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Antihyperglycemic effect of iridoid glucoside, isolated from the leaves of Vitex negundo in streptozotocin-induced diabetic rats with special reference to glycoprotein components.

ARTICLE INFO

Keywords: Vitex negundo Iridoid glucoside Antihyperglycemic effect Streptozotocin Glycoproteins

ABSTRACT

The aim of present study was to isolate an iridoid glucoside from the leaves of Vitex negundo and evaluates its effects on dearrangement in plasma and tissues glycoprotein components in streptozotocin-induced diabetic rats. The levels of blood glucose, plasma and tissues glycoproteins such as hexose, hexosamine, fucose and sialic acid were significantly increased whereas plasma insulin levels were significantly decreased in diabetic rats. On oral administration of iridoid glucoside at a concentration of 50 mg/kg b.w. once daily to diabetic rats for the period of 30 days, reversed the above-mentioned hyperglycemia-induced biochemical changes to near normal levels. The anti-hyperglycemic effect of iridoid glucoside was comparable with glibenclamide, a known hypoglycemic drug. Based on the results obtained from the present study, it may be concluded that iridoid glucoside possesses significant productive effect on glycoprotein metabolism in addition to its antidiabetic effect.

Introduction

Diabetes mellitus (DM), a chronic disease affecting millions of individuals worldwide, characterized by absolute or relative deficiencies in insulin secretion and/or insulin action associated with chronic hyperglycemia and disturbances of carbohydrate, lipid and protein metabolism. Based on the World Health Organization (WHO) report, the number of diabetic patients is expected to increase from 171 million in year 2000 to 366 million or more by the year 2030 (Wild et al. 2004). Hyperglycemia, due to uncontrolled glucose regulation is considered as the causal link between diabetes and diabetic complications. A number of studies emphasizes that alterations in glucose metabolism leads to hyperglycemia-induced cell damage by four key metabolic pathways, viz., increased polyol pathway flux, increased glycation of proteins (enzymatic or non enzymatic), increased hexosamine pathway flux and activation of protein kinase C (PKC) isoforms (Rolo and Palmeira 2006). Among the above stated possibilities, glycosylation of proteins has been the prime subject of much interest.

Glycoproteins are carbohydrate linked protein macromolecules found in the cell surface, which form the principal component of animal cells. Hexose, hexosamine and sialic acid are the basic components of the glycoproteins. They play an important role in membrane transport, cell differentiation and recognition, the adhesion of macromolecules to the cell surface and the secretion and absorption of macromolecules (Mittal et al. 1996). Impaired metabolism of glycoproteins play a major role in the pathogenesis of diabetes mellitus (Knecht et al. 1990). It has been reported that alterations occur in the concentrations of various glycoproteins in human diabetes (Sharma et al. 1987). The raised levels of glycoproteins in diabetics may also be an indicator of angiopathic complications (Konukoglu et al. 1999). Several workers have suggested that elevated levels of glycoproteins in plasma, liver and kidney tissues in the diabetic condition could be a consequence of impaired carbohydrate metabolism. Insulin deficiency and high levels of plasma glucose in the diabetic condition may result in an increased synthesis of glycoproteins (Patti et al. 1999). This increase in plasma glycoprotein has been associated with the severity and duration of diabetes.

Hyperglycemia in experimental diabetic rats leads to a decreased utilization of glucose by insulin dependent pathways, thereby enhancing the formation of glycoproteins (Youngren et al. 1996). At the cell surface or inside the cells, the glycoprotein components such as fucose and sialic acid form specific structures, called glycanic chains covalently linked to lipids or proteins. An increase in the biosynthesis and or a decrease in the metabolism of glycoproteins could be related to the deposition of these materials in the basal membrane of pancreatic cells. In recent times, many traditionally important medicinal plants have been tested for their efficacy against impaired glycoprotein levels in diabetes (Ramkumar et al. 2007).

