Hypoglycaemic effect of Triticum repens P. Beauv. in normal and diabetic rats

The hypoglycaemic effect of an aqueous extract of Triticum repens (TR) rhizomes was investigated in normal and streptozotocin (STZ) diabetic rats. After a single oral administration of the aqueous extract (20mg/kg) a significant decrease on blood glucose levels in STZ diabetic rats (p<0.001) was observed; the blood glucose levels were normalized after 2 weeks of daily oral administration of TR aqueous extract (20mg/kg) (p<0.001). Significant reduction on blood glucose levels were noticed in normal rats after both acute (p<0.001) and chronic treatment (p<0.001). In addition, no changes were observed in basal plasma insulin concentrations after treatment in either normal or STZ diabetic rats indicating that the underlying mechanism of this pharmacological activity seems to be independent of insulin secretion. We conclude that the aqueous extract of TR exhibits a potent hypoglycaemic activity in STZ rats without affecting basal plasma insulin concentrations.     

Anti-hyperglycaemic activity of the aqueous extract of Origanum vulgare growing wild in Tafilalet region

The effect of an aqueous extract of Origanum vulgare (OV) leaves on blood glucose levels was investigated in normal and streptozotocin (STZ) diabetic rats. In normal rats, the blood glucose levels were slightly decreased 6 h after a single oral administration (P<0.05) as well as 15 days after once daily repeated oral administration of aqueous OV extract (P<0.05) (20 mg/kg). After a single dose or 15 daily doses, oral administration of the aqueous extract (20 mg/kg) produced a significant decrease on blood glucose levels in STZ diabetic rats (P<0.001). In STZ rats, the blood glucose levels were normalised from the fourth day after daily repeated oral administration of aqueous OV extract (20 mg/kg) (P<0.001). However, this effect was less pronounced 2 weeks after daily repeated oral administration of OV extract. In addition, no changes were observed in basal plasma insulin concentrations after treatment in either normal or STZ diabetic rats indicating that the aqueous OV extract acted without changing insulin secretion. We conclude that an aqueous extract of OV exhibits an anti-hyperglycaemic activity in STZ rats without affecting basal plasma insulin concentrations.     

Effect of the desert plant Retama raetam on glycaemia in normal and streptozotocin-induced diabetic rats

The effect of the aqueous extract of Retama raetam (RR) on blood glucose levels was investigated in fasting normal and streptozotocin-induced diabetic rats after single and repeated oral administration. The aqueous extract of RR at a dose of 20mg/kg significantly reduced the blood glucose in normal rats 6h after a single oral administration (P<0.005) and two weeks after repeated oral administration (P<0.05). This hypoglycaemic effect is more pronounced in streptozotocin (STZ) diabetic rats (P<0.001). The aqueous extract of RR had no effect on basal plasma insulin levels indicating that the underlying mechanism of RR activity is extra-pancreatic. These findings suggest that the aqueous extract of RR possess significant hypoglycaemic effect in both normal and STZ diabetic rats.     

Caraway and caper: potential anti-hyperglycaemic plants in diabetic rats

The hypoglycaemic effect of aqueous extracts of Carum carvi (CC) and Capparis spinosa L. (CS) fruit were investigated in normal and streptozotocin (STZ) diabetic rats. After a single dose or 14 daily doses, oral administration of the aqueous CC and CS extracts (20 mg/kg) produced a significant decrease on blood glucose levels in STZ diabetic rats (P < 0.001); the blood glucose levels were nearly normalised 2 weeks after daily repeated oral administration of both aqueous CC and CS extracts (20 mg/kg) (P < 0.001). No highly significant changes on blood glucose levels were noticed in normal rats after both acute and chronic treatments with CS and CC. In addition, no changes were observed in basal plasma insulin concentrations after treatment with these plants in either normal or STZ diabetic rats indicating that the underlying mechanism of this pharmacological activity seems to be independent of insulin secretion. We conclude that aqueous extracts of CC and CS exhibit a potent anti-hyperglycaemic activity in STZ rats without affecting basal plasma insulin concentrations.     

