Abstract
Purpose
Chronic hyperglycemia and deficiency of insulin are peculiar features of diabetes mellitus alters glycoprotein levels in various tissues leads to impaired metabolism of glycoproteins which play a major role in the pathogenesis of diabetic complications. Boswellia ovalifoliolata is a medicinal plant known for its many medicinal properties including diabetes. In this background our study was aimed to evaluate the effect of aqueous extract of stem bark of Boswellia ovalifoliolata (AESBBO) on antidiabetic and glycoprotein metabolism.
Methods
Diabetes was induced in rats by intraperitoneal administration of streptozotocin at a dose of 50 mg/kg bw. After induction of diabetes rats were treated with AESBBO at dosage of 200 mg/kg for a long term treatment of 40 days. Finally, by the end of study all the rats were dissected blood, liver, and kidney tissue samples were collected to investigate the long term effects of AESBBO on diabetes and glycoprotein metabolism.
Results
Treatment with AESBBO significantly reduced the fasting blood glucose levels whereas the levels of insulin and hemoglobin were increased with decreased levels of glycosylated hemoglobin. The long term treatment of AESBBO significantly decreased the levels of plasma, liver and kidney tissue glycoproteins such as fucose, hexose, hexosamine and sialic acid.
Conclusions
This study concludes that the aqueous extract of stem bark of Boswellia ovalifoliolata possesses a protective role on abnormal glycoprotein metabolism in addition to its antihyperglycemic activity.
Keywords: Boswellia ovalifoliolata, Streptozotocin, Hyperglycemia, Glycoprotein metabolism
Introduction
Diabetes mellitus is a heterogeneous endocrine metabolic disorder characterized by chronic hyperglycemia caused due to insulin deficiency or defects in insulin action with impaired function of carbohydrate, lipid and protein metabolism [1]. Insulin deficiency or defects in insulin action leads to hyperglycemia which affects the functions of various organs due to uncontrolled glucose regulation ultimately leads to various diabetic complications [2]. Recent reports made clear that changes in glucose metabolism leads to diabetes induced cell damage by various metabolic pathways such as increased polyol pathway, increased hexosamine pathway, activation of protein kinase C (PKC) isoforms and increased glycation of proteins. Glycosylation of proteins is a primary cause among above stated possibilities which most interest. All the mechanisms were activated by a single upstream event of mitochondrial over production of reactive oxygen species (ROS) which leads to oxidative stress. ROS generated by high glucose is causally linked to elevated glucose and other metabolic abnormalities. Both oxidative stress and oxidative damage to the tissues are very common end points in diabetes associated complications. The increase in glycoxidation products in plasma and tissue proteins suggests that oxidative stress is increased in diabetes which includes autooxidation of glucose, shifts in redox balances, and abnormally increased plasma and tissue concentrations of glycoproteins. Recent reports suggested that changes in glycoprotein proportions leads to the pathogenesis of diabetes associated complications. The changes in glycoprotein levels are known to occur in acute illnesses which called acute phase reactants [3].
Glycoproteins were chiefly distributed proteins with one or more covalently linked carbohydrate molecules which act as enzymes, hormones, constituents of extracellular membranes and blood group antigens [4]. Glycoproteins involve in recognition, membrane transport, absorption of macromolecules, cell differentiation, excretion and the adhesion of macromolecules to the cell surface [5]. It is reported that hyperglycemia results in structural and functional changes of both circulating and membrane bound glycoproteins [6]. In hyperglycemic condition utilization of glucose by insulin independent pathways leads to the synthesis of glycoproteins which may be a predictor of angiopathic complications [7]. So, the elevated levels of glycoproteins are the principle cause for the pathogenesis of liver and kidney diseases in diabetic condition. The activities of glycoproteins such as sialic acid, hexosamine, hexose, and fucose were evaluated in our study which play important role in protein stability, function and turnover and also encodes for diverse biological functions. Fucose is a characteristic constituent of many glycoproteins, alterations in the expression of fucosylated oligosaccharides leads to different pathological conditions including cancer and atherosclerosis. Protein bound hexose in the cell membrane provides hydrophobic areas, whereas protein bound hexosamine provides cationic charges on the cell membrane surface and make the membrane more polar. Sialic acid is the terminal residue of the oligosaccharide side chain of glycoproteins and widely occurs in the exposed positions of molecules like hormones, enzymes and also on tissues. Elevated levels of serum sialic acid are considered to be a good predictor of cardiovascular disease. Sialic acid contributes to the negative charges on this membrane, thus possibly playing a role in the selective glomerular permeability to negative charge.
