EFFECTS OF NATURAL PRODUCTS ON DYSLIPOPROTEINEMIA AND OXIDATIVE
STRESS IN ALLOXAN INDUCED DIABETIC RATS
Presentation for PhD Medical Biochemistry
Chattrapati Sahu Ji Maharaj University,
KanpurVishnu Kumar
Supervisor
Dr. R.K. SinghDr. R.K. SinghSenior Prof. & Head,
Department of Biochemistry,Chattrapati Sahuji Maharaj Medical
University,(Formerly- King George’s Medical
University)Lucknow, U. P., India.
Introduction
• Despite years of intensive research, diabetes continues to be a daunting global challenge. It is equally challenging problem in this region as well. Design of newer, safer and effective chemotherapeutic agents is one-way of addressing this situation. This in turn enforces the need to develop protocols to evaluate the efficacy of herbal drugs.
• Among all these drugs, herbal drugs seen to be one of the best choices due to their proven non toxic behavior as they have been in vogue for centuries in India and many other countries. Moreover, they are usually cost effective as well. This prompted us to undertake the present study.
• Since the time of Charaka and Susruta many herbal medicines in different oral formulations have been recommended for diabetes.
• Crude extracts of plant such as Anthocephalus indicus (Kadam), Hibiscus rosa sinensis (Gudhal), Cassia tora (Chakvat), Tinospora cordifolia (Gurch) not only possess hypolipidemic, antidiabetic and antioxidant activities but some of them are also said to act as tonic, stimulant, hepatoprotective and purifier of seminal fluid.
“Any species capable of Any species capable of independent existence independent existence that contains one or that contains one or more unpaired more unpaired electrons”. electrons”.
During metabolism During metabolism molecular oxygen molecular oxygen consumed by aerobic consumed by aerobic cells is reduced to cells is reduced to water.water.
Oxygen is partially Oxygen is partially reduced it becomes reduced it becomes ‘activated’. This ‘activated’. This partial reduction leads partial reduction leads to successive formation to successive formation of reactive oxygen of reactive oxygen metabolites. metabolites.
Reactive Oxygen Reactive Oxygen SpeciesSpecies
Prevalence of diabetes in India is 2.4% in rural and 8.2% in urban areas. (Ramachandran et al., 1993)
The rate of prevalence increases per year. It has been reported that in February, 2005 approximately 60 million of people in India are suffering from this disease (Yusuf, 2005).
The most common lipid abnormalities in diabetes are hypertriglyceridemia and hyper cholesterolemia (WHO, 2006).
type-I diabetes mainly occurs in childhood and puberty and is characterized by absolute insulin deficiency.
Type-II diabetes usually develops in adults over age 40, and is characterized by insulin resistance (Berdanier, 2001).
Moreover it has been suggested that the deficiency of antioxidant and trace elements such as Zn, Cu, Cr, Ni, Mn may also play a role in diabetes mellitus with dyslipoproteinemia (Feher et al., 1982).
Free oxygen radicals and oxidative stress is responsible for diabetic dyslipoproteinemia (Sharma and Garg, 2009).
Severe hyperglycemia cause generation of reactive oxygen species which are involved in peroxidative degradation of lipid.
Retinal oxidative stress is increased in diabetic patients and rats due to down regulation of antioxidant defence enzymes like glutathione reductase (GSH) (Li et al., 1999; Kowluru et al., 1999).
Prevention of diabetes still lies in realm of future on until then tens of million will continue to suffer from this disease.
AIM AND OBJECTIVES
•The present study was designed, to explore the hypoglycemic, antioxidant and lipid lowering activities in few medicinal plants on diabetic models.
• In India people from all socio-economic strata are suffering from dyslipoproteinemia due to diabetes mellitus.
• Recently there has been a growing demand for newer, safer and less toxic antidyslipoproteinemic agents for the treatment of diabetic dyslipoproteinemia, as the adverse effects of glibenclamide and other lipid lowering drugs are quite well known and reported.
• Natural products are the best option to treatment of diabetic dyslipoproteinemia. Accordingly we have selected four medicinal plants A. indicus, H. rosa sinensis, C. tora and T. cordifolia which are known to posses potent biological activities, but hypoglycemic, lipid lowering and antioxidant activities are not well studied.