Study of the hypoglycaemic activity of Fraxinus excelsior and Silybum marianum in an animal model of type 1 diabetes mellitus

The hypoglycaemic effect of the aqueous extracts of Fraxinus excelsior (FE) seed and Silybum marianum (SM) aerial part was investigated in normal and streptozotocin (STZ) diabetic rats. After a single dose or 15 daily doses, oral administration of the aqueous extracts (20 mg/kg) produced a significant decrease of blood glucose levels in both normal and STZ diabetic rats (P < 0.001). From the first week, the body weight was increased in normal rats (P < 0.05) and decreased in STZ rats (P < 0.01) after FE administration. In addition, no changes were observed in basal plasma insulin concentrations after both FE and SM treatments in either normal and STZ diabetic rats indicating that these plants exert their pharmacological activity without affecting insulin secretion. We conclude that the aqueous extracts of FE and SM exhibit potent hypoglycaemic and anti-hyperglycaemic activities in normal and STZ rats, respectively, without affecting basal plasma insulin concentrations.     

Hypoglycaemic effect of Helicteres isora bark extract in rats

The hypoglycaemic effect of the aqueous extract of the bark of Helicteres isora L. (Sterculiaceae) was investigated in normal, glucose load conditions and streptozotocin (STZ)-induced diabetic rats. In normal rats, the aqueous extract of the bark of Helicteres isora L. (100 and 200 mg/kg/p.o.) significantly (P<0.001) reduced the blood glucose levels from 64.5-48.5 and 67-47 mg% 2h after oral administration of bark extract and also significantly lowered the blood glucose in STZ diabetic rats from 68-105 and 66-85.5 mg% 21 days after daily oral administration of the extract (P<0.001). The results suggested that the aqueous extract of bark of Helicteres isora L. possesses a potential hypoglycaemic effect in diabetic rats.     

Study of hypoglycaemic and hypolipidemic effects of Inula viscosa L. aqueous extract in normal and diabetic rats

The present study was designed to examine the hypoglycaemic and hypolipidemic activity of Inula viscsa aqueous extract on normal and diabetic rats. In normal rats, a significant reduction in blood glucose levels 2 h was observed after a single oral administration (p<0.001). Repeated daily oral administration significantly reduced blood glucose levels after 4 days of treatment (p<0.01). In diabetic rats, a significant reduction in blood glucose levels was observed 1 h after a single oral administration (p<0.001). Repeated oral administration reduced blood glucose levels at the 4th day (p<0.001). No change in total plasma cholesterol and triglyceride levels was observed after both a single and repeated oral administration in both normal and diabetic rats. In addition, plasma insulin levels and body weight remained unchanged after 15 days of repeated oral administration in normal and diabetic rats. We conclude that Inula viscosa possess a hypoglycaemic but not hypolipidemic activity in normal and diabetic rats. The observed hypoglycaemic activity seems to be independent of insulin secretion.     

Effect of Lepidium sativum L. on renal glucose reabsorption and urinary TGF-beta 1 levels in diabetic rats

The purpose of this study was to determine the mechanism underlying the hypoglycaemic activity of the aqueous extract perfusion of Lepidium sativum L. (LS) in normal and streptozotocin-induced diabetic rats. The aqueous LS extract was administered intravenously and the blood glucose levels were determined within 4 h of treatment. Plasma insulin concentrations and glycosuria were determined. The 24 h urinary transforming growth factor-beta1 (ELISA) was evaluated in diabetic and control rats 15 days after oral treatment with the aqueous LS extract at a dose of 20 mg/kg. The study showed that LS at a dose of 10 mg/kg/h reduced blood glucose levels both in normal and diabetic rats (p < 0.001). At the same time as a potent increase of glycosuria was observed both in normal and diabetic rats (p < 0.001). In addition, oral administration of LS for 15 days normalized glycaemia (p < 0.001), enhanced glycosuria (p < 0.05 vs diabetic control) and decreased the amount of urinary TGF-beta1 (p < 0.01) in diabetic rats. It is concluded that the aqueous LS extract caused a potent inhibition of renal glucose reabsorption which in turn reduced blood sugar. This renal effect is at least one mechanism explaining the observed hypoglycaemic activity of this plant in normal and diabetic rats.     

