Histological studies on the retina and cerebellum of Wistar rats treated with ArteetherTM

Introduction: Arteether TM, a derivative of artemisinin, is among the recent drugs that have given renewed hope for combating malarial menace. The present study investigated the effects of arteetherTM on the histology of the retina and cerebellum of Wistar rats. Materials and Methods: Twenty adult albino Wistar rats weighing 150-200 g, were randomly divided into four groups (A, B, C and D) of five animals each and used for this study. Group A rats were given intramuscular (i.m.) arteetherTM (3 mg/kg b.w.) daily for 3 days. Group B rats were given i.m. arteetherTM (6 mg/kg b.w.) daily for 3 days. Group C rats were also given i. m. of arteetherTM (3 mg/kg b. w.) daily for 3 days, and the same dose was repeated at two-weekly intervals for 4 further weeks; while Group D rats which received normal saline (0.9 % w/v, 3 ml/kg b.w.), served as controls. At the end of the experiment, the rats were sacrificed by cervical dislocation. The retina and cerebellum were excised and processed routinely for histopathology changes, using haematoxylin and eosin stain (H & E), as well as Nissl stain. Results: Results obtained showed normal cellular components of the retina and cerebellum in all groups, and no cyto-pathological changes were observed. Conclusion: Thus, this study showed that under light microscopic examination, therapeutic doses of arteetherTM caused no significant cyto-pathologic changes in the retina and cerebellum of Wistar rats.(AU)

Comparative anti-inflammatory properties of Capsaicin and ethyl-aAcetate extract of Capsicum frutescens linn [Solanaceae] in rats.

BACKGROUND: The analgesic effect of capsaicin (the active ingredient in Capsicum frutescens Linn. [Solanaceae]) had been reported in several studies. Current research is being directed at producing analgesics, anti-inflammatory agents with better side effect profile. OBJECTIVES: To investigate if either the ethyl acetate extract of Capsicum frutescens Linn. [Solanaceae] (CFE) or capsaicin (Fluka Biotechnika-CPF) (in addition to the known analgesic properties) has any anti-inflammatory effect comparable to nonsteroidal anti-inflammatory analgesics (NSAIDS). METHODS: The effects of ethyl acetate extract of Capsicum frutescens Linn. [Solanaceae] (CFE) and capsaicin (Fluka Biotechnika-CPF) was examined on rat hind paw. Inflammation was induced in the rat's hind paw by subplantar injections of fresh egg albumin (0.5 ml/kg). Diclofenac (100 mg/kg) was used as the reference anti-inflammatory agent for comparison, while distilled water was used as the placebo. The leucocytes count, corticosterone and C - reactive protein (CRP) levels were measured as biomarkers of inflammation. Data obtained were pooled and analysed using repeated ANOVA, in a general linear model with the CPSS software. RESULTS: Sub-plantar injections of fresh egg albumin (0.5 ml/kg) produced profound and time-related oedema in the rat hind paw of the 'control' rats. Diclofenac (DIC, 100 mg/kg, i.p.) and reference capsaicin (CPF, 2.5 mg/kg, i.p.) significantly inhibited paw swelling at (p<0.05-0.001) (CI 95%) compared to distilled water-treated 'controls'. While the corticosterone levels were all very low in 7 rats treated with capsaicin, the leucocytes count was within normal range in 9 rats. However, in 16 specimens randomly assigned for CRP levels, there were very high CRP readings, up to a magnitude of 10 times the normal range. CONCLUSIONS: Capsaicin in both forms (CFE and CPF) produced anti-inflammatory effects that were comparable to diclofenac in the experimental rat model at p<0.05. It may be concluded that capsaicin has both analgesic and anti-inflammatory properties.

Effects of Ficus exasperata vahl. (moraceae) leaf aqueous extract on the renal function of streptozotocin-treated rats.