Plants have always been an exemplary source of drugs and many of the currently available drugs have been derived directly or indirectly from them. A wide array of plant derived active principles has demonstrated activity consistent with their possible use in the treatment of diabetes mellitus (Witters 2001). Vitex negundo Linn belongs to the family verbanaceae commonly known as chase tree and also called Nochi in Tamil, Nirgundi in Hindi. It grows gregariously in waste lands and found throughout India.

Vitex negundo (Linn.) is one of the common plants used in traditional medicine and reported to have variety of pharmacological activities (Baral and Kurmi 2006; Kirtikar and Basu 1935). Although, all parts of V. negundo are used as an indigenous system of medicine, the leaves are the most potent for medicinal use. The decoction of leaves is used for treatment of eye-disease, toothache inflammation, leucoderma, enlargement of the spleen, skin-ulcers, in catarrhal fever, rheumatoid arthritis, gonorrhoea and bronchitis, anti-bacterial, anti-pyretic, anti-inflammatory, antioxidant and anti-histaminic agents (Tiwari and Tripathi 2007). Apart from this medicinal values, these leaves were also reported to have possess several chemical constituents such as volatile oils (Singh et al. 1999; Mallavarapu et al. 1994; Dayal and Singh 2000; Taneja et al. 1979), flavonoids (Achari et al. 1984; Banerji et al. 1969; Subramanian and Misra 1979), flavonoid glycoside (Misra and Subramanian 1980; Sathiamoorthy et al. 2007) iridoid glucoside or negundo side (Dutta et al. 1983; Sehgal et a1.1983). These are the chemical constituents reported from the leaves of V. negundo so far. To our knowledge, there is no investigation had been carried out on the effect of iridoid glucoside in STZ-induced diabetic rats with special reference to glycoprotein component.

Therefore, the primary objectives of this study were to isolate the iridoid glucoside from V. negundo leaves and assess its effect on dearrangement in glycoprotein levels in the streptozotocin-induced diabetic rats. The results were also compared with glibenclamide as a reference drug.

Materials and methods

Plant material

Vitex negundo leaves were collected from the premises of University of Madras, Guindy Campus, Chennai. Authentication of the plant was carried out by Prof. M. Periyasamy, Centre for Advanced Study in Botany, University of Madras and voucher specimens of the plant retained in the department herbarium.

Isolation and characterization of a compound

The leaves of Vitex negurido were shade dried for 2-3 weeks. The shade dried leaves were pulverized and subjected for extracdon. Pulverized leaves (500 g) were extracted in a Soxhiet extractor with methanol.The filtrate was filtered through Buchner funnel and concentrate using vacuum rotary evaporator at 40 C. The methanolic extract was fractionated sequentially with petroleum, diethyl ether, chloroform and n-butanol. The n-butanolic concentrate was checked on checked on thin layer chromatography (TLC) with chloroform and methanol (10:2.5 ratio) used as a mobile phase in which two spots were appeared. The n-butanalic concentrate was chromatographed on silica gel column (Merk 60 -120 mesh, 750g, 3.5 i.d. x 60 cm) and eluted successively with chloroform and methanol (100:25). A total of 50 fractions were collected at an interval of 5 ml each and monitored by thin layer chromatography (precoated silica gel merk-60 [F.sub.254] 0.25 mm thick plate). Fraction from 1 to 5 formed as a yellow coloured and showed single spot on TLC and pooled together in a cleaned vial and evaporated to dryness. Crystallization was made by ethyl acetate and methanol. The structure of the compound was confirmed by iridoid glucoside on the basis of IR, (1) H NMR, (13) C NMR, MS at Indian Institute of Technology, Chennai. IR (KBr)[[lambda].sub.max] 1697 [cm.sub.-1] (C=0), 3408 [cm.sub.-1] (-OH), 1600cm (1) (C=C). MS m/z 496, m.p. 110, NMR ([CD.sub.3]OD) 1.31 (s, 3H), 1.36-1.38 (m, 1H), 1.60-1.72 (m, 3H), 2.0 (bs, 4H), 2.15-2.18 (m, 1H), 2.23 (dd, 1H), 3.40 (t, 1H), 3.54-3.60 (m, 21-1), 3.74-3.76 (m, 1H), 4.0 (t, 11-1), 4.47 (t, 1H), 5.0 (s, 1H), 5.34 (d, 1H), 5.54 (d, 1H), 6.84 (d, 2H), 7.38 (s, 1H), 7.82 (d, 2H), 11.0 (s, 1H). General molecular formula of this compound is [C.sub.23][H.sub.28][O.sib.12]. The yield of this compound was 700 mg from 400 g of crude extract. The chemical structure of iridoid glucoside is given in Fig. 1. The remaining one more (compound) spot is under process.

