Asiatic acid influences parasitaemia reduction and ameliorates malaria anaemia in P. berghei infected Sprague-Dawley male rats.

BACKGROUND: Current malaria treatment is either "anti-parasitic", "anti-infectivity" or both without addressing the pathophysiological derangement (anti-disease aspect) associated with the disease. Asiatic acid is a natural phytochemical with oxidant, antioxidant and anti-inflammatory properties whose effect on malarial and accompanying pathophysiology are yet to be investigated. Asiatic acid influence in P. berghei-infected Sprague Dawley rats on %parasitaemia and malarial anaemia were investigated. METHODS: Plasmodium berghei-infected rats (90-120 g) were orally administered with Asiatic acid (5, 10, 20 mg/kg) and 30 mg/kg chloroquine as a positive control. Changes in %parasitaemia and haematological parameters in Asiatic acid administered rats were monitored in a 21 day study and compared to controls. RESULTS: All animals developed stable parasitaemia (15-20 %) by day 7. Asiatic acid doses suppressed parasitaemia, normalised haematological measurements and influenced biophysical characteristics changes. Most positive changes were associated with intragastric administration of 10 mg/kg Asiatic acid dose. Peak %parasitaemia in Asiatic acid administration occurred at days 12 with a shorter time course compared to day 9 for chloroquine (30 mg/kg) treatment with a longer time course. CONCLUSIONS: Oral Asiatic acid administration influenced %parasitaemia suppression, ameliorated malarial anaemia and increased biophysical properties on infected animals. Asiatic acid may be a replacement alternative for chloroquine treatment with concomitant amelioration of malaria pathophysiology. Due to different action time courses, Asiatic acid and chloroquine may be possible candidates in combination therapy.

The effects of medicinal plants on renal function and blood pressure in diabetes mellitus.

Diabetes mellitus is one of the most common chronic global diseases affecting children and adolescents in both the developed and developing nations. The major types of diabetes mellitus are type 1 and type 2, the former arising from inadequate production of insulin due to pancreatic ß-cell dysfunction, and the latter from reduced sensitivity to insulin in the target tissues and/or inadequate insulin secretion. Sustained hyperglycaemia is a common result of uncontrolled diabetes and, over time, can damage the heart, eyes, kidneys and nerves, mainly through deteriorating blood vessels supplying the organs. Microvascular (retinopathy and nephropathy) and macrovascular (atherosclerotic) disorders are the leading causes of morbidity and mortality in diabetic patients. Therefore, emphasis on diabetes care and management is on optimal blood glucose control to avert these adverse outcomes. Studies have demonstrated that diabetic nephropathy is associated with increased cardiovascular mortality. In general, about one in three patients with diabetes develops end-stage renal disease (ESRD) which proceeds to diabetic nephropathy (DN), the principal cause of significant morbidity and mortality in diabetes. Hypertension, a well-established major risk factor for cardiovascular disease contributes to ESRD in diabetes. Clinical evidence suggests that there is no effective treatment for diabetic nephropathy and prevention of the progression of diabetic nephropathy. However, biomedical evidence indicates that some plant extracts have beneficial effects on certain processes associated with reduced renal function in diabetes mellitus. On the other hand, other plant extracts may be hazardous in diabetes, as reports indicate impairment of renal function. This article outlines therapeutic and pharmacological evidence supporting the potential of some medicinal plants to control or compensate for diabetes-associated complications, with particular emphasis on kidney function and hypertension.

Lactogenic activity of rats stimulated by Gunnera perpensa L. (Gunneraceae) from South Africa.

Gunnera perpensa L. (Gunneraceae) is a medicinal plant used by Zulu traditional healers to stimulate milk production. The effect of an aqueous extract of the rhizome of the plant on milk production in rats was investigated. Female lactating rats that received oral doses of the extract of G.perpensa significantly (p<0.05) produced more milk than controls. The plant extract did not however, significantly influence the levels of prolactin, growth hormone, progesterone, cortisol, ALT, AST and albumin in the blood. The mammary glands of rats treated with the extract showed lobuloalveolar development. The extract (0.8 µg/ml) was also found to stimulate the contraction of the uterus and inhibit (23%) acetylcholinesterase activity. The cytotoxicity of the extract (LC50) to two human cell lines (HEK293 and HepG2) was 279.43 µg/ml and 222.33µg/ml, respectively. It is inferred that the plant extract exerts its activity on milk production and secretion by stimulating lobuloalveolar cell development and the contraction of myoepithelial cells in the alveoli. It is concluded that Gunnera perpensa contains constituents with lactogenic activity that apparently contribute to its effectiveness in folk medicine.

