SlideShare a Scribd company logo
1 of 9
Download to read offline
IOSR Journal of Pharmacy (IOSRPHR)
ISSN: 2250-3013, Vol. 2, Issue 4 (July2012), PP 49-57
www.iosrphr.org

 and antihyperglycemia effects of resvertrol and its derivative on
                    alloxan diabetic rabbits
            Essam F.Al-Jumaily1 Redha I. Al-Bayati2 and Zuhair A. Shafiq1
             1
                 Biotechnology Dept. Genetic Engineering and Biotechnology Institute for postgraduate
                                     studies –Baghdad University –Baghdad , Iraq
                       2
                         Chemistry Dept. Science College, Al-Msairitey University, Baghdad, Iraq



Abstract:
         Background and objective:Resveratrol is a non flavonoid polyphenol ( Vitis vinifera) posses three
phenolic hydroxyl group and shown to its biological effects. The derivations of resveratrol associated with
the available oral hypoglycermic agents for treatment of diabetes mellutes type 2..
         Materials and methods: The study has also employed an in vivo evaluation of resveratrol and its
derivative in female rabbits at concentrations ( 1 mg / kg) given orally for 42 days after inducing diabetes
mellitus type 2 by alloxan (100mg/1kg body weight). The serum was isolated from heart blood for the
biochemical tests, including Glucose, Total protein Albumin and Insulin. At day 42 the animal was killed
and the liver and pancreas were kept in 10% formalin for preparation of histopathological sections.
         Results: Statistical analysis showed a significant decrease in Glucose, total protein , Creatinine of
serum blood levels on treated rabbits p > 0.05, However resveratrol and its derivative treated rabbits
showed statistically significant increase in Insulin blood serum levels p > 0.05. Examination of the liver
tissue confirmed potential histopathological effects for resveratrol , while derivative has normal
appearance in a dose dependent manner.
Examination of the pancreas tissue confirmed potential histopathological effects for resveratrol, and its
derivatives has normal appearance in a dose dependent manner. The derivatives compound showed a
significant differences than the other compounds extract regarding the serum activity of Insulin and
hisopathological changes especially in pancreas.

Keywords––Reveratrol (non flavonoid polyphenol); hypoglycermic; Vitis vinifera ; hisopathological;
glbcimaide

                                                I. INTRODUCTION
         Resveratrol (3,5,4 – trihydroxy stilbene), is a non Flavonoid polyphenol and it has three phenolic
hydroxyl groups and shown to have its biological effects [1]. Phenolic and polyphenolic compounds, possess an
aromatic ring bearing one or more hydroxyl substituents [2]. These compounds are phytoalexins and have
antidiabeteic properties [3]. Resveratrol may offer benefits in preventing or managing conditions associated
with high blood sugar [4] . The derivatives of resveratrol associated with the available oral hypoglycemic
agents for the treatment of diabetes mellitus Epsilon-vinifera a resveratrol dimer, ,Piceatanol an active
metabolic of resveratrol found in red wine , Piceid a resveratrol glucoside , Trans – diptoindonesin B a
resveratrol trimer [5].
         These plants produce trans-resveratrol to protect themselves after exposure to ultraviolet radiation,
ozone or certain biologic agents. It functions as a ribonucleotide reductase inhibitor [6].The effects of resveratrol
are currently a topic of numerous animal and human studies. Its effects on the lifespan of many model
organisms remain controversial with uncertain effects in fruit flies, nematode worms and short-lived fish [7]. In
the only positive human trial, extremely high doses (3–5 g) of resveratrol, in a proprietary formulation designed
to enhance its bioavailability, significantly lowered blood sugar. Despite mainstream press alleging resveratrol's
anti-aging effects, there is no accepted data to form a scientific basis for the application of these claims to
mammals [8].

                               II.        MATERIALS AND METHODS
 2.1. Plant materials
         Local black grapes cultivated Iraqi were collected from the local market and classified as Vitis vinifera
by the herbarium of the Biology Department, College of Science, Baghdad University . The grape skin extract
was prepared; all steps were done away from direct light and extensive stress that led to oxidation of the plant
                                                         49
Antidiabetic and antihyperglycemica effects of resvertrol and its derivative…..

extract. About 500 grams of fresh skin grapes was shaken with 2.5 litters' 99.9% ethyl acetate in cool dark place
for 72 hours. The extract was filtered and the filtrate was dried at 30-40°C by a rotary evaporator to get 1/10
(one tenth) its original volume to be stored at –20°C till the followings steps. The following steps were followed
for the isolation of resveratrol:
2.2. Preparation of Resveratrol Derivative
 5-(4-(4-(2-(benzo [d] thiazol-2-yl) hydrazinyl) butanoyloxy)styryl)-1,3-phenylene bis(4-(2-(benzo[d]thiazol-2-
                                             yl) hydrazinyl)butanoate)


                                                                              S
                                                                                         N




                                                                         HN H N
                                                                 O    O




                                                                                      N HN H
                                                                                                   N

                                 S                                   O            O            S
                                              O
                                      NH NH




                                N                 O



 1.6gm ( 0.003 mole) of compound (2) was dissolved in 50ml of absolute ethanol then 1.58g 0.0096 moles of 2-
 Mercptobenzothiazole then reflux for 8h. The solvent was removed and the precipitates was filtrated and dried
                                                         [9].
2.3. Induction of Diabetes
         5,6-dioxyuracil,was used which marketing name (alloxan) and whose diabetogenic property is
established with rabbits. The alloxan injection depends on the weight of the animal: 70 mg of alloxan dissolved
in 3 ml of distilled water for 1 kg of rabbit weight. The alloxan solution is injected through the marginal vein of
the ear after fasted for 24 h before injection. This single dose of alloxan produced type 1 diabetes having fasting
blood sugar level of 155±10.71 mg/dl after10 days of injection of alloxan and this diabetic state was maintained
throughout the`1 duration of the experiment .Therefore, the health status of rabbits was closely monitored until
the hyperglycemia appeared and was detected weekly by determination of blood sugar quantity .
 2.4. Purified Resveratrol and its Derivative Dilutions
         Pure resveratrol 100 mg was dissolved in 100ml PBS and 0.1ml DMSO as organic solvent for
dissolving the substance. The stock was kept in a dark container at –20°C after sterilization with 0.22μm
Millipore filter.
         Resveratrol derivative 50mg were dissolved in 0.05ml DMSO and complete the volume to 50 ml with
PBS. Then it was sterilized and kept in a dark container at –20°C.
2.5. Experimental Design:
          Fifteen adult female rabbits were randomly divided into four groups and treated daily as follows for
six weeks: The rabbits in first group received regular standard diet, tap water and served as control. After
feeding them for about 1 week, their body weights and fasting blood sugar levels were taken. Other parameters
which included levels were also taken and recorded.
 Group 2: Diabetic rabbits without treatment
         At the expiration of 1 week, alloxan was subject into the control group and they formed group (2)
rabbits. The rabbits were confirmed diabetic after estimation of their fasting blood sugar level, 2weeks after
injection of alloxan. A rabbit was considered to be diabetic if it had a fasting blood sugar where level > 115
mg/dl. Other parameters were also taken and recorded.
Group 3: Diabetic rabbits after treatment with glbcimaide
         At the expiration of 2 weeks of induction of diabetes into the rabbits of group (2), they were force fed
with glbcimaide 0.05mg orally for a period of 6 weeks and, thus they formed the rabbits of group 3. At the end
of 4 weeks their fasting blood glucose levels was estimated and recorded. Other parameters were also taken and
recorded.
Group 4: Diabetic rabbits after treatment with Resveratrol
         At the expiration of 2 weeks of induction of diabetes into the rabbits of group (2), they were force fed
with resveratrol 1mg/ml orally for a period of 6 weeks and, thus they formed the rabbits of group 4. At the end
of 4 weeks their fasting blood glucose levels were estimated and recorded. Other parameters were also taken and
recorded.
Group 5: Diabetic rabbits after treatment with Resveratrol derivative

                                                       50
Antidiabetic and antihyperglycemica effects of resvertrol and its derivative…..

         At the expiration of 2 weeks of induction of diabetes into the rabbits of group (2), they were force fed
with resveratrol derivative 1mg/ml orally for a period of 6 weeks and they thus formed the rabbits of group (3).
At the end of 4 weeks their fasting blood glucose levels was estimated and recorded. Other parameters were also
taken and recorded.
2.6. Biochemical Estimation:
         The fasting blood glucose levels was estimated according to (Young et al., 2000)[10] ; Total protein
(Young et al., 2000 )[10]; serum triglyceride (Young et al.,2000)[10]; serum creatinine ( Young et al. 2000) [10]
; serum insulin ( Young et al.,2000)[10].
2.7. Histopathological studies:
         Tissue samples from liver & pancreas after delivery were prepared for histopathological studies
according to the methods of Junqueira et al.[11].
2.8. Statistical Analysis
         Data were analyzed by using the SPSS package programmed. Multiple range test was used to detect the
significant differences [12].The method which was used to measure the significances at level 0.05 or 0.01 was
taken from [13].
                                                  III.        RESULTS
         Table (1) shows the diabetic rabbits treated with the resveratrol and its derivative decreased
significantly lower (p<0.05) in comparison with the control antidiabetic group after 3, 4 and 6 weeks of the
injection of the alloxan.For the rabbits in the groups treated with resveratrol and its derivatives, the food and
water intake was decreased and the volume of urine decreased in comparison with the rabbits in the control
antidiabetic groups. It can therefore be concluded that the preliminary study shows that the resveratrol and its
derivative decreases the serum glucose level in diabetic rabbits. The resveratrol derivative shows significant
value after one week of treatment 109.0mg/dL±2.5 in comparison with resveratrol had normal values after 6
weeks.
               Table (1): The effect of resveratrol and its derivative on serum glucose concentration
                                      (mg/dL) of rabbits' groups with weeks.

          Groups       Treatment periods

                       WK0       PT         Wk1          Wk2     Wk3        Wk4      Wk5      Wk6

          C            98±       98±        92.0±0.      96±     102±       101±     100±     99±
                       2a        2e         5e           2e      1e         0.5d     0.5d     3c
                       A         A          A            A       A          A        A        A
          D            92±       247±       275±         255±    276±       267±     270±     271±
                       2.0a      3.5d       2.5a         2.5a    3a         3.5a     3.5a     2a
                       C         B          A            AB      A          AB       A        A
          DI           96±       250±       240±         233±    247±       244±     230±     229±
                       1.50a C   5d         5b           1.5a    3.5b       2.0b     1.5b     4.5b
                                 A          AB           AB      AB         AB       AB       B
          DR           102±      263±       180±         177±    160±       150±     120±     100±
                       0.5a      1.5d       2.5c         0.5b    3c         2.5c     0.25c    0.5c
                       A         A          B            B       BC         C        D        E
          DRD          93±       289.0±     109.0±       100±    93±        85±      72±      66±
                       3.0a      3c         2.5e B       0.05d   1.5e       1.5e     1e       3e
                       BC        A                       BC      BC         CD       D        D

                                       Each value represents mean  SD
         Values with non-identical superscripted (a, b, c, d, e& f) are considered as significantly different
(p<0.05) among the same group of rabbits, Values with non-identical superscripted (A, B, C, D, E& F) are
considered as significantly different (p<0.05) among the different groups of rabbits, N( number of
animals)=3.
         C=Control; D=Diabetic; DI=Diabetic after treated with glbcimide; DR= Diabetic after treated
with resveratrol;DRD= Diabetic after treated with its derivative
         WK0=Zero week; PT=Pretreatment; WK1=First week; WK2=Second week; WK3=Third week;
WK4=Fourth week; WK5=Fifth week; WK6=Sixth week.
         Table (2) show significant increase in the level of Serum total protein which is a sign of renal
dysfunction in the diabetic rabbits when compared to control rabbits. The diabetic rabbits treated with the
resveratrol and its derivative showed significant decrease in levels of Serum Total protein (p<0.05) . Resvertrol
                                                         51
Antidiabetic and antihyperglycemica effects of resvertrol and its derivative…..

and its derivative show significant value after one week of treatment 6.6±0.03 and 7.1±0.02 respectively. In
diabetes, protein catabolism increases due to deficiency of carbohydrate-derived energy in connection with low-
serum insulin.
          Table (2): The effect of resveratrol and their derivatives on serum total protein concentration
                                      mg/dL of rabbits' groups with weeks.

