Protective role of wild garlic on isoproterenol-induced myocardial necrosis in wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tulbaghia violacea Harv. (TVL) is a folk medicine, native to South Africa which has previously shown antioxidant, anti-hypertensive and anti-diabetic effects. THE AIM OF THE STUDY: The aim of the current study was to investigate the protective role of wild garlic or TVL on isoproterenol (ISO)-induced myocardial necrosis in rats. MATERIALS AND METHODS: Animal (n = 6 each group) were pre and co-treated with TVL (60 mg/kg body weight) daily for 30 days. Myocardial necrosis was administrated by subcutaneous injection of ISO (85 mg/kg body weight) into rats on 29th and 30th day. On the 31st day, rats were anaesthetized and blood, heart samples were obtained for the biochemical, histopathological and molecular study. The specific protein target analysis from TVL was done by reverse docking study (reverse pharmacophore mapping) using PharmMapper. RESULTS: The levels of cardiac markers, lipid peroxidation products, and heart rate were considerably increased in ISO-induced myocardial necrosis in rats whilst plasma enzymatic antioxidants were significantly decreased. Myocardial necrotic mRNA genes were increased in ISO-induced myocardial necrosis in rats compared to controls. Pre and co-treatment with TVL and ramipril of myocardial necrosis in rats showed significant effects on all the biochemical and molecular studies evaluated. TVL reduced heart rate, prevented oxidative stress and downregulated the Fas-receptor and caspase-mediated apoptosis-signaling pathway, and heart muscle damage in myocardial necrosis in rats. The specific target protein [disulfide, bis (2-sulfhydrylethyl] from TVL mediates the protective effects. CONCLUSION: Wild garlic or TVL extract has shown a protective effect on ISO-induced myocardial necrosis in rats by increasing antioxidant production confirmed with docking studies.

METABOLIC EFFECTS OF TULBAGHIA VIOLACEA HARV. IN A DIABETIC MODEL.

BACKGROUND: Diabetes mellitus (DM) is a cluster of metabolic diseases with chronic hyperglycemia as a defining feature, associated with long-term organ damage and dysfunction. In this study we examined the effect of Tulbaghia violacea rhizome methanolic extract on blood glucose and lipids in normal and streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Male Wistar rats (250-300g) were injected intraperitoneally (i.p.) with streptozotocin (60mg/kg body weight) to induce diabetes; or provided with distilled water for the control (CON) (3 ml/kg/b.w.) animals and treatment with TVL (60mg/kg.b.w). The rats were divided into 5 groups of 6 animals per group as follows: Non-diabetic control (NDC)-received distilled water (3ml/kg.b.w), Non-diabetic TVL (ND+TVL)-received TVL (60mh/kg b.w), Diabetic control (DC)-received distilled water (3ml/kg.b.w), Diabetic experimental (D+TVL)-received TVL (60mg/kg.b.w), Diabetic experimental (D+M)-received Metformin (250 mg/kg.b.w). All doses were administered daily via oral gavage. RESULTS: TVL-treated animals showed reduced blood glucose, increased plasma insulin, reduced plasma TG, TC, VLDL and increased HDL. Furthermore we found decreased thiobarbituric acid reactive substances (TBARS) and increased superoxide dismutase (SOD) activity and nitric oxide significantly. Regarding renal parameters we found increased blood urea nitrogen (BUN), and improved renal morphology in TVL-treated animals. CONCLUSION: Tulbaghia violacea has a hypoglycaemic effect which could due to its effects on multiple pathways of the hyperglycemic process. Further work is needed to identify the mechanism of its antidiabetic effect.

Antioxidant, antidiabetic and hypolipidemic effects of Tulbaghia violacea Harv. (wild garlic) rhizome methanolic extract in a diabetic rat model.