In diabetic state, the deficiency of insulin secretion causes derangement of glycoproteins, which results in basal membrane thickening. Excess availability of glucose in the hyperglycaemic state accelerates the synthesis of glycoproteins. The elevated levels of glycoproteins in diabetic condition could be a consequence of abnormal carbohydrate metabolism. This is due to depressed utilization of glucose by insulin independent pathways, thereby enhancing the formation of sialic acid, hexosamine, hexose and fucose for the accumulation of glycoproteins. Recent scientific reports suggested that impaired metabolism of glycoproteins play a vital role in the pathogenesis of liver and kidney diseases in diabetic state. It was reported that elevated concentration of glycoproteins were found in diabetic vascular lesions, particularly in the glomerulus [8] which results in the development of diabetic glomerulosclerosis and renal failure. Similar changes may also occur in the liver due to the elevated levels of glycoproteins [9]. So the measurement of circulating glycoproteins more reliable but from the pathological point of view the levels of tissue glycoproteins were probably more important in diabetes and the relationship between the serum and tissue glycoprotein levels requires further clarification. Though insulin and synthetic oral hypoglycemic agents are available to manage diabetes, still it remains a challenge in preventing the onset of diabetic complications [10]. Therefore, there is a need for the novel therapeutic drug that can overcome the demerits of existing therapeutic modalities. Plants are an exemplary source of drugs and a wide range of plant-derived active principles were commonly used in the treatment of diabetes, which are easily available, economical, and are free from adverse side effects.
Boswellia ovalifoliolata is a member of Burseraceae family which extensively investigated and reported for various therapeutic purposes such as certain cancers like leukemia and breast cancer and also reported for antioxidant activity [11–13]. The use of stem bark was reported for rheumatic pains, stomach ulcers [14]. Tribes in the surrounding areas of Tirupati were using stem bark of Boswellia ovalifoliolata for diabetes without scientific evidence [15]. So, it needs to evaluate scientifically for its efficacy and safety. To date, there is no scientific data exists to explain the effect of B. ovalifoliolata on the components of glycoprotein in diabetic rats. Therefore, the present study was designed to assess the role of B. ovalifoliolata on the levels of plasma and tissue glycoprotein components in streptozotocin (STZ) induced diabetic rats. Therefore, our study was aimed to evaluate the potential effect of aqueous extract of stem bark of Boswellia ovalifoliolata (AESBBO) in the management of diabetes and also its effect on plasma and tissue glycoproteins in STZ-induced diabetic rats. The efficacy produced by AESBBO is compared with a standard oral hypoglycemic drug glibenclamide. Glibenclamide is a cardinal drug widely used in the management of non insulin dependent diabetes mellitus. It is a potent drug that improves glycemic control by acting on both insulin secretion and on insulin action but associated with one or more side effects such as nausea, angioedema and low blood sugar. In our investigation glibenclamide used as reference drug and the results produced were compared with results produced by AESBBO.
Materials and methods
Plant material
The stems bark of Boswellia ovalifoliolata (SBBO) Bal. & Henry was collected from Tirumala hills, Tirupati, India. The plant was identified and authenticated by the taxonomist of the herbarium and a voucher specimen (Accession Number: 516) was deposited for future reference at Sri Venkateswara University, India. The stem bark of Boswellia ovalifoliolata was dried in shade, powdered, sieved and the powder was used for the preparation of aqueous extract.
Preparation of aqueous extract
1000 g of dry stem bark powder of B. ovalifoliolata was suspended in 3000 mL of distilled water in a glass jar for 72 h at room temperature. The solvent was filtered using a muslin cloth and the filtration was repeated 3 to 4 times until the filtrate gave no coloration. The filtrate was concentrated at 40 ± 5 °C under reduced pressure in the Buchi rotavapour R-200 and finally freeze dried.
