In Malaysia, Tinospora crispa extract is taken orally by Type 2 (non-insulin-dependent) diabetic patients to treat hyperglycaemia. We have evaluated the claimed hypoglycaemic property by adding aqueous extract to the drinking water of normal and alloxan-diabetic rats. After one week, fasting blood glucose levels were significantly (p less than 0.01) lower and serum insulin levels were significantly (p less than 0.01) higher in treated diabetic animals (10.4 +/- 1.0 mmol/l and 12.8 +/- 1.1 muU/ml respectively) compared to untreated diabetic controls (17.4 +/- 1.7 mmol/l and 8.0 +/- 0.7 muU/ml respectively). The insulinotropic action of T. crispa was further investigated in vitro using isolated human or rat islets of Langerhans and HIT-T15 cells. In static incubations with rat islets and HIT-T15 B cells, the extract induced a dosage dependent stimulation and potentiation of basal and glucose-stimulated insulin secretion respectively. This insulinotropic effect was also evident in perifused human and rat islets and HIT-T5 B-cells. The observations that (i) in all three models insulin secretory rates rapidly returned to basal levels on removal of the extract and (ii) in rat islets, a second challenge with T. crispa induced an additional, stimulated response, are all consistent with physiological release of insulin by B cells. Moreover, the rate of HIT-T15 glucose utilisation was not affected by incubation with T. crispa, suggesting that the cells were viable throughout. These are the first studies to provide biochemical evidence which substantiates the traditional claims for an oral hypoglycaemic effect of Tinospora crispa, and which also show that the hypoglycaemic effect is associated with increased insulin secretion.
In Malaysia, an aqueous extract of Tinospora crispa stems is taken orally to treat diabetes mellitus. In the present study, normal and alloxan-diabetic rats were used to evaluate the hypoglycaemic properties of the extract. A hypoglycaemic effect was observed in moderately diabetic rats with concomitant improvement in insulinaemia. After a 2-week treatment with the extract (4 g/l in the drinking water), these rats also showed improvement in glucose tolerance. Moreover, acute intravenous treatment with the extract (50 mg/kg) caused an increase in plasma insulin levels. The data support the traditional belief that T. crispa extract could improve diabetic conditions by virtue of its action on the endocrine pancreas.
This study examined the effects of streptozotocin-induced diabetes on blood pressure and cardiac tissue kallikrein levels in WKYR and SHR. Streptozotocin-induced diabetes caused significant (p < 0.001) increase in SBP and DBP in WKYR and SHR as compared with their respective controls. We also observed that the active cardiac tissue kallikrein levels reduced greatly (p < 0.001) in diabetic WKYR and SHR than the normal rats. These findings suggest for the first time that the cardiac tissue kallikrein formation may have a greater role in the regulation of blood pressure and cardiac function.
We investigated the cardiac tissue kallikrein and kininogen levels, left ventricular wall thickness and mean arterial blood pressure of Wistar Kyoto and spontaneously hypertensive rats with and without streptozotocin-induced diabetes. The mean arterial blood pressure was highly elevated (P<0.001) in Wistar Kyoto diabetic and spontaneously hypertensive diabetic rats as compared with their respective controls. The cardiac tissue kallikrein and kininogen levels were reduced significantly (P<0.001) in diabetic Wistar Kyoto, spontaneously hypertensive and diabetic spontaneously hypertensive compared with Wistar Kyoto control rats. In addition, the left ventricular thickness was found to be increased (P<0.001) in diabetic Wistar Kyoto and spontaneously hypertensive rats in the presence and in the absence of diabetes. Our results indicate that reduced activity of the kinin-forming system may be responsible for inducing left ventricular hypertrophy in the presence of raised mean arterial blood pressure in diabetic and hypertensive rats. Thus, the kinin-forming components might have a protective role against the development of left ventricular hypertrophy. The possible significance of these findings is discussed.
