development of natural products for the treatment and management of type 2 diabetes...
TRANSCRIPT
FIRST UP CONSULTANTS
Development of natural
products for the treatment
and management of type 2
diabetes mellitus
Presenter:
Dr. Shadae Foster
The University of the West Indies, Mona
Dr. Lowell Dilworth
Dr. Rudy Lisa Lindo
Texas A&M University, Corpus Christi
Dr. Felix Omoruyi
RESEARCH TEAM
INTRODUCTION
Diabetes is an important public health problem and is one of four priority
noncommunicable diseases (NCDs) targeted for action by world leaders.
Challenges:
There is no cure for diabetes mellitus
Treatment is costly
Have undesirable side effects.
Possible Solution:
Natural alternative anti-hyperglycaemic remedies with minimal or no side
effects.
It is estimated that 425 million people are living with diabetes (IDF, 2018).
By 2045, projections show this number rising to some 629 million diabetics globally.
INTRODUCTION
Readily available
Cost effective
Safe
Unique natural
Minimal to no side effect
RATIONALE
Studies have reported that phytic acid and inositol individually showed insulin secretory and anti-cancer properties (Barker et al.2002, 2009; Berggren & Barker 2008).
However, a greater anti-cancer effect was observed when phytic acid and inositol were administered as a combination (Shamsuddin et al. 1998).
The use of phytic acid and inositol combinations in the treatment of type 2 diabetes has never been previously studied.
Our research group theorized that the combined phytic acid and inositol product may be more effective at managing diabetes than IP6 or inositol alone.
MAIN OBJECTIVE
This project assessed the efficacy of combined phytic acid and
inositol as a novel treatment option for type 2 diabetes
mellitus and its potential for nutraceutical applications.
Research has shown that inositol and
IP6 have virtually no toxicity and is
very safe for consumption, even with
long term administration. (Ullah and
Shamsuddin, 1990).
Phytic and inositol is naturally present (0.4%–6.4%) in all living cells and
wide variety of plant foods (Vucenik & Shamsuddin, 2003), especially:
Wheat bran
Whole grains
Legumes
PHYTIC ACID AND INOSITOL
Phytic acid was generally considered to be an anti-nutrient be
because interferes with the absorption of minerals from the diet.
However, Walker and colleagues (1998), demonstrated that the
“anti-nutrient” effect of phytic acid is only manifested when:
A large amount of phytic acid
A diet low in trace elements
PHYTIC ACID
METHOD
EXPERIMENTAL DESIGN
High-fat diet
Streptozotocin
(35 mg/kg bw)
Type 2 diabetics
Non-diabetics Normal Control (NC)
Standard rat chow
Non-diabetics
Diabetic Control (DC)
Phytic acid + Inositol
(IP6+INO)
High-fat control (HFC)
Glibenclamide (Glib)
(6 rats per group) •Blood glucose
•Body weight
•Food and fluid intake
•Insulin
•lipid composition
•Antioxidant activity
•Metabolic enzymes activity
•ATPase activity
•Histological study
•Hematological analysis
•Blood chemical parameters
RESULTS &
DISCUSSION
55
65
75
85
95
105
115
125
135
0 30 60 90 120 150 180 210
Blo
od
Glu
cose
Co
nce
ntr
atio
n (
mg/
dL)
Time (minute)
Figure 1. Oral glucose tolerance test of inositol, IP6 and
its combination at a dosage of 650 mg/kg body weight
via oral gavage versus a control in normoglycemic
Sprague-Dawley rats
Normal Control IP6 (650 mg/kg BW)
INO (650 mg/kg BW) IP6+INO (650 mg/kg BW)
*
* *
0
100
200
300
400
500
600
700
2 3 4 5 6 7 8
Mean N
on
-fast
ing B
loo
d G
luco
se (
mg/d
L)
Time (week)
Figure 2. Non-fasting Blood Glucose Concentration
in Diabetic Rats Treated with Combined IP6 &
Inositol Supplement or Glibenclamide versus
Controls
NC HFC DC IP6+INO Glib.