The present study was undertaken to evaluate the possible reno-protective effect of Ficus exasperata leaf aqueous extract (FEE) in a rat experimental paradigm of diabetes mellitus. Forty Wistar rats (weighing 200-230 g) were divided into four (A, B, C, and D) groups, each group consisting of 10 rats. Group A rats served as 'control' animals and received citrate buffer (pH 6.3) solution in quantities equivalent to intraperitoneally-administered volumes of streptozotocin (STZ) and FEE. Diabetes mellitus was induced in Groups B and C rats by intraperitoneal injections of STZ (75 mg/kg). Group C rats were additionally treated with FEE (100 mg/kg/day, p.o.) 4 weeks post STZ injections, for 4 consecutive weeks. Group D rats received FEE (100 mg/kg/day p.o.) only for 4 weeks. Post-euthanisation, kidney tissues were excised for histopathological evaluation and processed for light microscopy. Plasma malondialdehyde and tissue nitric oxide were determined. Serum creatinine, blood urea nitrogen, nitrite, and albumin concentrations were measured for the evaluation of renal function. The diabetic rats significantly lost more weight and their blood glucose levels were significantly elevated as compared to the 'control' group of animals. Renal dysfunction was evidenced by kidney hypertrophy, decreased renal blood flow, and increased serum creatinine and nitrite concentrations. Furthermore, vascular dysfunction, as evidenced by decreased carotid blood flow, was observed in the diabetic rats. FEE treatment positively ameliorated the alterations in the biochemical variables in the STZ + FEE-treated rats. In conclusion, our findings suggest that FEE treatment ameliorates STZ-induced nephrotoxicity.

Antipyretic and antinociceptive properties of Mentha longifolia Huds. (Lamiaceae) leaf aqueous extract in rats and mice.

The antipyretic and antinociceptive properties of Mentha longifolia Huds. (Lamiaceae) leaf aqueous extract were investigated using lipopolysaccharide (LPS)-induced pyrexia in rats, and acetic acid and hot plate analgesia tests in mice. Pentoxifylline, paracetamol and morphine were used as standard drugs for comparison. M. longifolia leaf aqueous extract and pentoxifylline (37.5-150 mg/kg i.p.) significantly (P < 0.05-0.02) reduced the LPS (50 g/kg i.m.)-elicited pyrexia. Pentoxifylline (50 mg/kg i.p.) also significantly (P < 0.01) reduced LPS (50 g/kg i.m.)-induced pyrexia. M. longifolia leaf aqueous extract (6.25-100 mg/kg i.p.) and paracetamol (500 mg/kg i.p.) profoundly inhibited the writhes produced by 3% acetic acid. Furthermore, the plant extract (25-400 mg/kg i.p.) and morphine (10 mg/kg i.p.) significantly (P < 0.001) delayed the hot plate reaction time in mice. The LD(50) values for oral and intraperitoneal administration of the plant extract were > 3200 mg/kg and 1730 mg/kg, respectively. Phytochemical analysis revealed the presence of flavonoids, saponins, tannins, reducing sugars, cardiac glycosides and triterpene steroids in the leaves of M. longifolia. These data indicate that M. longifolia leaf aqueous extract has antipyretic and antinociceptive properties. Furthermore, the relatively high LD(50) values obtained for oral and intraperitoneal administration of the plant extract demonstrate that the plant extract is non-toxic to mice.

Grapefruit juice improves glycemic control but exacerbates metformin-induced lactic acidosis in non-diabetic rats.

Recent clinical studies have indicated that grapefruit juice (GFJ) improves insulin resistance and reduces weight gain in humans. The effect of GFJ on glucose tolerance and metformin-induced lactic acidosis in normal, non-diabetic in rats is hereby investigated. Three groups (A, B, C) of 20 male Wistar rats each, were treated with stepwise, escalated oral doses of 0, 1.0, 2.0, 3.0 (group A), and 3.0 ml/kg body weight (groups B and C) of GFJ. Group C rats additionally received 250 mg/kg body weight of metformin. All the animals were sacrificed after 14 days of treatment. Fasting blood glucose levels were significantly (P < 0.0001) lower in GFJ-treated test (2.9 +/- 0.4 mmol/L) compared with control (3.7 +/- 0.39 mmol/L) rats, but 1.5-hr plasma insulin levels were similar. GFJ alone or in combination with metformin, significantly (P < 0.05) lowered blood glucose levels compared with control animals. Blood lactic acid levels were similar in GFJ-treated test (2.81 +/- 1.4 mmol/L) and control (2.54 +/- 0.7 mmol/L) rats, respectively, but were significantly increased (P = 0.0079) in rats that were treated with either metformin alone (5.38 +/- 2.53 mmol/L) or in combination with GFJ (8.31 +/- 3.48 mmol/L). Metformin concentration in liver tissue was significantly higher (P < 0.05) in GFJ-treated (397 +/- 19 microg/g) than in control (280 +/- 15 microg/g) rats, respectively. Plasma metformin levels were comparable between the control (95 +/- 8.1 microg/ml) and GFJ-treated test (108 +/- 20 microg/ml) rats, respectively. Liver tissue metformin concentrations and plasma lactic acid levels showed significant correlation in both control (P = 0.0122; r(2) = 0.9080) and GFJ-treated test rats (P = 0.0005; r(2) = 0.9893). Although GFJ may be beneficial to diabetic patients, it may exacerbate lactic acidosis in diabetic patients taking metformin concurrently.