         Groups      Treatment periods

                     WK0        PT         Wk1        Wk2        Wk3        Wk4      Wk5      Wk6

         C           6.9±       7.7±       7.1±       7.1±       7.1±0.0    6.9±     7±       7.1±
                     0.03 a     0.07 b     0.02 a A   0.02 a     2a A       0.03 a   0.05 b   0.02 b
                      A         A                     A                     A        A        A
         D           7.1±       5.1±       5.2±       5± 0.05    5±         5±       5.3±     5      ±
                     0.03 a     0.05e E    0.03 f E   e
                                                                 0.05e      0.05 e   0.01 f   0.05 e
                     B                                E          E          E        E        E
         DI          7.0±       5.3±       7.1±       7.2±       7.2±       7.1±     6.9±     7      ±
                     0. 02 a    0.08 e F   0.02fdc    0.06 b     0.06b A    0.02 b   0.03 a   0.023 b
                     A                     A          A                     B        D        A
         DR          7.1±       5.3±       6.6±       6.8±       6.8±       7.2±     6.8±     6.8 ±
                     0. 02a     0.05e      0.03 dc    0.10 c B   0.10 c B   0.06ba   0.10 b   0.10b B
                     B          F          CB                               A        C
         DRD         7.7 ±      5.4±       7.1±       7.2±       7.2±       7.2±     7.4±     7.3±
                     0.07a      0.1 e      0.02dc     0.06b      0.06 b B   0.06 b   0.02 a   0.02 a B
                     C          D          A          B                     B        A

                                     Each value represent mean + SD
        Values with non-identical superscripted (a, b, c, d, e& f) are considered as significantly different
(p<0.05) among the same group of rabbits, Values with non-identical superscripted (A, B, C, D, E& F) are
considered as significantly different (p<0.05) among the different groups of rabbits, N( number of
animals)=3.
        C=Control ;D=Diabetic; I=Diabetic after treated with glbcimide;DR= Diabetic after treated with
resveratrol;DRD= Diabetic after treated with derivative

      The results showed significant increase in the level of serum albumin which is asign of renal dysfunction
in the diabetic rabbits when compared with control rabbits (Table 3). The diabetic rabbits treated with
resveratrol and their derivatives decrease levels of Serum Albumin significantly (p<0.05). The results showed
significant decrease in the level of serum urea of rabbits treated with resveratrol and its derivative (p<0.05).
Resveratrol and its derivative show significant value after one week of treatment 3.7±0.1 and 4.2±0.05,
respectively.




                                                          52
Antidiabetic and antihyperglycemica effects of resvertrol and its derivative…..

       Table (3): The effect of resveratrol and its derivative on serum albumin concentration (mg/dL) of
                                          Rabbits' groups with weeks.
        Groups      Treatment periods

                      WK0        PT         Wk1        Wk2        Wk3        Wk4       Wk5          Wk6

         C            4.4±       4.3±       4.3±       4.2±       4.4±       4.2±      4.2±         4.3±
                      0.1 a      0.07 a     0.07 a     0.05 a     0.10 a     0.05 a    0.05 a       0.08 a
                       A         A          A          A          A          A         A            A
         D            4.2±       2.9±       2.9±       2.6±       2.7±       2.9±      2.9±         2.7±
                      0.1 a      0.15 b     0.22b      0.15b      0.17 b     0.22 b    0.1          0.18 b
                      A          B           B         B          B          B         B            B
         DI           4.3 ±      3.0±       3.9±       4.5±       4.4±       4.2±      4.4±         4.1
                      0.09 a A   0.15 b B   0.23a      0.25 a     0.20 a     0.04 a    0.1 a        ±0.02a
                                            A          A          A          A         A            A
         DR           4.2±       3.1±       3.7±       3.8±       4.0±       4.4±      4.4±         4.2±
                      0.05 a A   0.03 b B   0.1a       0.20a      0.10 a     0.2 a     0.1 a        0.05 a A
                                            A          A          A          A         A
         DRD          4.2 ±      2.9±       4.2±       4.3±       4.3±       4.4±      4.4±         4.3±
                      0.06 a A   0.21 b B   0.05 a     0.08 a     0.07 a     0.02 a    0.06     a
                                                                                                    0.10 a A
                                            A           A         A           A        A

                                    Each value represent mean  SD
        Values with non-identical superscripted (a, b, c, d, e& f) are considered as significantly different
(p<0.05) among the same group of rabbits, Values with non-identical superscripted (A, B, C, D, E& F) are
considered as significantly different (p<0.05) among the different groups of rabbits, N( number of
animals)=3.
        C=Control ;D=Diabetic; I=Diabetic after treated with glbcimide;DR= Diabetic after treated with
resveratrol ;DRD= Diabetic after treated with derivative.
        WK0=Zero week; PT=Pretreatment; WK1=First week; WK2=Second week; WK3=Third week;
WK4=Fourth week; WK5=Fifth week; WK6=Sixth week.

          The clinical significance of the creatinine level in plasma or serum is usually determined in conjugation
with the plasma urea level since there is an increase in both levels in postrenal azotemia, while the creatinine
clearance (CC), or urine levels, are diminished. The diabetic rabbits treated with the resveratrol and its
derivative showed significant decreased levels of serum creatinine (p<0.05). This further shows the ability of
the resveratrol and its derivative in treating diabetes associated renal complications and also supports the usage
of these compounds for kidney diseases. Resveratrol derivative show significant value after 2 weeks of
treatment 1.1mg /dL± 0.03. and resveratrol failed to reach to normal value as shown in table (4). Serum urea and
creatinine levels increased significantly in the diabetic control group with respect to the control group. The
levels of these parameters restored towards the control level after administration of resveratrol and its derivative
to the diabetic rabbits.This has been indicated here by high levels of serum urea and creatinine. High-serum
creatinine level is also the sign of muscle wastage.




                                                        53
Antidiabetic and antihyperglycemica effects of resvertrol and its derivative…..

                Table (4): The effect of resveratrol and their derivatives on serum creatinine
                            concentration mg/dL of rabbits' groups with weeks.
         Groups                                     Treatment periods

                          WK0        PT      Wk1        Wk2        Wk3       Wk4        Wk5         Wk6

         C              1±        0.9±        1±        1±         0.9±       0.9±       1.1±       0.9±
                       0.02a     0.024c      0.02d     0.02f       0.02f     0.024f     0.023d      0.24a
                         A         A           A         A           A         A           A          A
         D             1.1±       3.2±       3.6±      3.6±        3.9±       3.9±       3.8±       3.9 ±
                      0.02a C    0.15a       0.16a     0.16a       0.2 a      0.2 a      0.35a       0.2a
                                               A         A           A         A           A          A
         DI            0.9±        2.8±      3.2±      3.0±        3.1±       2.7±       2.2±       2.3 ±
                      0.24a D     0.12b      0.15b     0.14b       0.15b     0.14a       0.17b     0.11b C
                                    B          A         A           A         B           C
         DR             1.1±       3.0±      3.0±      2.9±        2.8±       2.3±       2.3±       2.2 ±
                       0.023a     0.14ab     0.14b     0.10b       0.12c     0.15b       0.15b      0.1b
                         C          A          A         B          BC         C           D          D
         DRD           1.0 ±       3.3±      1.2±      1.1±        1.1±       1.0±       1.0±       1.0±
                       0.02a      0.24a      0.02d     0.03ef      0.03f     0.05f       0.03d      0.02d
                         B          A          B         B           B         B           B          B

                                       Each value represent mean + SD
        Values with non-identical superscripted (a, b, c, d, e& f) are considered as significantly different
(p<0.05) among the same group of rabbits, Values with non-identical superscripted (A, B, C, D, E& F) are
considered as significantly different (p<0.05) among the different groups of rabbits.
        C=Control ;D=Diabetic; I=Diabetic after treated with glbcimide;DR= Diabetic after treated with
resveratrol;DRD= Diabetic after treated with derivative.

          The results showed significant increase in the level of serum insulin of rabbits treated with resveratrol
and its derivative significantly (p<0.05). Derivative show significant value after one week of treatment 0.8
 mole/L±0.02 respectively shown in table (5).
          Many herbal plants' extracts was able to recover the protein metabolic disorders possibly by stimulating
the existing βcells and or by regenerating βcells like other plant products. Since insulin inhibits adipose tissue
hormone sensitive lipase and reduces lipolysis, the aqueous-methanolic extract of S mahagoni seed may correct
the above mentioned disorders by mimicking insulin action [14].
              Table (5): The effect of resveratrol and its derivative on serum Insulin concentration
                                    ( mole/L) of rabbits' groups with weeks.

   Groups         Treatment periods

                  WK0           PT         Wk1        Wk2         Wk3        Wk4        Wk5           Wk6

   C              0.8± 0.02a    0.9±       1± 2.02d   1± 0.02f    0.9±       0.9±         1.1±        0.9±
                  A             0.024c     C          C           0.02 f B   0.024f B     0.023d      0.24a B
                                B                                                         C
   D              1.1± 0.02a    0.02±0.    0.03±      0.03±       0.03±      0.03±        0.03±       0.03    ±
                  B             15e        0.16e      0.16e A     0.2e       0.2 e        0.35e       0.2e
                                A           A                     A          A            A           A
   DI             0.9 ±         0.02±0.    0.3±       0.3±        0.3±       0.27±        0.22±       0.23±0.1
                  0. 24a        12e        0.15e      0.14e A     0.15d      0.14d        0.17d       1d A
                  A             A          A                      A           A           A
   DR             1.1±          0.02±0.    0.3±       0.32±       0.38±      0.38±        0.4±        0.42    ±
                  0.023a BA     14e A      0.14e      0.10d A     0.12d      0.15d        0.15d       0.1c
                                           A                      A          A             A          A
   DRD            1.0       ±   0.03±      0.8±       0.9±        1±         1.2±         1.3±        1.35±0.0
                  0.02a         0.24e A    0.02cd     0.03bc A    0.03ab     0.05a        0.03a       2a A
                  B                        A                      A          A            A

                                                       54
Antidiabetic and antihyperglycemica effects of resvertrol and its derivative…..

                                     Each value represent mean + SD.
        Values with non-identical superscripted (a, b, c, d, e& f) are considered as significantly different
(p<0.05) among the same group of rabbits, Values with non-identical superscripted (A, B, C, D, E& F) are
considered as significantly different (p<0.05) among the different groups of rabbits, N( number of
animals)=3.
        C=Control ;D=Diabetic; I=Diabetic after treated with glbcimide;DR= Diabetic after treated with
resveratrol;DRD= Diabetic after treated with derivative. WK0=Zero week; PT=Pretreatment;
WK1=First week; WK2=Second week; WK3=Third week; WK4=Fourth week; WK5=Fifth week;
WK6=Sixth week.

