Diabetes mellitus is a disease that affects the quality of life and life expectancy of its victim’s worldwide [
23]. Many deaths of diabetic subjects have been attributed to hyperglycemia and its accompanied vascular diseases. Hyperglycemia in particular, is the primary clinical manifestation of diabetes [
24] and is thought to contribute to diabetic complications by altering vascular cellular metabolism, vascular matrix and circulating lipoproteins [
25]. The major goal in the treatment of diabetes has been to keep both short-term and long-term glucose levels within acceptable limits, thereby reducing the risk of long term complications [
26].
The result of this study showed that there was a significant reduction in the blood glucose levels of all the diabetic rats treated with the extract compared with the control. The 100, 250 and 400 mg/kg body weight of the
Uvaria chamae extract achieved diabetic control at the 5
th day of treatment with a glucose reduction of 85.88, 80.00 and 85.48% respectively. This diabetic control was maintained till the end of the experiment. This marked reduction in plasma glucose concentration may be as a result of increased release of insulin from regenerated beta cells of the pancreas (Figs.
3,
4 and
5). The presence of phytochemicals such as flavonoids, alkaloids and tannins in the extract as reported in our previous study [
9] may also have contributed to its antidiabetic activity.
Besides hyperglycemia, diabetes mellitus is highly characterized by elevated levels of triglycerides and cholesterol in the blood associated with a modern lifestyle and increased consumption of a high fat diet [
27]. The reduced absorption of free fatty acids and free cholesterol by inhibition of pancreatic lipase and pancreatic cholesterol esterase reduces hyperlipidemia associated with diabetes mellitus [
28,
29]. This study revealed that the extract lowered the plasma total cholesterol and LDL-cholesterol levels significantly in the treated diabetic rats. This clearly demonstrated the presence of hypolipidemic agents in the extract. The hypolipidemic activity of the extract may be due to the inhibition of pancreatic lipase and pancreatic cholesterol esterase. The reduced plasma LDL-cholesterol reduces the risk of developing cardiovascular disease [
30].
Persistent hyperglycemia causes increase in cellular glucose level in tissues undergoing insulin-independent glucose uptake such as eye lens, retina, kidney, and peripheral nerves, leading to secondary late stage diabetic complications. Influx of excess glucose into polyol pathway causes accumulation of sorbitol in the tissues, resulting in hyperosmotic stress to the cells. This is postulated to be the primary cause of diabetic complications which include nephropathy, retinopathy, cataract, and neuropathy [
31]. Creatinine is the most commonly used indicator of renal function. A raised plasma level of creatinine is a recognised marker of renal dysfunction [
32]. The significant increase in the plasma creatinine levels of the diabetic rats’ untreated indicated renal impairment in this group of rats. Therefore, persistent hyperglycemia due to poorly controlled diabetes mellitus may lead to diabetic nephropathy. A number of extra renal factors influence the circulating urea concentration limiting its value as a test of kidney function. For example plasma urea concentration is increased by high protein diet, increased protein catabolism and dehydration. In the above pre-renal situations, the plasma creatinine concentration is usually normal [
33]. The raised plasma urea seen in the diabetic rats treated with insulin and the extract could be as a result of dehydration or induced diabetic state from streptozotocin. This assertion is corroborated by Parvizi et al. [
34], who reported that streptozotocin induced diabetes caused a significant increase in serum blood urea nitrogen level in type1 diabetes mellitus. ALT, AST and ALP are part of the liver enzymes [
35]. They are frequently used to diagnose or screen for hepatobiliary disease, examine the progression of a disease as well as to monitor or detect the hepatotoxicity that may arise from the use of drugs or substances [
36,
37]. The heart also releases AST and ALT, and an elevation in their plasma concentrations is an indicator of liver and heart damage [
19]. The results in this study showed that the activities of AST and ALT in the plasma of diabetic rats untreated were markedly elevated. These enzymes are usually found in large quantities in the liver where they play an important role in the metabolism of amino acid [
38]. However, as a result of damage or toxicity to the liver, these enzymes may leak from the hepatocytes into the circulation where their levels become elevated [
39]. Therefore, the elevated plasma levels of AST and ALT in the diabetic untreated rats suggested liver and heart damage. Administration of the root extract of
Uvaria chamae considerably reduced the elevated levels of AST and ALT in the diabetic rats. This showed that the extract is hepatocellular and cardio-protective. However, the elevated levels of AST, ALT and ALP in the diabetic rats treated with insulin during the period of the experiment could be as a result of damage to the liver and the heart from poorly controlled diabetes mellitus. Elevations of transaminases and alkaline phosphatase are common in diabetes mellitus [
40]. Weight loss is considered an important aspect of therapy for patients with diabetes. Excess weight places greater direct demand on the beta-cell and also aggravates insulin resistance. Numerous studies have shown that weight loss in patients with diabetes can result in improvement in glucose levels [
41]. The results of this study revealed that there was a significant weight reduction in the diabetic rats treated with the extract compared with the control. The weight loss may be due to suppression of appetite.