In view of the above consideration, the present study In view of the above consideration, the present study has been planned to investigate the status of various has been planned to investigate the status of various biochemical parameters in alloxan induced diabetic rats, biochemical parameters in alloxan induced diabetic rats, following treatment with various herbal hypolipidemic following treatment with various herbal hypolipidemic agentsagents To investigate level of Blood glucose
To assess the following lipid profile in serum lipoprotein (VLDL, LDL and HDL)1.Cholesterol2.Triglyceride 3.Phospholipids4.Apolipoprotein
Assessment of lipid peroxide levels in plasma Evaluation of antioxidant: status:
superoxidedismutase and catalaseEvaluation of lipases activity: following parameters
will be studied.1. Free fatty acids.2. Triglyceride lipase (TGL) activity.3. Lipoprotein lipase (LPL) activity.4. Post heparin lipolytic activity (PHLA).
•Evaluation of antioxidant status: The activities of the antioxidant enzyme Superoxide dismutase (SOD), Catalase (CAT) and Lipid peroxide (LPO) in different diabetic models.
•In vitro evaluation of antioxidant activity of A. indicus root extract.
•To evaluate the hypoglycemic activity of T cordifolia in human volunteers by studying following parameters in serum.BLG, TC, TG, Very Low Density Lipoprotein Total Cholesterol (VLDL-TC), Low Density Lipoprotein Total Cholesterol (LDL-TC), High Density Lipoprotein Total Cholesterol (HDL-TC) and lipid peroxide (LPO).
•Evaluation of effect of natural products on hepato specific parameters in serum of rats viz., Bilirubin (Bil.), Glutamate Pyruvate Transminase (GPT), Glutamate Oxaloacetate Transminase (GOT) and Alkaline phosphatase (ALP).
Material and Methods
1.Anthocephalus indicus (Kadam): Roots and fruits
2.Hibiscus rosa sinensis (Gurhal): Roots3.Cassia tora (Chakvat): seeds 4.Tinospora Cordifolia: stems
All plants were free from diseases, pesticidal /insecticidal effects and
authenticated by Department of Pharmacology Era’s Lucknow Medical College & Hospital, Lucknow. Herbaria were made and voucher specimens retained in the Department for future references
Study DesignStudy Design
Group-1. Healthy ControlGroup-1. Healthy ControlGroup-2. Diabetic ControlGroup-2. Diabetic ControlGroup-3. Diabetic + Group-3. Diabetic + Anthocephalus indicusAnthocephalus indicus (Root)- (Root)- 500mg/kg bw500mg/kg bwGroup-4. Diabetic + Group-4. Diabetic + Hibiscus rosa sinensisHibiscus rosa sinensis (Root) (Root) 500mg/kg bw500mg/kg bw
Group-5. Diabetic + Group-5. Diabetic + Cassia toraCassia tora (Seed) (Seed) 500mg/kg bw500mg/kg bw
Group-6. Diabetic + Group-6. Diabetic + Tinospora CordifoliaTinospora Cordifolia (Stem) (Stem) 500mg/kg bw500mg/kg bw
Group-7. Diabetic+ Group-7. Diabetic+ Gliblenclamide (600 Gliblenclamide (600 µµg/ kgg/ kg b.w.)b.w.)
Experimental design for alloxan model
Experimental design for triton model
In this model animals divided in the following groups.
• Group 1: Normal rats fed on 0.2 aqueous gum acacia.
• Group 2: Triton treated rats fed on 0.2% gum acacia.
• Group 3: Triton treated rats fed on A. indicus (roots).
• Group 4: Triton treated rats fed on A. indicus (Fruits)
• Group 5: Triton treated rats fed on Guggulipid
• Group 6: Triton treated rats fed on Gemfibrozil.
Experimental design for HFD model
The study comprised of the following groups
(Each group consist 6 rats)• Group 1: Normal rats fed on 0.2% aqueous gum acacia.
• Group 2: HFD treated rats fed on 0.2% Normal saline.
• Group 3: HFD and A. indicus Fruits extract treated.
• Group 4: HFD and guggulipid treated.