55
65
75
85
95
105
115
125
135
0 30 60 90 120 150 180 210
Blo
od
Glu
cose
Co
nce
ntr
atio
n (
mg
/dL)
Time (minute)
Figure 1. Oral glucose tolerance test of inositol, IP6 and its combination
at a dosage of 650 mg/kg body weight via oral gavage versus a control in
normoglycemic Sprague-Dawley rats
Normal Control IP6 (650 mg/kg BW) INO (650 mg/kg BW) IP6+INO (650 mg/kg BW)
*
* *
0
20
40
60
80
100
120
140
160
Total Cholesterol Triglyceride HDLMea
n L
ipid
Conce
ntr
atio
n (
mg/d
L)
Figure 3. Serum Lipid Profile of Diabetic Rats
Treated With IP6 & Inositol Combination versus
Glibenclamide NC HFC DC IP6+INO Glib
a
a a a
ab
ab
bc
ab
a a
a
a
c
a
Table 1. Liver Lipid Profile of Diabetic Rats Treated with
Combined IP6 and Inositol Supplement or Glibenclamide
versus Control
Groups
Triglyceride
(mg/g tissue wet
weight)
HDL
(mg/g tissue wet weight)
NC 13.22 ± 1.4a 0.134 ± 0.019a
HFC 19.80 ± 2.49a 0.114 ± 0.016ab
DC 26.93 ± 3.21b 0.067 ± 0.016b
IP6+INO 16.57± 0.63a 0.134 ± 0.020a
Glib 19.69 ± 1.52a 0.119 ± 0.022ab
Note: The bars and figures with different superscript letters are
significantly different at p < 0.05.
NC
HFC
IP6 &
INO Glib
Figure 4. Photomicrograph of haematoxylin and eosin stained pancreas tissue section of the
normal control (NC), high-fat control (HFC), IP6 and inositol treated diabetic group (IP6 &
INO) and glibenclamide treated diabetic group (Glib). Mag × 200
DC
Figure 5 Photomicrograph of Haematoxylin and Eosin Stained Pancreas Tissue
Section of the Diabetic Control (DC) Mag × 200
Table 6: The diameter of islets and number of islets/pancreas section in diabetic
rats treated with combined IP6 & inositol supplement or glibenclamide
Groups Diameter of islets
(mm)
Number of islets/pancreas
(N/10 mm2)
NC 0.367 ± 0.042a 13.60 ± 1.28a
HFC 0.217 ± 0.060b 14.00 ± 1.67a
DC 0.100 ± 0.00b 5.00 ± 0.07b
IP6+INO 0.183 ± 0.047b 10.33 ± 1.33a
Glib 0.200 ± 0.045b 4.75 ± 0.25b
Summary
Reducing blood glucose level
Reducing insulin resistance
Regulate appetite (Polyphagia)
Regulate thirst (Polydipsia)
Regulate lipid abnormalities
(Dyslipidemia)
Regulate body weight
Reduce oxidative stress
As effective More effective
No Adverse effects on liver integrity
Summary
No Adverse effects on kidney integrity
Pancreatic Restorative/Protective Effects
TRANSLATIONAL RESEARCH
LAB MARKET
Poor
Lifestyle
Practices
Product Development- Multi-functional
Easy and Convenient
Replace unhealthy Food
Help with portion and calorie control
Low glycemic index and lipid level
Balance nutrition
Filling and satisfying
Diabetic meal replacement beverage -
Multi-functional
Regulate appetite
Assist with weight loss
Lower cholesterol levels
Regulate blood glucose level
Increase antioxidant level
Reduce insulin resistance
Improve pancreatic function
Balance nutrition
Nutraceutical Supplement
There is a shift in the consumer
preference from pharmaceutical
drugs containing synthetic
ingredients to nutraceuticals
supplements.