Phytochemical analysis of aqueous extract
Aqueous extract of SBBO was screened for various phytochemicals using standard methods of phytochemical analysis [16].
Animals
Male albino Wistar strain rats weighing 180–200 g were selected and divided into different groups. The rats were fed on pellet diet and water ad libitum, the rats were maintained at a constant temperature (25 °C) on a 12 h light and 12 h dark cycle according to the guidelines of Institutional animal ethics committee, Sri Venkateswara University, Tirupati, India (IAEC approval no: 31/2012–2013/(i)/a/CPCSEA/IAEC/SVU/CAR-YKP dt. 01-07-2012).
Induction of diabetes by streptozotocin
The rats were made diabetic by the administration of single intraperitoneal injection of streptozotocin at a dosage of 50 mg/kg bw which dissolved in freshly prepared citrate buffer (0.1 M, pH 4.5). 20% glucose solution was provided for STZ induced rats for 24 h to prevent rats from STZ caused hypoglycemia mortality. After 72 h of STZ administration, the rats which marked with hyperglycemia with fasting plasma glucose above 250 mg/dL were considered as diabetic rats and were used for the experiment.
Dose optimization study of aqueous extract of stem bark of Boswellia ovalifoliolata (AESBBO): Experimental design
Dose dependent optimization study was performed in overnight fasting rats. After an overnight fasting the initial fasting plasma glucose was measured for randomization. After randomization the respective treatment was given to all groups of rats.
The animals were divided in to 6 groups and each group consisting of 6 rats.
Group 1 Normal rats (N)
Group 2 Diabetic control rats (DC)
Group 3 DC rats treated with AESBBO 100 mg/kg bw
Group 4 DC rats treated with AESBBO 200 mg/kg bw
Group 5 DC rats treated with AESBBO 300 mg/kg bw
Group 6 DC rats treated with glibenclamide (GLI) 0.02 g/kg bw
Evaluation of long term treatment of AESBBO on glycemic control and glycoprotein metabolism: Experimental design
All the rats were randomly divided into five groups of six rats each. The AESBBO at dose of 200 mg/kg bw exhibited maximum reduction of blood glucose among other doses. The active dose of 200 mg was used for the long term effects of AESBBO on plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and the levels of glycoproteins.
Group 1 Normal rats (N)
Group 2 Normal rats treated with 200 mg AESBBO /kg bw / day for 40 days (NT)
Group 3 Diabetic control rats (DC)
Group 4 DC rats treated with 200 mg AESBBO /kg bw /day for 40 days
Group 5 DC rats treated with 0.02 g of glibenclamide /kg bw /day for 40 days.
The aqueous extract of stem bark of Boswellia ovalifoliolata (200 mg/kg bw) and glibenclamide (0.02 g) was administered to the rats every day morning for 40 days by gastric intubation using oral gavage needle. Finally, at the end of the 40 days treatment all the five groups of rats were kept for overnight fasting, anaesthetized with ether and sacrificed by cervical dislocation. The blood sample were collected, processed for plasma and used for the biochemical analysis of fasting blood glucose, insulin, hemoglobin, glycosylated hemoglobin, and glycoproteins. The plasma proteins were precipitated by adding 95% ethanol and the precipitate was used for the estimation of protein bound hexose and hexosamine. The liver and kidney samples were dissected out and washed with ice cold saline, patted dry and weighed. 10% tissue homogenate was prepared with 0.1 M Tris-HCl buffer, Ph 7.4. After centrifugation the clear supernatant was obtained and used for tissue glycoprotein assays.
Extraction of glycoproteins from plasma
To 100 μL of fasting plasma sample add 5.0 mL of methanol, mixed well and centrifuged for 10 min at 3000 rpm. After centrifugation the supernatant was decanted and the precipitate was again washed with 5.0 mL of 95% ethanol, re-centrifuged and formed supernatant was decanted to obtain the precipitate of glycoproteins. This was used for the estimation of hexose, hexosamine, fucose and sialic acid.