3.1. Examinations of the Liver and Pancreas Sections
           These rabbits were excluded from the study. Necropsy was performed after euthanasia, or death in one
rabbit, in the individual group and in one normal rabbit. The light microscopic examination by specific staining
of pancreatic beta cells in control tissues showed normal appearance of islet of langerhans which was not
observed in diabetic pancreas figure(1) and (2) respectively. The pancreas was examined mainly, especially the
pancreatic islets. Pancreatic section of rabbits treated with resveratrol and its derivative showed no notable
histological changes. Secretion from remnant pancreatic beta cells which in turn enhances the glucose utilization
by peripheral tissue of diabetic rabbits. The histopathology examination showed that pancreatic islets
disappeared and that the exocrine tissue remained relatively inaffected; any remaining islets were considerably
atrophied compared with the normal pancreas. In the pancreatic section of rabbits treated with derivative no
notable histological changes appear figures (3) and (4).




                                                                   Islet of langerhans



                                                           Necrosis

                                                                Degenerative changes
               Islet of langerhans

Figure (1) Section of control non-diabetic pancreas         Figure (2) Section of diabetic pancreas
 Rabbit with normal looking appearance of exocrine            rabbit shows degenerative changes &
  of Islet of langerhans (X200) (H&E).                         necrosis & endocrine (Islet of langerhans)
                                                                 (X200) (H&E).



                 Islet of langerhans




                                                                                  Islet of langerhans
Degenerative

             Necrosis




Figure: (3) Section of diabetic pancreas rabbit         Figure :(4) Section of diabetic pancreas rabbit

                                                      55
Antidiabetic and antihyperglycemica effects of resvertrol and its derivative…..

after treated with resveratriol shows degenerative                     after treated with derivative shows normal &
necrosis of islet of langerhans (X200) (H&E).                      looking of islet of langerhans (X200) (H&E)

                                                        IV.        DISCUSSION
          Thus, the significant anti-diabetic effect of resveratrol and its derivative may be due to the presence of
phenolics and or their synergistic properties. This may be due to the presence of hydroxyl as shown in
resveratrol and heterocyclic amide rings as shown in its derivative [15]. These results agreed with the study of
diabetes induced by Streptozotocin resulted in a significant elevation in blood glucose level in comparison with
the control group after administration of aqueous methanolic (2: 3) extract of S. mahagoni seed to the diabetic
rabbits for 21 days [14]. A significant reduction in blood glucose level was noted this was close to the control
level.
          The results also agreed with the study of the protective effect of plant compound idopyranose isolated
from the plant, Vitex negundo evaluated against streptozotocin-induced diabetics. Wister rats showed significant
reduction in blood glucose [16].
          These findings indirectly show that the blood glucose levels in the groups treated with resveratrol and
its derivative may have been lowered not by insulin but by derivatives; this is because almost all of the
pancreatic islet beta cells were destroyed and therefore resulted in insulin deficiency [17].
          The anti- hyperglycemic activity of resveratrol and its derivative probably caused by stimulation of
insulin have also been reported to have a similar effect as observed in the present investigation. Significant
increase in the lymphocytes induced by resveratrol and its derivative reflects possible imunomodulatory effects
alloxan-induced diabetic rats. It is well known that certain polyphenols and their derivatives exhibit
hypoglycemic activity and are known for their ability of beta-cell regeneration of pancreas. It can therefore be
concluded that the preliminary study shows that the resveratrol and its derivative decreases the blood glucose
level in diabetic rabbits.
          Correction of oxidative injury which is associated with diabetes is another possibility of the recovery in
glycemic disorders. Resveratrol and their derivatives are able to recover the protein metabolic disorders possibly
by stimulating the existing β-cells and or by regenerating βcells like other plant products [18].

                                                       V.         CONCLUSION:
         The results suggested the resveratrol and its derivative are safe and potent hypoglycemic agent which is
capable for normalizing other biochemical and hematological abnormalities associated with diabetes mellitus
type 2.

REFERENCES
  [1].    F.A.Tomas- Barberan and R.J.Robins. Phytochemistry of fruit and vegetables. (Clarendon press- Oxford. New York. 1997).
  [2].    J.B. Harborne. Phytochemical Methods.( Chapman and Hall. London. 1984).
  [3].    J.Bruneton, Pharmacognosy phytochemistry Medicinal plants ,( 2nd edition , TEC 8 DOC .Paris, France) 1999.
  [4].    L.Barclay, . Growing evidence links, resveratrol to extended life span. Life Extension Magazine , 13, 2007, 1-8.
  [5].    Y.D.Kim, K.G.Park, Y.S.Lee, Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent
          regulation of the orphan nuclear receptor SHP. Diabetes. 57(,2) : 2008, 306–314.
  [6].    T.Pussa T, J.Floren, P.Huldhepp and A. Raal. Survery of grape wine vitis vinefera sternpoly phenols by liquid chroma tography
          – Diode array detection tandem mass , spectrometry. J. Agric. Food chem, (54): 2006. 7488-7494 .
  [7].    T.M.Bass, D.Weinkove, K.Houthoofd, D.Gems, L. Partridge, Effects of resveratrol on lifespan in Drosophila melanogaster and
          Caenorhabditis elegans. Mechanisms of Ageing and Development .(128) .10: 2007, 546–52.
  [8].    B.D.Gehm, J.M.McAndrews, P.Y.Chien, J.L.Jameson, Resveratrol, a polyphenolic compound found in grapes and wine, is an
          agonist for the estrogen receptor . Proceedings of the National Academy of Sciences of the United States of America 94, (25)
          1997 : 14138–43.
  [9].    W.W. Stephen ; N.H.J. Kelly. Organic Chemistry. 2006, 71, 1080
  [10].   D.S. Young , et al; Effect of drugs on clinical laboratory tests,5th ed, AACC Press,(2000).
  [11].   L.C. Junqueira, and J.Carneiro Basic Histology, tenth edition. The McGraw-Hill Companies, USA.(2003).
  [12].   D.Duncan , (1955). Multiple range and Multiple F-test Biometrics -11 :1-42.
  [13].   R.G.Steel, and J.H.Torrie ,(1980) Principles and procedures of statistics.,2 nd.ed,McGraw.Hill Book Co .New York , Ny.
  [14].   I. Debasis De, K. Chatterjee, A. K. Ali, B. Tushar Kanti and G.Debidas, Antidiabetic Potentiality of the Aqueous-Methanolic
          Extract of Seed of Swieteniamahagoni (L.) Jacq. in Streptozotocin-Induce DiabeticMale Albino Rat: A Correlative and
          Evidence-Based Approach with Antioxidative and Antihyperlipidemic Activities. Hindawi Publishing Corporation Evidence-
          Based Complementary and Alternative Medicine, Article ID 892807, 2011, 11.
  [15].   J.H.Black and J.M.Beale ,Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry. (Lippincott
          Willamsand Wilkins. London. 2004).




                                                                 56
Antidiabetic and antihyperglycemica effects of resvertrol and its derivative…..

[16].   R. Manikandan, R. Sundaram, P. Srinivasan, S. Beulaja and C. Arulvasu. Isolation of 1, 2 di-substituted idopyranose from Vitex
        negundo and its effects on diabetic ratsInternational J. of Pharmaceuticals Analysis, 1, 2, 2009, pp-4-10.
[17].   C.M.Cam, H.G.Cros,J.J.Serrano,R.Lazaro,H.J.McNeill.In vivo antidiabetic actions of naglivan,an organic vanadyl compound
        instreptozotocin-induced diabetes. Diabetes Res. and Clin. Practice,( 20), 2003, 111-121.
[18].   M. Kaleem, P. Medha, Q.U. Ahmed, M. Asif, B. Bano, Beneficial effects of Annona squamosa extract in streptozotocin-induced
        diabetic rats Singapore Med J . 49,(10), 2008 : 800 .




                                                               57

More Related Content

What's hot

New oxidative determination of some new Antihypertensive drugs in pure form a...
New oxidative determination of some new Antihypertensive drugs in pure form a...New oxidative determination of some new Antihypertensive drugs in pure form a...
New oxidative determination of some new Antihypertensive drugs in pure form a...iosrjce
 
Standardization of plectranthus amboinicus
Standardization  of plectranthus  amboinicusStandardization  of plectranthus  amboinicus
Standardization of plectranthus amboinicusshveta arya
 
Classification of secondary metabolites and their applications.
Classification of secondary metabolites and their applications.Classification of secondary metabolites and their applications.
Classification of secondary metabolites and their applications.Saurabh Kumar
 
Antioxidant activity of Indian propolis and its chemical constituents
Antioxidant activity of Indian propolis and its chemical constituentsAntioxidant activity of Indian propolis and its chemical constituents
Antioxidant activity of Indian propolis and its chemical constituentsAbu Sayeed
 
Isolation, in vitro antidiabetic, antioxidant activity and molecular docking ...
Isolation, in vitro antidiabetic, antioxidant activity and molecular docking ...Isolation, in vitro antidiabetic, antioxidant activity and molecular docking ...
Isolation, in vitro antidiabetic, antioxidant activity and molecular docking ...iosrjce
 
317 - In-vitro Antioxidant studies on ethanolic extracts of Boswellia ovalifo...
317 - In-vitro Antioxidant studies on ethanolic extracts of Boswellia ovalifo...317 - In-vitro Antioxidant studies on ethanolic extracts of Boswellia ovalifo...
317 - In-vitro Antioxidant studies on ethanolic extracts of Boswellia ovalifo...pharmaindexing
 
Profiling and Characterization Antioxidant Activities in Anoectochilus formos...
Profiling and Characterization Antioxidant Activities in Anoectochilus formos...Profiling and Characterization Antioxidant Activities in Anoectochilus formos...
Profiling and Characterization Antioxidant Activities in Anoectochilus formos...Cây thuốc Việt
 
Synthesis and pharmacological screening of some benzoxazole derivatives as an...
Synthesis and pharmacological screening of some benzoxazole derivatives as an...Synthesis and pharmacological screening of some benzoxazole derivatives as an...
Synthesis and pharmacological screening of some benzoxazole derivatives as an...tejasatyasai
 
Drugs from plants extraction, purification &amp; analysis.
Drugs from plants  extraction, purification &amp; analysis.Drugs from plants  extraction, purification &amp; analysis.
Drugs from plants extraction, purification &amp; analysis.Dr. Amsavel A
 
Biosynthesis isolation and example for some alkaloids
Biosynthesis isolation and example for some alkaloidsBiosynthesis isolation and example for some alkaloids
Biosynthesis isolation and example for some alkaloidsshveta arya
 
Phytochemical Profile and in vitro and in vivo Anticonvulsant and Antioxidant...
Phytochemical Profile and in vitro and in vivo Anticonvulsant and Antioxidant...Phytochemical Profile and in vitro and in vivo Anticonvulsant and Antioxidant...
Phytochemical Profile and in vitro and in vivo Anticonvulsant and Antioxidant...Self-employed researcher
 
Phytochemical investigation of tropical medicinal plants - Stereospermum cola...
Phytochemical investigation of tropical medicinal plants - Stereospermum cola...Phytochemical investigation of tropical medicinal plants - Stereospermum cola...
Phytochemical investigation of tropical medicinal plants - Stereospermum cola...researchplantsciences
 
Phytochemical Investigation and the study of Drug Potential of Phytocompound ...
Phytochemical Investigation and the study of Drug Potential of Phytocompound ...Phytochemical Investigation and the study of Drug Potential of Phytocompound ...
Phytochemical Investigation and the study of Drug Potential of Phytocompound ...Halavath Ramesh
 

What's hot (20)

2003. the survey of trypanocidal constituents in some mexican plants.
2003. the survey of trypanocidal constituents in some mexican plants.2003. the survey of trypanocidal constituents in some mexican plants.
2003. the survey of trypanocidal constituents in some mexican plants.
 