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.

Analgesic, anti-inflammatory and hypoglycaemic effects of Securidaca longepedunculata (Fresen.) [Polygalaceae] root-bark aqueous extract.

The present study was undertaken to investigate the analgesic, anti-inflammatory and hypoglycaemic properties of Securidaca longepedunculata (Fresen.) root-bark aqueous extract (SLE) in mice and rats. The analgesic effect of SLE was evaluated by 'hot-plate' and 'acetic acid' analgesic test methods in mice; while its anti-inflammatory and hypoglycaemic effects were examined in rats, using fresh egg albumin-induced pedal oedema, and streptozotocin (STZ)-induced diabetes mellitus models. Morphine (MPN, 10 mg/kg), diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used as reference drugs for comparison. SLE (50-800 mg/kg i. p.) produced dose-dependent, significant (p < 0.05-0.001) analgesic effects against thermally- and chemically-induced nociceptive pain in mice. The plant's extract (SLE, 50-800 mg/kg p. o.) also dose-dependently and significantly inhibited (p < 0.05-0.001) fresh egg albumin-induced acute inflammation, and caused significant hypoglycaemia (p < 0.05-0.001) in normal (normoglycaemic) and STZ-treated diabetic (hyperglycaemic) rats. The results of this experimental animal study indicate that S. longepedunculata root-bark aqueous extract (SLE) possesses analgesic, anti-inflammatory and hypoglycaemic properties. These findings lend pharmacological credence to the anecdotal, folkloric and ethnomedical uses of S. longepedunculata root-bark in the treatment, management and/or control of painful, arthritic, inflammatory conditions, as well as in the management and/or control of type 2 diabetes mellitus in some rural communities of South Africa.

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

Insulin-induced immunohistochemical and morphological changes in pancreatic beta-cells of streptozotocin-treated diabetic rats.

This study was undertaken to investigate insulin-induced changes in the immunohistochemistry and morphometry of pancreatic beta-cells, plasma insulin and blood glucose concentrations of streptozotocin (STZ)-treated diabetic rats. Fifty male Wistar rats (200-250 g) were randomly divided into three experimental groups (viz., A: control group, B: STZ-treated group, and C: STZ+insulin-treated group). Diabetes was induced in group B and group C rats by single intraperitoneal injections of STZ (75 mg/kg body weight), while each animal in the "control" group A received equal volume of citrate buffer solution (pH 6.3) intraperitoneally. STZ+insulin-treated group C diabetic rats were additionally treated with subcutaneous injections of lente insulin (0.5 U/kg body weight) daily from Day 10 to Day 30 of our 40-day study period. The rats used were sacrificed at different time intervals (10th, 20th, 30th and up to the 40th day) following STZ treatment. Fragments of endocrine pancreas of each rat were randomly processed for immunohistochemistry staining and pancreatic insulin content. In diabetic state, pancreatic beta-cells showed a weak immunostaining for insulin on Day 10. Thereafter, insulin administration (in the group C rats) caused a significant decrease (p < 0.05) in the elevated blood glucose levels, and a significant increase (p < 0.05) in the serum insulin concentrations. The surviving beta-cells regenerated and virtually regained their normal immunostaining and functional status for insulin. On the 30th day, the pancreatic insulin contents of the insulin-treated group C rats showed approximately 45-fold increase in immunoreactivity when compared with the immunoreactivity of the same STZ+insulin-treated rats on Day 10 of the 40-day study period. The present study illustrates the sequence of morphological changes that occur in the islets of Langerhans following STZ administration and subsequent insulin treatment. The study also suggests that administration of a moderate single dose of STZ in Wistar rats produces specific necrosis of beta-cells, typical of type 1 insulin-dependent diabetes. The experimental evidence obtained in this study appears to suggest that induction of regenerative stimulus (by insulin treatment) in diabetic state triggers pancreatic regenerative processes, thereby restoring functional activities of the pancreas.