Extraction of glycoproteins from liver and kidney tissues
For the extraction of glycoproteins from the liver or kidney tissues, a known weight of the tissue was homogenized in 7.0 mL of methanol. The total contents were filtered and homogenized with 14 mL of chloroform. This mixture was filtered and the residue was successively homogenized in chloroform-methanol (2:1 v/v) and each time the extract was filtered. The residues of defatted tissues were obtained and the filtrate was decanted. A weighed amount of defatted tissue was suspended in 3.0 mL of 2 N HCl and heated at 90 °C for 4 h. The sample was cooled and neutralized with 3.0 mL of 2 N NaOH. Samples from this were used for the estimation of hexose, hexosamine, fucose and sialic acid in tissues [17, 18].
Biochemical analysis
Plasma biochemical markers such as fasting blood glucose, insulin, hemoglobin, glycosylated hemoglobin levels were measured in plasma samples by using commercial kits. The plasma and tissue hexose content were estimated by the method of Niebes [19], sialic acid in plasma and tissues were estimated by the method of Warren [20] and hexosamine by the method of Wagner [21]. Fucose was estimated by the method of Dische and Shettles [22]. The liver tissue glycogen levels were estimated by calorimetric micro-method of Kemp and Van Hejnigen [23].
Statistical analysis
Values are given as means ± SD for six rats in each group (n = 6). The data statistical analysis was performed using SPSS 17.0 (SPSS, Cary, NC, USA). The statistical significance was evaluated by one way analysis of variance (ANOVA) and the individual comparisons were obtained by Duncan’s multiple range test (DMRT). Values were considered statistically significant when p ≤ 0.05.
Results
Phytochemical analysis of aqueous extract
Phytochemical analysis revealed the presence of different types of phytoconstituents such as flavonoids, saponins, carbohydrates and tannins in the aqueous extract of stem bark of Boswellia ovalifoliolata (Table 1).
Table 1.
The Phytochemical analysis of AESBBO
| S. No. | Phytoconstituent | Aqueous Extract |
|---|---|---|
| 1. | Alkaloids | – |
| 2. | Flavonoids | + |
| 3. | Glycosides | – |
| 4. | Steroids | – |
| 5. | Triterpenes | – |
| 6. | Saponins | + |
| 7. | Carbohydrates | + |
| 8. | Tannins | + |
AESBBO: Aqueous stem bark of Boswellia ovalifoliolata
+ Presence of the phytoconstituent
- Absence of the phytoconstituent
Evaluation of dose optimization study of aqueous extract of stem bark of Boswellia ovalifoliolata (AESBBO)
The effect of different doses of AESBBO on the fasting blood glucose levels of diabetic rats is given in Fig. 1. Among the different doses of AESBBO the dose at 200 mg/kg bw produced the maximum fall of 74% in the FBG levels of diabetic rats after 6h of treatment. The other doses (100 mg/kg bw and 300 mg/kg bw) of aqueous extract produced a fall of 30% and 50% in FBG levels of the diabetic rats. Treatment with glibenclamide at a dose of 0.02 g/kg bw also resulted significant decrease in fating blood glucose levels after 6h of treatment.
Fig. 1.
Effect of different doses of aqueous extract of stem bark of Boswellia ovalifoliolata (AESBBO) in normal and STZ-diabetic rats. N: Normal; DC: Diabetic Control; GLI: Glibenclamide; STZ: Streptozotocin. Data was presented as Mean ± SD (n = 6 each group). Statistically significance compared to their respective controls ***p < 0.001; **p < 0.01; *p < 0.05. Groups compared using one way ANOVA
Evaluation of long term treatment effect of AESBBO (200 mg/kg bw) on the levels of plasma glucose, insulin, hemoglobin and glycosylated hemoglobin levels
Before starting the treatment the fasting plasma glucose levels of diabetic control rats (Group 3) were significantly increased after STZ induction when compare to normal rats (Group 1). However, by the end of 40 days treatment, there was a significant decrease observed in FBG levels of diabetic rats treated with AESBBO (Group 4), while there was a further increase in the blood glucose levels of diabetic control rats (Group 3). The treatment with glibenclamide (Group 5) also produced significant decrease in the fasting blood glucose levels (Fig. 2a). The insulin levels of diabetic control rats (Group 3) were significantly lower than those of normal rats (Group 1) but after treatment with AESBBO for 40 days showed a significant increase in insulin levels. The treatment with glibenclamide (Group 5) also showed a significant increase in insulin levels (Fig. 2b).