New oxidative determination of some new Antihypertensive drugs in pure form a...
New oxidative determination of some new Antihypertensive drugs in pure form a...New oxidative determination of some new Antihypertensive drugs in pure form a...
New oxidative determination of some new Antihypertensive drugs in pure form a...
 
Dissert ppt
Dissert pptDissert ppt
Dissert ppt
 
3. inhibidores etileno guayaba
3.  inhibidores etileno guayaba3.  inhibidores etileno guayaba
3. inhibidores etileno guayaba
 
Standardization of plectranthus amboinicus
Standardization  of plectranthus  amboinicusStandardization  of plectranthus  amboinicus
Standardization of plectranthus amboinicus
 
4.6 alkaloids 2020
4.6 alkaloids 20204.6 alkaloids 2020
4.6 alkaloids 2020
 
Classification of secondary metabolites and their applications.
Classification of secondary metabolites and their applications.Classification of secondary metabolites and their applications.
Classification of secondary metabolites and their applications.
 
Antioxidant activity of Indian propolis and its chemical constituents
Antioxidant activity of Indian propolis and its chemical constituentsAntioxidant activity of Indian propolis and its chemical constituents
Antioxidant activity of Indian propolis and its chemical constituents
 
Isolation, in vitro antidiabetic, antioxidant activity and molecular docking ...
Isolation, in vitro antidiabetic, antioxidant activity and molecular docking ...Isolation, in vitro antidiabetic, antioxidant activity and molecular docking ...
Isolation, in vitro antidiabetic, antioxidant activity and molecular docking ...
 
Lecture 4
Lecture 4Lecture 4
Lecture 4
 
Atropine
AtropineAtropine
Atropine
 
317 - In-vitro Antioxidant studies on ethanolic extracts of Boswellia ovalifo...
317 - In-vitro Antioxidant studies on ethanolic extracts of Boswellia ovalifo...317 - In-vitro Antioxidant studies on ethanolic extracts of Boswellia ovalifo...
317 - In-vitro Antioxidant studies on ethanolic extracts of Boswellia ovalifo...
 
Profiling and Characterization Antioxidant Activities in Anoectochilus formos...
Profiling and Characterization Antioxidant Activities in Anoectochilus formos...Profiling and Characterization Antioxidant Activities in Anoectochilus formos...
Profiling and Characterization Antioxidant Activities in Anoectochilus formos...
 
Synthesis and pharmacological screening of some benzoxazole derivatives as an...
Synthesis and pharmacological screening of some benzoxazole derivatives as an...Synthesis and pharmacological screening of some benzoxazole derivatives as an...
Synthesis and pharmacological screening of some benzoxazole derivatives as an...
 
Drugs from plants extraction, purification &amp; analysis.
Drugs from plants  extraction, purification &amp; analysis.Drugs from plants  extraction, purification &amp; analysis.
Drugs from plants extraction, purification &amp; analysis.
 
Biosynthesis isolation and example for some alkaloids
Biosynthesis isolation and example for some alkaloidsBiosynthesis isolation and example for some alkaloids
Biosynthesis isolation and example for some alkaloids
 
Rutin
RutinRutin
Rutin
 
Phytochemical Profile and in vitro and in vivo Anticonvulsant and Antioxidant...
Phytochemical Profile and in vitro and in vivo Anticonvulsant and Antioxidant...Phytochemical Profile and in vitro and in vivo Anticonvulsant and Antioxidant...
Phytochemical Profile and in vitro and in vivo Anticonvulsant and Antioxidant...
 
Phytochemical investigation of tropical medicinal plants - Stereospermum cola...
Phytochemical investigation of tropical medicinal plants - Stereospermum cola...Phytochemical investigation of tropical medicinal plants - Stereospermum cola...
Phytochemical investigation of tropical medicinal plants - Stereospermum cola...
 
Phytochemical Investigation and the study of Drug Potential of Phytocompound ...
Phytochemical Investigation and the study of Drug Potential of Phytocompound ...Phytochemical Investigation and the study of Drug Potential of Phytocompound ...
Phytochemical Investigation and the study of Drug Potential of Phytocompound ...
 

Similar to IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research paper publishing, where to publish research paper, journal publishing, how to publish research paper, Call for research paper, international journal, publishing a paper, call fo

Effects of Metformin, Pioglitazone and Aqueous Extract of Delonix Regia on Bl...
Effects of Metformin, Pioglitazone and Aqueous Extract of Delonix Regia on Bl...Effects of Metformin, Pioglitazone and Aqueous Extract of Delonix Regia on Bl...
Effects of Metformin, Pioglitazone and Aqueous Extract of Delonix Regia on Bl...iosrjce
 
The Effect Of Roselle Extract (Hibiscus Sabdariffa Linn.) On Blood Glucose ...
	 The Effect Of Roselle Extract (Hibiscus Sabdariffa Linn.) On Blood Glucose ...	 The Effect Of Roselle Extract (Hibiscus Sabdariffa Linn.) On Blood Glucose ...
The Effect Of Roselle Extract (Hibiscus Sabdariffa Linn.) On Blood Glucose ...iosrphr_editor
 
Liraglutide in Diabetes
Liraglutide in Diabetes Liraglutide in Diabetes
Liraglutide in Diabetes SAKEEL AHMED
 
Antidiabetic and Cytoprotective Effect of Ethanolic Extract of SalaciaNitida ...
Antidiabetic and Cytoprotective Effect of Ethanolic Extract of SalaciaNitida ...Antidiabetic and Cytoprotective Effect of Ethanolic Extract of SalaciaNitida ...
Antidiabetic and Cytoprotective Effect of Ethanolic Extract of SalaciaNitida ...IOSRJPBS
 
Comparative Study of The Antioxidant Activities of Monodora Myristica And A. ...
Comparative Study of The Antioxidant Activities of Monodora Myristica And A. ...Comparative Study of The Antioxidant Activities of Monodora Myristica And A. ...
Comparative Study of The Antioxidant Activities of Monodora Myristica And A. ...iosrjce
 
In vivo study on the efficacy of hypoglycemic activity of Spirulina plantesis...
In vivo study on the efficacy of hypoglycemic activity of Spirulina plantesis...In vivo study on the efficacy of hypoglycemic activity of Spirulina plantesis...
In vivo study on the efficacy of hypoglycemic activity of Spirulina plantesis...Open Access Research Paper
 
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...iosrphr_editor
 
EVALUATION OF ANTI HYPERLIPIDEMIC ACTIVITY OF ETHANOLIC EXTRACT OF AMARANTHUS...
EVALUATION OF ANTI HYPERLIPIDEMIC ACTIVITY OF ETHANOLIC EXTRACT OF AMARANTHUS...EVALUATION OF ANTI HYPERLIPIDEMIC ACTIVITY OF ETHANOLIC EXTRACT OF AMARANTHUS...
EVALUATION OF ANTI HYPERLIPIDEMIC ACTIVITY OF ETHANOLIC EXTRACT OF AMARANTHUS...gynomark
 
Protective effects of commelina benghalensis linn (root) extract on ethanol i...
Protective effects of commelina benghalensis linn (root) extract on ethanol i...Protective effects of commelina benghalensis linn (root) extract on ethanol i...
Protective effects of commelina benghalensis linn (root) extract on ethanol i...IJSIT Editor
 
In Vitro and in Vivo Evaluation of Antidiabetic Activity of Leaf Essential Oi...
In Vitro and in Vivo Evaluation of Antidiabetic Activity of Leaf Essential Oi...In Vitro and in Vivo Evaluation of Antidiabetic Activity of Leaf Essential Oi...
In Vitro and in Vivo Evaluation of Antidiabetic Activity of Leaf Essential Oi...China
 
In vitro antidiabetic activity of Clerodendrum viscosum Vent
In vitro antidiabetic activity of Clerodendrum viscosum VentIn vitro antidiabetic activity of Clerodendrum viscosum Vent
In vitro antidiabetic activity of Clerodendrum viscosum VentSriramNagarajan17
 
Effect of crude oil pollution on phytochemical and anti diabetic potentials o...
Effect of crude oil pollution on phytochemical and anti diabetic potentials o...Effect of crude oil pollution on phytochemical and anti diabetic potentials o...
Effect of crude oil pollution on phytochemical and anti diabetic potentials o...ijtsrd
 
Study the efficacy of Rhizophora mucornata Poir. leaves for diabetes therapy ...
Study the efficacy of Rhizophora mucornata Poir. leaves for diabetes therapy ...Study the efficacy of Rhizophora mucornata Poir. leaves for diabetes therapy ...
Study the efficacy of Rhizophora mucornata Poir. leaves for diabetes therapy ...Open Access Research Paper
 
Ameliorating Effect of Frankincense on Red Blood Cells of Alloxan Induced-Dia...
Ameliorating Effect of Frankincense on Red Blood Cells of Alloxan Induced-Dia...Ameliorating Effect of Frankincense on Red Blood Cells of Alloxan Induced-Dia...
Ameliorating Effect of Frankincense on Red Blood Cells of Alloxan Induced-Dia...inventionjournals
 

Similar to IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research paper publishing, where to publish research paper, journal publishing, how to publish research paper, Call for research paper, international journal, publishing a paper, call fo (20)

Journal club 5 17 feb
Journal club 5 17 febJournal club 5 17 feb
Journal club 5 17 feb
 
A0430105
A0430105A0430105
A0430105
 
A0430105
A0430105A0430105
A0430105
 
Effects of Metformin, Pioglitazone and Aqueous Extract of Delonix Regia on Bl...
Effects of Metformin, Pioglitazone and Aqueous Extract of Delonix Regia on Bl...Effects of Metformin, Pioglitazone and Aqueous Extract of Delonix Regia on Bl...
Effects of Metformin, Pioglitazone and Aqueous Extract of Delonix Regia on Bl...
 
The Effect Of Roselle Extract (Hibiscus Sabdariffa Linn.) On Blood Glucose ...
	 The Effect Of Roselle Extract (Hibiscus Sabdariffa Linn.) On Blood Glucose ...	 The Effect Of Roselle Extract (Hibiscus Sabdariffa Linn.) On Blood Glucose ...
The Effect Of Roselle Extract (Hibiscus Sabdariffa Linn.) On Blood Glucose ...
 
Liraglutide in Diabetes
Liraglutide in Diabetes Liraglutide in Diabetes
Liraglutide in Diabetes
 
Antidiabetic and Cytoprotective Effect of Ethanolic Extract of SalaciaNitida ...
Antidiabetic and Cytoprotective Effect of Ethanolic Extract of SalaciaNitida ...Antidiabetic and Cytoprotective Effect of Ethanolic Extract of SalaciaNitida ...
Antidiabetic and Cytoprotective Effect of Ethanolic Extract of SalaciaNitida ...
 
Comparative Study of The Antioxidant Activities of Monodora Myristica And A. ...
Comparative Study of The Antioxidant Activities of Monodora Myristica And A. ...Comparative Study of The Antioxidant Activities of Monodora Myristica And A. ...
Comparative Study of The Antioxidant Activities of Monodora Myristica And A. ...
 
