**4. Discussion**

Diabetes mellitus is a metabolic disorder that has arguably achieved epidemic proportions. It is known to affect more than 371 million persons globally, and is projected to affect 522 million people by the year 2030 [1, 2 and 11]. Phytotherapy for some decades has played an important role in the management of the disease especially in resource-poor countries. Clearly, the identification of plant materials that can manage diabetes and its complications would save millions of people, especially in developing countries, from untimely death.

The presence of secondary metabolites such as alkaloids, polyphenols, flavonoid, saponins, tannins, and terpenoid in the ethanolic extract of *Acacia ataxacantha* bark may contribute to its hypoglyceamic activity and medicinal value. These compounds have been shown to be responsible for hypoglyceamic activity in *Momordica charantia* [37]. The activities of flavonoids and polyphenol have been ascribed to the structural relationship between different parts of their chemical structures [38].

**3.8. Effects of ethanolic extract of** *Acacia ataxacantha* **bark on pancreatic superoxide**

Values are means (n=6) ± S.D (bars with different superscripts are significantly different at p<0.05).

millions of people, especially in developing countries, from untimely death.

diabetic rats

**4. Discussion**

**Figure 9.** Effects of ethanolic extract of *Acacia ataxacantha* bark on the superoxide dismutase activity of STZ-induced

Diabetes mellitus is a metabolic disorder that has arguably achieved epidemic proportions. It is known to affect more than 371 million persons globally, and is projected to affect 522 million people by the year 2030 [1, 2 and 11]. Phytotherapy for some decades has played an important role in the management of the disease especially in resource-poor countries. Clearly, the identification of plant materials that can manage diabetes and its complications would save

The presence of secondary metabolites such as alkaloids, polyphenols, flavonoid, saponins, tannins, and terpenoid in the ethanolic extract of *Acacia ataxacantha* bark may contribute to its

Figure 9 shows the effects of ethanolic extract of *Acacia ataxacantha* bark on the activity of pancreatic superoxide dismutase. There were significant alterations (p<0.05) in the superoxide dismutase activity in the pancreas of all the tretment groups except the groups administered 500 mg/kg b.w of the extract and metformin, which compared favourably with the control.

**dismutase activities of streptozotocin-induced diabetic rats**

14 Antioxidant-Antidiabetic Agents and Human Health

STZ is a broad spectrum antibiotic extracted from *Streptomyces acromogenes*. The STZ-induced diabetes causes the destruction of pancreatic β cells of islets, which leads to a reduction of insulin release and increase in blood glucose. STZ – induced diabetes has been described as a useful experimental model to study the antidiabetic activity of several agents [39]. STZ is well known for its selective pancreatic islet β-cell cytotoxicity used to induce diabetes mellitus in animals. It interferes with cellular metabolic oxidative mechanisms [39]. Significant elevation was observed in fasting blood glucose in diabetic rats. This observed hyperglycemia may be due to induced gluconeogenesis in the absence of insulin [40]. However, marked reductions observed after 2 days and the progressive decrease till the 6th day which was highest in 125 mg/kg and 250 mg/kg b.w of the extract compared well with the standard drug (metformin). These decreases could be due to the direct stimulation of the secretion of insulin thus promot‐ ing glucose uptake metabolism by inhibiting hepatic gluconeogenesis through the stimulation of a regeneration process and revitalization of the remaining beta cells [41].

The increased levels of hepatic glucose in streptozotocin - induced diabetic rats were reduced following the administration of ethanolic extract of *Acacia ataxacantha* bark. The reduced glucose levels suggests that ethanolic extract of *Acacia ataxacantha* bark may have exerted insulin-like effect on peripheral tissues by either promoting glucose uptake metabolism by inhibiting hepatic gluconeogenesis [42] or by absorption of glucose into the muscle and adipose tissues [43] through the stimulation of a regeneration process and revitalization of the remaining beta cells [42,43].

Glycogen is the primary intracellular storable form of glucose in various tissues and its level in such tissues especially the liver is a direct reflection of insulin activity [44]. The glycogen content was decreased in the liver of diabetic rats in this study. But upon oral administration of ethanolic extract of *Acacia ataxacantha* bark, glycogen content were increased significantly which is comparable to that of metformin, thus confirming its insulin potentiating action to a marked extent. This may be due to the activation of glycogen synthase system and inhibition of glycogen phosphorylase [45] by the extract. It may also be due to decreased enzymatic activities of hexokinase and phosphofructokinase resulting in depletion of liver and muscle glycogen [46].

The concentrations of total protein, bilirubin and albumin may indicate state of the liver and type of damage [47]. Bilirubin is formed by the breakdown of hemoglobin in the liver, spleen and bone marrow [48]. An increase in tissue or serum albumin concentrations results in jaundice. Jaundice occurs in toxic or infectious diseases of the liver [49]. The significant increase in the total bilirubin, conjugated bilirubin and albumin levels in the diabetic control rats and reduction following oral administration of ethanolic extract of *Acacia ataxacantha* bark are indicative of amelioration of the adverse effects caused by diabetes.