Anti-malarial drug formulations and novel delivery systems: a review.

Artemisinin combination therapies have decreased malaria associated morbidity and mortality in several parts of the world. On the other hand, malaria cases have increased in sub-Saharan Africa largely due to falciparum resistance to the most frequently used drugs (chloroquine and sulphadoxine/pyrimethamine (SP) combination). Therapeutic failure has also been attributed in part to adverse effects of anti-malarial drugs and patients' non-compliance due to inconvenient dosing schedules. We consider that formulation and evaluation of novel drug delivery systems is not only less expensive than developing new drugs, but may also improve delivery of anti-malarials at the desired rates. In this review we evaluate the therapeutic efficacy of existing anti-malarial drugs and assess the feasibility of developing novel formulations and delivery systems.

Synergistic antihyperglycemic effects between plant-derived oleanolic acid and insulin in streptozotocin-induced diabetic rats.

Studies from our laboratories indicate that Syzygium cordatum leaf extract contains triterpene mixtures [oleanolic acid (OA) and ursolic acid (UA)] with hypoglycemic properties. The aims of this study were to investigate the hypoglycemic effects of Syzygium aromaticum-derived OA and whether OA influenced the blood glucose lowering effects of insulin in streptozotocin (STZ)-induced diabetic rats. We envisaged that OA may provide a strategy with different mechanism of action for effective diabetic therapy because no single-marketed antidiabetic drug is capable of achieving long-lasting blood glucose control. The effects of various doses of OA and/or standard antidiabetic drugs on blood glucose were monitored in nondiabetic and STZ-induced diabetic rats given a glucose load after an 18-h fast. Rats treated with deionized water and standard antidiabetic drugs acted as untreated and treated positive controls, respectively. Blood glucose concentrations were measured at 15-min intervals for the first hour and hourly thereafter for 3 h. Blood glucose concentrations were also monitored in animals treated with OA and/or standard antidiabetic drugs for 5 weeks. OA like insulin decreased blood glucose concentrations in nondiabetic and STZ-induced diabetic rats. Combined OA and insulin treatment had even greater antihyperglycemic response, suggestive of a synergistic effect of the two. After 5 weeks, STZ-induced diabetic rats exhibited hyperglycemia and depleted hepatic and muscle glycogen concentrations. OA treatment lowered the blood glucose with concomitant restoration of glycogen concentrations to near normalcy. Our results suggest that OA may have a role in improving insulin sensitivity. These findings merit further research in this field.

The renal effects of blood glucose-lowering plant-derived extracts in diabetes mellitus--an overview.

Diabetes mellitus, a disorder characterized by chronic hyperglycemia and excessive urine excretion, is associated with complications such as atherosclerosis, cardiac dysfunction, and nephropathy. Renal disease, which develops through a number of metabolic pathways in diabetes, is characterized by functional as well as structural abnormalities of the kidney. The most common cause of end-stage renal disease (ESRD) is diabetic nephropathy, which accounts for significant morbidity and mortality. Current conventional diabetes therapy using blood glucose-lowering medications has limitations in averting the development of renal diseases. The onset of diabetic nephropathy is associated with a progressive rate of decline in renal function, urinary albumin excretion, and glomerular filtration rate (GFR). Diabetes mellitus treatment should therefore aim to intervene on promoters of the decline in renal function in diabetes to avert adverse outcomes. Preventing the pathogenesis of nephropathy with therapeutic interventions based on specific alterations in kidney function represents a plausible approach. Cumulative evidence suggests that some herbal extracts with hypoglycaemic properties may have beneficial effects on some processes associated with a decline in renal function, as well as reduce the severity of nephropathy in diabetic experimental animals. On the other hand, some herbal extracts may be hazardous in diabetes, as reports indicate impairment of renal function. This review outlines current evidence supporting plant extracts with the potential of averting progressive renal diabetic complications as well as the nephrotoxicity of some herbal extracts.

Renal effects of plant-derived oleanolic acid in streptozotocin-induced diabetic rats.