Besnard et al.
Besnard et al.Besnard et al.
Besnard et al.
 
In vivo study on the efficacy of hypoglycemic activity of Spirulina plantesis...
In vivo study on the efficacy of hypoglycemic activity of Spirulina plantesis...In vivo study on the efficacy of hypoglycemic activity of Spirulina plantesis...
In vivo study on the efficacy of hypoglycemic activity of Spirulina plantesis...
 
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...
 
EVALUATION OF ANTI HYPERLIPIDEMIC ACTIVITY OF ETHANOLIC EXTRACT OF AMARANTHUS...
EVALUATION OF ANTI HYPERLIPIDEMIC ACTIVITY OF ETHANOLIC EXTRACT OF AMARANTHUS...EVALUATION OF ANTI HYPERLIPIDEMIC ACTIVITY OF ETHANOLIC EXTRACT OF AMARANTHUS...
EVALUATION OF ANTI HYPERLIPIDEMIC ACTIVITY OF ETHANOLIC EXTRACT OF AMARANTHUS...
 
Protective effects of commelina benghalensis linn (root) extract on ethanol i...
Protective effects of commelina benghalensis linn (root) extract on ethanol i...Protective effects of commelina benghalensis linn (root) extract on ethanol i...
Protective effects of commelina benghalensis linn (root) extract on ethanol i...
 
In Vitro and in Vivo Evaluation of Antidiabetic Activity of Leaf Essential Oi...
In Vitro and in Vivo Evaluation of Antidiabetic Activity of Leaf Essential Oi...In Vitro and in Vivo Evaluation of Antidiabetic Activity of Leaf Essential Oi...
In Vitro and in Vivo Evaluation of Antidiabetic Activity of Leaf Essential Oi...
 
Jofre et al 2013
Jofre et al 2013Jofre et al 2013
Jofre et al 2013
 
KEHILI 2014
KEHILI 2014KEHILI 2014
KEHILI 2014
 
In vitro antidiabetic activity of Clerodendrum viscosum Vent
In vitro antidiabetic activity of Clerodendrum viscosum VentIn vitro antidiabetic activity of Clerodendrum viscosum Vent
In vitro antidiabetic activity of Clerodendrum viscosum Vent
 
Effect of crude oil pollution on phytochemical and anti diabetic potentials o...
Effect of crude oil pollution on phytochemical and anti diabetic potentials o...Effect of crude oil pollution on phytochemical and anti diabetic potentials o...
Effect of crude oil pollution on phytochemical and anti diabetic potentials o...
 
Study the efficacy of Rhizophora mucornata Poir. leaves for diabetes therapy ...
Study the efficacy of Rhizophora mucornata Poir. leaves for diabetes therapy ...Study the efficacy of Rhizophora mucornata Poir. leaves for diabetes therapy ...
Study the efficacy of Rhizophora mucornata Poir. leaves for diabetes therapy ...
 
Ameliorating Effect of Frankincense on Red Blood Cells of Alloxan Induced-Dia...
Ameliorating Effect of Frankincense on Red Blood Cells of Alloxan Induced-Dia...Ameliorating Effect of Frankincense on Red Blood Cells of Alloxan Induced-Dia...
Ameliorating Effect of Frankincense on Red Blood Cells of Alloxan Induced-Dia...
 

More from iosrphr_editor

Congenital Agenesis Of The Corpus Callosum With Intracerebral Lipoma And Fron...
Congenital Agenesis Of The Corpus Callosum With Intracerebral Lipoma And Fron...Congenital Agenesis Of The Corpus Callosum With Intracerebral Lipoma And Fron...
Congenital Agenesis Of The Corpus Callosum With Intracerebral Lipoma And Fron...iosrphr_editor
 
“Hemodynamic and recovery profile with Dexmedetomidine and Fentanyl in intrac...
“Hemodynamic and recovery profile with Dexmedetomidine and Fentanyl in intrac...“Hemodynamic and recovery profile with Dexmedetomidine and Fentanyl in intrac...
“Hemodynamic and recovery profile with Dexmedetomidine and Fentanyl in intrac...iosrphr_editor
 
Correlation of Estrogen and Progesterone Receptor expression in Breast Cancer
Correlation of Estrogen and Progesterone Receptor expression in Breast CancerCorrelation of Estrogen and Progesterone Receptor expression in Breast Cancer
Correlation of Estrogen and Progesterone Receptor expression in Breast Canceriosrphr_editor
 
Analytical Study of Urine Samples for Epidemiology of Urinary Tract Infection...
Analytical Study of Urine Samples for Epidemiology of Urinary Tract Infection...Analytical Study of Urine Samples for Epidemiology of Urinary Tract Infection...
Analytical Study of Urine Samples for Epidemiology of Urinary Tract Infection...iosrphr_editor
 
Chest sonography images in neonatal r.d.s. And proposed grading
Chest sonography images in neonatal r.d.s. And proposed gradingChest sonography images in neonatal r.d.s. And proposed grading
Chest sonography images in neonatal r.d.s. And proposed gradingiosrphr_editor
 
The Comprehensive Review on Fat Soluble Vitamins
The Comprehensive Review on Fat Soluble VitaminsThe Comprehensive Review on Fat Soluble Vitamins
The Comprehensive Review on Fat Soluble Vitaminsiosrphr_editor
 
Sulphasalazine Induced Toxic Epidermal Necrolysis A Case Report
Sulphasalazine Induced Toxic Epidermal Necrolysis A Case ReportSulphasalazine Induced Toxic Epidermal Necrolysis A Case Report
Sulphasalazine Induced Toxic Epidermal Necrolysis A Case Reportiosrphr_editor
 
Evaluation the efficacy of IVIgG in treatment of Hemolytic Disease of Newborn
Evaluation the efficacy of IVIgG in treatment of Hemolytic Disease of NewbornEvaluation the efficacy of IVIgG in treatment of Hemolytic Disease of Newborn
Evaluation the efficacy of IVIgG in treatment of Hemolytic Disease of Newborniosrphr_editor
 
FIBROLIPOMATOUS HAMARTOMA OF ULNAR NERVE: A RARE CASE REPORT.
FIBROLIPOMATOUS HAMARTOMA OF ULNAR NERVE: A RARE CASE REPORT.FIBROLIPOMATOUS HAMARTOMA OF ULNAR NERVE: A RARE CASE REPORT.
FIBROLIPOMATOUS HAMARTOMA OF ULNAR NERVE: A RARE CASE REPORT.iosrphr_editor
 
SELF MEDICATION PRACTICES FOR ORAL HEALTH PROBLEMS AMONG DENTAL PATIENTS IN B...
SELF MEDICATION PRACTICES FOR ORAL HEALTH PROBLEMS AMONG DENTAL PATIENTS IN B...SELF MEDICATION PRACTICES FOR ORAL HEALTH PROBLEMS AMONG DENTAL PATIENTS IN B...
SELF MEDICATION PRACTICES FOR ORAL HEALTH PROBLEMS AMONG DENTAL PATIENTS IN B...iosrphr_editor
 
Clinico-haematological Profile of Falciparum Malaria in a Rural Hospital of T...
Clinico-haematological Profile of Falciparum Malaria in a Rural Hospital of T...Clinico-haematological Profile of Falciparum Malaria in a Rural Hospital of T...
Clinico-haematological Profile of Falciparum Malaria in a Rural Hospital of T...iosrphr_editor
 
Indonesian Wild Ginger (Zingiber sp) Extract: Antibacterial Activity against ...
Indonesian Wild Ginger (Zingiber sp) Extract: Antibacterial Activity against ...Indonesian Wild Ginger (Zingiber sp) Extract: Antibacterial Activity against ...
Indonesian Wild Ginger (Zingiber sp) Extract: Antibacterial Activity against ...iosrphr_editor
 
A case of allergy and food sensitivity: the nasunin, natural color of eggplant
A case of allergy and food sensitivity: the nasunin, natural color of eggplantA case of allergy and food sensitivity: the nasunin, natural color of eggplant
A case of allergy and food sensitivity: the nasunin, natural color of eggplantiosrphr_editor
 
Complete NMR Assignment of MogrosidesII A2, II E andIII A1Isolated from Luo H...
Complete NMR Assignment of MogrosidesII A2, II E andIII A1Isolated from Luo H...Complete NMR Assignment of MogrosidesII A2, II E andIII A1Isolated from Luo H...
Complete NMR Assignment of MogrosidesII A2, II E andIII A1Isolated from Luo H...iosrphr_editor
 
Nanoemulsion and Nanoemulgel as a Topical Formulation
Nanoemulsion and Nanoemulgel as a Topical FormulationNanoemulsion and Nanoemulgel as a Topical Formulation
Nanoemulsion and Nanoemulgel as a Topical Formulationiosrphr_editor
 
Pharmacokinetics of High-Dose Methotrexate in Egyptian Children with Acute Ly...
Pharmacokinetics of High-Dose Methotrexate in Egyptian Children with Acute Ly...Pharmacokinetics of High-Dose Methotrexate in Egyptian Children with Acute Ly...
Pharmacokinetics of High-Dose Methotrexate in Egyptian Children with Acute Ly...iosrphr_editor
 
Epidemiology of Tuberculosis (TB) in Albania 1998-2009
Epidemiology of Tuberculosis (TB) in Albania 1998-2009Epidemiology of Tuberculosis (TB) in Albania 1998-2009
Epidemiology of Tuberculosis (TB) in Albania 1998-2009iosrphr_editor
 
Total Phenol and Antioxidant from Seed and Peel of Ripe and Unripe of Indones...
Total Phenol and Antioxidant from Seed and Peel of Ripe and Unripe of Indones...Total Phenol and Antioxidant from Seed and Peel of Ripe and Unripe of Indones...
Total Phenol and Antioxidant from Seed and Peel of Ripe and Unripe of Indones...iosrphr_editor
 
A Review on Step-by-Step Analytical Method Validation
A Review on Step-by-Step Analytical Method ValidationA Review on Step-by-Step Analytical Method Validation
A Review on Step-by-Step Analytical Method Validationiosrphr_editor
 
A Cross Sectional Study of Ethnic Differences in Occurrence and Severity of A...
A Cross Sectional Study of Ethnic Differences in Occurrence and Severity of A...A Cross Sectional Study of Ethnic Differences in Occurrence and Severity of A...
A Cross Sectional Study of Ethnic Differences in Occurrence and Severity of A...iosrphr_editor
 

More from iosrphr_editor (20)

Congenital Agenesis Of The Corpus Callosum With Intracerebral Lipoma And Fron...
Congenital Agenesis Of The Corpus Callosum With Intracerebral Lipoma And Fron...Congenital Agenesis Of The Corpus Callosum With Intracerebral Lipoma And Fron...
Congenital Agenesis Of The Corpus Callosum With Intracerebral Lipoma And Fron...
 
“Hemodynamic and recovery profile with Dexmedetomidine and Fentanyl in intrac...
“Hemodynamic and recovery profile with Dexmedetomidine and Fentanyl in intrac...“Hemodynamic and recovery profile with Dexmedetomidine and Fentanyl in intrac...
“Hemodynamic and recovery profile with Dexmedetomidine and Fentanyl in intrac...
 