Experimental design for Clinical trial
• Patients study comprise of the following groups
(Each group were consist 15 patients)
• Group 1 – Healthy control
• Group 2 – Diabetic control
• Group 3 – Diabetic + T. cordifolia
• Group 4 – Diabetic + Glibenclamide
1.Blood Glucose Henry et al., 1974.2.Lipoproteins: -Lipoprotein (VLDL + LDL) and -Lipoprotein (HDL) will be precipitated by polyanionic precipitation method of Burstein et al., 1982.3.Total Cholesterol: Zlatkis et al., 1953.4.Phospholipids: Fiske and Subbarow, 1952.5.Triglyceride: Handel et al., 1965.6.Apolipoproteins Separation of apolipoproteins by their selective precipitation with TCA, alcohol and acetone method of Radding & Steinberg, 1960.7.Lipid-peroxides: Ohkawa et al., 1979.8.Free Fatty Acids: Mosinger, 1965.9.Triglyceride Lipase (TGL) Activity: Mayes and Felts, 1968.10.Lipoprotein Lipase (LPL) Activity: Wing and Robinson, 1968.11.Superoxide dismutase (SOD) activity: Mc Cord et al., 1969.12.Total protein: Lowry et al., 1951.13.Catalase activity: Aebi et al., 1964.
Biochemical Parameters
SYSTEMS USED IN THE EVALUATION OF ANTIOXIDANT ACTIVITIES IN VITRO
• Xanthine-xanthine oxidase system (Bindoli et al., 1985)
• NBT – PMS – NADPH system (McCord & Fridovick ,1969)
• Effects of drug on generation of hydroxyl radical in vitro (Richmond et al., 1981)
• Fe2+ Na ascorbate –H2O2– deoxyribose system: to investigate the effect of test substances on OH– Generation in vitro (Halliwell et al., 1987)
Parameters for evaluation of adverse effects• Bilirubin (Bil) by Jendrassik et al., 1938 • Serum Glutamic pyruvic transminase (SGPT) by Reitman and
Frankel, 1957
• Serum Glutamic oxaloactic transminase (SGOT) by Reitman and Frankel, 1957
• Alkaline Phosphatase (ALP) by Bessay et al., 1964
RESULTS
Effect of A. indicus, H. rosa sinensis, C. tora and T. cordifolia on blood glucose, serum lipids and Protein in alloxan
induced hyperglycemic rats.26
0.61
183.
43
174.
06 250.
27
196.
56
99.9
3
48.4
1
11.9
7
25.5
4
18.5
9
9.23
20.4
396.7
7
53.8
2
55.5
3
50.4
5
43.5
2
45.6
3
31.4
2
4.05
8.84
5.42
9.83 27.0
3
-27.
19
-20.
46
-23.
24
-21.
92
-19.
29
-2.5
Alloxantreated
Alloxan+A. indicus
Alloxan+Hibiscus
Alloxan+C. tora
Alloxan+T. Cordifolia
Alloxan+Glibenclamide
050100150200250300
-50
BLG (mg/dl) TLC (mg/dl) TG (mg/dl) PL (mg/dl)Protein (g/dl)
0
49.6
2
13.7
3
24.2
5
0
27.3
2
1.94
23.5
5
0
88.6
4
48.0
8
33.0
4
0
17
8.61
5.1
Control Alloxantreated
Alloxan+A indicus
Alloxan+Glibenclamide
0
20
40
60
80
100
TC PL TG Apo.
Effect of A. indicus root extract and glibenclamide on Very Low Density lipoprotein profile in alloxan
induced hyperglycemic rats.
VLDL
0
302.
34
129.
93
147.
97
0
44.5
1
16.3
7
43.2
0
84.9
4
49.9
5
40.3
5
0 19.9
6
1.92
9.16
Control Alloxantreated
Alloxan+A. indicus
Alloxan+Glibenclamide
050100150200250300350
TC PL TG Apo.
Effect of A. indicus root extract and glibenclamide on Low Density Lippprotein profile in alloxan induced
hyperglycemic rats.
LDL
Effect of A. indicus root extract and glibenclamide on High Density Lipoprotein profile in alloxan induced
hyperglycemic rats.
0
-24.
87
-15.
73
-20.
43
0
-25
-15.
33
-22.
14
0
-13
-5.9
4
-6.7
0
-27
-12.
98
-18.
79
Control Alloxantreated
Alloxan+A. indicus
Alloxan+Glibenclamide
05
-5-10-15-20-25-30
TC PL TG Apo.
