The effects of ginseng (Panax quinquefolius) treatment on chronic diabetic complications Subhrojit Sen & Subrata Chakrabarti Dept. of Pathology University of Western Ontario
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
The effects of ginseng (Panax quinquefolius)treatment on chronic diabetic complications
Subhrojit Sen & Subrata ChakrabartiDept. of Pathology
University of Western Ontario
• Diabetes mellitus is a heterogeneous clinical syndrome in which the central feature is a chronic elevation of the blood glucose concentration.
• It occurs due to deficiency of insulin (absolute) or resistance to insulin (relative).
• 40% diabetics develop long term complications affecting various organs including retina, heart and kidney.
Introduction
Types of diabetes Type I diabetesResults from the body's failure to produce insulin. It is estimated that 5-10% of Americans who are diagnosed with diabetes have type 1 diabetes.
Type II diabetesResults from insulin resistance (a condition in which the body fails to properly use insulin), combined with relative insulin deficiency. Most Americans who are diagnosed with diabetes have type 2 diabetes.
Gestational diabetesOccurring during pregnancy. Gestational diabetes affects about 4% of all pregnant women - about 135,000 cases in the United States each year.
Retinopathy
Chronic diabetic complications
Nephropathy
Diabetic Neuropathy
Diabetic Cardiomyopathy
CHRONIC COMPLICATIONS OF DIABETES
Others
Retinopathy
Progressive Backgroundi) Neovascularization i) increased capillary
permeability ii) closure of retinal
capillariesiii) vascular leakage
retinal edema iv) accumulation of
lipids v) retinal ischemia
Nephropathy:• Microalbuminuria • elevated blood pressure progresses to macroproteinuria • decline in renal function.
Diabetic Neuropathy:• Peripheral • Focal
Diabetic cardiomyopathy:
• microvascular narrowing
• micro aneurysm (increased risk of rupture)
• hypertrophy
• defects in collagen structure
• myocardial fibrosis
• perivascular fibrosis
Signalling pathways involved in diabetic complications
Hyperglycemia
Aldose reductase pathway
Protein kinase C
Oxidative stress
AGE/RAGE
Growth factors (TGF-β, VEGF etc.)
ET
vasoconstrictionPermeability
PKC, MAPK
Blood flow
Growth Factors Extracellular Matrix Protein
Angiogenesis
Khan et al, Current Vascular Pharmacology, 2006, Vol 4, No. 1
Ginseng has been shown to have antioxidant effect. Prevents oxidative lipid peroxidation and kidney damage in rats. Ginsenosides are the active components of ginseng found mainly in the roots. Structurally, ginsenosides are divided into two types: protopanaxadiol ginsenosides (PPDGs) and protopanaxatriol ginsenosides (PPTGS).
North American Ginseng
Objective
The present study will investigate the • effects of ginseng on glucose-induced changes in human vascular endothelial cells (HUVECs) • biochemical, functional and structural changes in heart, kidney and retina of insulin-dependent (IDDM) and noninsulin-dependent (NIDDM) mouse model.
Experiments on HUVECs
HUVECs were incubated with 25 mM glucose for 24 hrs. Aqueous and ethanolic extracts of ginseng were given at conc. of 5 mg/ml.
Glucose-induced i) fibronectin (FN) ii) FN protein level iii) EDB+FNiv) Vascular Endothelial Growth Factor (VEGF) v) endothelin (ET-1) mRNA levels were measured.