Fig. 2.
Effect of AESBBO (200 mg/kg bw) on the levels of fasting plasma glucose, insulin, hemoglobin and glycosylated hemoglobin (HbA1c) levels in normal and STZ-diabetic rats. A. Glucose, B. Insulin, C. Hemoglobin, D. HbA1c. AESBBO: Aqueous Extract of Stem Bark of Boswellia ovalifoliolata; STZ: Streptozotocin; BT: Before treatment; AT: After treatment; N: Normal; DC: Diabetic Control; GLI: Glibenclamide; STZ: Streptozotocin; Hb: Hemoglobin; HbA1c: Glycosylated hemoglobin. Data was presented as Mean ± SD (n = 6 each group). Statistically significance compared to their respective controls ***p < 0.001; **p < 0.01; *p < 0.05. Groups compared using one way ANOVA
Reduced hemoglobin levels were observed in diabetic control rats (Group 3) but after treatment with AESBBO for 40 days resulted a significant increase in hemoglobin concentration (Group 4). The treatment with glibenclamide (Group 5) also showed a significant increase in hemoglobin concentration (Fig. 2c). The glycosylated hemoglobin (HbA1c) levels of diabetic control rats (Group 3) were significantly higher than those of normal rats (Group 1) but after treatment with AESBBO for 40 days significantly reduced the levels of HbA1c (Group 4), which indicating improvement in glycemic control in diabetic rats upon treatment with AESBBO. Glibenclamide treatment also showed a significant reduction in HbA1c and significant improved glycemic control (Group 5) (Fig. 2d).
Evaluation of long term treatment effect of AESBBO (200 mg/kg bw) on plasma glycoproteins
The long term treatment of AESBBO showed the changes in the levels of protein bound sialic acid, hexosamine, hexose, and fucose in plasma of control and experimental rats. Significantly elevated levels of plasma glycoproteins such as sialic acid, hexosamine, hexose, and fucose were observed in diabetic control rats (Group 3) when compared to normal rats (Group 1) due to oxidative stress. But, the oral administration of AESBBO at a dose of 200 mg/kg bw for 40 days significantly reduced the levels of glycoproteins near to normal levels in diabetic treated rats (Group 4) when compared to diabetic control rats (Group 3). However, oral administration of glibenclamide also resulted significant reduction in the levels of protein bound sialic acid, hexosamine, hexose, and fucose in plasma (Group 5). There were no significant changes observed in the levels of plasma glycoproteins in normal and normal treated rats (Group 1 & 2) (Fig. 3).
Fig. 3.
Effect of AESBBO (200 mg/kg bw) on plasma glycoproteins in normal and STZ-diabetic rats. AESBBO: Aqueous Extract of Stem Bark of Boswellia ovalifoliolata; STZ: Streptozotocin; N: Normal; DC: Diabetic Control; GLI: Glibenclamide. Data was presented as Mean ± SD (n = 6 each group). Statistically significance compared to their respective controls ***p < 0.001; **p < 0.01; *p < 0.05. Groups compared using one way ANOVA
Evaluation of long term treatment effect of AESBBO (200 mg/kg bw) on liver and kidney tissue glycoproteins
AESBBO showed significant effect on the levels of liver and kidney tissue glycoproteins. Before treatment the levels of sialic acid, hexosamine, hexose, and fucose were significantly increased due to inflammatory processes, free radicals formation, oxidative stress, and lipid peroxidation which associate with liver and kidney damage in diabetic control rats (Group 3) compared to than those of normal rats (Group 1). The long term treatment of diabetic rats with AESBBO for 40 days significantly reduced the levels of sialic acid, hexosamine, hexose, and fucose. However, oral administration of glibenclamide also significantly reduced the levels of protein bound sialic acid, hexosamine, hexose, and fucose in liver and kidney tissues (Group 5). There were no significant changes observed in the levels of tissue glycoproteins in normal and normal treated rats (Group 1 & 2) (Figs. 4 and 5).