The present investigation was aimed at evaluating the cardiac and total plasma kininogen levels, as well as LVWT in hypertensive and diabetic rats. STZ-induced diabetes produced a significant (P < 0.001) rise in mean arterial blood pressure (BP). The LVWT increased (P < 0.001) in SHR with and without diabetes) and diabetic WKYR. The cardiac tissue, as well as total plasma kininogen levels fell significantly (P < 0.001) in diabetic WKYR and SHR with and without diabetes compared to the control WKYR. These findings suggest that reduced kininogen levels may indicate a deficiency in kinin generation in the heart and in the peripheral circulation in diabetic and hypertensive rats. This effect may contribute to the development of LVH.
Reproductive dysfunction in the female diabetic rat is associated with impaired hypothalamic-hypophyseal system, anovulation, insufficiency of ovarian steroidogenesis and spontaneous failure of pregnancy. Formation of decidua, the highly modified endometrium of pregnancy and pseudopregnancy could only be achieved when the uterus was sensitized by a sequence of oestrogen and progesterone. In this study, we examined whether the impaired expression of endometrial decidualization in the pseudopregnant rat is linked with diabetes-associated hypersecretion of testosterone. Rats were made pseudopregnant by sterile mating. Diabetes was induced by streptozotocin on day 1 p.c. Deciduogenic stimulus was given on day 5 p.c. Treatment of cyproterone acetate (10 mg kg(-1)) was scheduled from day 5 through day 9 p.c. Animals were killed on day 10 p.c, and the degree of endometrial decidual growth, plasma levels of oestradiol, progesterone, ACTH and testosterone were determined. Results showed that compared to controls there was a concomitant drop in endometrial decidual growth concurrently with impaired levels of oestradiol and progesterone in diabetic pseudopregnant rats. ACTH and testosterone levels were, however, profoundly elevated. Cyproterone acetate treatment in the diabetic pseudopregnant rat resulted in a simultaneous elevation of oestradiol and progesterone, which eventually helped the endometrial differentiation to decidua in the diabetic pseudopregnant rat parallel to controls. Present experimental data suggest that diabetes-associated impaired endometrial decidualization in the pseudopregnant rat is possibly caused by testosterone-induced oestrogen deficiency.
Haruan has been proved to influence the different phases of wound healing process. The current research focuses on the effects of haruan on the different constituents of extracellular matrix of healing wounds in normal and diabetic rats. Anaesthetized normal and streptozotocin induced diabetic rats were provided with excision wounds at the back and then animals were divided into four groups as: group 1, wounds treated with cetrimide+haruan cream; group 2, wounds treated with haruan cream; group 3, wounds treated with cetrimide (commercial) cream; and group 4, wounds untreated and served as control. Animals were sacrificed after 3, 6, 9 and 12 days. These wounds were used to determine the hexosamine, protein, uronic acid and glycosaminoglycan contents and the wound contraction. The results suggested a marked increase (P<0.05) in the uronic acid, hexosamine and dermatan sulfate contents on day 3 of group 1 when compared with groups 2-4. Wound contraction of group 1 was also markedly enhanced of group 1 (P<0.01) when compared with groups 2- 4. On the basis of these results, we conclude that haruan enhances the synthesis of different glycosaminoglycans in healing wounds, which are the first component of extracellular matrix to be synthesized during the wound healing process. The enhanced levels of glycosaminoglycans may help in the formation of a resistant scar and enhanced wound contraction represents the positive influence of haruan on the fibroplastic phase of wound healing.
We investigated the total urinary kallikrein levels, left-ventricular wall thickness and mean arterial blood pressure of nontreated and captopril-treated diabetic and nondiabetic spontaneously hypertensive rats. The mean arterial blood pressure was significantly elevated in diabetic spontaneously hypertensive rats as compared to nondiabetic spontaneously hypertensive rats. Captopril treatment caused a significant reduction in the arterial blood pressure of both nondiabetic and diabetic spontaneously hypertensive rats. The left-ventricular wall thickness was also significantly reduced in diabetic and nondiabetic spontaneously hypertensive treated with captopril as compared to nontreated diabetic and nondiabetic spontaneously hypertensive rats. The total urinary kallikrein levels were significantly raised in captopril-treated diabetic and nondiabetic spontaneously hypertensive rats against the values obtained from nontreated diabetic and nondiabetic spontaneously hypertensive rats. These results indicate that blood pressure reduction and left ventricular wall regression with captopril treatment might be due to enhanced renal kallikrein formation. The significance of these findings is discussed.
