Centella asiatica alleviates diabetes-induced changes in fatty acid profile and oxidative damage in rat testis.

The in vivo effects of Centella asiatica L. Urban (Family: Apiaceae; CA) on diabetes-induced testicular fatty acid misdistribution and oxidative injury were investigated. Diabetic rats were treated with vehicle, CA or metformin daily for 14 days by oral gavage. Fatty acid (FA) content in testis was analysed using gas chromatography-flame ionisation detection while redox indices were measured as peroxide value (PV), malondialdehyde (MDA), oxygen radical antioxidant capacity (ORAC), reduced glutathione (GSH), glutathione S-transferase (GST) and glutathione peroxidase (GPx) activities. Diabetes increased omega-6 (61%), and decreased omega-3 (23%) and monounsaturated fatty acids (MUFA; 18%) compared to non-diabetic controls. Oxidative injury in diabetic rats was confirmed by increases in PV (112%) and MDA (77%) in addition to decreases in GSH (41%) and activities of GST (19%) & GPx (24%) compared to non-diabetic controls. CA treatment led to 17% reduction in omega-6 and 33% rise in MUFA compared to diabetic controls. Additionally, CA ameliorated the oxidative injury and improved antioxidant capacity by increasing GSH (49%), GST (16%) and GPx (23%) when compared to diabetic controls. Data suggest CA potential in alleviating the alterations caused by diabetes in testes through effects on omega-6 and MUFA; and via increased GSH level and dependent enzyme activities.

Effects of Centella asiatica on skeletal muscle structure and key enzymes of glucose and glycogen metabolism in type 2 diabetic rats.

BACKGROUND: Dysregulation of glucose and glycogen metabolism are crucial mechanisms implicated in type 2 diabetes mellitus (T2DM). Centella asiatica (L.) Urban (Apiaceae) has been utilized as a traditional medicine in Africa and Asia for centuries and is commercially available as a dietary supplement. AIM: We explored for the first time, the possible efficacy of Centella asiatica (CA) extract in ameliorating T2DM-induced changes in key enzymes involved in glucose and glycogen metabolism in the rat skeletal muscle. METHODS: Diabetic rats were orally treated with vehicle, CA (500 and 1000 mg/kg) or metformin (300 mg/kg) daily for 14 days. Skeletal muscle activities of hexokinase (HK), phosphofructokinase (PFK) and fructose 1,6-bisphosphatase (FBPase) were determined by spectrophotometric assays while those of glycogen synthase (GS) and glycogen phosphorylase (GP) were assayed radio-chemically. Histological examination of skeletal muscle was also performed. RESULTS: Rats with induced T2DM had reduced activities of HK (25%), PFK (88%), and GS (38%) when compared to non-diabetic rats. Treatment of diabetic rats with CA500 increased the activities of PFK (7-fold), and FBPase (23%). Further, treatment of diabetic rats with CA1000 also increased the activities of GS (27%) and GP (50%) with little change in these parameters for diabetic rats treated with CA500. These effects probably led to the reduced blood glucose level and elevated skeletal muscle glycogen content observed in CA-treated rats relative to diabetic controls. Furthermore, CA treated rats had reduced the morphological damage of skeletal muscle fibres compared to the non-treated diabetic control rats. CONCLUSION: Our findings strongly suggest that the anti-diabetic effects of CA in part target muscle glucose and glycogen metabolism and hence supporting its folkloric medical use as an anti-diabetic remedy.

The effect of Psidium guajava aqueous leaf extract on liver glycogen enzymes, hormone sensitive lipase and serum lipid profile in diabetic rats.

