Protective Effects of Annona Muricata Linn. (Annonaceae) Leaf Aqueous Extract on Serum Lipid Profiles and Oxidative Stress in Hepatocytes of Streptozotocin-Treated Diabetic Rats

Extracts from various morphological parts of Annona muricata Linn. (Annonaceae) are widely used medicinally in many parts of the world for the management, control and/or treatment of a plethora of human ailments, including diabetes mellitus (DM). The present study was undertaken to investigate the possible protective effects of A. muricata leaf aqueous extract (AME) in rat experimental paradigms of DM. The animals used were broadly divided into four (A, B, C and D) experimental groups. Group A rats served as ‘control’ animals and received distilled water in quantities equivalent to the administered volumes of AME and reference drugs' solutions intraperitoneally. Diabetes mellitus was induced in Groups B and C rats by intraperitoneal injections of streptozotocin (STZ, 70 mg kg−1). Group C rats were additionally treated with AME (100 mg kg−1 day−1, p.o.) as from day 3 post STZ injection, for four consecutive weeks. Group D rats received AME (100 mg kg−1 day−1 p.o.) only for four weeks. Post-euthanization, hepatic tissues were excised and processed biochemically for antioxidant enzymes and lipid profiles, such as catalase (CAT), reactive oxygen species (ROS), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), thiobarbituric acid reactive substances (TBARS), triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL), respectively. Treatment of Groups B and C rats with STZ (70 mg kg−1 i. p.) resulted in hyperglycaemia, hypoinsulinaemia, and increased TBARS, ROS, TC, TG and LDL levels. STZ treatment also significantly decreased (p<0.05) CAT, GSH, SOD, GSH-Px activities, and HDL levels. AME-treated Groups C and D rats showed significant decrease (p<0.05) in elevated blood glucose, ROS, TBARS, TC, TG and LDL. Furthermore, AME treatment significantly increased (p<0.05) antioxidant enzymes' activities, as well as serum insulin levels. The findings of this laboratory animal study suggest that A. muricata extract has a protective, beneficial effect on hepatic tissues subjected to STZ-induced oxidative stress, possibly by decreasing lipid peroxidation and indirectly enhancing production of insulin and endogenous antioxidants

Artocarpus Communis Forst. Root-Bark Aqueous Extract- and Streptozotocin-Induced Ultrastructural and Metabolic Changes in Hepatic Tissues of Wistar Rats

Decoctions and infusions of Artocarpus communis (Forst.) (family: Moraceae) root-bark are commonly used traditionally among the Yoruba-speaking people of Western Nigeria as folk remedies for the management, control and/or treatment of an array of human diseases, including type 2, adult-onset diabetes mellitus. Although numerous bioactive flavonoids have been isolated from the roots, stem-bark and leaves of A. communis, to the best of our knowledge, the effects of the plant's root-bark extract on animal model of diabetes mellitus and on liver tissues have hitherto, not been reported in the biomedical literature. In view of this, the present study was undertaken to investigate the glycaemic effect of, and hepatic tissue ultrastructural, morphological and metabolic changes induced by, A. communis root-bark aqueous extract (ACE) in Wistar rats. The ultrastructural, morphological and metabolic effects of ACE have been compared with those induced by streptozotocin (STZ) in rat experimental paradigms. Four groups (A, B, C and D) of Wistar rats, each group containing 10 rats, were used. Diabetes mellitus was induced in the diabetic groups B and C animals by intraperitoneal injections of STZ (75 mg/kg body weight), while group A rats received A. communis root-bark aqueous extract (ACE, 100 mg/kg body weight, i.p.) alone. Control group D rats received distilled water in quantities equivalent to the volume of ACE administered intraperitoneally. The rats in group C were additionally treated with ACE (100 mg/kg body weight i. p.) daily from day 3 to day 10 after STZ treatment. Hepatic glucokinase, hexokinase, glutamate dehydrogenase, succinate dehydrogenase, β-hydroxybutyrate dehydrogenase, serum insulin and blood glucose levels of the animals were measured and recorded before and after ACE, STZ and STZ+ACE treatments. Hepatic tissues were also processed for transmission electron microscopy. Electron microscopic examinations showed toxic, deleterious alterations in the ultrastructures of groups A, B and C hepatic cells, the most prominent deleterious effects being on the hepatocytes. Ultrastructural changes observed within the hepatocytes of groups A, B and C rats include disrupted mitochondria with increase in lipid droplets, extensive hepatocellular vacuolation, scanty rough endoplasmic reticulum (RER) and ribosomes. Large glycogen clusters were also noticed displacing the mitochondria and RER in group A rats. Group A rats also developed significant hyperglycemia (p<0.05) immediately after ACE administration, while groups B and C rats developed hyperglycemia 24 hours after STZ treatment. When compared with the control group D rats, the activities of all the three subsystems were disrupted, leading to overall inhibition of oxidative phosphorylation of the liver mitochondria in groups A, B and C rats, but remain normal in the untreated group D control rats. The findings of the present study indicate that A. communis root-bark aqueous extract induces hyperglycaemia in the experimental animal model used, and that the plant's extract disrupts the ultrastructural characteristics and architecture of hepatocytes as well as oxidative energy metabolism