Animal models used in the present study
Type 1 diabetes STZ mice
Type 2 diabetes db/db mice
Type 1
STZ induction (IP, 65 mg/kg BW)Type 2 db/db mice
Mice
Control Diabetic
DC
Diabetic+
Ginseng (DT)
(200mg/Kg BW for 2 months
after onset of diabetes
by oral gavage)
Diabetic
db/db
Control
NC
Experimental Design
NC
Experimental parameters Body weight
Heart weight
Biochemical parameters from- blood :
a) Glucose- urine
a) Albumin by ELISAb) Creatinine by ALKALINE PICRATE
METHOD
Preliminary results on HUVEC
NG: 5mM glucose; HG: 25mM High glucose; I = insulin; GA: aqueous extract of ginseng; GE = ethanolicextract of ginseng. * = significantly different from other groups
ALCOHOLIC EXTRACTS APPEARED TO BE MORE EFFECTIVE
FN-mRNA levels in Endothelial cells
0
0.51
1.5
2
Groups
mR
NA/
18s
RN
A
*
EDB+FN mRNA levels in endothelial cells
0
0.5
1
1.5
2
2.5
NG HG NGI HGI NGGA HGGA NGGE HGGE
Groups
mR
NA/
18 s
RN
A
*
0
1
2
NG HG NGI HGI NGGE HGGE NGGA HGGA
Groups
Con
c. o
f fib
rone
ctin
(ng/
ml)
*
**
NG: 5mM glucose; HG: 25mM High glucose; I = insulin; GA: aqueous extract of ginseng; GE = ethanolic extract of ginseng. * = significantly different from other groups, * *= significantly different with HG and HGGA.
ALCOHOLIC EXTRACTS APPEARED TO BE MORE EFFECTIVE
FN protein levels in endothelial cells
ET-1 mRNA levels in endothelial cells
0
1
2
NG HG NGI
HGI
NGGA
HGGA
NGGE
HGGE
Groups
mR
NA
/18
sR
NA
VEGF mRNA levels in endothelial cells
0
1
2
NG HG NGI HGI NGGA HGGA NGGE HGGE
Groupsm
RN
A/1
8s
RN
A
NG: 5mM glucose; HG: 25mM High glucose; I = insulin; GA: aqueous extract of ginseng; GE = ethanolic extract of ginseng. * = significantly different from other groups
ALCOHOLIC EXTRACTS APPEARED TO BE MORE EFFECTIVE
*
*
Preliminary results on diabetic mouse modelGroups Body
wt. (gms)
Heartwt.
(mgm)
Fasting Blood
Glucosemmol/L
Urinary Albumin (μg/ml)
Urinary Creatinine
(mg/ml)
NC 28 5.5 124.1 10.2 8.86 2.7 0.128 0.01 0.225 0.05
DC 24 1.6 121.12 2.5 27.4 5.5* 0.182 0.02* 0.350 0.025*
DT(ginsengtreated)
27.2 1.7 133.96 5.5 15.28 8.5 0.138 0.007 0.235 0.02
db/db 44.4 1.5* - 29.08 2.5* 0.184 0.02 0.312 0.01*
THE ABOVE PARAMETERS WERE MEASURED AFTER 2 MONTHS OF ONSET OF DIABETES IN CASE OF IDDM MODEL. THE PARAMETERS IN db/db MICE
WERE MEASURED AT 12 WEEKS OF AGE (Duration of diabetes 4 weeks).
Conclusion
In HUVECs:Glucose caused upregulation of FN, EDB+FN, VEGF and
ET-1.Treatment with both aqueous and ethanolic extract of
ginseng (5mg/ml) caused diminution of the above parameters.
In STZ mice:Treatment with ethanolic extract of ginseng (200mg/kg BW/day) for 2 months caused significant diminution of fasting blood glucose, urinary albumin and creatinine levels.
In db/db mice:Enhancement of fasting blood glucose, urinary albumin and creatinine levels occurred after 12 weeks of age.
AcknowledgementI sincerely acknowledge the guidance of my supervisor, Dr.
Subrata Chakrabarti and Dr. Ed Lui, Dept. of Physiology & Pharmacology.
I also acknowledge the guidance and help provided by all members of my laboratory.
1) Shali Chen
2) Biao Feng
3) Jane Chiu
4) Kara McArthur
5) Yuexiu Wu
6) Chunyan Wang
7) Biju George
Related Documents
