• Control . - . - FTE
•••• - PAE
3.3. Chronic studies
3.3.1. Effects of test extracts on long term blood glucose concentration 3.3.1.1. Non-diabetic rats
Table 4 shows the effects of chronic administration of vehicle and test extracts on blood glucose in non-diabetic rats at the end of 6 weeks of treatment. Initial blood glucose concentrations were similar in all groups. Standard drugs, glibenclamide and metformin, significantly reduced (P < 0.05) blood glucose concentrations in non- diabetic rats, by comparison with the control group.
Group A extracts (APE and SBE)
Oral administration of group A extracts once a day for 6 weeks had marginal blood glucose lowering effects in non-diabetic rats (Table 4). Although, APE and SBE reduced blood glucose concentration in non-diabetic rats at the end of 6 weeks, these were not statistically different from corresponding control values.
Group B extracts (FTE and P AE)
Also shown in Table 4 are the effects of group B test extracts on blood glucose concentrations at the end of 6 weeks of treatment in non-diabetic rats. FTE demonstrated the most potent blood glucose lowering effects after 6 weeks of treatment, in comparison to corresponding control values, P < 0.05. Treatment with
P AE for 6 weeks reduced blood glucose in non-diabetic rats but levels did not reach statistical significance.
3.3.1.2. STZ-induced diabetic rats
Animals became diabetic 24 hours after induction by i.p. administration of STZ and this was sustained for the rest of the study period. Seven days after induction of diabetes, vehicle treated diabetic controls exhibited fasting glycaemic levels of 24.6 ±
1.5 mmoVI (n = 60), compared with 4.2 ± 0.1 mmoVl (n = 6), P < 0.05, in the corresponding no-diabetic control, and citrated buffer treated controls. STZ-induced diabetic rats exhibited marked polyuria, polyphagia and polydipsia. Furthermore, diabetic animals begun to exhibit severe wasting compared with the control animals.
Table 4 also summarises effects of chronic administration of test extracts on blood glucose in STZ-induced diabetic animals. Vehicle treated STZ-induced diabetic control rats exhibited 5-fold more glycaemia than vehicle treated non-diabetic rats.
While metformin significantly reduced blood glucose concentrations, P < 0.05, in STZ-induced diabetic rats, glybenclamide demonstrated no effects.
Group A extracts (APE and SHE)
In contrast to non-diabetic rats, oral administration of APE and SBE (120 mg/kg) once daily, for 6 weeks markedly reduced blood glucose concentrations in STZ-
Group B extracts (FTE and P AE)
FTE and P AE significantly reduced blood glucose concentrations in STZ-induced diabetic rats, P < 0.05, compared with STZ-induced diabetic control animals at the end of 6 weeks (Table 4).
3.3.1.3. Summary of effects of test extracts on chronic blood glucose concentration
Non-diabetic rats
• APE, SBE and P AE demonstrate mild hypoglycaemic effects that were not statistically significant.
• FTE reduced blood glucose concentrations.
STZ-induced diabetic rats
• APE, SBE, FTE and P AE reduced blood glucose concentration in diabetic rats.
3.3.2. Chronic effects of test extracts on mean arterial blood pressure
Table 4 also shows effects of chronic administration of test extracts on mean arterial pressure, after 6 weeks in non-diabetic rats. Blood pressure values remained unchanged in control non-diabetic rats at the end of 6 weeks in comparison to the first week.
3.3.2.1. Non-diabetic rats
Group A extracts (APE and SBE)
As shown in Table 4, APE and SBE reduced mean arterial pressure in non-diabetic rats. In comparison to control values, the effects of SBE were significant, P < 0.05, while those of APE were, however, not statistically significant.
Group B extracts (FTE and P AE)
Also shown in Table 4 are effects of group B test extracts on blood pressure in non- diabetic rats. Chronic administration of group FTE reduced mean arterial pressure in non-diabetic rats, P < 0.05. In contrast, PAE did not demonstrate vasodepressive significant vasodepressive effects in non-diabetic rats after 6 weeks.
3.3.2.2. STZ-induced diabetic rats
Table 4 also illustrates the effects oflong term administration of test extracts on blood pressure in STZ-induced diabetic rats. STZ-induced diabetic control rats exhibited higher mean arterial pressure values than control non-diabetic animals.
Group A extracts (APE and SBE)
Group B extracts (FTE and P AE)
Like group A extracts, all group B test extracts (120 mg/kg) reduced blood pressure in diabetic rats in comparison to control values, P < 0.05.