This study determined the effects of palm vitamin E (TRF) diet on the levels of blood glucose, glycated hemoglobin (gHb), serum advanced glycosylation end-products (AGE) and malondialdehyde (MDA) of diabetic Sprague-Dawley rats. The rats received either control (normal rat chow), TRF diet (normal chow fortified with TRF at 1 g/kg) or Vitamin C diet (vitamin E-deficient but contained vitamin C at 45 g/kg). The animals were maintained on the respective diet for 4 weeks, made diabetic with streptozotocin (STZ), then followed-up for a further 8 weeks. At week-4, mean serum AGE levels of rats given TRF diet (0.7 +/- 0.3 units/ml) were significantly lower than those of control or Vitamin C diet rats (p pounds 0.03). The levels increased after STZ and became comparable to the other groups. At week 12, blood glucose (20.9 +/- 6.9 mM) and gHb (10.0 +/- 1.6%) of rats on TRF diet remained significantly low compared to that of control or Vitamin C diet rats (p pounds 0.03). MDA however, was not affected and remained comparable between groups throughout the study. This study showed that TRF may be a useful antioxidant; effectively prevented increase in AGE in normal rats, and caused decrease in blood glucose and gHb in diabetic rats. Further studies are needed to elucidate the mechanisms of action of TRF.
Vitamin E is composed of various subfamilies that include tocopherols and tocotrienols. These compounds have antioxidant properties but differ in structure, dietary source and potency. In this study we evaluated the efficacy of alpha-tocopherol as an antioxidant and its role in wound closure in normal and streptozotocin-induced diabetic rats. The healing of 6 cm linear incisions created on the back of each male Sprague-Dawley rat (250-300 g) was monitored by measuring the length of the wounds daily. The rats were divided into two categories; normal and streptozotocin-induced diabetic rats. For each category, the animals were further divided into two groups; those untreated and those receiving 200 mg/kg bodyweight alpha-tocopherols daily by oral gavage. All rats were fed standard food and water ad libitum. Blood samples were taken at 0, 5 and 10 days after the wounds were created for the determination of malondialdehyde levels and red cell superoxide dismutase, catalase and glutathione peroxidase activities. The results showed that alpha-tocopherol reduced plasma malondialdehyde levels, increased glutathione peroxidase activity and accelerated the rate of wound closure in treated rats.
1. Diabetes and hypertension are both associated with an increased risk of renal disease and are associated with neuropathies, which can cause defective autonomic control of major organs including the kidney. This study aimed to examine the alpha(1)-adrenoceptor subtype(s) involved in mediating adrenergically induced renal vasoconstriction in a rat model of diabetes and hypertension. 2. Male spontaneously hypertensive rats (SHR), 220-280 g, were anaesthetized with sodium pentobarbitone 7-day poststreptozotocin (55 mg x kg(-1) i.p.) treatment. The reductions in renal blood flow (RBF) induced by increasing frequencies of electrical renal nerve stimulation (RNS), close intrarenal bolus doses of noradrenaline (NA), phenylephrine (PE) or methoxamine were determined before and after administration of nitrendipine (Nit), 5-methylurapidil (5-MeU), chloroethylclonidine (CEC) and BMY 7378. 3. In the nondiabetic SHR group, mean arterial pressure (MAP) was 146+/-6 mmHg, RBF was 28.0+/-1.4 ml x min(-1) x kg(-1) and blood glucose was 112.3+/-4.7 mg x dl(-1), and in the diabetic SHR Group, MAP was 144+/-3 mmHg, RBF 26.9+/-1.3 ml(-1) min x kg(-1) and blood glucose 316.2+/-10.5 mg x dl(-1). Nit, 5-MeU and BMY 7378 blunted all the adrenergically induced renal vasoconstrictor responses in SHR and diabetic SHR by 25-35% (all P<0.05), but in diabetic rats the responses induced by RNS and NA treated with 5-MeU were not changed. By contrast, during the administration of CEC, vasoconstrictor responses to all agonists were enhanced by 20-25% (all P<0.05) in both the SHR and diabetic SHR. 4. These findings suggest that alpha(1A) and alpha(1D)-adrenoceptor subtypes contribute in mediating the adrenergically induced constriction of the renal vasculature in both the SHR and diabetic SHR. There was also an indication of a greater contribution of presynaptic adrenoceptors, that is, alpha(1B)-, and/or alpha(2)-subtypes.