The kidneys remove metabolic wastes such as urea, uric acid, creatinine and ions and thus optimum chemical composition of body fluids is maintained. The concentrations of these metabolites increase in blood during renal diseases or renal damage associated with uncon‐ trolled diabetes mellitus. Blood urea and creatinine are considered as significant markers of renal dysfunction [50]. Observed increase in urea and creatinine level in the diabetic control were reduced following the administration of ethanolic extract of *Acacia ataxacantha* bark to a level close to the value obtained for the normal control. Due to continuous catabolism of amino acid during diabetic state, high quantity of urea will be formed from urea cycle. On the other hand, it may be as a result of repression of glycolytic enzymes, thus glucose is channeled into pentose phosphate pathway resulting in the increased availability of ribose-5-phosphate which may lead to increased formation of phosphoribosyl pyrophosphate (PRPP) and ultimately resulting in high concentration of uric acid in the blood [51].

muscles, kidney, and pancreas and to a lesser amount in red blood cells. Its serum concentra‐ tion is proportional to the amount of cellular leakage or damage and it is released into the serum in larger quantities when any one of these tissues is damaged and its increase is usually associated with heart attack or liver disease. While on the other hand, alanine aminotransferase is an enzyme found mainly in the liver and elevated levels in serum usually indicates liver damage [61]. The mechanism by which the serum aspartate and alanine aminotransferases are raised in diabetic untreated may involve increased liberation of these enzymes from tissues (mainly liver), owing to oxidative stress or the formation of advanced glycosylation end product [57]. The increase in the activities of these enzymes in serum of diabetic control might be induced due to liver dysfunction. Ohaeri [62] reported that liver was necrotized in STZinduced diabetic rats. Therefore an increase in the activities of ALT and AST in the serum might be mainly due to the leakage of these enzymes from the liver cytosol into the blood stream [63] which gives an indication of hepatotoxic effect of STZ. Reduction in the activities of ALT and AST in the serum might consequently be due to alleviation of liver damage caused by STZ–

Lipid Profile, Antidiabetic and Antioxidant Activity of *Acacia ataxacantha* Bark Extract in...

http://dx.doi.org/10.5772/57151

17

induced diabetic mellitus [64], while 500mg/kg body weight might be toxic.

converting them to hydrogen peroxides and molecular oxygen [67].

**5. Conlusion**

Malondialdehyde is used as a biomarker to measure level of oxidative stress in an organism [65]. Malondialdehyde participate in a variety of chemical and biological reactions including covalent binding to protein, RNA, and DNA. The significant increase (p<0.05) in pancreatic malondialdehyde concentration in the diabetic but treated groups was reduced upon oral administration of the ethanolic extract of *Acacia ataxacantha* bark. These may be due to the presence of antioxidant phytochemicals in the extract which reduced the oxidative stress that caused lipid peroxidation thereby reducing the generation of free radicals and thus may have prevented the damage of cellular organelles either by decreasing localized oxygen concentra‐ tion, presenting first chain initiation by scavenging initial radicals and binding metals or by decomposing peroxide. Antioxidant enzymes have been shown to play important role in maintaining physiological levels of oxygen and hydrogen peroxide by hastening the dismu‐ tation of oxygen radicals and eliminating organic peroxide and hydro-peroxides generated from inadvertent exposure to STZ [66]. In the enzymatic antioxidant defense system, SOD is one of the important enzymes that scavenge the superoxide radicals by converting them to hydrogen peroxides and molecular oxygen [67]. The observed decrease in the pancreatic SOD activity in diabetic control rats could result from inactivation by H2O2 or by glycosylation of the enzymes, which has been reported to occur in diabetes [68, 69]. However, the increased SOD activity following oral administration of ethanolic extract of *Acacia ataxacantha* bark might be due to presence of antioxidant phytochemicals which scavenge the superoxide radical by

Overall, it may be concluded that ethanolic extract of *Acacia ataxacantha bark* at 125 mg/kg b.w exhibited promising antidiabetic activity in streptozotocin-induced diabetic rats. Thus, the antihyperglyceamic and anti-dyslipidemic activity of ethanolic extract of *Acacia ataxacantha* bark could represent a protective mechanism against the development of atherosclerosis,

Lipids play a vital role in the pathogenesis of diabetic mellitus. Diabetic is associated with profound alterations in the plasma lipid, triglycerides and lipoprotein profile and with an increased risk of coronary heart disease [52]. The most common lipid abnormalities in diabetes are hypertriglyceridemia and hypercholesterolemia. The increase in the levels of serum lipids such as cholesterol and triglycerides in the diabetic rats may be due to the fact that under normal circumstances, insulin activates lipoprotein lipase and hydrolyses triglycerides. Insulin increases uptake of fatty acids into adipose tissue and increases triglyceride synthesis. Moreover, insulin inhibits lipolysis. In case of insulin deficiency, lipolysis is not inhibited but an increased lipolysis which finally leads to hyperlipidemia. In diabetic condition, the concentration of serum free acids is elevated as a result of free fatty acid outflow from fat deposited, where the balance of the free fatty acid esterification-triglyceride lipolysis cycle is displaced in favour of lipolysis [53].