Correlation of Estrogen and Progesterone Receptor expression in Breast Cancer
Correlation of Estrogen and Progesterone Receptor expression in Breast CancerCorrelation of Estrogen and Progesterone Receptor expression in Breast Cancer
Correlation of Estrogen and Progesterone Receptor expression in Breast Cancer
 
Analytical Study of Urine Samples for Epidemiology of Urinary Tract Infection...
Analytical Study of Urine Samples for Epidemiology of Urinary Tract Infection...Analytical Study of Urine Samples for Epidemiology of Urinary Tract Infection...
Analytical Study of Urine Samples for Epidemiology of Urinary Tract Infection...
 
Chest sonography images in neonatal r.d.s. And proposed grading
Chest sonography images in neonatal r.d.s. And proposed gradingChest sonography images in neonatal r.d.s. And proposed grading
Chest sonography images in neonatal r.d.s. And proposed grading
 
The Comprehensive Review on Fat Soluble Vitamins
The Comprehensive Review on Fat Soluble VitaminsThe Comprehensive Review on Fat Soluble Vitamins
The Comprehensive Review on Fat Soluble Vitamins
 
Sulphasalazine Induced Toxic Epidermal Necrolysis A Case Report
Sulphasalazine Induced Toxic Epidermal Necrolysis A Case ReportSulphasalazine Induced Toxic Epidermal Necrolysis A Case Report
Sulphasalazine Induced Toxic Epidermal Necrolysis A Case Report
 
Evaluation the efficacy of IVIgG in treatment of Hemolytic Disease of Newborn
Evaluation the efficacy of IVIgG in treatment of Hemolytic Disease of NewbornEvaluation the efficacy of IVIgG in treatment of Hemolytic Disease of Newborn
Evaluation the efficacy of IVIgG in treatment of Hemolytic Disease of Newborn
 
FIBROLIPOMATOUS HAMARTOMA OF ULNAR NERVE: A RARE CASE REPORT.
FIBROLIPOMATOUS HAMARTOMA OF ULNAR NERVE: A RARE CASE REPORT.FIBROLIPOMATOUS HAMARTOMA OF ULNAR NERVE: A RARE CASE REPORT.
FIBROLIPOMATOUS HAMARTOMA OF ULNAR NERVE: A RARE CASE REPORT.
 
SELF MEDICATION PRACTICES FOR ORAL HEALTH PROBLEMS AMONG DENTAL PATIENTS IN B...
SELF MEDICATION PRACTICES FOR ORAL HEALTH PROBLEMS AMONG DENTAL PATIENTS IN B...SELF MEDICATION PRACTICES FOR ORAL HEALTH PROBLEMS AMONG DENTAL PATIENTS IN B...
SELF MEDICATION PRACTICES FOR ORAL HEALTH PROBLEMS AMONG DENTAL PATIENTS IN B...
 
Clinico-haematological Profile of Falciparum Malaria in a Rural Hospital of T...
Clinico-haematological Profile of Falciparum Malaria in a Rural Hospital of T...Clinico-haematological Profile of Falciparum Malaria in a Rural Hospital of T...
Clinico-haematological Profile of Falciparum Malaria in a Rural Hospital of T...
 
Indonesian Wild Ginger (Zingiber sp) Extract: Antibacterial Activity against ...
Indonesian Wild Ginger (Zingiber sp) Extract: Antibacterial Activity against ...Indonesian Wild Ginger (Zingiber sp) Extract: Antibacterial Activity against ...
Indonesian Wild Ginger (Zingiber sp) Extract: Antibacterial Activity against ...
 
A case of allergy and food sensitivity: the nasunin, natural color of eggplant
A case of allergy and food sensitivity: the nasunin, natural color of eggplantA case of allergy and food sensitivity: the nasunin, natural color of eggplant
A case of allergy and food sensitivity: the nasunin, natural color of eggplant
 
Complete NMR Assignment of MogrosidesII A2, II E andIII A1Isolated from Luo H...
Complete NMR Assignment of MogrosidesII A2, II E andIII A1Isolated from Luo H...Complete NMR Assignment of MogrosidesII A2, II E andIII A1Isolated from Luo H...
Complete NMR Assignment of MogrosidesII A2, II E andIII A1Isolated from Luo H...
 
Nanoemulsion and Nanoemulgel as a Topical Formulation
Nanoemulsion and Nanoemulgel as a Topical FormulationNanoemulsion and Nanoemulgel as a Topical Formulation
Nanoemulsion and Nanoemulgel as a Topical Formulation
 
Pharmacokinetics of High-Dose Methotrexate in Egyptian Children with Acute Ly...
Pharmacokinetics of High-Dose Methotrexate in Egyptian Children with Acute Ly...Pharmacokinetics of High-Dose Methotrexate in Egyptian Children with Acute Ly...
Pharmacokinetics of High-Dose Methotrexate in Egyptian Children with Acute Ly...
 
Epidemiology of Tuberculosis (TB) in Albania 1998-2009
Epidemiology of Tuberculosis (TB) in Albania 1998-2009Epidemiology of Tuberculosis (TB) in Albania 1998-2009
Epidemiology of Tuberculosis (TB) in Albania 1998-2009
 
Total Phenol and Antioxidant from Seed and Peel of Ripe and Unripe of Indones...
Total Phenol and Antioxidant from Seed and Peel of Ripe and Unripe of Indones...Total Phenol and Antioxidant from Seed and Peel of Ripe and Unripe of Indones...
Total Phenol and Antioxidant from Seed and Peel of Ripe and Unripe of Indones...
 
A Review on Step-by-Step Analytical Method Validation
A Review on Step-by-Step Analytical Method ValidationA Review on Step-by-Step Analytical Method Validation
A Review on Step-by-Step Analytical Method Validation
 
A Cross Sectional Study of Ethnic Differences in Occurrence and Severity of A...
A Cross Sectional Study of Ethnic Differences in Occurrence and Severity of A...A Cross Sectional Study of Ethnic Differences in Occurrence and Severity of A...
A Cross Sectional Study of Ethnic Differences in Occurrence and Severity of A...
 

IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research paper publishing, where to publish research paper, journal publishing, how to publish research paper, Call for research paper, international journal, publishing a paper, call fo