Hypoglycaemic effect of spergularia purpurea in normal and streptozotocin-induced diabetic rats

Single and repeated oral administration of the water extracts of Spergularia purpurea (SP) at a dose of 10 mg/kg were tested on hypoglycaemic activity in normal and streptozotocin-induced diabetic rats. In normal rats, the water extract of SP decreased significantly the plasma glucose levels 4 h after single oral administration (P<0.01), and one week after repeated oral administration (P<0.05). A significant decrease of plasma glucose levels was observed 6 h after a single oral administration of the water extract of S. purpurea in severe hyperglycaemic rats (n=6) from 22.78+/-0.60 to 11.21+/-0.49 mmol/l (P<0.001). On other hand, water extract of S. purpurea normalised plasma glucose levels after two weeks of repeated oral administration in diabetic rats; 24.05+/-1.16 versus 7.18+/-0.51 mmol/l (P<0.001) at the start and 2 weeks after water extract administration, respectively. We conclude that the water extract of SP induces hypoglycaemic activity when administered orally in normal and STZ diabetic rats. In order to determine the active principle (s) responsible of the hypoglycaemic effect, preliminary phytochemical analysis of the water extract has been investigated.     

Hypoglycaemic activity of Retama raetam in rats

The purpose of this study was to determine the underlying mechanism of the hypoglycaemic activity of an aqueous extract perfusion of Retama raetam (RR) in normal and streptozotocin-induced diabetic rats. The aqueous extract was administered intravenously and the blood glucose changes were determined within 4 h after starting the treatment. Plasma insulin concentrations and glycosuria were determined. The aqueous RR extract at a dose of 10 mg[sol ]kg[sol ]h produced a significant decrease in blood glucose levels in normal rats (p < 0.001) and an even more marked decrease in diabetic rats (p < 0.001). This hypoglycaemic effect might be due to an extra-pancreatic action of the aqueous extract of RR, since the basal plasma insulin concentrations were unchanged after RR treatment. A potent increase of glycosuria was observed both in normal and diabetic rats (p < 0.001). It is concluded that an aqueous extract perfusion of RR caused a potent inhibition of renal glucose reabsorption. This renal effect is at least one mechanism to explain the observed hypoglycaemic activity of this plant in normal and diabetic rats.     

Phlorizin-like effect of Fraxinus excelsior in normal and diabetic rats

The purpose of this study was to determine the underlying mechanism of the hypoglycaemic activity of the aqueous extract perfusion of Fraxinus excelsior L. (FE) in normal and streptozotocin-induced diabetic rats. The aqueous extract was administered intravenously and the blood glucose changes were determined within four hours after starting the treatment. Plasma insulin concentrations and glycosuria were determined. The aqueous extract at a dose of 10 mg/kg/h produced a significant decrease in blood glucose levels in normal rats (P < 0.001) and even more in diabetic rats (P < 0.001). This hypoglycaemic effect might be due to an extra-pancreatic action of the aqueous extract of FE, since the basal plasma insulin concentrations were unchanged after FE treatment. A potent increase of glycosuria was observed both in normal and diabetic rats (P < 0.001). We conclude that aqueous extract perfusion of FE caused a potent inhibition of renal glucose reabsorption. This renal effect might be at least one mechanism explaining the observed hypoglycaemic activity of this plant in normal and diabetic rats.     

Cholesterol and triglycerides lowering activities of caraway fruits in normal and streptozotocin diabetic rats

The purpose of this study was to examine the effect of single and repeated oral administration of the aqueous extract of Carum carvi L. fruits at a dose of (20mg/kg) on lipid metabolism in normal and streptozotocin-induced diabetic rats (STZ). After a single oral administration, Carum carvi extract produced a significant decrease on triglycerides levels in normal rats (p<0.05). In STZ diabetic rats, cholesterol levels were decreased significantly 6h after Carum carvi treatment (p<0.05). On the other hand, repeated oral administration of Carum carvi extract exhibited a significant hypotriglyceridemic and hypocholesterolemic activities in both normal (p<0.01 and <0.001 respectively) and STZ diabetic rats (p<0.001) 15 days after Carum carvi treatment. We conclude that the aqueous extract of Carum carvi (20mg/kg) exhibits a potent lipid lowering activity in both normal and severe hyperglycemic rats after repeated oral administration of Carum carvi aqueous extract.     