BACKGROUND: The prevalence of diabetes mellitus (DM) continues to rise alarmingly despite years of intensive research. The need to explore alternative remedies such as traditional phytotherapy has therefore become increasingly important in the management and treatment of DM. METHODS: Diabetes was induced by a single intraperitoneal (i.p) injection of streptozotocin (40 mg/kg.b.w) in male Wistar rats. The rats were divided into 5 groups as follows: non-diabetic control fed distilled water, diabetic control fed distilled water, diabetic group treated with Tulbaghia violacea (TVL) (60 mg/kg.b.w), diabetic group treated with TVL (120 mg/kg.b.w), and diabetic group treated with glibenclamide (10 mg/kg.b.w). Food and water intake, as well as urine output were measured daily, whilst body weight and fasting blood glucose were monitored weekly. On day 42, an oral glucose tolerance test was performed on all groups. After 7 weeks, the animals were sacrificed by halothane overdose, blood was removed by cardiac puncture and tissues were harvested. Assays were performed for the determination of plasma insulin, liver glycogen content, lipid peroxidation, antioxidant enzyme levels, plasma nitric oxide levels and serum lipid and liver enzyme levels. RESULTS AND DISCUSSION: TVL treatment improved body weights, significantly reduced fasting blood glucose levels, improved glucose tolerance and significantly increased plasma insulin and liver glycogen content. TVL treatment also reduced liver thiobarbituric acid reactive substances (TBARS) levels, increased liver superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) and increased plasma nitric oxide (NO) levels. Furthermore, TVL administration reduced serum triglycerides, VLDL, total-cholesterol levels and increased HDL-cholesterol levels. TVL also reduced serum levels of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). CONCLUSION: Data obtained in this study demonstrated the hypoglycemic, antioxidant, hepatoprotective and hypolipidemic effects of TVL in STZ-induced diabetic rats.

Effects of Tulbaghia violacea Harv. (Alliaceae) rhizome methanolic extract on kidney function and morphology in Dahl salt-sensitive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tulbaghia violacea has been used traditionally for the treatment of several ailments, including hypertension. The herb has been shown to have antihypertensive properties which have been attributed to its angiotensin-converting enzymeinhibitory (ACEI) activity. It could, therefore, prove beneficial in ameliorating renal pathology associated with hypertension. To evaluate the effects of long-term administration of Tulbaghia violacea on renal function and morphology in the Dahl salt-sensitive (DSS) rat model. MATERIALS AND METHODS: Male DSS rats were treated intra-peritoneally (i.p.) as follows: methanolic extract of Tulbaghia violacea: (TVL) (50 mg/kg/b.w.), captopril: (CAP) (25 mg/kg/b.w.), or distilled water, control: (CON) (3 ml/kg/b.w.). Blood pressure (BP) was measured bi-weekly, whilst 24-h urine volumes and electrolyte concentrations were assessed weekly. Animals were sacrificed on day 49 by halothane overdose. Blood was removed for determination of plasma and serum electrolytes. Left kidney tissues were harvested for the determination of nuclear factor-kappaß (NF-kß) and transforming growth factor-ß (TGF-ß) gene expressions. RESULTS: TVL significantly reduced mean arterial pressure (MAP) and diastolic blood pressure (DBP). TVL showed reduced blood urea nitrogen, serum creatinine, total protein in urine as well as increased serum total protein. TVL decreased thiobarbituric acid reactive substances (TBARS) and increased glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity and nitric oxide significantly. NF-kß and TGF-ß) gene expressions were significantly reduced in TVL and CAP treated rats. Moreover, renal morphology improved significantly in TVL and CAP treated animals. CONCLUSION: TVL and CAP demonstrated marked improvement in renal function and morphology.