Screening of aqueous extract of Phyllantus niruri (PL), Zingiber zerumbet (ZG), Eurycoma longifolia (TA-a and TA-b) and Andrographis paniculata (AP) to determine their blood glucose lowering effect were conducted in normoglycaemic and Streptozotocin-induced hyperglycaemic rats. Significant reduction in blood glucose level at 52.90% was shown when hyperglycaemic rats were treated with 50 mg/kg body weight (BW) aqueous extract of AP. This effect is enhanced when freeze-dried material was used, where 6.25 mg/kg BW gave 61.81% reduction in blood glucose level. In the administration of TA-a and TA-b, positive results in hyperglyacaemic rats were only obtained when 150 mg/kg BW of the aqueous extract was used. No significant reduction in blood glucose level were shown in hyperglycaemic rats treated with PL and ZG at all concentrations used (50, 100 and 150 mg/kg BW). In normoglycaemic rats, no significant reduction was noted when all the same extracts were used.
The present study aims to investigate the effect of cocoa extract on serum glucose levels and lipid profiles in streptozotocin-diabetic rats. Cocoa extract (contained 285.6 mg total polyphenol per gram extract) was prepared from fermented and roasted (140 degrees C, 20 min) beans by extracting using 80% ethanol in the ratio of 1-10. The extract of three dosages (1, 2, and 3%) was fed to normal and diabetic rats for a period of 4 weeks. In hyperglycaemic group, cocoa extract (1 and 3%) diets were found to significantly lower (p<0.05) the serum glucose levels compared to the control. Furthermore, supplementation of 1 and 3% cocoa extract had significantly reduced (p<0.05) the level of total cholesterol in diabetic rats. In addition, 1, 2, and 3% cocoa extract diets had significantly lowered (p<0.05) the total triglycerides. Interestingly, this study found that serum HDL-cholesterol had increased significantly (p<0.05) in diabetic rats fed with 2% cocoa extract, while the LDL-cholesterol had decreased significantly (p<0.05) in the 1% treated group. These results indicate that cocoa extract may possess potential hypoglycaemic and hypocholestrolemic effects on serum glucose levels and lipid profiles, respectively. The results also found that the effect of cocoa extract was dose-dependent.
The effect of supplementing 200 mg/kg body weight palm vitamin E (PVE) and 200 mg/kg body weight alpha-tocopherol (alpha-Toc) on the healing of wounds in streptozotocin-induced diabetic rats was evaluated. The antioxidant potencies of these two preparations of vitamin E were also evaluated by determining the antioxidant enzyme activities, namely, glutathione peroxidase (GPx) and superoxide dismutase (SOD), and malondialdehyde (MDA) levels in the healing of dermal wounds. Healing was evaluated by measuring wound contractions and protein contents in the healing wounds. Cellular redistribution and collagen deposition were assessed morphologically using cross-sections of paraffin-embedded day-10 wounds stained according to the Van Gieson method. GPx and SOD activities as well as MDA levels were determined in homogenates of day-10 dermal wounds. Results showed that PVE had a greater potency to enhance wound repair and induce the increase in free radical-scavenging enzyme activities than alpha-Toc. Both PVE and alpha-Toc, however, were potent antioxidants and significantly reduced the lipid peroxidation levels in the wounds as measured by the reduction in MDA levels.