Hypoglycaemic effect of Rubus fructicosis L. and Globularia alypum L. in normal and streptozotocin-induced diabetic rats

The present study investigates the effect of oral administration of the aqueous extract of Rubus fructicosis L. (RF) and Globularia alypum L. (GA) leaves on blood glucose levels in normal and streptozotocin (STZ) diabetic rats. In normal rats, single and repeated oral administration of RF lowered significantly the blood glucose levels, while, GA treatment did not change blood glucose levels. In STZ rats, single and repeated oral administration of both RF and GA produced significant decrease of blood glucose levels. RF and GA treatments did not affect insulin secretion both in normal and STZ rats, indicating that mechanism(s) by which these plants decrease blood glucose levels is extra-pancreatic at least, for the doses used. In addition, the acute toxicity study revealed that the aqueous extracts may be considered relatively safe since that the LD(50) value was over 8.1 and 14.5 g/kg for RF and GA respectively. These findings indicate that RF and GA represent an effective blood glucose lowering and a potential source for discovery of new orally active component(s) for future therapy.     

Hypoglycaemic effect of the lyophilised aqueous extract of Ajuga iva in normal and streptozotocin diabetic rats

The purpose of this study was to examine the hypoglycaemic effect of the lyophilised aqueous extract of the whole plant of Ajuga iva (L.) Schreber (Labiatae) in normal and streptozotocin-induced diabetic rats. Single and repeated oral administration of the extract of Ajuga iva L (AI) at a dose of 10 mg/kg produced a slight and significant decrease in plasma glucose levels in normal rats 6 h after administration and after 3 weeks of treatment. AI reduced plasma glucose levels of streptozotocin diabetic rats from 337±9.3 to 102.2±17.7 mg/dl after 6 h of oral administration (P<0.001). Repeated oral administration of AI to streptozotocin diabetic rats significantly decreased the plasma glucose levels after 1 week of treatment (112±14.4 mg/dl at 1 week vs 337±9.3 mg/dl at the baseline values, (P<0.001). It continuously decreased thereafter and showed a rapid normalisation after 1 week of AI treatment. It is concluded that these results demonstrated that the water extract of the whole plant of AI possess a strong hypoglycaemic effect in diabetic rats, and support therefore, its traditional use in diabetes mellitus control.     

Effect of Artemisia santonicum L. on blood glucose in normal and alloxan-induced diabetic rabbits

The hypoglycaemic effect of panicles of Artemisia santonicum L. in normal and alloxan-induced diabetic rabbits was investigated. Blood glucose levels were determined after oral administration of an aqueous extract of Artemisia santonicum L. In normal and diabetic rabbits, 2 mL/kg (0.42 g/kg) aqueous extract significantly (p < 0.01) reduced blood glucose levels 6 h after administration, which was consistent and time-dependent.     

Effect of guava (Psidium guajava Linn.) leaf soluble solids on glucose metabolism in type 2 diabetic rats

This study investigated the effect of aqueous and ethanol soluble solid extracts of guava (Psidium guajava Linn.) leaves on hypoglycemia and glucose metabolism in type 2 diabetic rats. Low-dose streptozotocin (STZ) and nicotinamide were injected into Sprague-Dawley (SD) rats to induce type 2 diabetes. Acute and long-term feeding tests were carried out, and an oral glucose tolerance test (OGTT) to follow the changes in plasma glucose and insulin levels was performed to evaluate the antihyperglycemic effect of guava leaf extracts in diabetic rats.The results of acute and long-term feeding tests showed a significant reduction in the blood sugar level in diabetic rats fed with either the aqueous or ethanol extract of guava leaves (p < 0.05). Long-term administration of guava leaf extracts increased the plasma insulin level and glucose utilization in diabetic rats. The results also indicated that the activities of hepatic hexokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase in diabetic rats fed with aqueous extracts were higher than in the normal diabetic group (p < 0.05). On the other hand, diabetic rats treated with the ethanol extract raised the activities of hepatic hexokinase and glucose-6-phosphate dehydrogenase (p < 0.05) only. The experiments provided evidence to support the antihyperglycemic effect of guava leaf extract and the health function of guava leaves against type 2 diabetes.     