Previous studies from our laboratories indicate that the anti-diabetic effects of Syzygium cordatum (Hochst.) [Myrtaceae] leaf extract in streptozotocin-induced diabetic rats may be attributed in part to mixtures of triterpenes, oleanolic acid (3ss-hydroxy-olea-12-en-28-oic acid, OA) and ursolic acid (3ss -hydroxyl-urs-12-en-28-oic acid, UA). For the bioactive compounds to have potential in diabetes management, they should alleviate or prevent complications of diabetes mellitus, kidney function, and cardiovascular disorders. This study was, therefore, designed to assess whether S. cordatum leaf derived OA influenced renal function evaluated by the ability to increase urinary Na(+) outputs parameters and creatinine clearance (Ccr) of streptozotocin (STZ)-induced diabetic rats. Extraction and fractionation of S. cordatum powdered leaf ethyl acetate-solubles (EAS) yielded mixtures of OA/UA and methyl maslinate/methyl corosolate. Recrystallization of OA/UA mixture using ethanol afforded OA, the structure of which was confirmed by NMR spectroscopy ((1)H & (13)C). Acute effects of OA on kidney function and mean arterial blood pressure (MAP) were investigated in anesthetized rats challenged with hypotonic saline after a 3.5-h equilibration for 4h of 1 h control, 1.5 h treatment, and 1.5 h recovery periods. OA was added to the infusate during the treatment period. Chronic effects of OA were studied in individually caged rats treated twice daily with OA (60 mg/kg, p.o.) for five weeks. By comparison with respective control animals administration, OA significantly increased Na(+) excretion rates of non-diabetic and STZ-induced diabetic rats without affecting urine flow, K(+) and Cl(-) rates. At the end of five weeks, OA treatment significantly (p < 0.05) increased Ccr in non-diabetic (2.88 +/- 0.14 vs. 3.71 +/- 0.30 ml/min) and STZ-diabetic rats (1.81 +/- 0.32 vs. 3.07 +/- 0.16 ml/min) with concomitant reduction of plasma creatinine concentration (n = 6 in all groups). OA also caused significant decreases in MAP in non-diabetic and STZ-induced diabetic rats. These findings suggest that OA may have beneficial effects on some processes associated with renal derangement of STZ-induced diabetic rats.

Effects of Persea americana Mill (Lauraceae) ["Avocado"] ethanolic leaf extract on blood glucose and kidney function in streptozotocin-induced diabetic rats and on kidney cell lines of the proximal (LLCPK1) and distal tubules (MDBK).

Extracts of Persea americana Mill (Lauraceae) ("Avocado") have been traditionally used to treat hypertension and diabetes mellitus. Accordingly, we studied the hypoglycaemic and renal function effects of P. americana leaf ethanolic extracts (PAE) in STZ-induced diabetic rats. Oral glucose tolerance responses to various doses of PAE were monitored in fasted rats following a glucose load. Rats treated with deionized water or standard hypoglycaemic drugs acted as untreated and treated positive controls, respectively. Acute renal effects of PAE were investigated in anesthetized rats challenged with 0.077 M NaCl after a 3.5-h equilibration for 4 h comprising 1 h control, 1.5 h treatment and 1.5 h recovery periods. PAE was added to the infusate during the treatment period. Hepatic glycogen concentration was measured after 6 weeks of daily treatment with PAE. PAE induced dose-dependent hypoglycaemic responses in STZ-induced diabetic rats while subchronic PAE treatment additionally increased hepatic glycogen concentrations. Acute PAE infusion decreased urine flow and electrolyte excretion rates, whilst subchronic treatment reduced plasma creatinine and urea concentrations. These results indicate not only the basis of the ethnomedicinal use of P. americana leaf extract in diabetes management, but also of need for further studies to identify and evaluate the safety of PAE's bioactive compounds.

Sclerocarya birrea [(A. Rich.) Hochst.] [Anacardiaceae] stem-bark ethanolic extract (SBE) modulates blood glucose, glomerular filtration rate (GFR) and mean arterial blood pressure (MAP) of STZ-induced diabetic rats.