HDL
Effect of H. rosa sinensis root extract on serum Very Low Density lipoprotein profile in alloxan induced
diabetic rats
0
49.6
2
28.0
9
24.2
5
0
27.3
2
9
23.5
5
0
88.6
4
44.1
9
33.0
4
0
17
10.9
4
5.1
Control Alloxantreated
Alloxan+Hibiscus
Alloxan+Glibenclamide
0
20
40
60
80
100
TC PL TG Apo.
VLDL
VLDL
Effect of H. rosa sinensis root extract on serum Low Density Lipoprotein profile in alloxan induced
diabetic rats0
302.
34
156.
23
147.
97
0
44.5
1
31
4.3
0
84.9
4
52 40.3
5
0
19.9
6
12.7
2
9.16
Control Alloxantreated
Alloxan+Hibiscus
Alloxan+Glibenclamide
0
50
100
150
200
250
300
350
TC PL TG Apo.
LDL
Effect of H. rosa sinensis root extract on serum High Density Lipoprotein profile in alloxan
induced diabetic rats
0
-24.
87
-24.
97 -20.
43
0
-25 -1
9.13
-22.
14
0
-13
-10.
36 -6.7
0
-27
-16.
3
-18.
79
Control Alloxantreated
Alloxan+Hibiscus
Alloxan+Glibenclamide
05
-5-10-15-20-25-30
TC PL TG Apo.
HDL
Effect of C. tora seed extract on serum Very Low Density Lipoprotein profile in alloxan induced
diabetic rats.
0
49.6
2
15.6
5
24.2
5
0
27.3
2
2.98
23.5
5
0
88.6
4
38.9
7
33.0
4
0
7 9.78
5.1
Control AlloxanC. tora
Alloxan+C. tora
Alloxan+Glibenclamide
0
20
40
60
80
100
TC PL TG Apo.
VLDL
Effect of C. tora seed extract on serum Low Density Lipoprotein profile in alloxan induced
diabetic rats.
0
302.
34
148.
68
147.
97
0
44.5
1
30.4 43.2
0
84.9
4
43.5
8
40.3
5
0
19.9
6
7.9
9.61
Control Alloxantreated
Alloxan+C. tora
Alloxan+Glibenclamide
050100150200250300350
TC PL TG Apo.
LDL
Effect of C. tora seed extract on serum High Density Lipoprotein profile in alloxan induced diabetic
rats.
0
-24.
87
-24.
13 -20.
43
0
-25
-14.
73
-22.
14
0
-13 -7
.67
-6.7
0
-27
-16.
95
-18.
79
Control Alloxantreated
Alloxan+C. tora
Alloxan+Glibenclamide
05
-5-10-15-20-25-30
TC PL TG Apo.
HDL
Effect of T. cordifolia stem extract on serum Very Low Density Lipoprotein profile in alloxan
induced diabetic rats.0
49.6
2
15.3
4
24.2
5
0
27.3
2
10.6
5 23.5
5
0
88.6
4
38.8
4
33.0
4
0
7 7.41
5.1
Control Alloxantreated
Alloxan+T. cordifolia
Alloxan+Glibenclamide
0
20
40
60
80
100
TC PL TG Apo.
VLDL
Effect of T. cordifolia stem extract on serum Low Density Lipoprotein profile in alloxan induced
diabetic rats.
0
302.
34
137.
31
147.
97
0
44.5
1
16.8
1
43.2
0
84.9
4
42.4
4
40.3
5
0
19.9
6
10.3
3
9.61
Control Alloxantreated
Alloxan+T. cordifolia
Alloxan+Glibenclamide
050100150200250300350
TC PL TG Apo.
LDL
Effect of T. cordifolia stem extract on serum High Density Lipoprotein profile in alloxan induced
diabetic rats.
0
-24.
87
-17.
62
-20.
43
0
-25
-17.
88
-22.
14
0
-13 -8
.43
-6.7
0
-27
-19.
57
-18.
79
Control Alloxantreated
Alloxan+T. cordifolia
Alloxan+Glibenclamide
05
-5-10-15-20-25-30
TC PL TG Apo.