Diabetes mellitus is characterized by hyperglycaemia that results from defects in insulin secretion or insulin action and is accompanied by general disturbances metabolism. Psidium guajava (PG) leaf is known to have antidiabetic effects that include lowering of blood glucose. The aim of the study was to investigate the effect of PG leaf extract on tissue activity of glycogen synthase (GS) and glycogen phosphorylase (GP); tissue activity of hormone sensitive lipase (HSL); serum lipid profile; and serum enzyme biomarkers of tissue damage. Diabetes was induced in male Sprague-Dawley rats with a single dose of 40 mg/kg body weight streptozotocin. The aqueous extract of PG leaves was used to treat both normal and diabetic animals (400 mg/kg body weight) for 2 weeks while control animals were treated with the vehicle. At the end of the treatment period, blood, liver and adipose tissue samples were collected from the euthanized animals. The results show that PG extract significantly decreased (P < 0.05) HSL activity in adipose tissue and liver of diabetic animals which was accompanied by increased glycogen levels, reduced serum triglycerides, total cholesterol, LDL-cholesterol and increased HDL-cholesterol. This study demonstrates that P. guajava has significant anti-diabetic effects that include increased glycogen storage and reduced HSL activity in the liver and adipose tissue with an improved serum lipid profile.

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.

Effect of oleanolic acid on small intestine morphology and enzymes of glutamine metabolism in diabetic rats.

The small intestine (SI) is the main site for food absorption and glutamine utilization hence critical in metabolic disorders that involve energy balance such as diabetes. This study investigates the effects of oleanolic acid (OA) on SI morphology and some enzymes of glutamine metabolism in male Sprague-Dawley diabetic rats. High dose STZ-induced diabetes (HDD) and low dose STZ-induced diabetes (LDD) were induced by intraperitoneal injection of 60 and 40 mg streptozotocin/kg body weight respectively. Non-diabetic and diabetic rats were treated for two weeks with OA, insulin or OA + insulin in HDD study while animals in the in LDD study were treated with OA. There was significant (P<0.05) increase in the weight of the SI of diabetic animals and of villus height (VH) in the jejunum and duodenum of HDD animals. OA and insulin treatment significantly decreased VH in duodenum of HDD animals while OA treatment profoundly increased VH in normal rats. Jejunal of phosphate-dependent glutaminase (PDG) activity was unaffected by diabetes however alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase activities were significantly (P<0.05) elevated by diabetes and treatments decreased these elevated aminotransferase activities. It is suggested that the intestine meets the energy demand in diabetes by modulating the activities of aminotransferases without change in PDG activity.

Host pregnancy influences the establishment of Trichinella zimbabwensis in Balb C mice.

In order to determine the effect of host pregnancy in the establishment of Trichinella zimbabwensis, 120 female Balb C mice were divided into 4 groups of 30 mice each. Group 1 animals were orally infected with 50 T. zimbabwensis larvae per gram (LPG) of body weight on day 0; group 2 were mated on day 0 and not infected; group 3 were mated at day 0 and infected with 50 LPG at day 7 post-mating and Group 4 were control animals which were neither mated nor infected. Six animals from each group were sacrificed and the number of adult parasites in the intestines as well as larvae in the muscles were determined at day 0, 7, 14, 21 and 28 post-infection for group 1; 0, 7, 14, 21 and 28 post-mating for group 2 and days 7, 14, 21, 28 and 35 post-mating for group 3. In addition, levels of progesterone and cortisol were measured in all groups at the same intervals. Our results showed that pregnancy reduced the number of larvae establishing in muscles with progesterone levels significantly higher in pregnant than in non-pregnant Balb C mice (P < 0.05). There were no significant differences in cortisol levels between pregnant and non-pregnant mice. High progesterone level in pregnant mice was assumed to have parasiticidal effect on the new-born larvae (NBL). Further research is needed to determine the direct effect of progesterone on Trichinella NBL and how this can be exploited in designing remedies for preventing Trichinella infection in susceptible domestic animals and humans.

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

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-1ß, 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-1ß, 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.

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.

In vivo effects of diabetes, insulin and oleanolic acid on enzymes of glycogen metabolism in the skin of streptozotocin-induced diabetic male Sprague-Dawley rats.