The present study investigated the action of des-aspartate-angiotensin I (DAA-I) on the pressor action of angiotensin II in the renal and mesenteric vasculature of WKY, SHR and streptozotocin (STZ)-induced diabetic rats. Angiotensin II-induced a dose-dependent pressor response in the renal vasculature. Compared to the WKY, the pressor response was enhanced in the SHR and reduced in the STZ-induced diabetic rat. DAA-I attenuated the angiotensin II pressor action in renal vasculature of WKY and SHR. The attenuation was observed for DAA-I concentration as low as 10(-18) M and was more prominent in SHR. However, the ability of DAA-I to reduce angiotensin II response was lost in the STZ-induced diabetic kidney. Instead, enhancement of angiotensin II pressor response was seen at the lower doses of the octapeptide. The effect of DAA-I was not inhibited by PD123319, an AT2 receptor antagonist, and indomethacin, a cyclo-oxygenase inhibitor in both WKY and SHR, indicating that its action was not mediated by angiotensin AT2 receptor and prostaglandins. The pressor responses to angiotensin II in mesenteric vascular bed were also dose-dependent but smaller in magnitude compared to the renal vasculature. The responses were significantly smaller in SHR but no significant difference was observed between STZ-induced diabetic and WKY rat. Similarly, PD123319 and indomethacin had no effect on the action of DAA-I. The findings reiterate a regulatory role for DAA-I in vascular bed of the kidney and mesentery. By being active at circulating level, DAA-I subserves a physiological role. This function appears to be present in animals with diseased state of hypertension and diabetes. It is likely that DAA-I functions are modified to accommodate the ongoing vascular remodeling.
This study was conducted to evaluate the oxidative damage in diabetic mellitus induced rats. The evaluation of DNA damage was carried out by the Alkaline Comet Assay using peripheral lymphocyte cells taken from streptozotocin-induced diabetic rats (50 mg/kg) and control rats. The levels of malondealdehyde (MDA), 4-hydroxynonenal (4-HNE), fasting blood glucose (FBG) and HbA1c were also measured. All the induced diabetic rats were hyperglycemic until the end of the study with significantly higher levels of FBG and HbA1c as compared to the control rats. The results showed the percentage of tail DNA and tail moment values were also significantly higher in the diabetic induced rats. The same observations were made on the levels of plasma MDA and 4-HNE. In conclusion, this study indicated that hyperglycemic condition in diabetic induced rats could generate oxidative DNA damage.
In this study, the effects of palm vitamin E (PV) supplementation on glycemic control and lipid profile in diabetic-induce Sprague-Dawley rats have been evaluated. Diabetes in the rats was induced by a single intravenous streptozotocin (50 mg/kg body weight). The diabetic rats were divided into two groups; supplemented with 200 mg/kg body weight/day of PV and non-supplemented with PV (No PV group). Non-diabetic rats (NDM) formed the control group and only received saline injection. After eight weeks of daily supplementation, PV significantly lowered the fasting blood glucose (FBG) and glycosylated haemoglobin (HbA1c) levels (p
Strobilanthes crispus (Acanthaceae) has been used traditionally as antidiabetic, diuretic, antilytic, and laxative and has been proven scientifically to possess high antioxidant activity, anti-AIDS, and anticancer properties. It is commonly consumed in the form of herbal tea. The ethnopharmacological value of this plant, such as the development of nutraceutical S. crispus herbal tea (fermented and unfermented) and assessment of their antihyperglycemic properties were investigated. The antidiabetic properties of S. crispus fermented and unfermented tea was carried out in normal and streptozotocin-induced hyperglycaemic rats for 21 days. Glucose and lipid profile (total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol) were determined at day 0 (baseline), day 7, and day 21. The results showed that the hot water extract of both fermented and unfermented S. crispus tea reduced blood glucose in hyperglycaemic rats. S. crispus unfermented tea also reduced glucose level in normal rat. Both fermented and unfermented S. crispus tea also showed to improve lipid profile. Antioxidant and polyphenol content that present in the extracts might contribute to the antihyperglycemic and antilipidemic properties. Further study is needed to be carried out in pre-clinical and clinical environment to prove its efficacy in human.