HDL is an anti-atherogenic lipoprotein. It transports cholesterol from peripheral tissues into the liver and thereby acts as a protective factor against coronary heart disease. The level of HDL-cholesterol slightly increased after administration of ethanolic extract of *Acacia ataxacan‐ tha* bark at 250 mg/kg and 500 mg/kg b.w. This might be due to increase in the activity of lecithin cholesterol acyl transferase (LCAT), which may contribute to the regulation of blood lipids [54]. Administration of ethanolic extract of *Acacia ataxacantha* bark lowered cholesterol level at all doses while 250 mg/kg and 500 mg/kg b.w were able to reduce triglycerides and LDLcholesterol levels. Significant lowering of total cholesterol, triglycerides, LDL-cholesterol and rise in HDL-cholesterol is a very desirable biochemical state for prevention of atherosclerosis and ischaemic conditions [55].

Liver is the vital organ of metabolism, detoxification, storage and excretion of xenobiotic and their metabolites [56]. Aspartate aminotransferase, alanine aminotransferase, albumin and bilirubin are considered as part of liver toxicity markers [57]. In streptozotocin-induced diabetic animals, change in the serum enzymes is directly related to change in the metabolic functions of aspartate aminotransferase, alanine aminotransferase, albumin and bilirubin [58, 59]. It has been reported that the increased aminotransferase activities under insulin deficiency [60] were responsible for the increased gluconeogenesis and ketogenesis during diabetic. Aspartate aminotransferase is an enzyme found mainly in the cell of the liver, heart, skeletal muscles, kidney, and pancreas and to a lesser amount in red blood cells. Its serum concentra‐ tion is proportional to the amount of cellular leakage or damage and it is released into the serum in larger quantities when any one of these tissues is damaged and its increase is usually associated with heart attack or liver disease. While on the other hand, alanine aminotransferase is an enzyme found mainly in the liver and elevated levels in serum usually indicates liver damage [61]. The mechanism by which the serum aspartate and alanine aminotransferases are raised in diabetic untreated may involve increased liberation of these enzymes from tissues (mainly liver), owing to oxidative stress or the formation of advanced glycosylation end product [57]. The increase in the activities of these enzymes in serum of diabetic control might be induced due to liver dysfunction. Ohaeri [62] reported that liver was necrotized in STZinduced diabetic rats. Therefore an increase in the activities of ALT and AST in the serum might be mainly due to the leakage of these enzymes from the liver cytosol into the blood stream [63] which gives an indication of hepatotoxic effect of STZ. Reduction in the activities of ALT and AST in the serum might consequently be due to alleviation of liver damage caused by STZ– induced diabetic mellitus [64], while 500mg/kg body weight might be toxic.

Malondialdehyde is used as a biomarker to measure level of oxidative stress in an organism [65]. Malondialdehyde participate in a variety of chemical and biological reactions including covalent binding to protein, RNA, and DNA. The significant increase (p<0.05) in pancreatic malondialdehyde concentration in the diabetic but treated groups was reduced upon oral administration of the ethanolic extract of *Acacia ataxacantha* bark. These may be due to the presence of antioxidant phytochemicals in the extract which reduced the oxidative stress that caused lipid peroxidation thereby reducing the generation of free radicals and thus may have prevented the damage of cellular organelles either by decreasing localized oxygen concentra‐ tion, presenting first chain initiation by scavenging initial radicals and binding metals or by decomposing peroxide. Antioxidant enzymes have been shown to play important role in maintaining physiological levels of oxygen and hydrogen peroxide by hastening the dismu‐ tation of oxygen radicals and eliminating organic peroxide and hydro-peroxides generated from inadvertent exposure to STZ [66]. In the enzymatic antioxidant defense system, SOD is one of the important enzymes that scavenge the superoxide radicals by converting them to hydrogen peroxides and molecular oxygen [67]. The observed decrease in the pancreatic SOD activity in diabetic control rats could result from inactivation by H2O2 or by glycosylation of the enzymes, which has been reported to occur in diabetes [68, 69]. However, the increased SOD activity following oral administration of ethanolic extract of *Acacia ataxacantha* bark might be due to presence of antioxidant phytochemicals which scavenge the superoxide radical by converting them to hydrogen peroxides and molecular oxygen [67].