The skin is the largest organ in the body and diabetes induces pathologic changes on the skin that affect glucose homeostasis. Changes in skin glycogen and glucose levels can mirror serum glucose levels and thus the skin might contribute to whole body glucose metabolism. This study investigated the in vivo effects of diabetes, insulin and oleanolic acid (OA) on enzymes of glycogen metabolism in skin of type 1 diabetic rats. Diabetic and non-diabetic adult male Sprague-Dawley rats were treated with a single daily dose of insulin (4 IU/kg body weight), OA (80 mg/kg body weight) and a combination of OA + insulin for 14 days. Glycogen phosphorylase (GP) expression; and GP, glycogen synthase (GS) and hexokinase activities as well glycogen levels were evaluated. The results suggest that diabetes lowers hexokinase activity, GP activity and GP expression with no change in GS activity whilst the treatments increased GP expression and the activities of hexokinase, GP and GS except for the GS activity in OA treated rats. Glycogen levels were increased slightly by diabetes as well as OA treatment. In conclusion diabetes, OA and insulin can lead to changes in GS and GP activities in skin without significantly altering the glycogen content. We suggest that the skin may contribute to whole body glucose homeostasis particularly in disease states.

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

BACKGROUND: 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. METHODS: Diabetic and non-diabetic rats were treated with insulin (4 IU/kg), OA (80 mg/kg), and the combination of OA + insulin in acute 60-min and sub-chronic 14-day studies. Single and daily doses were administered in the acute and sub-chronic studies, respectively. In acute studies, phosphorylated (p-) Akt and p-glycogen synthase (GS) expression was evaluated. In sub-chronic studies, GS and glycogen phosphorylase (GP) expression and activity were evaluated, as were glycogen levels. RESULTS: The findings show that OA enhances insulin-stimulated hypoglycemic effects in diabetic rats. In the acute study, OA increased levels of p-Akt and decreased levels of p-GS. In the sub-chronic study, OA increased both GS and GP activity, whereas OA + insulin increased GS and decreased GP activity. Treatment of rats with OA and OA + insulin increased GS expression in the skeletal muscle of diabetic rats and decreased GP expression. Glycogen levels were increased by OA but decreased OA + insulin treatment. CONCLUSION: Oleanolic acid in synergy with insulin can enhance activation of the insulin signaling pathway. Furthermore, the present study provides evidence of OA activation of insulin signaling enzymes independent of insulin.

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.

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. METHODS: The OA was isolated from Syzygium aromaticum ethyl acetate-soluble fractions followed by recrystallization with ethanol. It was diluted to required concentrations in freshly prepared dimethyl sulfoxide (2 mL) and normal saline (19 mL) before being administered to rats (p.o.). Glycogen concentrations were determined in isolated small intestines from fasted and non-fasted non-diabetic and streptozotocin-diabetic rats after 18 h treatment with 80 mg/kg, p.o., OA or standard hypoglycemic drugs (i.e. 100 µg/kg, s.c., insulin; 500 mg/kg, p.o., metformin). In a separate series of experiments, the effects of 30-min incubation with graded concentrations of OA (0.82-6.56 mmol/L) on d-glucose were evaluated by monitoring changes in glucose concentrations inside and outside of intestinal sacs isolated from fasted, non-diabetic rats and mounted in an organ bath containing Krebs-Henseleit bicarbonate buffer. RESULTS: All in vivo treatments increased the glycogen concentration in rat small intestine, although the effects of metformin treatment in non-fasted diabetic rats failed to reach statistical significance. In vitro, both OA (1.64-6.56 mmol/L) and phlorizin (10(-5) -10(-3) mol/L) decreased glucose transport from the mucosa to the serosa. CONCLUSION: The data suggest that OA may be a potential alternative drug treatment for postprandial hyperglycemia because of its inhibition of glucose uptake across the small intestine and its concomitant conversion of glucose to glycogen in the intestinal wall.

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 (C(Li)). Renal C(Li) 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 (FE(Na)) and lithium (FE(Li)) 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.

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.