Bubuya Masola

Antioxidant strategies in the management of diabetic neuropathy.

Chronic hyperglycaemia (an abnormally high glucose concentration in the blood) resulting from defects in insulin secretion/action, or both, is the major hallmark of diabetes in which it is known to be involved in the progression of the condition to different complications that include diabetic neuropathy. Diabetic neuropathy (diabetes-induced nerve damage) is the most common diabetic complication and can be devastating because it can lead to disability. There is an increasing body of evidence associating diabetic neuropathy with oxidative stress. Oxidative stress results from the production of oxygen free radicals in the body in excess of its ability to eliminate them by antioxidant activity. Antioxidants have different mechanisms and sites of actions by which they exert their biochemical effects and ameliorate nerve dysfunction in diabetes by acting directly against oxidative damage. This review will examine different strategies for managing diabetic neuropathy which rely on exogenous antioxidants.

The Effects of Syzygium aromaticum-Derived Oleanolic Acid on Glycogenic Enzymes in Streptozotocin-Induced Diabetic Rats

Studies indicate that the antihyperglycemic effects of Syzygium aromaticum-derived oleanolic acid (OA) are mediated in part through increased hepatic glycogen synthesis. Accordingly, this study assessed the influence of OA on the activity of glucokinase (GK) and hexokinase (HK) of skeletal muscle and liver tissues in streptozotocin (STZ)-induced diabetic rats. After 5 weeks of OA treatment, hepatic and gastrocnemius muscle glycogen concentrations and activities of GK and HK were measured spectrophotometrically in reactions where the oxidation of glucose-6-phosphate (G-6-PDH) formed was coupled to nicotinamide adenine dinucleotide phosphate (NADP+) reduction catalyzed by G-6-PDH dehydrogenase. Rats treated with deionized water or standard hypoglycemic drugs acted as untreated and treated positive controls, respectively. STZ-induced diabetic rats exhibited depleted glycogen levels and low activities of glycogenic enzymes in muscle and hepatic tissues. OA administration restored these biochemical alterations to near normalcy. The combination of OA and insulin did not significantly alter the activities of HK and GK of STZ-induced diabetic rats, suggesting that glycogen synthesis can also occur from precursors such as amino acids or fructose and lactate. The attenuation of the activities of glycogenic enzymes with concomitant increases of hepatic and muscle glycogen concentrations of STZ-induced diabetic rats provides a therapeutic strategy for diabetes treatment.

Effects of oleanolic acid on the insulin signaling pathway in skeletal muscle of streptozotocin‐induced diabetic male Sprague‐Dawley rats

  The pant‐derived triterpene oleanolic acid (OA) has been shown to have antidiabetic effects, but its action on the insulin signaling cascade has not been fully elucidated. The aim of the present study was to investigate the effects of OA on aspects of the phosphatidylinositol 3‐kinase/Akt insulin signaling cascade in skeletal muscle of streptozotocin‐induced type 1 diabetic male Sprague‐Dawley rats.

A systematic review of pentacyclic triterpenes and their derivatives as chemotherapeutic agents against tropical parasitic diseases.

Parasitic infections are among the leading global public health problems with very high economic and mortality burdens. Unfortunately, the available treatment drugs are beset with side effects and continuous parasite drug resistance is being reported. However, new findings reveal more promising compounds especially of plant origin. Among the promising leads are the pentacyclic triterpenes (PTs) made up of the oleanane, ursane, taraxastane, lupane and hopane types. This paper reviews the literature published from 1985 to date on the in vitro and in vivo anti-parasitic potency of this class of phytochemicals. Of the 191 natural and synthetic PT reported, 85 have shown high anti-parasitic activity against various species belonging to the genera of Plasmodium, Leishmania, Trypanosoma, as well as various genera of Nematoda. Moreover, structural modification especially at carbon 3 (C3) and C27 of the parent backbone of PT has led to improved anti-parasitic activity in some cases and loss of activity in others. The potential of this group of compounds as future alternatives in the treatment of parasitic diseases is discussed. It is hoped that the information presented herein will contribute to the full exploration of this promising group of compounds as possible drugs for parasitic diseases.

The Effects of Syzygium aromaticum-Derived Oleanolic Acid on Kidney Function of Male Sprague–Dawley Rats and on Kidney and Liver Cell Lines

Studies indicate that Syzygium spp-derived oleanolic acid (OA) enhances renal function of streptozotocin (STZ)-induced diabetic rats as evidenced by its reversal of the previously reported inability of the kidney to excrete Na+ in these animals. We postulated that OA influences Na+ excretion in the proximal tubule, the site where two-thirds of filtered NaCl is reabsorbed through a process mediated by transport proteins. Therefore, the study investigated the effects of OA on proximal tubular Na+ handling in male Sprague–Dawley rats using renal lithium clearance (CLi). Renal CLi has been used widely in animal and clinical studies to assess proximal tubular function. Sub-chronic doses of OA were administered to rats twice every third day for 5 weeks. Rats treated with deionized water served as control animals. Cytotoxicity of OA on kidney and liver cell lines was assessed by the MTT and comet assays. OA increased Na+ excretion of conscious male Sprague–Dawley rats from week 3 to week 5. By the end of the 5-week experimental period, OA treatment significantly reduced (p < 0.05) plasma creatinine concentration of STZ-induced diabetic rats with a concomitant elevation in glomerular filtration rate (GFR). Acute OA infusion was also associated with increases in fractional excretion of sodium (FENa) and lithium (FELi) in anesthetized rats in the absence of significant changes in GFR. The MTT assay studies demonstrated that OA increased the metabolic activity of kidney and liver cell lines. Taken together with previous observations, this study implicates the proximal tubule in OA-evoked increases in urinary Na+ output.