Effects of an aqueous extract of Triticum repens on lipid metabolism in normal and recent-onset diabetic rats

The aim of this study was to demonstrate the effects of single and repeated oral administration of the aqueous rhizomes extract of Triticum repens (TR) (20 mg/kg) on lipid metabolism in normal and streptozotocin-induced diabetic rats. In normal rats, the aqueous extract of TR induced a significant decrease in the plasma triglycerides concentrations 4 days (P<0.05) and 1 week after repeated oral administration (P<0.05). This reduction was abolished 2 weeks after once daily repeated oral administration. A significant decrease of plasma cholesterol levels was observed only 1 week (P<0.05) after repeated oral administration.

In diabetic rats, TR treatment caused a significant decrease in plasma triglycerides levels after a single (P<0.01) and repeated (P<0.001) oral administration. A strong decrease in cholesterol level was observed 6 h after a single oral administration of the aqueous extract TR (P<0.001). Four days after repeated oral administration of TR aqueous extract, the plasma cholesterol level was significantly decreased (P<0.05) and still dropped after 2 weeks (P<0.001).

On other hand, the repeated oral administration of aqueous TR extract caused a significant decrease in body weight 2 weeks after repeated oral treatment in diabetic rats (P<0.05).

We conclude that the aqueous extract of TR exhibits lipid and body weight lowering activities in severe hyperglycaemic rats after repeated oral administration of aqueous TR extract at a dose of 20 mg/kg.     

Effect of Retama raetam on lipid metabolism in normal and recent-onset diabetic rats

The purpose of this study was to examine the effect of single and repeated oral administration of the aqueous extract of Retama raetam (Forssk) Webb (RR) (20 mg/kg) on lipid metabolism in normal and streptozotocin-induced diabetic rats. In normal rats, the aqueous extract of RR induced a significant decrease of the plasma triglycerides concentrations one week after repeated oral administration (P<0.05). This reduction was maintained two weeks after once daily repeated oral administration (P<0.05). A significant decrease of plasma cholesterol levels was also observed one week (P<0.05) and two weeks (0.05) after repeated oral administration.

In diabetic rats, RR treatment caused a significant decrease of plasma triglycerides levels after a single (P<0.05) and repeated (P<0.001) oral administration. A significant decrease of cholesterol levels was observed four hours after a single oral administration of the RR aqueous extract (P<0.05). One week after repeated oral administration of RR aqueous extract, the plasma cholesterol levels were significantly decreased (P<0.05) and still dropped after two weeks (P<0.005).

On the other hand, the repeated oral administration of RR aqueous extract caused a significant decrease of body weight one week after repeated oral treatment in diabetic rats (P<0.05). We conclude that the aqueous extract of RR exhibits lipid and body weight lowering activities in both normal and severe hyperglycemic rats after repeated oral administration of RR aqueous extract at a dose of 20 mg/kg.     

Evaluation of the analgesic, anti-inflammatory and anti-diabetic properties of Sclerocarya birrea (A. Rich.) Hochst. stem-bark aqueous extract in mice and rats

In order to appraise some of the ethnomedical uses of Sclerocarya birrea (A. Rich.) Hochst., subspecies caffra (Sond.) Kokwaro [family: Anacardiaceae], the present study was undertaken to investigate the analgesic, anti-inflammatory and anti-diabetic properties of the plant's stem-bark aqueous extract in experimental models of pain, inflammation and diabetes mellitus. The analgesic effect of Sclerocarya birrea stem-bark aqueous extract was evaluated in mice, while its anti-inflammatory and anti-diabetic effects were investigated in rats. Diclofenac (DIC, 100 mg/kg p. o.) and chlorpropamide (250 mg/kg p. o.) were used respectively as reference analgesic, anti-inflammatory and anti-diabetic agents for comparison. Like diclofenac (DIC, 100 mg/kg p. o.), Sclerocarya birrea stem-bark aqueous extract (SBE, 100-800 mg/kg p. o.) produced dose-dependent, significant protection (p < 0.05-0.001) against electrical heat-induced pain. The plant extract (SBE, 25-800 mg/kg p. o.) also produced dose- and time-related, sustained and significant reductions (p < 0.05-0.001) in the fresh egg albumin-induced acute inflammation of the rat hind paw oedema. However, the analgesic and anti-inflammatory effects of the plant's extract were found to be approximately 10-15 times less than that of diclofenac. In one set of experiments involving hypoglycaemic/antidiabetic evaluation of the plant's extract, graded doses of Sclerocarya birrea stem-bark aqueous extract (SBE, 25-800 mg/kg p. o.) were separately administered to groups of fasted normal and fasted diabetic rats. In another set of experiments, a single dose of the plant's aqueous extract (SBE, 800 mg/kg p. o.) was used. The hypoglycaemic effect of this single dose of Sclerocarya birrea stem-bark aqueous extract (SBE, 800 mg/kg p. o.) was compared with that of chlorpropamide (250 mg/kg p. o.) in both fasted normal and fasted streptozotocin (STZ)-treated diabetic rats. Following acute treatment, relatively moderate to high doses of Sclerocarya birrea stem-bark aqueous extract (SBE, 25-800 mg/kg p. o.) produced dose-dependent, significant reductions (p < 0.05-0.001) in the blood glucose concentrations of both fasted normal and fasted diabetic rats. Chlorpropamide (250 mg/kg p. o.) also produced significant reductions (p < 0.05-0.001) in the blood glucose concentrations of the fasted normal and fasted diabetic rats. Administration of the single dose of Sclerocarya birrea stem-bark aqueous extract (SBE, 800 mg/kg p. o.) significantly reduced (p < 0.01-0.001) the blood glucose levels of both fasted normal (normoglycaemic) and fasted STZ-treated, diabetic rats. The results of this experimental animal study indicate that Sclerocarya birrea stem-bark aqueous extract possesses analgesic, anti-inflammatory and hypoglycaemic properties. These experimental findings lend pharmacological support to the suggested folkloric uses of the plant's stem-bark in the management and/or control of pain, inflammatory conditions, and adult-onset, type-2 diabetes mellitus in some communities of South Africa.     

