变学的影响

目的 :观察尿毒清片对正常大鼠利尿及血瘀大鼠血液流变学的影响并与原剂型比较 ,为其临床应用和剂型改革提供实验依据。方法 :用代谢笼试验方法 ,观察尿毒清片对 1%生理盐水溶液负荷大鼠排尿的影响 ;采用LG R80全自动血液粘度测试仪测定血瘀大鼠模型全血、血浆的粘度变化 ;分离血浆 ,用比浊法测定纤维蛋白原含量。结果 :尿毒清片各剂量组对正常大鼠均具有利尿作用 ,但只有大、中剂量增加 6h内尿量具有统计学意义 ;清片各剂量组均可明显降低血瘀大鼠的全血粘度 ,降低血浆纤维蛋白原含量 ,作用强于尿毒清颗粒剂组。结论 :尿毒清片具有利尿 ,改善血瘀大鼠的血液流变学的作用 ,有利于延缓CRF的进程。     

Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats

The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.     

Pharmacological basis for the empirical use of Eugenia uniflora L. (Myrtaceae) as antihypertensive.

The rational basis for the use of Eugenia uniflora L. (Myrtaceae) as antihypertensive in Northeastern Argentina was assessed in normotensive rats. Intraperitoneal administration of the aqueous crude extract (ACE) decreased blood pressure (BP) of normotensive rats dose-dependently until 47.1 +/- 8.2% of control. The effective-dose 50 was 3.1 +/- 0.4 mg dried leaves/kg (d.l./kg) (yielding of ACE: 17% w/w). To determine the origin of hypotensive activity. Alpha-adrenergic antagonistic and vasorelaxant ACE activities were tested. The dose-response curve for phenylephrine on BP was inhibited non-competitively until 80% of its maximal effect (at 8 mg d.l. ACE/kg). Perfusion pressure (PP) of rat hindquarters (previously vasoconstricted by high-K+) was decreased by ACE in a concentration-dependent manner until -32.3 +/- 11.5% of tonic contraction at 1.2 g d.l. ACE/100 ml. In addition, A.C.E demonstrated diuretic activity at a dose (120 mg d.l./kg) higher than the hypotensive one. It was almost as potent as amiloride, but while amiloride induced loss of Na+ and saving of K+, ACE induced decrease in Na+ excretion. The results suggest that the empirical use of Eugenia uniflora L. (Myrtaceae) is mostly due to a hypotensive effect mediated by a direct vasodilating activity, and to a weak diuretic effect that could be related to an increase in renal blood flow.     

Effects of Opuntia megacantha on blood glucose and kidney function in streptozotocin diabetic rats

The purpose of the study was to investigate the effects of Opuntia megacantha leaf extracts on blood glucose concentrations and kidney function in normal and streptozotocin (STZ)-diabetic rats. STZ-diabetic and non-diabetic rats were orally administered extracts of O. megacantha leaves (20 mg/100 g body weight) daily for 5 weeks and respective control rats were administered normal saline (0.1 ml/100 mg body weight). Urine volume, urinary outputs of Na+, K+ and creatinine were monitored daily over the 5-week period. Plasma concentrations of Na+, K+, urea and creatinine and the glomerular filtration rate (GFR) as assessed by creatinine clearance were determined after 5 weeks. Plasma glucose concentrations in STZ-diabetic and non-diabetic rats were reduced by the administration of leaf extracts of O. megacantha. However, leaf extracts increased urinary Na+ output in STZ-diabetic and non-diabetic rats, concomitantly with a reduction in plasma concentration of the ion. O. megacantha leaf extracts significantly increased plasma creatinine and urea concentrations in non-diabetic and STZ-diabetic rats. Administration of the leaf extract was also associated with an increased GFR in STZ-diabetic rats (from 1.8 +/- 0.3 ml/min to 2.8 +/- 0.3 ml/min, n = 8) although the rate was unaltered in non-diabetic rats. The results suggest that leaf extracts of O. megacantha not only reduce blood glucose levels, but may be toxic to the kidney as shown by the elevation in plasma urea and creatinine concentrations and the reduction of plasma Na+ concentration.     

Stevioside effect on renal function of normal and hypertensive rats.

Physiological and pharmacological experiments have suggested that stevioside from the leaves of Stevia rebaudiana acts as a typical systemic vasodilator. The effect of stevioside on renal function in both normal and with experimental renal hypertension rats (GII) was evaluated using clearance techniques. Stevioside provoked hypotension, diuresis and natriuresis in both the normal and hypertensive rats. Normal rats presented an increase in renal plasma flow (RPF) and glomerular filtration rate (GFR) constant following stevioside administration. The last effect is in part due to vasodilation of both the afferent and efferent arterioles. Moreover, stevioside infusion in hypertensive rats caused an increase in RPF and GFR. These data are consistent with impairment of a renal autoregulation mechanism in this experimental hypertensive model.     

Vandellia cordifolia regulated cell proliferation and cytokines production in human mononuclear cells

Vandellia cordifolia (V. cordifolia) used for treatment inflammation in traditional Chinese medicine was selected for immunopharmacological activity test. The effects of V. cordifolia extracted fractions on human mononuclear cells (HMNC) proliferation were determined by tritiated thymidine uptake. The results indicated that VC-ME fraction suppressed HMNC proliferation activated with phytohemagglutinin (PHA) and stimulated cell cycle progression was arrested at the G0/G1 stage. The inhibitory mechanisms may involve the blocking of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production, since VC-ME suppressed IL-2 and IFN-gamma production of HMNC in a dose-dependent manner. Therefore, it is suggested that immunomodulatory agents are contained in V. cordifolia.     

Acute diuretic effect of continuous intravenous infusion of an aqueous extract of Coriandrum sativum L. in anesthetized rats

AIM OF THE STUDY: The present investigation was carried out to evaluate the acute diuretic activity of continuous intravenous infusion of an aqueous extract of the seed of Coriandrum sativum L. Apiaceae (coriander) in rats. MATERIALS AND METHODS: The aqueous extract of coriander seed was administered by continuous intravenous infusion (120 min) at two doses (40 and 100mg/kg) to anesthetized Wistar rats. Furosemide (10mg/kg), a standard diuretic was used as the reference drug. Excretion of water and electrolytes (sodium, potassium and chloride) in urine was measured, and glomerular filtration rate (equal to creatinine clearance) was determined. RESULTS: The crude aqueous extract of coriander seeds increased diuresis, excretion of electrolytes, and glomerular filtration rate in a dose-dependent way; furosemide was more potent as a diuretic and saluretic. The mechanism of action of the plant extract appears to be similar to that of furosemide. CONCLUSIONS: The aqueous extract of coriander seed possesses diuretic and saluretic activity, thus, validating the use of coriander as a diuretic plant in Moroccan pharmacopoeia.