Studies in our laboratories suggest that Sclerocarya birrea stem-bark ethanolic extract (SBE) has hypoglycemic properties. Accordingly, we investigated the effects of SBE on major complications of diabetes mellitus; blood glucose, renal function and mean arterial blood pressure (MAP) in non-diabetic and STZ-induced diabetic rats. Oral glucose tolerance test responses to various SBE doses (60, 120 and 240 mg kg(-1)) were studied in fasted rats following glucose load (0.86 g kg(-1), p.o.). Rats treated with deionized water (3 ml kg(-1) p.o.), or standard hypoglycemic drugs (insulin, 100 microg kg(-1), s.c.; metformin, 500 mg kg(-1), p.o. or glibenclamide, 500 microg kg(-1), p.o) acted as untreated and treated positive controls, respectively. Blood was collected in non-diabetic rats after 45 min of SBE, metformin or glibenclamide for plasma insulin determination. Acute SBE effects on renal function and MAP were studied in anesthetized rats challenged with hypotonic saline after 3.5h equilibration for 4h of 1h control, 1.5h treatment and 1.5h recovery periods. SBE was added to the infusate during the treatment period. Chronic effects were monitored for 5 weeks in animals daily treated with SBE (120 mg kg(-1) p.o.) while hepatic glycogen concentration was measured at the end of the experimental period. SBE exhibited dose-dependent reduction in blood glucose concentration. SBE and metformin did not affect plasma insulin secretion in non-diabetic rats, while glibenclamide increased plasma insulin concentration. The hypoglycemic effect of SBE treatment was associated with increased hepatic glycogen synthesis. Acute SBE administration did not significantly alter kidney function, but chronic SBE treatment for decreased plasma urea and creatinine concentrations of STZ-diabetic rats with concomitant increase in GFR by comparison with control rats at the corresponding period (0.7+/-0.2 vs. 1.4+/-0.3 ml min(-1)). SBE treatment reduced blood pressure in all groups of animals. The observations suggest that SBE has reno- and cardio-protective effects in diabetes mellitus. The current results indicate the basis for SBE use as complementary remedy in diabetes.

Cardiovascular Effects of Helichrysum ceres S Moore [Asteraceae] Ethanolic Leaf Extract in Some Experimental animal Paradigms : Cardiovascular Topic

The aim of this study was to examine some in vivo and in vitro cardiovascular effects of Helichrysum ceres leaf ethanolic extract (HCE) in experimental animal paradigms. The acute effects of HCE on blood pressure were studied in anaesthetised normotensive male Wistar rats challenged with intravenous hypotonic saline infusion after a 3.5-hour equilibration for four hours of one-hour control; 1.5-hour treatment and 1.5-hour recovery periods. HCE was added to the infusate during the treatment period. Sub-chronic hypotensive effects of HCE were examined in weanling Dahl Salt-sensitive (DSS) genetically hypertensive rats; which progressively develop hypertension with age; treated with HCE (80 mg / kg) every third consecutive day for seven weeks. isolated atrial muscle strips; portal veins and descending thoracic aortic rings of healthy normotensive Wistar rats were used to investigate the vascular effects of HCE. Acute HCE administration caused a significant (p 0.05) fall in blood pressure in the normotensive anaesthetised Wistar rats. DSS hypertensive rats treated with HCE displayed low arterial blood pressure and heart rate values from weeks five to seven. HCE produced concentration-dependent negative inotropic and chronotropic effects on rat isolated electrically driven left; and spontaneously beating right atrial muscle preparations; respectively. HCE also evoked concentration-dependent relaxation responses of endothelium-intact aortic rings and portal veins isolated from healthy normotensive Wistar rats. The vasorelaxant effects of HCE in intact aortic rings were significantly reduced; but not completely abolished by adding endothelial-derived factor (EDRF) inhibitor; L-NAME; suggesting that the vasorelaxant effect of the extract is mediated via EDRF-dependent and independent mechanisms. The results of the study suggest that the hypotensive action of HCE is elicited; in part; directly by decreasing myocardial contractile performance and total peripheral vascular resistance due to its negative inotropic and chronotropic effects on rat isolated atrial muscle strips; and vasorelaxant effects on isolated vascular smooth muscles. The observed cardiovascular effects of HCE partly support the basis for its use in the management of high blood pressure in folkloric medicine

Effects of Ficus thonningii (Blume) [Morarceae] stem-bark ethanolic extract on blood glucose, cardiovascular and kidney functions of rats, and on kidney cell lines of the proximal (LLC-PK1) and distal tubules (MDBK).