Animals

Male albino Wistar rats weighing 180-200g body weight were procured from the Central Animal House Facility University of Madras Taramani Campus, Chennai, Tamil Nadu, India. They were maintained at an ambient temperature of 25 [+ or -] 2 C and 12/12 h of light/dark cycle. Animals were given standard commercial rat chow and water ad libitum and housed under standard environmental conditions throughout the study. The experiments were conducted according to the ethical norms approved by the Ministry of Social Justices and Empowerment, Government of India and Institutional Animal Ethics Committee Guidelines.

Sources of chemicals

All fine chemicals including streptozotocin were purchased from Sigma Chemical Company (St. Louis, MO, USA). All other chemicals used were of good quality and analytical grade and obtained from Himedia, Mumbai, India.

Experimental induction of diabetes

Diabetes was induced in overnight fasted experimental rats by a single intraperitoneal injection of streptozotocin (40 mg/kg bodyweight) dissolved in freshly prepared citrate buffer (0.1 M, pH 4.5). Streptozotocin injected animals were allowed to drink 20% glucose solution overnight to overcome the initial drug-induced hypoglycemic mortality. Control rats were injected with same volume of isotonic saline. After 96 h, plasma glucose was determined and those rats with fasting blood glucose greater than 240 mg/dl were used in the present study.

Experimental design

The animals were divided into seven groups of six animals in each. Iridoid glucoside and glibenclamide were dissolved in distilled water and administered orally using an intragastric tube for a period of 30 days.

Group I: Normal control rats (received distilled water)

Group II: Normal control rats treated with 50 mg/kg b.w. of iridoid glucoside

Group III: Diabetic induced rats

Group IV: Diabetic rats treated with 50 mg/kg b.w. of iridoid glucoside

Group V: Diabetic rats treated with5 mg/kg b.w. of glibenclamide

After 30 days of treatment, the animals were deprived of food overnight, anaesthetized and sacrificed by cervical decapitation. Blood sample was collected in a tube containing potassium oxalate and sodium fluoride (3:1) for the estimation of glucose, insulin and glycoproteins. Liver and kidney were dissected out, washed in ice-cold saline, patted dry and weighed.

Extraction of glycoproteins

To 0.1 ml of plasma, 5.0 ml of methanol was added, mixed well and centrifuged for 10 min at 3000 x g. The supernatant was decanted and the precipitate was again washed with 5.0 ml of 95% ethanol, recentrifuged and the supernatant was decanted to obtain the precipitate of glycoproteins. This was used for the estimation of hexose and hexosamine.

For extraction of glycoproteins from the tissues, a known weight of the tissue was homogenized in 7.0 ml of methanol. The contents were filtered and homogenized with 14.0 ml of chloroform. This was filtered and the residue was successively homogenized in chloroform-methanol (2:1, v/v) and each time the extract was filtered. The residue (defatted tissues) was obtained and the filtrate decanted. A weighed amount of defatted tissue was suspended in 3.0 ml of 2 N HCl and heated at 90 [degrees]C for 4 h. The sample was cooled and neutralized with 3.0 ml of 2 N NaOH. Aliquots from this were used for estimation of fucose, hexose, hexosamine and sialic acid.