3.3.2.3. Summary of effects on long term blood pressure Non-diabetic rats
• APE, SBE and FTE reduced blood pressure in non-diabetic rats
• P AE had no effects on blood pressure in non-diabetic rats
STZ-induced diabetic rats
• APE, SBE, FTE and P AE were vasodepressive in STZ-induced diabetic rats.
Table 4
Weekly blood glucose concentration (mmol/l) and mean arterial pressure (rrunHg) in separate groups of control and treated non-diabetic and STZ-induced diabetic rats.
Treated animals were administered with test extracts (p.o.) daily for 6 weeks (n = 8 in each group).
Group/treatment
Non-diabetic rats Control
Glibenclamide Metformin APE SBE FTE PAE
STZ-induced diabetic rats Control
Glibenclamide Metformin APE SBE FTE PAE
Parameter Blood [glucose]
(mmol/L)
week 1 week 6
5.4±O.1 5.5±O.1 5.3±O.2 3.4±O.1 5.2±O.4 3.5±O.3 5.2±O.3 5.O±O.3 5.3±O.2 4.9±O.1 5.3±O.2 3.8±O.2 5.4±O.3 5.O±O.l
24.6±1.6 25±1 24.3±2.2 24±3 24.6±3.l 11±3*
24.8±1.5 19±2*
26.4±2.3 18±1*
24.5±3.2 19±2*
23.6±2.6 16±2*
*
*
*
Mean arterial pressure (mmHg)
week 1 week6
117±6 117±2
117±4 116±6
118±3 112±3*
118±2 116±2
117±3 98±2*
116±2 96±3*
116±1 118±2
114±2 123±2
115±3 122±4
114±4 108±4*
113±3 111±8*
114±1 117±3*
115±3 114±6*
1,14±2 1l0±2*
3.3.3. Effects of test extracts on long term renal function 3.3.3.1. Non-diabetic rats
Effects of chronic administration of test extracts on Na+ and K+ excretion and urine flow rates per 24h in non-diabetic rats are shown are in Figures 18 and 19. Animals were treated once daily at 09hOO for 6 weeks. Control animals were administered with deionised (3 ml/kg).
Group A extracts (APE and SBE)
Figure 18 illustrates effects of chronic administration of group A extracts (120 mglkg) once daily for 6 weeks on Na+ and K+ excretion and urine flow rates per 24h, in non- diabetic rats. APE significantly reduced Na+ and K+ excretion rates in non-diabetic rats. APE reduced urine flow rate in non-diabetic rats but this was not statistically significant. SBE failed to show any effects on renal Na+ and K+ excretion rates, and urine flow rates in non-diabetic rats compared with control animals.
Group B extracts (FTE and P AE)
Effects of chronic treatment of non-diabetic rats with group B extracts on Na+, K+
excretion and urine flow rates per 24h are shown in Figure 19. None of group B extracts had any effects on Na + and K+ excretion and urine flow rates, in non-diabetic rats during 6 weeks of treatment.
3.3.3.2. STZ-induced diabetic rats
Effects oflong term administration of test extracts on renal Na+ and K+ excretion, and urine flow rates per 24h in STZ-induced diabetic rats are shown in Figures 20 and 2l.
Control diabetic rats had reduced urinary Na+ excretion rates compared with control non-diabetic rats. Na+ excretion rate in control STZ-induced diabetic animals was approximately half that of non-diabetic control rats, while K+ excretion rates was five times lower. STZ-induced diabetic rats were polyuric, exhibiting seven times more urine flow rate, compared with non-diabetic control groups.
Group A extracts (APE and SBE)
Figure 20 shows effects of long term treatment of group A extracts to STZ-induced diabetic rats on Na+, K+ and urine flow rates per 24h. APE reduced Na+ and K+
excretion and urine flow rates in STZ-induced diabetic rats, P < 0.05 (Figure 20). In contrast, chronic treatment of STZ-induced diabetic rats with SBE did not have any effects on Na+ and K+ excretion, and, urine flow rates.
Group B extracts (FTE and P AE)
Figure 21 illustrates the effects of long term treatment of group B extracts to STZ- induced diabetic rats on Na+ and K+ excretion and urine flow rates per 24h. Group B extracts had no effects on Na+ and K+ excretion, and urine flow rates.
3.3.3.3. Summary of effects on renal function
Non-diabetic rats
• APE depressed Na+ and K+ excretion rates in non-diabetic rats but its effects on urine flow rate were not significant
• SBE, FTE and PAE had no effects on chronic Na+ and K+ excretion, and urine flow rates.
STZ-induced diabetic rats
• APE depressed Na+ and K+ excretion and urine flow rates.
• SBE, FTE and PAE had no effects on Na+ and K+ excretion, and urine flow rates in STZ-induced diabetic rats.
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