Previous observations indicate that Ficus thonningii (Blume) [Moraceae] stem-bark extracts may be useful in the control of diabetes mellitus. Accordingly, we investigated in some experimental animal paradigms the effects of F. thonningii stem-bark ethanolic extract (FTE) on renal and cardiovascular functions as complications of diabetes. Oral glucose tolerance tests were conducted in separate groups of non-diabetic and STZ-treated diabetic rats given glucose load (0.86 g x kg(-1), p.o.) after 18-h fast, followed by various FTE doses (60, 120, and 240 mg x kg(-1)). Rats treated with deionized water (3 mL x kg(-1) p.o.), or metformin (500 mg x kg(-1) p.o.) acted as untreated and treated positive controls, respectively. Blood glucose was monitored at 15-min intervals for the first hour, and hourly thereafter for 3 h. Acute effects of FTE on kidney function and mean arterial blood pressure (MAP) were investigated in anaesthetized rats challenged with hypotonic saline after a 3.5-h equilibration for 4 h of 1 h control, 1.5 h treatment, and 1.5 h recovery periods. FTE was added to the infusate during the treatment period. Chronic effects of FTE were studied in individually caged rats treated daily with FTE (120 mg x kg(-1), p.o.) for five weeks. Cytotoxicity of FTE was assessed by dye-reduction colorimetric (MTT) assay on MDBK and LLCPK1 kidney cell lines exposed for 24 h, 48 h, and 72 h to graded concentrations of the extract. Myocardial contractile performance was evaluated on rat isolated atrial muscle strips. FTE, like metformin, decreased blood glucose levels in non-diabetic and STZ-diabetic rats. Both acute and chronic FTE treatments did not affect renal function. In vitro studies demonstrated that FTE increased MDBK cell metabolic activity by an average of 15% (72 h), and LLCPK1 mirrored the controls. Acute intravenous infusion of FTE reduced the MAP from 119 +/- 1 mmHg to 98 +/- 4 mmHg. The MAP also was reduced throughout the five-week experimental study period. FTE also produced concentration-dependent, negative inotropic and chronotropic effects on rat isolated, electrically driven left-, and spontaneously beating right-, atrial muscle preparations. Our experimental findings suggest that FTE possesses reno- and cardio-protective effects in diabetes mellitus.

Cardiovascular effects of Persea americana Mill (Lauraceae) (avocado) aqueous leaf extract in experimental animals.

The cardiovascular effects of Persea americana Mill (Lauraceae) aqueous leaf extract (PAE) have been investigated in some experimental animal paradigms. The effects of PAE on myocardial contractile performance was evaluated on guinea pig isolated atrial muscle strips, while the vasodilatory effects of the plant extract were examined on isolated portal veins and thoracic aortic rings of healthy normal Wistar rats in vitro. The hypotensive (antihypertensive) effect of the plant extract was examined in healthy normotensive and hypertensive Dahl salt-sensitive rats in vivo. P americana aqueous leaf extract (25-800 mg/ml) produced concentration-dependent, significant (p < 0.05-0.001), negative inotropic and negative chronotropic effects on guinea pig isolated electrically driven left and spontaneously beating right atrial muscle preparations, respectively. Moreover, PAE reduced or abolished, in a concentration-dependent manner, the positive inotropic and chronotropic responses of guinea pig isolated atrial muscle strips induced by noradrenaline (NA, 10(-10)-10(-5) M), and calcium (Ca(2+), 5-40 mM). PAE (50-800 mg/ml) also significantly reduced (p < 0.05-0.001) or abolished, in a concentration-dependent manner, the rhythmic, spontaneous, myogenic contractions of portal veins isolated from healthy normal Wistar rats. Like acetylcholine (ACh, 10(-8)-10(-5) M), the plant extract (25- 800 mg/ml) produced concentration-related relaxations of isolated endothelium-containing thoracic aortic rings pre-contracted with noradrenaline. The vasorelaxant effects of PAE in the isolated, endothelium-intact aortic rings were markedly inhibited or annulled by N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-5) M), a nitric oxide synthase inhibitor. Furthermore, PAE (25-400 mg/kg iv) caused dose-related, transient but significant reductions (p < 0.05-0.001) in the systemic arterial blood pressure and heart rates of the anaesthetised normotensive and hypertensive rats used. The results of this laboratory animal study indicate that PAE caused bradycardia, vasorelaxation and hypotension in the mammalian experimental models used. The vasorelaxant action of PAE was endothelium dependent, and was, therefore, possibly dependent on the synthesis and release of nitric oxide (NO). The vasorelaxant effects of PAE appeared to contribute significantly to the hypotensive (antihypertensive) effects of the plant extract. However, the findings of this study tend to suggest that P americana leaf could be used as a natural supplementary remedy in essential hypertension and certain cases of cardiac dysfunctions in some rural Africa communities.

Some in vitro and in vivo cardiovascular effects of Hypoxis hemerocallidea Fisch & CA Mey (Hypoxidaceae) corm (African potato) aqueous extract in experimental animal models.