Biochemical analysis

Determination of plasma glucose and insulin Plasma glucose was estimated by the method of Trinder using a reagent kit (Trinder 1969). Plasma insulin was assayed with an ELISA kit by the method of Burgi et al. (1988).

Determination of glycoproteins

The plasma and tissue hexose content was estimated by the method of Niebes (1972). Sialic acid in plasma and tissues were estimated by the method of Warren (1959) and hexosamine by the method of Wagner (1979). Fucose was estimated by the method of Dische and Shettles (1948).

Statistical analysis

Data were analyzed with SPSS/10 student software. Hypothesis testing methods included one-way analysis of variance (ANOVA) followed by LSD. The values are expressed as mean [+ or -] S.D. and results were considered significantly different if p-values less than 0.05. Statistically significant variations are compared as follows: normal control rats versus drug control rats (iridoid glucoside alone treated rats), control versus diabetic control, diabetic rats versus iridoid glucoside treated diabetic rats and iridoid glucoside treated diabetic rats versus glibenclamide treated diabetic rats.

Results

Table 1 shows the level of blood glucose and plasma insulin in control and experimental diabetic animals. There was a significant elevation in

blood glucose level with significant decrease in plasma insulin levels in streptozotocin diabetic rats, compared with normal rats. Administration of iridoid glucoside and gliben-climide tended to bring blood glucose and plasma insulin towards near normal levels. Administration of iridoid glucoside at con-centration of 50 mg/kg b.w. was as effective as glibenclamide. The plasma glucose and insulin levels of normal rats were not altered when administered with iridoid glucoside at 50 mg/kg body weight.

Table 1
Changes in the levels of blood glucose and insulin of control and
experimental animals.

Groups                          Glucose (mg/dl)           Insulin
                                                        ([micro]U/ml)

Normal control              93.66 [+ or -] (a), (b),    16.8 [+ or -]
                                                  *    1.40 (a), (b),
                                                                    *

Diabetic induced          251.83 [+ or -] 22.42 (c),     8.4 [+ or -]
                                                  *           0.85(c),
                                                                    *

Normal + iridoid                 90.83 [+ or -] 7.27   17.20 [+ or -]
glucoside                                                       1.39

Diabetic + iridoid          108.83 [+ or -] 6.79 (d)   14.22 [+ or -]
glucoside                                                    1.86 (d)

Diabetic + glibenclamide        103.5 [+ or -] 11.62   15.88 [+ or -]
                                                                 1.78

Values are given as mean [+ or -] S.D. for six animals in each group.
Values are considered significantly different at p < 0.05 with post
hoc LSD test.
(a.) Control vs. drug control (iridoid glucoside alone treated rat).
(b.) Control rat vs. diabetic rat.
(c.) Diabetic rat vs. iridoid glucoside treated diabetic rat.
(d.) Iridoid glucoside treated diabetic rat vs. glibenclamide.
* p<0.05


Table 2 shows the changes in the level of plasma glycoproteins of control and experimental rats. There was a significant increase of plasma glycoproteins in diabetic rats when compared to normal control rats. Administration of iridoid glucoside and glibenclamide to diabetic rats resulted in significant reduction of glycoproteins in the plasma when compared to diabetic untreated rats.

Table 2
Changes in the levels of plasma glycoproteins in control and
experimental animals.

Groups            Hexose(mg/dl)    Hexosamine    Fucose      Sialic
                                   (mg/dl)       (mg/dl)     acid
                                                             (mg/dl)

Normal control     83.09 [+ or -]   68.73 [+ or    37.93 [+    55.39 [+
                   6.52 (a), (b),  -] 5.24 (a),  or -] 3.46  or -] 6.52
                                *      (b),   *   (a), (b),   (a), (b),
                                                          *           *

Diabetic          129.87 [+ or -]   86.46 [+ or    55.45 [+    75.17 [+
induced               7.76 (c), *  -] 8.52 (c),       or -]  or -] 6.02
                                              *  6.38, (c),    (c),   *
                                                          *