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.

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.

Hypoglycaemic and hypotensive effects of Globimetula cupulata (DC) Van Tieghem (Loranthaceae) aqueous leaf extract in rats.

The leaves of some mistletoes, specifically Loranthus micranthus Linn, Tapinanthus dodoneifolius (DC) Danser and Globimetula cupulata (DC) Van Tieghem (family: Loranthaceae), are used traditionally in Nigerian folk medicine to manage, control and/or treat a plethora of human ailments, including diabetes mellitus and hypertension. In order to scientifically appraise some of the folkloric, ethnomedical uses of Globimetula species, the present study was undertaken to investigate the hypoglycaemic and hypotensive effects of Globimetula cupulata aqueous leaf extract (GCE, 50-800 mg/kg po) in rat experimental paradigms. The hypoglycaemic effect of the plant extract was examined in normal (normoglycaemic) and diabetic (hyperglycaemic) rats using a streptozotocin (STZ)-induced diabetes model. Normotensive Wistar and hypertensive Dahl salt-sensitive rats were used to investigate the hypotensive (antihypertensive) effect of the plant extract. Metformin (MFM, 500 mg/kg po) was used as the reference hypoglycaemic agent for comparison. Acute oral administrations of G cupulata aqueous leaf extract (GCE, 50-800 mg/kg po) caused dose-related, significant (p < 0.05-0.001) hypoglycaemia in normal and STZ-treated diabetic rats. Furthermore, acute intravenous administrations of GCE (50-800 mg/kg iv) produced dose-dependent, significant reductions (p < 0.05-0.001) in systemic arterial blood pressure and heart rates of the normotensive and hypertensive rats used. Although the exact hypoglycaemic and hypotensive mechanisms of action of the plant extract still remain speculative, it is unlikely that the extract induced hypotension in the mammalian experimental animal model via cholinergic mechanisms, since its cardiovascular effects were resistant to atropine pretreatment. However, the findings of this experimental study indicated that Globimetula cupulata aqueous leaf extract possesses hypoglycaemic and hypotensive properties. This therefore lends pharmacological support to the folkloric, ethnomedical uses of the plant in the management and/ or control of diabetes mellitus and hypertension among the Yoruba-speaking people of western Nigeria.

Antiinflammatory and analgesic effects of Psidium guajava Linn. (Myrtaceae) leaf aqueous extract in rats and mice.

In many parts of Africa, the leaf, stem-bark, and roots of Psidium guajava Linn. (Family: Myrtaceae) are used traditionally for the management, control, and/or treatment of an array of human disorders. In an effort to scientifically appraise some of the ethnomedical properties of P. guajava leaf, and probe its efficacy and safety, the present study was undertaken to examine the antiinflammatory and analgesic properties of the plant's leaf aqueous extract in some experimental animal paradigms. The antiinflammatory property of the aqueous leaf extract was investigated in rats, using fresh egg albumin-induced pedal (paw) edema, while the analgesic effect of the plant extract was evaluated by the "hot-plate" and "acetic acid" test models of pain in mice. Diclofenac (100 mg/kg, i.p.) and morphine (10 mg/kg, i.p.) were used respectively as standard, reference antiinflammatory and analgesic agents for comparison. P. guajava leaf aqueous extract (PGE, 50-800 mg/kg, i.p.) produced dose-dependent and significant (p < 0.05-0.001) inhibition of fresh egg albumin-induced acute inflammation (edema) in rats. The plant extract (PGE, 50-800 mg/kg, i.p.) also produced dose-dependent and significant (p < 0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain in mice. The numerous tannins, polyphenolic compounds, flavonoids, ellagic acid, triterpenoids, guiajaverin, quercetin, and other chemical compounds present in the plant are speculated to account for the observed antiinflammatory and analgesic effects of the plant's leaf extract. In summary, the findings of this experimental animal study indicate that the leaf aqueous extract of P. guajava possesses analgesic and antiinflammatory properties, and thus lend pharmacological credence to the suggested ethnomedical, folkloric uses of the plant in the management and/or control of painful, arthritic and other inflammatory conditions in some rural communities of Africa.

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.