This study was undertaken to investigate some cardiovascular effects of Hypoxis hemerocallidea Fisch & CA Mey (Hypoxidaceae) corm (African potato) aqueous extract in experimental animal paradigms. The effect of the corm aqueous extract (APE) on myocardial contractile performance was evaluated on guinea-pig isolated atrial muscle strips in vitro; whereas the antihypertensive (hypotensive) effect of the plant extract was examined in hypertensive Dahl salt-sensitive rats in vivo. APE (25-400 mg/ml) produced concentration-dependent, significant (p < 0.05-0.001) negative inotropic and negative chronotropic effects on guinea-pig isolated electrically driven left, and spontaneously beating right atrial muscle preparations, respectively. Moreover, APE reduced or abolished, in a concentrationdependent manner, the positive inotropic and chronotropic responses of guinea-pig isolated atrial muscle strips induced by noradrenaline (NA, 1-100 microM) and calcium (Ca2+, 5-40 mM). The negative inotropic and chronotropic effects of APE on guinea-pig atrial muscle strips were not modified by exogenous administration of atropine (ATR, 7.5 x 10(-7)-2.5 - 10(-6) M) to the bath fluid. APE also significantly reduced (p < 0.05-0.001) or abolished in a concentration-dependent manner, the rhythmic, spontaneous, myogenic contractions of portal veins isolated from rats. Furthermore, APE caused dose-related transient but significant (p < 0.05-0.001) reductions in the systemic arterial blood pressure and heart rates of the hypertensive rats used. Although the exact mechanisms of the cardiodepressant and the transient hypotensive (antihypertensive) actions of APE could not be established in the present study, we exclude the involvement of the cholinergic system; since the extract's cardiovascular effects were resistant to atropine pretreatment. However, the results of this laboratory animal study indicated that APE caused bradycardia and brief hypotension in the mammalian experimental models used. These observations tend to suggest that the herb may be used as a natural supplementary remedy in some cases of cardiac dysfunctions and in essential hypertension. The findings of this experimental animal study lend pharmacological support to the folkloric, anecdotal uses of the African potato in the management and/or control of certain cardiac dysfunctions and essential hypertension in some rural communities of southern Africa.

Effects of oral administration of some herbal extracts on food consumption and blood glucose levels in normal and streptozotocin-treated diabetic rats.

Previous studies in our laboratories suggest that oral administration of some herbal extracts reduce blood glucose concentrations in rats, possibly by interfering with food consumption and/or gastrointestinal absorption of food. Accordingly, we monitored the amounts of food consumed and body weights in separate groups of nondiabetic and streptozotocin-treated diabetic rats, orally treated with some plant extracts (20 mg 100 g -1 body weight) daily for 5 weeks. Control animals were administered the vehicle, citrate buffer (0.1 ml 100 g -1 body weight). Separate groups of rats administered allopathic hypoglycemic drugs metformin (50 mg 100 g -1 body weight) or glibenclamide (5 microg 100 g -1 body weight) acted as positive control animals. After 5 weeks, blood glucose concentrations were reduced in all the groups. Tapinanthus nyasicus leaf, Ficus thoningii bark, Solanum incanum fruit, and Morus alba leaf extracts decreased weekly food consumption throughout the 5-week study period. Similar results were obtained for the groups treated with metformin or glibenclamide. However, food consumption was increased by S. incanum root, Aloe chabaudii leaf, or Allium sativum bulb extracts, and this was associated with high prevalence of diarrhea. The herbal extracts and metformin did not affect serum insulin concentration in nondiabetic rats, while glibenclamide increased serum insulin concentration. In conclusion, it may be inferred that the herbal extracts examined produced hypoglycemia, probably by interfering with either food intake or gastrointestinal glucose absorption (as reported for metformin). These findings merit long-term investigation.

Effects of Hypoxis hemerocallidea (Fisch. & C.A. Mey.) [Hypoxidaceae] corm (African Potato) aqueous extract on renal electrolyte and fluid handling in the rat.