Normal + iridoid   82.05 [+ or -]   67.76 [+ or    36.43 [+    54.29 [+
glucoside                    6.49       -] 6.84       or -]       or -]
                                                       4.82        4.79

Diabetic +         85.23 [+ or -]   73.84 [+ or    40.92 [+    57.08 [+
iridoid                  7.09 (d)   -] 6.79 (d)  or -] 4.06  or -] 4.59
glucoside                                               (d)         (d)

Diabetic +         84.42 [+ or -]   72.48 [+ or    39.15 [+    56.23 [+
glibenclamide                8.78       -] 6.73       or -]       or -]
                                                       5.32        4.67

Values are given as mean [+ or -] S.D. for six animals in each group.
Values are considered significantly different at p< 0.05 with post
hoc LSD test.
(a.) Control vs. drug control (iridoid glucoside alone treated rat).
(b.) Control rat vs. diabetic rat.
(c.) Diabetic rat vs. iridoid glucoside treated diabetic rat.
(d.) Iridoid glucoside created diabetic rat vs. glibenclamide.
* p<0.05.


The levels of liver and kidney glycoprotein of control and experimental rats were shown in Tables 3 and 4. The levels of glycoproteins (hexose, hexosamine, fucose and sialic acid) were significantly increased in diabetic rats and those levels were brought back to near normal either treatment with iridoid glucoside or glibenclamide.

Table 3
Changes in the levels of liver glycoproteins in control and experimental
animals.

Groups          Hexose      Hexosamine{mg/g)  Fucose(mg/g)    Sialic
                (mg/g)                                        acid
                                                              (mg/g)

Normal control    35.29 [+    17.43 [+ or -]  13.43 [+ or -]   8.50 [+
                or -] 3.13   1.20  (a), (b),      1.58  (a),     or -]
                 (a), (b),                 *          (b), *      0.80
                         *                                        (a),
                                                                (b), *

Diabetic          57.85 [+    31.53 [+ or -]     21.01 [+ or  14.88 [+
induced         or -] 4.35     2.86 (c),   *     -]2.46 (c),     or -]
                  (c),   *                                 *      1.44
                                                                (c), *

Normal +          34.27 [+    18.66 [+ or -]  12.64 [+ or -]   7.87 [+
iridoid              or -]              1.67            1.90     or -]
glucoside             3.27                                        0.92

Diabetic +        38.13 [+    20.30 [+ or -]  15.20 [+ or -]   9.02 [+
iridoid         or -] 3.22          2.73 (d)        1.64 (d)     or -]
glucoside              (d)                                        1.08
                                                                   (d)

Diabetic +        36.90 [+    19.45 [+ or -]  14.43 [+ or -]   8.78 [+
glibenclamide        or -]              1.73            1.62     or -]
                      3.59                                        0.75

Values are given as mean [+ or -] S.D. for six animals in each group.
Values are considered significantly different at p < 0.05 with post
hoc LSD test.
(a.) Control vs. drug control (iridoid glucoside alone treated rat).
(b.) Control rat vs. diabetic rat.
(c.) Diabetic rat vs iridoid glucoside treated diabetic rat.
(d.) Iridoid glucoside treated diabetic rat vs. glibenclamide.
* p<0.05.
Table 4
Changes in the levels of kidney glycoproteins in control and
experimental animals.

Groups              Hexose       Hexosamine      Fucose      Sialic
                                                             acid

Normal control      24.24 [+ or  14.03 [+ or -]    11.06 [+  6.95 [+ or
                        -] 2.34  1.92 (a), (b),  or -] 1.54     -] 0.89
                      (a), (b),               *   (a), (b),   (a), (b),
                              *                           *           *

Diabetic induced    42.49 [+ or  27.13 [+ or -]  2333 [+ or    11.26 [+
                        -] 4.80   2.45   (c), *     -] 2.44  or -] 1.46
                         (c), *                      (c), *      (c), *