HDL
52.38
38.09
44.04
37.5
36.9
11.9
-19.53 -5
.89
-5.4
3.31
-7.15
-5.74
-25
-6.61
-7.37
-2.8
-6.24
-4.43
Control Alloxan+A. indicus
Alloxan+Hibiscus
Alloxan+C. tora
Aloxan+T. Cordifolia
Alloxan+Glibenclamide
0
20
40
60
-20
-40
Serum FFA (%) Hepatic TGL (%)Total hepatic LPL (%)
EFFECT OF A. INDICUS, H. ROSA SINENSIS, C. TORA AND T. CORDIFOLIA AND GLIBENCLAMIDE ON SERUM, FREE FATTY ACIDS, HEPATIC
TRIGLYCERIDE LIPASE AND TOTAL HEPATIC LIPOPROTEIN LIPASE ACTIVITY IN ALLOXAN INDUCED DIABETIC RATS.
EFFECT OF A. INDICUS, H. ROSA SINENSIS, C. TORA, T. CORDIFOLIA AND GLIBENCLAMIDE ON SERUM LIPID PEROXIDE, HEPATIC SOD AND
HEPATIC CATALASE IN ALLOXAN INDUCED DIABETIC RATS
228.
93
112.
45
118.
68
206.
22
115.
38
103.
29
-24
-3.9
2
-3.9
2
-13
-4.2
8
-3.5
7
-25
11.5
4
11.6
1
21.0
2
7.38 31
.76
Control Alloxantreated
Alloxan+A. indicus
Alloxan+Hibiscus
Alloxan+C. tora
Aloxan+T. Cordifolia
Alloxan+Glibenclamide
0
50
100
150
200
250
-50
Serum LPO (%) Hepatic SOD (%)Hepatic CAT(%)
EFFECT OF A. INDICUS FRUITS EXTRACT ON TRITON INDUCED HYPERLIPIDEMIA
0
155
95
65.2
6
0
196.
97
175.
98
105
0
161.
46
102
68.4
8
0
-25.
33
-12.
4
-8.2
Control Tritontreated
Triton+A. indicus
Triton+Guggulipid
0
50
100
150
200
250
-50
TC (mg/dl)(%) PL (mg/dl)(%)TG (mg/dl)(%)PHLA (nmolFFA/ hr/ml serum)(%)
EFFECT OF A. INDICUS FRUITS EXTRACT ON CHOLESTEROL RICH-HIGH FAT DIET INDUCED HYPERLIPIDEMIA
0
118.
85
70.9
52.2
5
0
110.
05
60.3
7
51.5
6
0
93.0
7
44.5
8
26.8
4
0
-35.
42
-21.
02
-17.
14
Control HFDtreated
HFD+A. indicus
HFD+Guggulipid
020406080100120140
-20-40
TC (mg/dl)(%) PL (mg/dl)(%)TG (mg/dl)(%)PHLA (nmolFFA/ hr/ml serum)(%)
EFFECTS OF A. INDICUS FRUIT EXTRACT ON LIVER LIPIDS IN CHOLESTEROLRICH-HFD INDUCED HYPERLIPIDEMIA
0
52.1
5
20.2
4
4.13
0
76.3
2
30.2
1
10.6
5
0
42.2
6
4.32
2.68
0
-35 -1
8
-13.
44
Control HFDtreated
HFD+A. indicus
HFD+Guggulipid
0
20
40
60
80
100
-20
-40
TC (mg/dl)(%) PL (mg/dl)(%)TG (mg/dl)(%)LPA (nmolFFA/ hr/mg protein)(%)
Effect of A. indicus roots in triton induced hyperlipidemia
0
265.
3
185.
52
128.
02
0
103.
15
57.0
3
25.1
2
0
125.
1
74.5
5
60.3
6
0
81.3
3
40.3
3
140
-32.
96
-11.
02
6.71
Control HFDtreated
HFDA. indicus
HFD+Gemfibrozil
0
50
100
150
200
250
300
-50
TC (mg/dl)(%) PL (mg/dl)(%) TG (mg/dl)(%)Protein (g/dl)(%)PHLA (nmolFFA/ hr/ml serum) (%)
Effect of A. indicus on enzymic generation of superoxide anions
48.4
4
43.9
4
41.0
3
35.1
8
32.1
8
30.3
3
26.3
3
23.8
6
116.
03
105.
03
98.1
6
82.4
3
79.8
6
73.1
6
69.8
8
65.9
6
None 50 100 200 250 300 400 5000
20
40
60
80
100
120
140
Enzymic system-A (Xn-Xn OD system) (n mol uric acid/min)Enzymic system-B (Xn-Xn OD-NBT system) (n mole formazone formed/min)
ENZYMIC GENERATION OF SUPEROXIDE ANION
334.