Cardiovascular effects of Tulbaghia violacea Harv. (Alliaceae) root methanolic extract in Dahl salt-sensitive (DSS) rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In African folk medicine, Tulbaghia violacea Harv.(Alliaceae), a herbaceous plant also known by other common local names such as 'wild garlic', 'society garlic' and 'sweet garlic', has been used for the management, control and/or treatment of several human ailments; including hypertension. The aim of the present study was to investigate the cardiovascular effects of methanolic extract of Tulbaghia violacea Harv. in Dahl salt-sensitive (DSS) rats. MATERIALS AND METHODS: DSS rats were treated intraperitoneally (i.p) as follows: distilled water, control (CON) (3 ml/kg/b.w.); captopril (CAP) (25 mg/kg/b.w.); or methanolic extract of Tulbaghia violacea (TVL) (50 mg/kg/b.w.) for 7 weeks. Systolic blood pressure (SBP) was measured bi-weekly whilst 24-hour urine volumes and sodium concentrations were assessed weekly. Animals were sacrificed on day 49 by halothane overdose. Blood was removed for the determination of aldosterone concentration and angiotensin converting enzyme (ACE) activity. Left kidney was harvested for angiotensin Ia (AT1a) receptor gene expression. RESULTS: CON showed a significant percentage increase in SBP (mmHg) on day 49 compared to day 0 (baseline values) (9.75±1.7% vs. 2.33±0.77%; p<0.05). CAP and TVL showed significant percentage decreases in SBP at week 7 when compared to baseline (8.13±1.23% and12.88±3.12% p<0.01). Urine volumes (ml) increased significantly in CAP from week 1 to week 4 (9.63±2.22 vs.10.97±1.75 p<0.05) and in TVL from week 2 to 7 (9.23±0.91 vs. 11.90±1.17 p<0.05). Urinary sodium concentration (mmol/L/24 h urine samples) was significantly higher in CAP (0.72±0.07 vs.1.31±0.03 p<0.05) and in TVL (0.71±0.09 vs. 1.68±0.16; p<0.05) at week 7 compared to baseline levels. There was no significant difference in the plasma aldosterone levels (pmol/L) of all the three groups. Serum ACE (U/L) activity was significantly higher in CAP compared to CON and TVL (277.0±11.6 vs. 121.5±3.93; and 147.0±6.63; p<0.05 respectively). CAP showed a significant 6.4 fold increase in AT1a mRNA expression vs. CON (p<0.05) and a 4.5 fold increase vs. TVL (p<0.05). There was no significant difference between CON and TVL treated rats. CAP and TVL showed no significant change in the expression of AT2. CONCLUSION: This study showed that TVL possesses antihypertensive effect in Dahl salt-sensitive rats when administered over a long-term.

Cardiovascular effects of Ekebergia capensis Sparrm (Meliaceae) ethanolic leaf extract in experimental animal paradigms.

The purpose of this study was to examine the in vivo effects of Ekebergia capensis leaf ethanolic extract (EKE) on the blood pressure of anaesthetised normotensive male Wistar rats and conscious weanling Dahl salt-sensitive (DSS) rats, which develop hypertension as they age. To investigate possible mechanism(s) of the extract's hypotensive effects, the contractile or relaxant responses to EKE in the absence or presence of reference drugs were evaluated in Wistar rat isolated aortic rings precontracted with methoxamine hydrochloride (ME, 10 microM). Acute intravenous administration of EKE elicited hypotensive responses in anaesthetised animals, while sub-chronic treatment with the extract averted the development of high blood pressure in weanling DSS rats. Isometric recordings of methoxamine hydrochloride (ME) pre-contracted, isolated, endothelium-intact and -denuded aortic rings revealed concentration-dependent relaxation responses to EKE (1-160 mg/ml). The potency was significantly less in the endothelium- denuded rings. Inhibitors of endothelium-derived relaxing factor (EDRF), L-NAME, methylene blue and indomethacin significantly reduced EKE-evoked vasorelaxations in endothelium-intact aortic rings. These results indicate that the vasorelaxant effect of EKE was in part mediated via EDRF-dependent or -independent pathways. These observations suggest that the hypotensive effect of EKE was in part mediated via modulation of total peripheral resistance of the vascular smooth muscles.

Cardiovascular effects of Helichrysum ceres S Moore [Asteraceae] ethanolic leaf extract in some experimental animal paradigms.

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 saltsensitive (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 concentrationdependent 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.