  • 1. IOSR Journal of Pharmacy (IOSRPHR) ISSN: 2250-3013, Vol. 2, Issue 4 (July2012), PP 49-57 www.iosrphr.org and antihyperglycemia effects of resvertrol and its derivative on alloxan diabetic rabbits Essam F.Al-Jumaily1 Redha I. Al-Bayati2 and Zuhair A. Shafiq1 1 Biotechnology Dept. Genetic Engineering and Biotechnology Institute for postgraduate studies –Baghdad University –Baghdad , Iraq 2 Chemistry Dept. Science College, Al-Msairitey University, Baghdad, Iraq Abstract: Background and objective:Resveratrol is a non flavonoid polyphenol ( Vitis vinifera) posses three phenolic hydroxyl group and shown to its biological effects. The derivations of resveratrol associated with the available oral hypoglycermic agents for treatment of diabetes mellutes type 2.. Materials and methods: The study has also employed an in vivo evaluation of resveratrol and its derivative in female rabbits at concentrations ( 1 mg / kg) given orally for 42 days after inducing diabetes mellitus type 2 by alloxan (100mg/1kg body weight). The serum was isolated from heart blood for the biochemical tests, including Glucose, Total protein Albumin and Insulin. At day 42 the animal was killed and the liver and pancreas were kept in 10% formalin for preparation of histopathological sections. Results: Statistical analysis showed a significant decrease in Glucose, total protein , Creatinine of serum blood levels on treated rabbits p > 0.05, However resveratrol and its derivative treated rabbits showed statistically significant increase in Insulin blood serum levels p > 0.05. Examination of the liver tissue confirmed potential histopathological effects for resveratrol , while derivative has normal appearance in a dose dependent manner. Examination of the pancreas tissue confirmed potential histopathological effects for resveratrol, and its derivatives has normal appearance in a dose dependent manner. The derivatives compound showed a significant differences than the other compounds extract regarding the serum activity of Insulin and hisopathological changes especially in pancreas. Keywords––Reveratrol (non flavonoid polyphenol); hypoglycermic; Vitis vinifera ; hisopathological; glbcimaide I. INTRODUCTION Resveratrol (3,5,4 – trihydroxy stilbene), is a non Flavonoid polyphenol and it has three phenolic hydroxyl groups and shown to have its biological effects [1]. Phenolic and polyphenolic compounds, possess an aromatic ring bearing one or more hydroxyl substituents [2]. These compounds are phytoalexins and have antidiabeteic properties [3]. Resveratrol may offer benefits in preventing or managing conditions associated with high blood sugar [4] . The derivatives of resveratrol associated with the available oral hypoglycemic agents for the treatment of diabetes mellitus Epsilon-vinifera a resveratrol dimer, ,Piceatanol an active metabolic of resveratrol found in red wine , Piceid a resveratrol glucoside , Trans – diptoindonesin B a resveratrol trimer [5]. These plants produce trans-resveratrol to protect themselves after exposure to ultraviolet radiation, ozone or certain biologic agents. It functions as a ribonucleotide reductase inhibitor [6].The effects of resveratrol are currently a topic of numerous animal and human studies. Its effects on the lifespan of many model organisms remain controversial with uncertain effects in fruit flies, nematode worms and short-lived fish [7]. In the only positive human trial, extremely high doses (3–5 g) of resveratrol, in a proprietary formulation designed to enhance its bioavailability, significantly lowered blood sugar. Despite mainstream press alleging resveratrol's anti-aging effects, there is no accepted data to form a scientific basis for the application of these claims to mammals [8]. II. MATERIALS AND METHODS 2.1. Plant materials Local black grapes cultivated Iraqi were collected from the local market and classified as Vitis vinifera by the herbarium of the Biology Department, College of Science, Baghdad University . The grape skin extract was prepared; all steps were done away from direct light and extensive stress that led to oxidation of the plant 49
  • 2. Antidiabetic and antihyperglycemica effects of resvertrol and its derivative….. extract. About 500 grams of fresh skin grapes was shaken with 2.5 litters' 99.9% ethyl acetate in cool dark place for 72 hours. The extract was filtered and the filtrate was dried at 30-40°C by a rotary evaporator to get 1/10 (one tenth) its original volume to be stored at –20°C till the followings steps. The following steps were followed for the isolation of resveratrol: 2.2. Preparation of Resveratrol Derivative 5-(4-(4-(2-(benzo [d] thiazol-2-yl) hydrazinyl) butanoyloxy)styryl)-1,3-phenylene bis(4-(2-(benzo[d]thiazol-2- yl) hydrazinyl)butanoate) S N HN H N O O N HN H N S O O S O NH NH N O 1.6gm ( 0.003 mole) of compound (2) was dissolved in 50ml of absolute ethanol then 1.58g 0.0096 moles of 2- Mercptobenzothiazole then reflux for 8h. The solvent was removed and the precipitates was filtrated and dried [9]. 2.3. Induction of Diabetes 5,6-dioxyuracil,was used which marketing name (alloxan) and whose diabetogenic property is established with rabbits. The alloxan injection depends on the weight of the animal: 70 mg of alloxan dissolved in 3 ml of distilled water for 1 kg of rabbit weight. The alloxan solution is injected through the marginal vein of the ear after fasted for 24 h before injection. This single dose of alloxan produced type 1 diabetes having fasting blood sugar level of 155±10.71 mg/dl after10 days of injection of alloxan and this diabetic state was maintained throughout the`1 duration of the experiment .Therefore, the health status of rabbits was closely monitored until the hyperglycemia appeared and was detected weekly by determination of blood sugar quantity . 2.4. Purified Resveratrol and its Derivative Dilutions Pure resveratrol 100 mg was dissolved in 100ml PBS and 0.1ml DMSO as organic solvent for dissolving the substance. The stock was kept in a dark container at –20°C after sterilization with 0.22μm Millipore filter. Resveratrol derivative 50mg were dissolved in 0.05ml DMSO and complete the volume to 50 ml with PBS. Then it was sterilized and kept in a dark container at –20°C. 2.5. Experimental Design: Fifteen adult female rabbits were randomly divided into four groups and treated daily as follows for six weeks: The rabbits in first group received regular standard diet, tap water and served as control. After feeding them for about 1 week, their body weights and fasting blood sugar levels were taken. Other parameters which included levels were also taken and recorded. Group 2: Diabetic rabbits without treatment At the expiration of 1 week, alloxan was subject into the control group and they formed group (2) rabbits. The rabbits were confirmed diabetic after estimation of their fasting blood sugar level, 2weeks after injection of alloxan. A rabbit was considered to be diabetic if it had a fasting blood sugar where level > 115 mg/dl. Other parameters were also taken and recorded. Group 3: Diabetic rabbits after treatment with glbcimaide At the expiration of 2 weeks of induction of diabetes into the rabbits of group (2), they were force fed with glbcimaide 0.05mg orally for a period of 6 weeks and, thus they formed the rabbits of group 3. At the end of 4 weeks their fasting blood glucose levels was estimated and recorded. Other parameters were also taken and recorded. Group 4: Diabetic rabbits after treatment with Resveratrol At the expiration of 2 weeks of induction of diabetes into the rabbits of group (2), they were force fed with resveratrol 1mg/ml orally for a period of 6 weeks and, thus they formed the rabbits of group 4. At the end of 4 weeks their fasting blood glucose levels were estimated and recorded. Other parameters were also taken and recorded. Group 5: Diabetic rabbits after treatment with Resveratrol derivative 50
  • 3. Antidiabetic and antihyperglycemica effects of resvertrol and its derivative….. At the expiration of 2 weeks of induction of diabetes into the rabbits of group (2), they were force fed with resveratrol derivative 1mg/ml orally for a period of 6 weeks and they thus formed the rabbits of group (3). At the end of 4 weeks their fasting blood glucose levels was estimated and recorded. Other parameters were also taken and recorded. 2.6. Biochemical Estimation: The fasting blood glucose levels was estimated according to (Young et al., 2000)[10] ; Total protein (Young et al., 2000 )[10]; serum triglyceride (Young et al.,2000)[10]; serum creatinine ( Young et al. 2000) [10] ; serum insulin ( Young et al.,2000)[10]. 2.7. Histopathological studies: Tissue samples from liver & pancreas after delivery were prepared for histopathological studies according to the methods of Junqueira et al.[11]. 2.8. Statistical Analysis Data were analyzed by using the SPSS package programmed. Multiple range test was used to detect the significant differences [12].The method which was used to measure the significances at level 0.05 or 0.01 was taken from [13]. III. RESULTS Table (1) shows the diabetic rabbits treated with the resveratrol and its derivative decreased significantly lower (p<0.05) in comparison with the control antidiabetic group after 3, 4 and 6 weeks of the injection of the alloxan.For the rabbits in the groups treated with resveratrol and its derivatives, the food and water intake was decreased and the volume of urine decreased in comparison with the rabbits in the control antidiabetic groups. It can therefore be concluded that the preliminary study shows that the resveratrol and its derivative decreases the serum glucose level in diabetic rabbits. The resveratrol derivative shows significant value after one week of treatment 109.0mg/dL±2.5 in comparison with resveratrol had normal values after 6 weeks. Table (1): The effect of resveratrol and its derivative on serum glucose concentration (mg/dL) of rabbits' groups with weeks. Groups Treatment periods WK0 PT Wk1 Wk2 Wk3 Wk4 Wk5 Wk6 C 98± 98± 92.0±0. 96± 102± 101± 100± 99± 2a 2e 5e 2e 1e 0.5d 0.5d 3c A A A A A A A A D 92± 247± 275± 255± 276± 267± 270± 271± 2.0a 3.5d 2.5a 2.5a 3a 3.5a 3.5a 2a C B A AB A AB A A DI 96± 250± 240± 233± 247± 244± 230± 229± 1.50a C 5d 5b 1.5a 3.5b 2.0b 1.5b 4.5b A AB AB AB AB AB B DR 102± 263± 180± 177± 160± 150± 120± 100± 0.5a 1.5d 2.5c 0.5b 3c 2.5c 0.25c 0.5c A A B B BC C D E DRD 93± 289.0± 109.0± 100± 93± 85± 72± 66± 3.0a 3c 2.5e B 0.05d 1.5e 1.5e 1e 3e BC A BC BC CD D D Each value represents mean  SD Values with non-identical superscripted (a, b, c, d, e& f) are considered as significantly different (p<0.05) among the same group of rabbits, Values with non-identical superscripted (A, B, C, D, E& F) are considered as significantly different (p<0.05) among the different groups of rabbits, N( number of animals)=3. C=Control; D=Diabetic; DI=Diabetic after treated with glbcimide; DR= Diabetic after treated with resveratrol;DRD= Diabetic after treated with its derivative WK0=Zero week; PT=Pretreatment; WK1=First week; WK2=Second week; WK3=Third week; WK4=Fourth week; WK5=Fifth week; WK6=Sixth week. Table (2) show significant increase in the level of Serum total protein which is a sign of renal dysfunction in the diabetic rabbits when compared to control rabbits. The diabetic rabbits treated with the resveratrol and its derivative showed significant decrease in levels of Serum Total protein (p<0.05) . Resvertrol 51
  • 4. Antidiabetic and antihyperglycemica effects of resvertrol and its derivative….. and its derivative show significant value after one week of treatment 6.6±0.03 and 7.1±0.02 respectively. In diabetes, protein catabolism increases due to deficiency of carbohydrate-derived energy in connection with low- serum insulin. Table (2): The effect of resveratrol and their derivatives on serum total protein concentration mg/dL of rabbits' groups with weeks. Groups Treatment periods WK0 PT Wk1 Wk2 Wk3 Wk4 Wk5 Wk6 C 6.9± 7.7± 7.1± 7.1± 7.1±0.0 6.9± 7± 7.1± 0.03 a 0.07 b 0.02 a A 0.02 a 2a A 0.03 a 0.05 b 0.02 b A A A A A A D 7.1± 5.1± 5.2± 5± 0.05 5± 5± 5.3± 5 ± 0.03 a 0.05e E 0.03 f E e 0.05e 0.05 e 0.01 f 0.05 e B E E E E E DI 7.0± 5.3± 7.1± 7.2± 7.2± 7.1± 6.9± 7 ± 0. 02 a 0.08 e F 0.02fdc 0.06 b 0.06b A 0.02 b 0.03 a 0.023 b A A A B D A DR 7.1± 5.3± 6.6± 6.8± 6.8± 7.2± 6.8± 6.8 ± 0. 02a 0.05e 0.03 dc 0.10 c B 0.10 c B 0.06ba 0.10 b 0.10b B B F CB A C DRD 7.7 ± 5.4± 7.1± 7.2± 7.2± 7.2± 7.4± 7.3± 0.07a 0.1 e 0.02dc 0.06b 0.06 b B 0.06 b 0.02 a 0.02 a B C D A B B A Each value represent mean + SD Values with non-identical superscripted (a, b, c, d, e& f) are considered as significantly different (p<0.05) among the same group of rabbits, Values with non-identical superscripted (A, B, C, D, E& F) are considered as significantly different (p<0.05) among the different groups of rabbits, N( number of animals)=3. C=Control ;D=Diabetic; I=Diabetic after treated with glbcimide;DR= Diabetic after treated with resveratrol;DRD= Diabetic after treated with derivative The results showed significant increase in the level of serum albumin which is asign of renal dysfunction in the diabetic rabbits when compared with control rabbits (Table 3). The diabetic rabbits treated with resveratrol and their derivatives decrease levels of Serum Albumin significantly (p<0.05). The results showed significant decrease in the level of serum urea of rabbits treated with resveratrol and its derivative (p<0.05). Resveratrol and its derivative show significant value after one week of treatment 3.7±0.1 and 4.2±0.05, respectively. 52