Hypoglycaemic and hypotensive effects of Harpephyllum caffrum Bernh ex CF Krauss (Anacardiaceae) stem-bark aqueous extract in rats.

The stem bark of Harpephyllum caffrum Bernh ex CF Krauss (family: Anacardiaceae) is used traditionally in African folk medicine to manage, control and/or treat an array of human ailments, including diabetes mellitus and hypertension. In order to scientifically appraise some of the anecdotal, folkloric and ethnomedical uses of Harpephyllum caffrum, this study was undertaken to examine the hypoglycaemic and hypotensive effects of Harpephyllum caffrum stem bark aqueous extract (HCE) in rat experimental paradigms. The hypoglycaemic effect of the plant extract (HCE) was examined in normal and diabetic rats, using a streptozotocin (STZ)-induced diabetes mellitus model. Hypertensive, Dahl salt-sensitive rats were used to investigate the hypotensive (antihypertensive) effect of the plant extract. Chlorpropamide (250 mg/kg po) was used as the reference hypoglycaemic agent for comparison. Acute oral administrations of the plant extract (HCE, 50-800 mg/kg po) caused dose-related, significant (p < 0.05- 0.001) hypoglycaemia in normal (normoglycaemic) and STZ-treated diabetic rats. Furthermore, acute intravenous administrations of the plant extract (HCE, 25-400 mg/kg iv) produced dose-dependent, significant reductions (p < 0.05-0.001) in systemic arterial blood pressures and heart rates of the hypertensive, Dahl salt-sensitive rats used. Although the exact mechanisms of action of the plant extract still remain obscure at the moment, it is unlikely that the plant causes hypotension in the mammalian experimental animal model used, via the cholinergic mechanism, since its hypotensive effect was resistant to atropine pretreatment. The numerous polyphenolic compounds and flavonoids present in the plant are speculated to account for the observed hypoglycaemic and hypotensive effects of the extract. However, the findings of this experimental animal study indicate that the stem-bark aqueous extract of H caffrum possesses hypoglycaemic and hypotensive properties, and thus lend pharmacological support to the suggested folkloric, anecdotal and ethnomedical uses of the plant in the management and/or control of adult-onset type 2 diabetes mellitus and hypertension in some rural communities of southern African.

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.

Antiinflammatory, analgesic and hypoglycemic effects of Mangifera indica Linn. (Anacardiaceae) stem-bark aqueous extract.

Previous studies in our laboratories and elsewhere have shown that some members of Anacardiaceae family possess antiinflammatory, analgesic and hypoglycemic effects in man and mammalian experimental animals. The present study was, therefore, undertaken to examine the antiinflammatory, analgesic and antidiabetic properties of the stem-bark aqueous extract of Mangifera indica Linn., M. indica a member of the Anacardiaceae family, in rats and mice. The stem-bark powder of M. indica was Soxhlet extracted with distilled water and used. The analgesic effect of the plant's extract was evaluated by the hot-plate and acetic acid test models of pain in mice, while the antiinflammatory and antidiabetic effects of the stem-bark extract were investigated in rats, using fresh egg albumin-induced paw edema, and streptozotocin (STZ)-induced diabetes mellitus, respectively. Morphine (MPN, 10 mg/kg i.p.), diclofenac (DIC, 100 mg/kg i.p.), and chlorpropamide (250 mg/kg p.o.) were used respectively as reference analgesic, antiinflammatory, and hypoglycemic agents for comparison. M. indica stem-bark aqueous extract (MIE, 50-800 mg/kg i.p.) produced dose-dependent and significant (p<0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain stimuli in mice. MIE (50-800 mg/kg i.p.) also significantly (p<0.05-0.001) inhibited fresh egg albumin-induced paw edema, and caused significant (p<0.05-0.001) hypoglycemic effects in rats. It is suggested that the analgesic effects of MIE (50-800 mg/kg i.p.) may be peripherally and centrally mediated. The different chemical constituents of the plant, especially the polyphenolics, flavonoids, triterpenoids, mangiferin, and other chemical compounds present in the plant may be involved in the observed antiinflammatory, analgesic, and hypoglycemic effects of the plant's extract. However, the results of this experimental animal study lend pharmacological credence to the suggested folkloric uses of the plant in the management and control of painful, arthritic and other inflammatory conditions, as well as in the management of adult-onset type 2 diabetes mellitus in some rural African communities.