Normal + iridoid    23.04 [+ or  13.51 [+ or -]    10.16 [+  5.51 [+ or
glucoside                -] 2.1            0.99       or -]     -] 0.68
                                                       1.35

Diabetic + iridoid  27.63 [+ or  15.71 [+ or -]    16.73 [+  7.24 [+ or
glucoside               -] 2.17        2.70 (d)       or -]     -] l.26
                            (d)                    1.62 (d)         (d)

Diabetic +          26.21 [+ or  15.02 [+ or -]  1536 [+ or  6.66 [+ or
glibenclamide           -] 2.91            2.70     -] 1.41     -] 0.87

Values are given as mean [+ or -] S.D. for six animals in each group.
Values are considered significantly different at p < 0.05 with post
hoc LSD test.
(a.) Control vs. drug control (iridoid glucoside alone treated rat).
(b.) Control rat vs. diabetic rat.
(c.) Diabetic rat vs. iridoid glucoside treated diabetic rat.
(d.) Iridoid glucoside treated diabetic rat vs. glibenclamide.
* p<0.05.


Discussion

Streptozotocin-induced hyperglycemia in rodents is considered to be a good model for the preliminary screening of agents active against diabetes and is widely used (Ivorra et al., 1989). In this model, diabetes arises from destruction of the [3-islet cells of the pancreas, causing degranulation or reduction of insulin secretion. In this type I model of diabetes, insulin is markedly depleted, but not absent (Pushparaj et al. 2001). In the present study, STZ-induced diabetic rats showed significant increase in plasma glucose and decrease in insulin levels when compared normal rats. The increased levels of plasma glucose and decreased levels of insulin were brought back to near normal by the adminis-tration of iridoid glucoside in dose dependent manner and those results were similar to that of glibenclamide. Persistent hyper-glycemia the common characteristic of diabetes can cause most diabetic complications and it is normalized by the action of insulin (Gayathri and Kannabiran 2008). Blood glucose level is strictly controlled by insulin secretion from pancreatic cells and insulin action on liver, muscle and other target tissues (Hii and Howell 1984). Iridoid glucoside enhanced the insulin secretion from remnant pancreatic cells, which in turn enhance glucose utilization by peripheral tissues of diabetic rats either by promoting glucose uptake and metabolism, or by inhibiting hepatic gluconeogenesis and decreased blood glucose levels.

In previous report, cuminoside which are structurally related to iridoid glucoside isolated from Syzygium cumini has produced the same effects on streptozotocin induced diabetic rats (Farswan et al. 2009). Moreover, V. negundo leaves methanolic extract exhibited anti-hyperglcemic activity when rats simultaneously fed with glucose (Villasenor and Lamadrid 2006). There was a recent study from Manikandan et al. (2011) investigated the mechanism of an action of compound 1,2 di-substituted idopyranose isolated from V. negundo in streptozotocin-induced diabetic mice and found that it helped in the protection of hepatocytes, nephrocytes and pancreatic ([beta]-cells probably by its action against NF-kappaB and iNOS mediated inflammation. They also reported an increase in number of [beta]-cells.

Increased glycosylation of various proteins in diabetic patients have been reported (Rahman et al. 1990). In this study, we have observed the increased levels of hexose, hexosamine, fucose and sialic acid in the plasma and tissues of streptozotocin induced diabetic rats. The increase in plasma glycoprotein components has been associated with the severity and duration of diabetes. The secretion or shedding from cell membrane glycol conjugates into the circulation leads to the elevation of plasma glycoprotein components. STZ-induced diabetic rats exhibited a significant modification in the connective tissue macro-molecule (Berenson and Radhakrishnamurthy Dalferes 1972). This is due to the depressed utilization of glucose by insulin dependent pathways leads to increase the formation of hexose, hexosamine, sialic acid and fucose for the accumulation of glycoproteins (Spiro and Spiro 1971). Administration of iridoid glucoside to diabetic rats decreased plasma the levels of glycoprotein components. This could be due to the decreased hyperglycemic state with increased levels of plasma insulin in diabetic rats.