Hypoglycaemic effect of Clausena anisata (Willd) Hook methanolic root extract in rats

This study was designed to examine the hypoglycaemic effect of Clausena anisata (Willd) Hook [family: Rutaceae] root methanolic extract in normal (normoglycaemic) and in streptozotocin-treated diabetic rats. Young adult, male Wistar rats (Rattus norvegicus) weighing 250-300 g were used. Diabetes mellitus was induced in the group of diabetic 'test' rats by intraperitoneal injections of streptozotocin (STZ, 90 mg/kg). In one set of experiments, graded doses of the methanolic root extract of C. anisata (CAME, 100-800 mg/kg p.o.) were administered to both fasted normal and fasted diabetic rats. In another set of experiments, 800 mg/kg of CAME, a dose of the plant extract which produced maximal hypoglycaemic effect in both fasted normal and diabetic rats in the previous set of experiments, was used. The hypoglycaemic effect of this single dose of C. anisata root methanolic extract (i.e. CAME, 800 mg/kg p.o.) was compared with those of insulin (5 micro U/kg s.c.) and glibenclamide (0.2 mg/kg p.o.) in both fasted normal and fasted diabetic rats. Following acute treatment, relatively moderate to high doses of CAME (100-800 mg/kg p.o.) produced dose-dependent, significant reductions (P<0.05-0.001) in the blood glucose concentrations of both fasted normal and fasted diabetic rats. On their own, both insulin (5 micro U/kg s.c.) and glibenclamide (0.2 mg/kg p.o.) produced significant reductions (P<0.01-0.001) in the blood glucose concentrations of the fasted normal and diabetic rats. At a dose of 800 mg/kg p.o., CAME reduced the mean basal blood glucose concentrations of fasted normal and fasted diabetic rats by 57.52 and 51.30%, respectively. C. anisata contains a diverse group of chemical compounds (see Table 1). Since methanol extractives of plants are usually known to contain many chemical compounds, each of which is capable of producing definite biological activities via different mechanisms, it is difficult to draw any logical conclusion on the mechanism of the hypoglycaemic effect of such a diverse mixture of chemical compounds contained in the plant extract used in this study. While it is possible that the hypoglycaemic effect of the plant extract may be due, at least in part, to its terpenoid and coumarin contents, the mechanism of its hypoglycaemic action remains largely speculative, and is unlikely to be due to the stimulation of pancreatic beta-cells and subsequent secretion of insulin. Although C. anisata root methanolic extract is less potent than insulin as an antidiabetic agent, the results of this experimental animal study indicate that the herb possesses hypoglycaemic activity; and thus lend credence to the suggested folkloric use of C. anisata root in the management and/or control of adult-onset, Type-2 diabetes mellitus in some communities of South Africa.