  • 5. Antidiabetic and antihyperglycemica effects of resvertrol and its derivative….. Table (3): The effect of resveratrol and its derivative on serum albumin concentration (mg/dL) of Rabbits' groups with weeks. Groups Treatment periods WK0 PT Wk1 Wk2 Wk3 Wk4 Wk5 Wk6 C 4.4± 4.3± 4.3± 4.2± 4.4± 4.2± 4.2± 4.3± 0.1 a 0.07 a 0.07 a 0.05 a 0.10 a 0.05 a 0.05 a 0.08 a A A A A A A A A D 4.2± 2.9± 2.9± 2.6± 2.7± 2.9± 2.9± 2.7± 0.1 a 0.15 b 0.22b 0.15b 0.17 b 0.22 b 0.1 0.18 b A B B B B B B B DI 4.3 ± 3.0± 3.9± 4.5± 4.4± 4.2± 4.4± 4.1 0.09 a A 0.15 b B 0.23a 0.25 a 0.20 a 0.04 a 0.1 a ±0.02a A A A A A A DR 4.2± 3.1± 3.7± 3.8± 4.0± 4.4± 4.4± 4.2± 0.05 a A 0.03 b B 0.1a 0.20a 0.10 a 0.2 a 0.1 a 0.05 a A A A A A A DRD 4.2 ± 2.9± 4.2± 4.3± 4.3± 4.4± 4.4± 4.3± 0.06 a A 0.21 b B 0.05 a 0.08 a 0.07 a 0.02 a 0.06 a 0.10 a A A A A A A Each value represent mean  SD Values with non-identical superscripted (a, b, c, d, e& f) are considered as significantly different (p<0.05) among the same group of rabbits, Values with non-identical superscripted (A, B, C, D, E& F) are considered as significantly different (p<0.05) among the different groups of rabbits, N( number of animals)=3. C=Control ;D=Diabetic; I=Diabetic after treated with glbcimide;DR= Diabetic after treated with resveratrol ;DRD= Diabetic after treated with derivative. WK0=Zero week; PT=Pretreatment; WK1=First week; WK2=Second week; WK3=Third week; WK4=Fourth week; WK5=Fifth week; WK6=Sixth week. The clinical significance of the creatinine level in plasma or serum is usually determined in conjugation with the plasma urea level since there is an increase in both levels in postrenal azotemia, while the creatinine clearance (CC), or urine levels, are diminished. The diabetic rabbits treated with the resveratrol and its derivative showed significant decreased levels of serum creatinine (p<0.05). This further shows the ability of the resveratrol and its derivative in treating diabetes associated renal complications and also supports the usage of these compounds for kidney diseases. Resveratrol derivative show significant value after 2 weeks of treatment 1.1mg /dL± 0.03. and resveratrol failed to reach to normal value as shown in table (4). Serum urea and creatinine levels increased significantly in the diabetic control group with respect to the control group. The levels of these parameters restored towards the control level after administration of resveratrol and its derivative to the diabetic rabbits.This has been indicated here by high levels of serum urea and creatinine. High-serum creatinine level is also the sign of muscle wastage. 53
  • 6. Antidiabetic and antihyperglycemica effects of resvertrol and its derivative….. Table (4): The effect of resveratrol and their derivatives on serum creatinine concentration mg/dL of rabbits' groups with weeks. Groups Treatment periods WK0 PT Wk1 Wk2 Wk3 Wk4 Wk5 Wk6 C 1± 0.9± 1± 1± 0.9± 0.9± 1.1± 0.9± 0.02a 0.024c 0.02d 0.02f 0.02f 0.024f 0.023d 0.24a A A A A A A A A D 1.1± 3.2± 3.6± 3.6± 3.9± 3.9± 3.8± 3.9 ± 0.02a C 0.15a 0.16a 0.16a 0.2 a 0.2 a 0.35a 0.2a A A A A A A DI 0.9± 2.8± 3.2± 3.0± 3.1± 2.7± 2.2± 2.3 ± 0.24a D 0.12b 0.15b 0.14b 0.15b 0.14a 0.17b 0.11b C B A A A B C DR 1.1± 3.0± 3.0± 2.9± 2.8± 2.3± 2.3± 2.2 ± 0.023a 0.14ab 0.14b 0.10b 0.12c 0.15b 0.15b 0.1b C A A B BC C D D DRD 1.0 ± 3.3± 1.2± 1.1± 1.1± 1.0± 1.0± 1.0± 0.02a 0.24a 0.02d 0.03ef 0.03f 0.05f 0.03d 0.02d B A B B B B B B Each value represent mean + SD Values with non-identical superscripted (a, b, c, d, e& f) are considered as significantly different (p<0.05) among the same group of rabbits, Values with non-identical superscripted (A, B, C, D, E& F) are considered as significantly different (p<0.05) among the different groups of rabbits. C=Control ;D=Diabetic; I=Diabetic after treated with glbcimide;DR= Diabetic after treated with resveratrol;DRD= Diabetic after treated with derivative. The results showed significant increase in the level of serum insulin of rabbits treated with resveratrol and its derivative significantly (p<0.05). Derivative show significant value after one week of treatment 0.8  mole/L±0.02 respectively shown in table (5). Many herbal plants' extracts was able to recover the protein metabolic disorders possibly by stimulating the existing βcells and or by regenerating βcells like other plant products. Since insulin inhibits adipose tissue hormone sensitive lipase and reduces lipolysis, the aqueous-methanolic extract of S mahagoni seed may correct the above mentioned disorders by mimicking insulin action [14]. Table (5): The effect of resveratrol and its derivative on serum Insulin concentration ( mole/L) of rabbits' groups with weeks. Groups Treatment periods WK0 PT Wk1 Wk2 Wk3 Wk4 Wk5 Wk6 C 0.8± 0.02a 0.9± 1± 2.02d 1± 0.02f 0.9± 0.9± 1.1± 0.9± A 0.024c C C 0.02 f B 0.024f B 0.023d 0.24a B B C D 1.1± 0.02a 0.02±0. 0.03± 0.03± 0.03± 0.03± 0.03± 0.03 ± B 15e 0.16e 0.16e A 0.2e 0.2 e 0.35e 0.2e A A A A A A DI 0.9 ± 0.02±0. 0.3± 0.3± 0.3± 0.27± 0.22± 0.23±0.1 0. 24a 12e 0.15e 0.14e A 0.15d 0.14d 0.17d 1d A A A A A A A DR 1.1± 0.02±0. 0.3± 0.32± 0.38± 0.38± 0.4± 0.42 ± 0.023a BA 14e A 0.14e 0.10d A 0.12d 0.15d 0.15d 0.1c A A A A A DRD 1.0 ± 0.03± 0.8± 0.9± 1± 1.2± 1.3± 1.35±0.0 0.02a 0.24e A 0.02cd 0.03bc A 0.03ab 0.05a 0.03a 2a A B A A A A 54
  • 7. Antidiabetic and antihyperglycemica effects of resvertrol and its derivative….. Each value represent mean + SD. Values with non-identical superscripted (a, b, c, d, e& f) are considered as significantly different (p<0.05) among the same group of rabbits, Values with non-identical superscripted (A, B, C, D, E& F) are considered as significantly different (p<0.05) among the different groups of rabbits, N( number of animals)=3. C=Control ;D=Diabetic; I=Diabetic after treated with glbcimide;DR= Diabetic after treated with resveratrol;DRD= Diabetic after treated with derivative. WK0=Zero week; PT=Pretreatment; WK1=First week; WK2=Second week; WK3=Third week; WK4=Fourth week; WK5=Fifth week; WK6=Sixth week. 3.1. Examinations of the Liver and Pancreas Sections These rabbits were excluded from the study. Necropsy was performed after euthanasia, or death in one rabbit, in the individual group and in one normal rabbit. The light microscopic examination by specific staining of pancreatic beta cells in control tissues showed normal appearance of islet of langerhans which was not observed in diabetic pancreas figure(1) and (2) respectively. The pancreas was examined mainly, especially the pancreatic islets. Pancreatic section of rabbits treated with resveratrol and its derivative showed no notable histological changes. Secretion from remnant pancreatic beta cells which in turn enhances the glucose utilization by peripheral tissue of diabetic rabbits. The histopathology examination showed that pancreatic islets disappeared and that the exocrine tissue remained relatively inaffected; any remaining islets were considerably atrophied compared with the normal pancreas. In the pancreatic section of rabbits treated with derivative no notable histological changes appear figures (3) and (4). Islet of langerhans Necrosis Degenerative changes Islet of langerhans Figure (1) Section of control non-diabetic pancreas Figure (2) Section of diabetic pancreas Rabbit with normal looking appearance of exocrine rabbit shows degenerative changes & of Islet of langerhans (X200) (H&E). necrosis & endocrine (Islet of langerhans) (X200) (H&E). Islet of langerhans Islet of langerhans Degenerative Necrosis Figure: (3) Section of diabetic pancreas rabbit Figure :(4) Section of diabetic pancreas rabbit 55
  • 8. Antidiabetic and antihyperglycemica effects of resvertrol and its derivative….. after treated with resveratriol shows degenerative after treated with derivative shows normal & necrosis of islet of langerhans (X200) (H&E). looking of islet of langerhans (X200) (H&E) IV. DISCUSSION Thus, the significant anti-diabetic effect of resveratrol and its derivative may be due to the presence of phenolics and or their synergistic properties. This may be due to the presence of hydroxyl as shown in resveratrol and heterocyclic amide rings as shown in its derivative [15]. These results agreed with the study of diabetes induced by Streptozotocin resulted in a significant elevation in blood glucose level in comparison with the control group after administration of aqueous methanolic (2: 3) extract of S. mahagoni seed to the diabetic rabbits for 21 days [14]. A significant reduction in blood glucose level was noted this was close to the control level. The results also agreed with the study of the protective effect of plant compound idopyranose isolated from the plant, Vitex negundo evaluated against streptozotocin-induced diabetics. Wister rats showed significant reduction in blood glucose [16]. These findings indirectly show that the blood glucose levels in the groups treated with resveratrol and its derivative may have been lowered not by insulin but by derivatives; this is because almost all of the pancreatic islet beta cells were destroyed and therefore resulted in insulin deficiency [17]. The anti- hyperglycemic activity of resveratrol and its derivative probably caused by stimulation of insulin have also been reported to have a similar effect as observed in the present investigation. Significant increase in the lymphocytes induced by resveratrol and its derivative reflects possible imunomodulatory effects alloxan-induced diabetic rats. It is well known that certain polyphenols and their derivatives exhibit hypoglycemic activity and are known for their ability of beta-cell regeneration of pancreas. It can therefore be concluded that the preliminary study shows that the resveratrol and its derivative decreases the blood glucose level in diabetic rabbits. Correction of oxidative injury which is associated with diabetes is another possibility of the recovery in glycemic disorders. Resveratrol and their derivatives are able to recover the protein metabolic disorders possibly by stimulating the existing β-cells and or by regenerating βcells like other plant products [18]. V. CONCLUSION: The results suggested the resveratrol and its derivative are safe and potent hypoglycemic agent which is capable for normalizing other biochemical and hematological abnormalities associated with diabetes mellitus type 2. REFERENCES [1]. F.A.Tomas- Barberan and R.J.Robins. Phytochemistry of fruit and vegetables. (Clarendon press- Oxford. New York. 1997). [2]. J.B. Harborne. Phytochemical Methods.( Chapman and Hall. London. 1984). [3]. J.Bruneton, Pharmacognosy phytochemistry Medicinal plants ,( 2nd edition , TEC 8 DOC .Paris, France) 1999. [4]. L.Barclay, . Growing evidence links, resveratrol to extended life span. Life Extension Magazine , 13, 2007, 1-8. [5]. Y.D.Kim, K.G.Park, Y.S.Lee, Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP. Diabetes. 57(,2) : 2008, 306–314. [6]. T.Pussa T, J.Floren, P.Huldhepp and A. Raal. Survery of grape wine vitis vinefera sternpoly phenols by liquid chroma tography – Diode array detection tandem mass , spectrometry. J. Agric. Food chem, (54): 2006. 7488-7494 . [7]. T.M.Bass, D.Weinkove, K.Houthoofd, D.Gems, L. Partridge, Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans. Mechanisms of Ageing and Development .(128) .10: 2007, 546–52. [8]. B.D.Gehm, J.M.McAndrews, P.Y.Chien, J.L.Jameson, Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor . Proceedings of the National Academy of Sciences of the United States of America 94, (25) 1997 : 14138–43. [9]. W.W. Stephen ; N.H.J. Kelly. Organic Chemistry. 2006, 71, 1080 [10]. D.S. Young , et al; Effect of drugs on clinical laboratory tests,5th ed, AACC Press,(2000). [11]. L.C. Junqueira, and J.Carneiro Basic Histology, tenth edition. The McGraw-Hill Companies, USA.(2003). [12]. D.Duncan , (1955). Multiple range and Multiple F-test Biometrics -11 :1-42. [13]. R.G.Steel, and J.H.Torrie ,(1980) Principles and procedures of statistics.,2 nd.ed,McGraw.Hill Book Co .New York , Ny. [14]. I. Debasis De, K. Chatterjee, A. K. Ali, B. Tushar Kanti and G.Debidas, Antidiabetic Potentiality of the Aqueous-Methanolic Extract of Seed of Swieteniamahagoni (L.) Jacq. in Streptozotocin-Induce DiabeticMale Albino Rat: A Correlative and Evidence-Based Approach with Antioxidative and Antihyperlipidemic Activities. Hindawi Publishing Corporation Evidence- Based Complementary and Alternative Medicine, Article ID 892807, 2011, 11. [15]. J.H.Black and J.M.Beale ,Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry. (Lippincott Willamsand Wilkins. London. 2004). 56
  • 9. Antidiabetic and antihyperglycemica effects of resvertrol and its derivative….. [16]. R. Manikandan, R. Sundaram, P. Srinivasan, S. Beulaja and C. Arulvasu. Isolation of 1, 2 di-substituted idopyranose from Vitex negundo and its effects on diabetic ratsInternational J. of Pharmaceuticals Analysis, 1, 2, 2009, pp-4-10. [17]. C.M.Cam, H.G.Cros,J.J.Serrano,R.Lazaro,H.J.McNeill.In vivo antidiabetic actions of naglivan,an organic vanadyl compound instreptozotocin-induced diabetes. Diabetes Res. and Clin. Practice,( 20), 2003, 111-121. [18]. M. Kaleem, P. Medha, Q.U. Ahmed, M. Asif, B. Bano, Beneficial effects of Annona squamosa extract in streptozotocin-induced diabetic rats Singapore Med J . 49,(10), 2008 : 800 . 57