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

Research Paper - OXYTOCIN-LIKE EFFECT OF HARPAGOPHYTUM PROCUMBENS DC [PEDALIACEAE] SECONDARY ROOT AQUEOUS EXTRACT ON RAT ISOLATED UTERUS

Harpagophytum procumbens   DC[family: Pedaliaceae]is widely used in South African traditional medicine for the treatment, management and/or control of a variety of human ailments. Some traditional health practitioners of South Africa have claimed that H. procumbens secondary root is a useful obstetric remedy for induction or acceleration of labour, as well as for expulsion of retained placentas in pregnant women. In the present study, we have, therefore, examined the effects of Harpagophytum procumbens secondary root aqueous extract (HPE) on isolated uterine muscle strips taken from pregnant and non-pregnant, young female rats. The plant's extract (HPE, 10–800 μg/ml) induced concentration-related, significant (P&lt;0.05–0.001) increases in the baseline tone (basal tension), and caused powerful spontaneous, rhythmic, myogenic contractions of the oestrogen-dominated uterine muscle strips taken from stilboesterol-pretreated, non-pregnant female rats. Relatively low to high concentrations of H. procumbens secondary root aqueous extract (HPE, 10–800 μg/ml) also provoked concentration-dependent, significant (P&lt;0.05–0.001) increases in the baseline tone (basal tension) and contracted uterine muscle strips taken from female rats in the early, middle and late stages of pregnancy. Moderate to high concentrations of the plant’s extract (HPE, 200–1000 μg/ml) always provoked powerful contractions of isolated uterine muscle preparations of non-pregnant and pregnant rats. The results of this in vitro study indicate that H. procumbens secondary root aqueous extract (HPE)possesses significant contractile effect and/or uterotonic action on mammalian uterus. This finding probably suggests that the use of Harpagophytum procumbens secondary root preparations should be contra-indicated in pregnancy. The contractile effect and/or uterotonic action of the plant's extract may be due to release of uterotonic substances or mediators. However, the findings of the present laboratory animal study lend pharmacological credence to the suggested folkloric, obstetric uses of the plant’s secondary root for induction or acceleration of labour, as well as for expulsion of retained placentas in pregnant women in some communities of Southern Africa

Research Paper - CARDIOVASCULAR EFFECTS OF HARPAGOPHYTUM PROCUMBENS DC [PEDALIACEAE] SECONDARY ROOT AQUEOUS EXTRACT IN SOME MAMMALIAN EXPERIMENTAL ANIMAL MODELS

In an attempt to scientifically appraise the 'healing powers' and medicinal value of Harpagophytum procumbens DC root aqueous extract (HPE), and throw some light on the efficacy and safety of the medicinal plant product, the cardiovascular effects of the herb's root aqueous extract (HPE) have been investigated in some mammalian experimental animal models. The results of this laboratory animal study indicate that relatively low to moderate doses of H. procumbens root aqueous extract (HPE, 10-400 mg/kg i. v.) produced dose-dependent hypotensive and cardio-depressant effects on systemic arterial blood pressures and heart rates of pentobarbitone-anaesthetized rats. Relatively low to high concentrations of the plant's extract (HPE, 10-1000 μ g/ml) also produced concentration-related biphasic responses in isolated cardiac muscle strips of guinea-pigs and isolated portal veins of rats. Relatively low concentrations of the plant's extract (HPE, 10-100 μg/ml) always produced initial slight, transient and non-significant (P&gt;0.05) positive chronotropic responses in isolated spontaneously-beating right atria, but significant (P&lt;0.05) positive inotropic responses in isolated electrically-driven left atria of guinea-pigs. However, moderate to high concentrations of the plant's extract (HPE, 400-1000 μg/ml) always induced dose-dependent, significant (P&lt;0.05-0.001), secondary longer-lasting, negative chronotropic and inotropic responses of the isolated spontaneously-beating right-, and isolated electrically-driven left-, atrial muscle preparations of guinea-pigs. The plant's extract also produced concentration-related biphasic effects on rat isolated portal vein. Low to high concentrations of the plant's extract (HPE, 10-1000 μg/ml) always produced dose-dependent, initial slight, transient and significant (P&lt;0.05-0.001) contractions of the rat isolated portal veins, followed by secondary, longer-lasting, significant (P&lt;0.05-0.001) relaxations of the muscle preparations. Although the precise mechanisms of the hypotensive and cardio-depressant actions of HPE are unknown, &lt; the vasorelaxant action of the plant's extract is speculated to contribute, at least in part, to the hypotensive action of the plant's extract. The results of this laboratory animal study lend pharmacological credence to the suggested folkloric uses of Harpagophytum procumbens secondary root in the management and/or control of hypertension and certain cardiac disorders in some communities of South Africa

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