76
265.
36
241.
67
163.
86
155.
54
150.
44
148.
02
140.
45
None 50 100 200 250 300 400 5000
50
100
150
200
250
300
350
400
Generation of superoxide an ion in non enzymic system, of NADH-PMS-NBT (n mol formazone formed/min)
NON ENZYMIC GENERATION OF SUPEROXIDE ANION
Effect of A. indicus root extract on non enzymic generation of super oxide an ions
Effect of A. indicus root extract on enzymic generation of hydroxyl radical
549.17
507.5
505.66
411.87
377.5
348.98
305.94
282.15
None 50 100 200 250 300 400 5000
100
200
300
400
500
600
Generation of superoxide an ion in non enzymic system of hypXn-Xn OD Na-Salicylate (n mol 2,3 dihydroxy benzoate formed/hr)
Effect of A. indicus on Generation of Hydroxyl radical in non enzymic system
25.5
4
20.7
19.1
5
17.1
16.5
9
15.5
3
14.9
2
13.6
5
None 50 100 200 250 300 400 5000
5
10
15
20
25
30
Non enzymic system of Fe2+_Sod ascorbate -H2O2-deoxyribose (nmoL MDA formed/hr)
CLINICAL STUDIES EFFECT OF T. CORDIFOLA STEM POWDER ON BLOOD
GLUCOSE, SERUM LIPID PROFILE AND SERUM LIPID PEROXIDE LEVELS IN DIABETIC TYPE-II PATIENTS
0
86.8
5
60.1
9
7.73
0
34 18.5
7
10.7
2
0
59.0
9
30.1
3
22.4
6
0
58.1
40.5
28.6
3
0
59.8
9
30.6
5
23.1
1
0
-38.
69
-36.
22
-37.
53
0
252.
53
103.
22
115.
66
Healthycontrol
Diabeticcontrol
Diabetic+T. Cordifolia
Diabetic+Glibenclamide
050100150200250300
-50
BLG fasting (mg/dl)(%) TG (mg/dl) (%)TG (mg/dl) (%) LDL-TC (mg/dl) (%)VLDL-TC (mg/dl) (%) HDL-TC (mg/dl) (%)Serum LPO (nmol MDA/ml serum)
EFFECTS OF A. INDICUS, H. ROSA SINENSIS, C. TORA AND T. CORDIFOLIA ON HEPATO-SPECIFIC
PARAMETERS IN ALLOXAN INDUCED DIABETIC RATS 0
14.0
6
4.68
1.56
1.56 3.12
7.81
0
18.9
9
5.45
4.37
4.73
11.7 13.2
7
0
28
12.0
9
13.9
1
7.06 9.
35
19.5
1
0
20.5
2
10.5 12.3
2
5.84 9.
11
17.4
7
Control Alloxantreated
Alloxan+A. indicus
Alloxan+H. rosa
Alloxan+C. tora
Aloxan+T. Cordifolia
Alloxan+Glibenclamide
0
5
10
15
20
25
30
35
S. Bil (%)SGPT(%) SGOT(%) ALP (%)
Importance of the WorkThe proposed study will be helpful in the advancement
of pre existing knowledge of diabeticdyslipoproteinemia, macro and micro vascular complications of diabetes and its treatment through herbal preperations .
The research work would facilitate in the promotion of knowledge regarding the regulation of different types of dyslipoproteinemias.
Studies on dyslipoproteinemia and oxidative stress would further contribute to better understanding in the progression of diabetic complications.
This study will lead to the development of antidyslipoproteinemic drugs, from plant extract on animal models.
This work will be of great importance due to its significant role in inhibiting the process of micro and macrovascular complications, in diabetes mellitus.
CONCLUSION
On the basis of the results of the present study (Experimental and Clinical trial) it may be concluded that the herbal plants namely A. indicus, Hibiscus rosa sinesis, C. tora and T. cordifolia may be useful in the treatment of micro and macro vascular complications of diabetes mellitus without any side effect,
as they not only have antidyslipoproteinemic effect but also protect rats and human volunteers from
glucose oxidation and free radical mediated cellular injury by improving the activity of antioxidant enzymes. Moreover, they also improve the levels of hepatic lipoprotein lipases which are associated with diabetic
dyslipoproteinemia.
Top Related