Morphological Changes and Hypoglycemic Effects of Annona Muricata Linn. (Annonaceae) Leaf Aqueous Extract on Pancreatic Β-Cells of Streptozotocin-Treated Diabetic Rats

The present study was undertaken to investigate the leaf aqueous extract effects of Annona muricata Linn. on the morphology of pancreatic β-cells and oxidative stress induced by streptozotocin (STZ)-diabetic rats. Diabetes mellitus was induced in the diabetic animal groups B and C by intraperitoneal injections of STZ (75 mg/kg body weight), while the control group received equal volume of citrate buffer (pH 6.3) solution intraperitoneally. The rats in group C were given A. muricata leaf aqueous extract (AME, 100 mg/kg, p.o.) as from day 5 post STZ injections, and stopped on the 30th day of the study period. The pancreases of the rats were excised and randomly processed for histological staining and biochemical assays for antioxidant enzymes [such as glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA) and serum nitric oxide (NO)]. In diabetic state, pancreatic β-cells of STZ-treated group B rats histologically demonstrated marked alterations in the micro-anatomy and cellular integrities. The morphology of A. muricata-treated rats’ pancreases showed viable cellularity with distinct β-cell mass. STZ treatment significantly decreased GSH-Px, SOD, GSH, CAT and pancreatic/serum insulin levels (p<0.05). However, STZ treatment increased blood glucose concentrations, MDA, and NO. A. muricata-treated rats showed a significant decrease (p<0.05) in elevated blood glucose, MDA and NO. Furthermore, A. muricata treatment significantly increased (p<0.05) antioxidant enzymes’ activities, as well as pancreatic/serum insulin contents. In conclusion, the findings of the present study indicate that A. muricata treatment has beneficial effects on pancreatic tissues subjected to STZ-induced oxidative stress by directly quenching lipid peroxides and indirectly enhancing production of endogenous antioxidants. Annona muricata protected and preserved pancreatic β-cell integrity

Hypoglycaemic and Hypotensive Effects of Ficus Exasperata Vahl. (Moraceae) Leaf Aqueous Extract in Rats

The hypotensive and hypoglycaemic effects of Ficus exasperata (Vahl) (family: Moraceae) leaf aqueous extract (FEE) were investigated in experimental rat models. In this study, spontaneously-hypertensive rats (SHR) (type 1 diabetes), obese Zucker (type 2 diabetes) and Wistar rats were used. Three (A, B and C) groups of rats, each group consisting of 10 rats, were used. Group A Wistar rats received distilled water in quantities equivalent to the volume of streptozotocin (STZ) and FEE administered intraperitoneally to treated rats. Diabetes mellitus was induced in the SHR group B rats by multiple low-dose (MLD) intraperitoneal injections of STZ (40 mg/kg body weight) to induce type 1 diabetes. The animals in group C were the obese Zucker rats with non-insulin-independent diabetes mellitus (NDDM) (type 2 diabetes) on genetic basis. F. exasperata leaf aqueous extract (FEE, 100 mg/kg/day p.o.) was administered orally by orogastric intubation to fasted Groups B and C rats. In groups B and C rats, administration of FEE commenced 4 weeks post STZ injection, and continued for the next 4 consecutive weeks. Group A rats gave normal biochemical and morphological findings. Group B rats exhibited pronounced polyuria, hypoinsulinaemia, hyperlipidaemia and hyperglycaemia. These findings were also observed in group C rats, except that there was hyperinsilinaemia. Histopathological study of the aortic blood vessels showed extensive collagen fiber formation as well as perivascular fibrosis in both groups B and C rats. Four weeks of oral administration of F. exasperata leaf aqueous extract to diabetic groups of rats decreased blood glucose, blood pressure and lipid profiles. Administration of FEE (100 mg/kg p.o.) also restored the microanatomy of the blood vessels to almost normal levels. The findings of this study suggest that F. exasperata leaf aqueous extract possesses hypoglycaemic, hypotensive and hypolipidaemic properties. These findings lend biomedical and pharmacological support to the folkloric, ethnomedical uses of the plant in the management and/or control of diabetes and hypertension among the Yoruba-speaking people of Western Nigeria