Current biomedical evidence suggests that Hypoxis hemerocallidea (Fisch. & C.A. Mey.) [Hypoxidaceae] (African Potato [AP]) corm extract may be useful in the management of type 2 diabetes mellitus. However, more recent reports have also indicated that certain herbal extracts attenuate the deterioration of kidney function in diabetes mellitus. Accordingly, this study investigated the effects of short- (acute) and long-term (chronic) administration of H. hemerocallidea corm aqueous extract (APE) on renal fluid and electrolyte handling in male Wistar rats. Acute effects of APE were investigated in separate groups of anesthetized rats challenged with a continuous jugular infusion of 0.077 M NaCl at 9 mL x h(- 1). After a 3.5-h equilibration period, consecutive 30-min urine collections were made over the subsequent 4 h of 1-h control, 1.5-h treatment, and 1.5-h recovery periods for measurements of urine flow, Na+, and K+ excretion rates. To establish the effects of acute APE, the extract was added to the infusate at doses of 90, 180, or 360 microg x h (-1) in separate groups of rats during the treatment period. For chronic studies, individually caged rats were administered twice with APE (30 mg x kg (-1) PO) every third consecutive day at 09h00 and 17h00 for 5 weeks. Control rats received distilled water (3 mL x kg(-1)). Urine volume and total urinary outputs of creatinine, Na+, and K+ were determined from 24-h samples. Acute infusion of APE produced a dose-dependent, significant (p < 0.01) decrease in urine flow, K+, and Na+ excretion rates. Chronic APE treatment significantly reduced urinary Na+ output between weeks 2 and 5, without affecting either urine flow or K+ excretion rates. When compared with control animals, APE significantly reduced GFR (2.54+/-0.09 mL x min (-1) vs. 1.52+/-0.02 mL x min (-1)) and increased plasma creatinine concentration (55 +/- 3 micromol x L(-1) vs. 68 +/-6 micromol x L(-1)). The results from this study suggest that the H. hemerocallidea corm aqueous extract may impair kidney function.

Effects of Syzygium cordatum (Hochst.) [Myrtaceae] leaf extract on plasma glucose and hepatic glycogen in streptozotocin-induced diabetic rats.

The present study investigates the hypoglycaemic effect of Syzygium cordatum (Hochst.) [Myrtaceae] leaf extract in non-diabetic and streptozotocin (STZ)-induced diabetic rats. Oral glucose tolerance tests (OGGT) were conducted in non-diabetic and STZ-diabetic rats using orally administered glucose (1.4 g 100 g(-1) body weight) followed by either the leaf extract (6 mg 100 g(-1) body weight) or subcutaneous (sc) injection of metformin (50 mg 100 g(-1)). Weekly plasma glucose and terminal hepatic glycogen concentrations were recorded in control STZ-diabetic rats and diabetic rats orally treated with the leaf extract once every third day for 4 weeks. Administration of the leaf extract decreased plasma glucose from 7.7+/-0.9 mmol l(-1) to 3.7+/-0.6 mmol l(-1) (n = 6), and 21.1+/-2.2 mmol l(-1) to 12.5+/-1.8 mmol l(-1) (n = 7) by 2 1/2 h in non-diabetic and STZ-diabetic rats, respectively. OGTT data in metformin-treated rats were similar at the corresponding time in all groups, except for significant blood glucose reduction by the drug in non-diabetic rats between 1 and 1 1/2 h after treatment. Oral administration of the extract did not affect plasma glucose concentration in STZ-diabetic rats after 4 weeks, although it significantly increased hepatic glycogen content by comparison with untreated STZ-diabetic rats (28+/-5 mg 100 g(-1) body weight, n = 7, versus 16+/-3 mg 100 g(-1) body weight, n = 6). We conclude that Syzygium cordatum leaf extract contains compounds that could be effective in mild diabetes mellitus or in cases of glucose tolerance impairment. The possible mechanism(s) involved in the short-term hypoglycaemic effect of the extract could not be established by the current study.

Transdermal delivery of chloroquine by amidated pectin hydrogel matrix patch in the rat.

The aim of the present study was to investigate the suitability of amidated pectin matrix patch for transdermal chloroquine delivery in an effort to mask the bitter taste when orally administered. Chloroquine has easily measurable outputs that are linked to increased renal Na+ excretion. We thus monitored urinary Na+ output in separate groups intravenously administered chloroquine or topically applied pectin hydrogel chloroquine matrix patch. Male groups of anesthetized Sprague-Dawley rats were placed on a continuous jugular infusion of 0.077 M NaCl at 150 microL min(-1). After 3 h equilibration period, consecutive 20 min urine collections were made over the subsequent 4 h of 1 h control, 1 h 20 min treatment, and 1 h 40 min recovery periods for measurements of urine flow and Na+ and K+ excretion rates. The effects of intravenous chloroquine infusion or topical application of pectin hydrogel chloroquine matrix patch were examined in rats in which the drug was added to the infusate or patch applied onto the shaved area during the 1 h 20 min treatment period. The animals were switched back to the infusate alone for the final 1 h 40 min recovery period. Vehicle infused animals acted as controls. Trunk blood was collected after the treatment period from parallel groups for chloroquine measurements. The plasma chloroquine concentrations following iv chloroquine or application of pectin chloroquine hydrogel matrix patch were 9.3 +/- 0.8 mg L(-1) and 7.3 +/- 1.1 mg L(-1) respectively (n = 7 in both groups). Chloroquine infusion and pectin chloroquine patch significantly (p < 0.01) increased Na+ excretion to peak values of 14.1 +/- 0.9 micromol min(-1). and 20.35 +/- 1.0 micromol min(-1), respectively by comparison with controls (9.1 +/- 0.9 micromol min(-1)), at the corresponding period. The results suggest that the pectin chloroquine patch matrix preparation has potential applications for transdermal delivery of chloroquine and perhaps in the management of malaria.