The liver is primarily responsible for producing a large amount of glycoproteins present in blood. The elevated levels of plasma glycoproteins in diabetic condition could be a consequence of abnormal carbohydrate metabolism (Guillot et al. 1994). Synthesis of glucosamine from glucose is an insulin-dependent path way despite going through glucose-6-phosphatase. It is therefore conceivable that, in insulin deficiency as in diabetes mellitus glucose is redirected to an insulin-dependent pathway. This could lead to the accumulation of high levels of glucose in the blood, which may result in an increased synthesis of glycoproteins (Guillot et al. 1994). Hexose, hexosamine and sialic acid are the basic components of the glycosaminoglycans and glycoproteins. Increased depositions of these components have been observed in the liver of STZ-induced diabetic rats (Mittal et al. 1996; Robinson et al. 1955). Oral administration of iridoid glucoside to diabetic rats decreased the levels of glycoprotein components in liver. The possible mechanism by which iridoid glucoside brings about the normalization of glycoprotein components. This may be by potentiating of insulin release from beta cells of the islets of Langerhan's which might enhance glucose utilization.

Renal disease is one of the most common and severe complications in diabetes (Shanmugasundram et al. 1990). Diabetes mellitus affects the kidney and is the leading cause of diabetic nephropathy. In addition to prominent role played by factors such as oxidative stress, abnormal lipid metabolism and renal accumulation lipids and others, abnormal glycoprotein metabolism have also been proposed to play a pivotal role in the pathogenesis of diabetic nephropathy (Kim melsteil and Wilson 1936). The excess availability of glucose in the hyperglycemic state accelerates the synthesis of basement membrane components, i.e., glycoproteins (Spiro and Spiro 1971) and this leads to the thickening of capillary basement membrane (Rasch et al. 1955). This is due to depressed utilization of glucose by insulin-dependent pathway, thereby enhancing the formation of hexose and hexosamine for the accumulation of glycoproteins (Patti et al. 1999). The luminal surface of epithelial cells in kidney tubules is also lined with a thick carbohydrate rich glycoprotein layer (Mittal et al. 1996). Stimulation of kidney protein synthesis may contribute to explain the increase in the synthesis of glycoproteins (and therefore of the basement membrane) as well as the renal hypertrophy that occurs early in diabetes (Camerini Davalos et al. 1990). Treatment with iridoid glucoside reversed the alterations induced in levels of hexoses, hexosamine, fucose and sialic acid in the kidneys of diabetic rats. This may be due to the activation of glucose transport mechanism and also alters insulin binding receptor specificity (Marshall et al. 1991).

In conclusion, the data in our study suggests that iridoid glucoside the decreased hyperglycemic state in diabetic treated rats might have been responsible for the decrease of glycoproteins in plasma, liver and kidney. Iridoid glucoside may have beneficial effects in diabetes mellitus by the enhancement of insulin action, as evident by the decreased level of plasma glucose in diabetic rats treated with iridoid glucoside. The observed effect of iridoid glucoside on reversing the adverse effects of hyperglycemia provides an insight into the pathogenesis of diabetic complications and may be used to advantage in therapeutic approaches.

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Ramalingam Sundaram (a), Rajendran Naresh (a), Palanivelu Shanthib, Panchanatham Sachdanandam (a), (*)

(a.) Department of Medical Biochemistry, Dr. ALM P-G, Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu 600 113, India

(b.) Department of Pathology, Dr. ALM P-G, Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu 600 113, India

* Corresponding author. Tel.: +914424547082.

E-mail address: psachdanandam2000@yahoo.co.in (P. Sachdanandam).

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doi: 10.1016/j.phymed.2011.1006
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Author:Sundaram, Ramalingam; Naresha, Rajendran; Shanthi, Palanivelu; Sachdanandam, Panchanatham
Publication:Phytomedicine: International Journal of Phytotherapy & Phytopharmacology
Article Type:Report
Geographic Code:9INDI
Date:Mar 1, 2012
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