Fig. 4.
Effect of AESBBO (200 mg/kg bw) on liver glycoproteins in normal and STZ-diabetic rats. AESBBO: Aqueous Extract of Stem Bark of Boswellia ovalifoliolata; STZ: Streptozotocin; N: Normal; DC: Diabetic Control; GLI: Glibenclamide. Data was presented as Mean ± SD (n = 6 each group). Statistically significance compared to their respective controls ***p < 0.001; **p < 0.01; *p < 0.05. Groups compared using one way ANOVA
Fig. 5.
Effect of AESBBO (200 mg/kg bw) on kidney glycoproteins in normal and STZ-diabetic rats. AESBBO: Aqueous Extract of Stem Bark of Boswellia ovalifoliolata; STZ: Streptozotocin; N: Normal; DC: Diabetic Control; GLI: Glibenclamide. Data was presented as Mean ± SD (n = 6 each group). Statistically significance compared to their respective controls ***p < 0.001; **p < 0.01; *p < 0.05. Groups compared using one way ANOVA
Evaluation of long term treatment effect of AESBBO (200 mg/kg bw) on liver tissue glycogen
Liver tissue glycogen levels were decreased in diabetic control rats (Group 3) compared to than those of normal rats (Group 1). But, the oral administration of AESBBO at a dose of 200 mg/kg bw for 40 days significantly increased the levels of glycogen in diabetic treated rats (Group 4) when compared to diabetic control rats (Group 3). However, oral administration of glibenclamide also resulted a significant increase in liver glycogen (Group 5). There was no significant change observed in the levels of liver glycogen in normal and normal treated rats (Group 1 & 2) (Fig. 6).
Fig. 6.
Effect of AESBBO (200 mg/kg bw) on liver glycogen levels in normal and STZ-diabetic rats. AESBBO: Aqueous Extract of Stem Bark of Boswellia ovalifoliolata; STZ: Streptozotocin; N: Normal; DC: Diabetic Control; GLI: Glibenclamide. Data was presented as Mean ± SEM (n = 6 each group). Statistically significance compared to their respective controls ***p < 0.001; **p < 0.01; *p < 0.05. Groups compared using one way ANOVA
Discussion
Diabetes is a chronic and progressive endocrine metabolic disorder with increased levels of blood glucose. Long term elevated plasma glucose levels in diabetic condition results in structural and functional changes of both circulating and membrane bound proteins [6]. Most of the proteins in blood are glycoproteins which covalently linked carbohydrate protein molecules mostly found on the cell surface. They involve in the formation of principle components of cell membrane and also membranes of subcellular organelles [24]. In hyperglycemic condition glucose is redirected through the insulin independent pathways resulting in enhanced production of carbohydrate moieties of glycoproteins. Recently it has been reported that the increase in the activities of protein bound glycoproteins such as hexose, hexosamine, fucose and sialic acid in diabetic patients indicated the severe development of diabetic complications. Liver is the major site for glycoprotein synthesis whose functions are drastically altered in diabetes and also found in increased activities in diabetic vascular lesions particularly in the glomerulus. It is reported that oxidation of protein molecules is a common phenomenon mediated by elevated levels of ROS and oxidized proteins which in turn induce oxidative stress, a potential mediator of diabetes associated pathogenic complications [25].
In fact, the glucose will participate in the pathogenic mechanisms of glycation which known as nonenzymatic glycosylation results reduced total hemoglobin concentration in diabetic rats due to elevated levels of glycosylated hemoglobin. In severe diabetic state, the excess amount of glucose present in the blood ultimately reacts with hemoglobin to form glycosylated hemoglobin [26] which has altered affinity for oxygen and this may be a factor in tissue anoxia. In this study glycation of hemoglobin was found to be significantly increased in diabetic rats and this increase is directly proportional to fasting blood glucose concentration. But, the treatment with oral administration of AESBBO significantly elevated the concentration of hemoglobin and significantly reduced the levels of glycosylated hemoglobin. The treatment with AESBBO resulted a significant increase in the level of plasma insulin which clearly shows that AESBBO has a better effect on the secretion of insulin from pancreatic β-cells. AESBBO and glibenclamide significantly reduced fasting plasma glucose which may be due to reducing the rate of hepatic glucose production, glycogenolysis, and gluconeogenesis [27].