Effects of Helichrysum ceres extracts on renal function and blood pressure in the rat.

OBJECTIVE: To evaluate the effects of Helicrysum ceres root and leaf extracts on mean arterial blood pressure and renal fluid and electrolyte handling in anesthetized male Sprague-Dawley rats. DESIGN: Cross sectional study. SETTING: Departments of Physiology and Pharmacy, University of Zimbabwe. SUBJECTS: Eight separate groups comprising of control and treated Male Sprague-Dawley rats (n =6 in each group) were anesthetized and placed on a continuous jugular infusion of 0.077 M NaCl at 150 microL min(-1). The left carotid artery was cannulated with polythene tubing and then connected to a pressure transducer for blood pressure measurements. After 3 h equilibration period, consecutive 20 min urine collections and blood pressure measurements were made over the subsequent 4 h of 1 h 20 min control, 1 h treatment and I h 40 min post-equilibration periods for measurements of urine flow and Na+ and K+ excretion rates. Helichrysum ceres leaf extracts at 0.3, 0.6 and 1.2 microg min(-1) roots 0.3, 3 and 6 microg min(-1) were added to the infusate during the treatment period. To establish whether the extracts had activities comparable to drugs already in use, a separate group of animals was administered furosemide (0.12 microg min(-1)) during the treatment period. MAIN OUTCOME MEASURES: Hypotension, Natriuresis and Diuresis. RESULTS: Infusion of graded doses of aqueous leaf extracts of Helicrysum ceres provoked an increase in urine flow rates but did not achieve statistical significance. However, the extracts produced dose dependent decrease in potassium excretion as well as increases in urinary Na+ outputs and diuresis. Administration of the various doses of aqueous root extracts of Helicrysum ceres significantly increased urine flow rate and urinary Na+ excretion in all groups. The intravenous (i.v.) administration of the aqueous root or leaf extracts of Helichrysum ceres significantly depressed mean arterial blood pressure (MAP). The diuretic and natriuretic effects of plant extracts were not significantly different to that of furosemide. CONCLUSION: The results suggest that oral administration to rats of aqueous crude Helicrysum ceres root or leaves extracts induce hypotension and natriuresis.

Effects of Opuntia megacantha leaves extract on renal electrolyte and fluid handling in streptozotocin (STZ)-diabetic rats.

We previously demonstrated that Opuntia megacantha leaves' extracts can reduce blood glucose levels in diabetes mellitus. For O. megacantha leaves' extracts to have potential in the management of diabetes mellitus, it is necessary to establish its detailed effects on renal function since diabetes is associated with renal fluid and electrolyte disturbances. Therefore, the current study was designed to investigate the influence of the extracts on renal function in male diabetic Sprague-Dawley rats. Rats were made diabetic by an i.p. injection of streptozotocin (STZ, 60 mg/kg in citrate buffer). Vehicle injected animals acted as controls. Separate groups of nondiabetic and diabetic rats were orally administered O. megacantha leaves extracts (20 mg/100 g bw) or normal saline (0.1 ml x 100 g(-1) bw) daily for 5 weeks. Urine volume and total urinary outputs of Na+ and K+ were determined from 24 h samples. O. megacantha leaves' extracts significantly (p < 0.01) increased urinary Na+ output in diabetic and nondiabetic rats resulting in significantly (p < 0.01) low plasma concentration by comparison with untreated animals. Treatment with the extract significantly increased FE(Na+) and GFR in all groups. The urinary K+ outputs in nondiabetic was slightly lowered, but did not reach statistically significance. O. megacantha leaves' extracts did not alter plasma aldosterone and AVP concentrations in diabetic and nondiabetic rats in nondiabetic animals. It is concluded that O. megacantha leaves extracts modulate renal water and sodium handling. The mechanisms are not clear.