Protective Effect of Quercetin on the Morphology of Pancreatic β-Cells of Streptozotocin-Treated Diabetic Rats

This study was undertaken to investigate the protective effects of quercetin (QCT) on the morphology of pancreatic β-cells against diabetes mellitus and oxidative stress experimentally-induced by streptozotocin (STZ) treatment in Wistar rats. Fifty male and female Wistar rats (200–250 g) were randomly divided into three experimental groups (i. e., control, STZ-treated, and STZ + Quercetin-treated groups). Diabetes was induced in the diabetic groups (B and C) of animals, by a single intraperitoneal injection of STZ (75 mg/kg), while each of the rats in the ‘control’ group received equal volume of citrate buffer (pH 6.3) solution intraperitoneally. In group C rats, quercetin (QCT, 25 mg/kg/day i. p.) was injected daily for 3 days prior to STZ treatment, and QCT administration continued until the end of the study period (30 days). Diabetes mellitus was confirmed by using Bayer's Glucometer Elite® and compatible blood glucose test strips. The rats were sacrificed serially until the end of the study period (after 30 days). The pancreases of the sacrificed rats were excised and randomly processed for histological staining and biochemical assays for antioxidant enzymes [such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and serum nitric oxide (NO)]. In the diabetic state, pancreatic β-cells of STZ-treated group B rats histologically demonstrated an early chromatin aggregation, cytoplasmic vesiculation in the central β-cells, nuclear shrinkage, and lysis of β-cells with distortion of granules. The morphology of QCT-treated rats' pancreases showed viable cellularity with distinct β-cell mass. STZ treatment significantly decreased (p<0.05) GSHPx, SOD, CAT and pancreatic insulin content. However, STZ treatment increased blood glucose concentrations, MDA and serum NO. The QCT-treated group of animals showed a significant decrease (p<0.05) in elevated blood glucose, MDA and NO. Furthermore, QCT treatment significantly increased (p<0.05) antioxidant enzymes' activities, as well as pancreatic insulin contents. Quercetin (QCT) treatment protected and preserved pancreatic β-cell architecture and integrity. In conclusion, the findings of the present experimental animal study indicate that QCT treatment has beneficial effects on pancreatic tissues subjected to STZ-induced oxidative stress by directly quenching lipid peroxides and indirectly enhancing production of endogenous antioxidants