Sialic acid, hexosamine, hexose and fucose are the principal components of glycoproteins. The liver is a source and particularly responsible for producing glycoproteins abundantly in the blood and tissues. According to the search several traditional medicinal plant have been described as antidiabetic and protective role on glycoprotein components such as Cardiospermum halicacabum leaf extract showed protective effect on abnormal glycoprotein metabolism in addition to its antihyperglycemic activity [28]. Oral administration of hesperetin potentially ameliorated abnormalities in glycoprotein components in addition to its antidiabetic effect [29]. Myrtenal (monoterpene found in Mint) showed significant protective effect on glycoprotein metabolism [30]. The bark extract of Helicteres isora Linn. possesses beneficial effects on glycoprotein moiety in addition to its antidiabetic effect [31].
In our study, the levels of sialic acid were found to be increased in diabetic control rats may be due to elevated sialic acid synthesis or decreased sialidase activity. Treatment with AESBBO significantly decreased the levels of sialic acid which may be due to the regulation of sialidase activity by insulin and glycemic control which in line with previous report [28]. The levels of hexosamine were found to be increased in diabetic control rats which could be due to increased glycosylation and increased plasma glucose levels. But treatment with AESBBO significantly decreased the levels of hexosamine in plasma and tissue which could be due to improved glycemic levels. The levels of hexoses were found to be increased in diabetic control rats which may be due to the disturbances associated with carbohydrate metabolism. Treatment with AESBBO significantly decreased the levels of hexoses. The activities of fucose were increased in diabetic control rats with increased fasting blood glucose levels could be due to hyperglycemia and deficiency of insulin. But the treatment with AESBBO at a dose of 200 mg/kg bw significantly decreased the levels of fucose, this may be due to the improved levels of insulin and glycemic control which in line with previous reports [30, 32].
Administration of Boswellia ovalifoliolata at a dose of 200 mg/kg bw significantly reduced the levels of glycoproteins in plasma, liver and kidney tissues which could be due to decreased hyperglycemic state with increased plasma insulin levels. The increased levels of plasma and tissue glycoproteins in diabetic state could be a consequence of abnormal carbohydrate metabolism [33]. This could be due to the increased production of ROS, oxidative stress, and destruction of tissue which contributes directly to the both plasma and tissue glycoprotein activities. The increase in the glycoproteins proportion has been linked with the severity and period of the diabetes. Scientific approaches recently suggested that abnormal levels of glycoprotein in liver cirrhosis and diabetic glomerular basement membrane can follow prolonged hyperglycaemia which results in the development of liver cirrhosis, glomerulosclerosis and renal failure.
In the present study, long term oral administration of AESBBO significantly decreased plasma and tissue glycoprotein levels. This could be due to the decreased hyperglycemic state with increased levels of plasma insulin, activation of glucose transport mechanism and channelling of more glucose into insulin dependent pathways such as glycolysis, glycogenesis and inhibition of glycoprotein synthesis as indicated by increased levels of glycogen in treated diabetic rats. From the above findings we conclude that the aqueous extract of stem bark of Boswellia ovalifoliolata exhibits great potential as an antidiabetic agent by improving insulin levels and decreased glycoprotein components in plasma, liver and kidney. This shows the beneficial effects of AESBBO in controlling the progression and complications of diabetes.
Conclusion
This study concluded that the aqueous extract of stem bark of Boswellia ovalifoliolata ameliorated fasting blood glucose levels and glycoproteins components in streptozotocin induced diabetic rats. This antidiabetic effect may be due to the increased release of insulin from the existing β-cells and restored insulin sensitivity. AESBBO through its insulinotropic effect on remnant pancreatic-β cells reversed the altered glycoprotein levels in plasma, hepatic and renal tissues of diabetic rats and thus serves as a promising agent in the management of diabetes mellitus.
Compliance with ethical standards
Conflict of interest
The authors declare they have no conflicts of interest.
Footnotes
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