Effects of Syzygium aromaticum‐derived oleanolic acid on glucose transport and glycogen synthesis in the rat small intestine (丁香衍生物齐墩果酸对大鼠小肠中的葡萄糖转运以及糖原合成的影响)

Background:  In the present study, we investigated the effects of oleanolic acid (OA), which has hypoglycemic properties, on glucose transport and glycogen synthesis in the small intestine, an organ that secretes enzymes involved in carbohydrate metabolism.

Effects of Syzygium aromaticum-derived oleanolic acid on glucose transport and glycogen synthesis in the rat small intestine.

Background:  In the present study, we investigated the effects of oleanolic acid (OA), which has hypoglycemic properties, on glucose transport and glycogen synthesis in the small intestine, an organ that secretes enzymes involved in carbohydrate metabolism.

Centella asiatica enhances hepatic antioxidant status and regulates hepatic inflammatory cytokines in type 2 diabetic rats

Abstract Context: Neutralizing the over-activation of oxidative stress and inflammation remains an important goal in the management of type 2 diabetes mellitus (T2DM). Centella asiatica (L.) Urban (Apiaceae) (CA) has been used in traditional folklore in Africa and Asia to treat various ailments including diabetes. Objective: We investigated the hepatic antioxidant and anti-inflammatory potential of methanol extract of CA leaves in T2DM. Materials and methods: T2DM was induced in male Sprague-Dawley rats with 10% fructose in drinking water for 14 days followed by a single intraperitoneal injection of streptozotocin (40 mg/kg b.wt). Hepatic oxidant/antioxidant status was assessed by measuring the concentrations of malondialdehyde (MDA), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), Trolox equivalent antioxidant capacity (TEAC), reduced glutathione (GSH) and activities of glutathione S-transferase (GST) and glutathione peroxidase (GPX). The concentrations of cytokines IL-1β, IL-4, IL-6, IL-10, MCP-1 and TNF-α in the liver were determined. Results: Diabetes increased MDA formed (47%) and reduced FRAP (20%), TEAC (15%), GSH levels (32%), significantly; decreased GST and GPX activities in the liver and elevated levels of cytokines studied. Treatment of diabetic rats with 500 mg/kg b.wt CA for 14 days decreased MDA (44%); elevated FRAP (15%) and GSH (131%) levels and increased the activities of GST and GPX by 16%. Hepatic concentrations of IL-1β, MCP-1 and TNF-α in DCA group were reduced to 68%, 75% and 63% of DC values, respectively. Conclusions: The antioxidant and anti-inflammatory properties of CA may protect tissues such as the liver from diabetes-induced oxidative damage.

Centella asiatica ameliorates diabetes-induced stress in rat tissues via influences on antioxidants and inflammatory cytokines

Centella asiatica (L.) Urban (Family: Apiaceae) is a perennial herb that has been used to elevate mood, improve memory, treat wounds and manage kidney-related ailments in African traditional medicine practice. This study evaluated the potential benefits of C. asiatica (CA) on diabetes-induced stress in kidney and brain of rats. Following the induction of diabetes mellitus (DM), rats were orally treated with vehicle, CA or Metformin daily for 14 days. After treatment, renal and brain levels of inflammatory cytokines, TNF-α, IFN-γ, IL-4, and IL-10 were assessed. Oxidant and antioxidant biomarkers were also evaluated. Phyto-compounds in the crude methanol extract of CA were analyzed by Gas Chromatography-Mass Spectroscopy. Diabetes increased malondialdehyde (MDA) concentration by 39%; elevated levels of TNF-α (44%) and IFN-γ (20%); and reduced the antioxidant status in the kidney in comparison to normal control rats. In the brain, diabetic control rats had significantly greater levels of MDA, TNF-α, and IFN-γ (182%, 40%, and 20%, respectively) in addition to the lowered antioxidant status when compared to normal control rats. However, treatment with CA significantly reduced the renal levels of MDA (33%), TNF-α (78%), and IFN-γ (42%) while that of IL-10 increased by 18% when compared to diabetic control rats. In the brain, CA treatment elicited significant reductions in MDA (37%), TNF-α (30%), and IFN-γ (37%) levels while those of IL-4 and IL-10 increased by 94% and 20% respectively. In addition, the renal and brain antioxidant status was significantly boosted by CA treatment. Several medicinal compounds including ascorbic acid, asiatic acid, oleanolic acid, stevioside, stigmasterol, and α-humulene were identified in the crude extract of CA. Findings from this study suggest CA may protect diabetic tissues from stress via antioxidant and anti-inflammatory mechanisms that can be useful in the management of diabetic complications.

Effects ofSyzygium aromaticum-derived oleanolic acid on glucose transport and glycogen synthesis in the rat small intestine (丁香衍生物齐墩果酸对大鼠小肠中的葡萄糖转运以及糖原合成的影响): OA on glucose transport in the small intestine

Background:  In the present study, we investigated the effects of oleanolic acid (OA), which has hypoglycemic properties, on glucose transport and glycogen synthesis in the small intestine, an organ that secretes enzymes involved in carbohydrate metabolism.