Effect of Melatonin on Carbon Tetrachloride-Induced Kidney Injury in Wistar Rats

Exposure to carbon tetrachloride (CCl4) induces acute and chronic renal injuries as well as oxidative stress in rats. The aim of this study was to evaluate the effect of exogenous melatonin (MEL) treatment on CCl4-induced oxidative stress and nephrotoxicity in rats using histopathological and biochemical parameters. Serum creatinine, blood urea nitrogen (BUN), nitrite and albumin concentrations were measured for the evaluation of renal function. Antioxidant status in the kidney tissue was estimated by determining the activities of superoxide dismustase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and glutathione-S-transferase (GST) as well as thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) levels. For histopathological evaluation, kidney of all rats were excised and processed for light microscopy. CCl4 caused elevated level of TBARS and marked depletion of renal endogenous antioxidant enzymes. Furthermore, severe deterioration of renal function was observed in CCl4-treated rats as assessed by increased serum creatinine, BUN levels and decreased creatinine and urea clearance as compared with the control rats. MEL treatment positively ameliorated the alterations in these biochemical variables in the CCl4 + MEL-treated rats. MEL markedly reduced elevated TBARS and nitrite, significantly attenuated renal dysfunction, increased the levels of antioxidant enzymes. Kidney sections of CCl4-treated group showed, changes in microanatomy. In contrast, these deleterious histopathological alterations resulting from CCl4 nephrotoxin were absent after MEL treatment in CCl4 + MEL group of rats. In conclusion, our results demonstrated that MEL through its antioxidant activity effectively ameliorated CCl4induced nephrotoxicity

Hypoglycaemic And Hypotensive Effects Of Ficus Exasperata Vahl. (Moraceae) Leaf Aqueous Extract In Rats

The hypotensive and hypoglycaemic effects of Ficus exasperata (Vahl) (family: Moraceae) leaf aqueous extract (FEE) were investigated in experimental rat models. In this study, spontaneously-hypertensive rats (SHR) (type 1 diabetes), obese Zucker (type 2 diabetes) and Wistar rats were used. Three (A, B and C) groups of rats, each group consisting of 10 rats, were used. Group A Wistar rats received distilled water in quantities equivalent to the volume of streptozotocin (STZ) and FEE administered intraperitoneally to treated rats. Diabetes mellitus was induced in the SHR group B rats by multiple low-dose (MLD) intraperitoneal injections of STZ (40 mg/kg body weight) to induce type 1 diabetes. The animals in group C were the obese Zucker rats with non-insulin-independent diabetes mellitus (NDDM) (type 2 diabetes) on genetic basis. F. exasperata leaf aqueous extract (FEE, 100 mg/kg/day p.o.) was administered orally by orogastric intubation to fasted Groups B and C rats. In groups B and C rats, administration of FEE commenced 4 weeks post STZ injection, and continued for the next 4 consecutive weeks. Group A rats gave normal biochemical and morphological findings. Group B rats exhibited pronounced polyuria, hypoinsulinaemia, hyperlipidaemia and hyperglycaemia. These findings were also observed in group C rats, except that there was hyperinsilinaemia. Histopathological study of the aortic blood vessels showed extensive collagen fiber formation as well as perivascular fibrosis in both groups B and C rats. Four weeks of oral administration of F. exasperata leaf aqueous extract to diabetic groups of rats decreased blood glucose, blood pressure and lipid profiles. Administration of FEE (100 mg/kg p.o.) also restored the microanatomy of the blood vessels to almost normal levels. The findings of this study suggest that F. exasperata leaf aqueous extract possesses hypoglycaemic, hypotensive and hypolipidaemic properties. These findings lend biomedical and pharmacological support to the folkloric, ethnomedical uses of the plant in the management and/or control of diabetes and hypertension among the Yoruba-speaking people of Western Nigeria

Ocimum Gratissimum Linn Worsens Streptozotocin-Induced Nephrotoxicity in Diabetic Wistar Rats

Abstract Effects of ethanolic extract of Ocimum gratissimum leaves (O. gratissimum) on the kidneys in Streptozotocin-induced diabetic rats were studied. Thirty-six adult rats were assigned into six groups (A, B, C, D, E and F) of six rats each. Diabetes was induced with a single intraperitoneal injection of Streptozotocin. Group A (non diabetic control) and F (diabetic control) received normal saline orally, group B received a Metformin at 25 mg/kg while groups C, D and E had O. gratissimum at 400, 600 and 800 mg/kg. Body weight and fasting blood glucose levels were monitored weekly; blood levels of Creatinine (Cr) and Urea (U) were measured on day twenty eight. Animals were sacrificed and kidney sections processed for histological study. Statistical analysis was carried out using a one way ANOVA followed by a post-hoc test. Results showed significant reduction in body weight and blood glucose levels in the groups that received either metformin or O.gratissimum as well as dose dependent increase in blood urea and creatinine levels, histopathology revealed varying degrees of renal injury. The study concluded that O. gratissimum worsens diabetes induced renal injury