Social and Economic Value
Estimated global cost associated with diabetes in 2015 was $US 1.31 trillion (Bommer et al, 2017).
In 2011, the National Health Fund paid $JM 616,461,903 to beneficiaries for diabetes alone.
The nutraceutical drug market share was valued at over $US 383 billion in 2017 and is projected to reach $US 561.4 billion by 2023 (Staista, 2017).
Social and Economic Value
Diabetes
220,000
(13.6%)
Obesity (26.8%) and
overweight (58.4%)
Target market 10,000
Glucerna
$US 3.45
$US 9.9 million
Phytitol
$US 2.75
$US 8 million
Non-diabetics:
High cholesterol,
Prediabetics etc.
Net profit
$US 3.4
million
Social and Economic Value
How can Jamaica benefit from our nutraceutical innovation?
Improved well-being and quality of life
Reduction in the country’s healthcare bill
Increased foreign-exchange earnings
Increased employment
Improved social and economic well-being of all persons involved
What’s next?
Additional product research and development activities on the
project presented within is being undertaken to see to the
commercialization of our innovation.
Since we are developing finished formulations with the
inclusion of other ingredients besides our active ingredients, we
intend to undertake additional work which includes activities to
confirm the product stability and efficacy.
Other research projects
I’m currently undertaking research that will qualify and quantify the
nutritional, chemical and biological composition of under-utilized
plants in Jamaica that are currently being used by the indigenous
community members for its nutritional and medicinal properties.
This study aims to identify and assess the bioactive substances
present in the plants that will explain and verify their folkloric
medicinal uses and explore their potential for product development.
PUBLICATIONS (Peer reviewed Journal Articles):
Shadae R. Foster, Felix O. Omoruyi, Juan Bustamante, Ruby L. A. Lindo, & Lowell L. Dilworth (2016). The
effect of combined inositol hexakisphosphate and inositol supplement in streptozotocin-induced type 2 diabetic
rats. International Journal of Experimental Pathology, 97(5), 397-407.
Foster, S. R., Dilworth, L. L., Thompson, R. K., Alexander-Lindo, R. L., & Omoruyi, F. O. (2017). Effects of
combined inositol hexakisphosphate and inositol supplement on antioxidant activity and metabolic enzymes in
the liver of streptozotocin-induced type 2 diabetic rats. Chemico-Biological Interactions, 275:108-115.
Henry IC Lowe, Denise K Daley, John Lindo, Chenee Davis, Lois Rainford, Shelly-Ann Hartley, Charah
Watson, Cheryl Chambers, Glendee Reynolds-Campbell, Shadae R Foster, Percival Bahadoosingh, and
Camille Thoms-Rodriguez (2017). The Antibacterial and Antifungal Analysis of Crude Extracts from the
Leaves and Bark of Pimenta species found in Jamaica. Journal of medicinal Plant research, 11(38), 591-595,
DOI: 10.5897/JMPR2017.6435.
Shadae R Foster, Lowell L Dilworth, Felix O Omoruyi, Rory Thompson and Ruby L Alexander-Lindo.
(2017). Pancreatic and renal function in streptozotocin-induced type 2 diabetic rats administered combined
inositol hexakisphosphate and inositol supplement. Biomedicine and Pharmacotherapy, 96:72-77.
PUBLICATIONS (Peer reviewed Journal Articles – Pending)
Shadae R Foster, Cliff Riley, Melaine Randle, Yvonne Bailey Shaw, Charah T
Watson. Phytochemical screening of active secondary metabolites presents in raw and
differentially processed Entada Gigas seed: indigenous and medicinal uses. Journal of
Medicinal Plant Studies. Manuscript in preparation.
Shadae R Foster, Lowell L Dilworth, Jean Sparks, Ruby L Alexander-Lindo and
Felix O Omoruyi. Combined inositol hexakisphosphate and inositol supplement
consumption improves serum alpha-amylase activity and hematological parameters in
streptozotocin-induced type 2 diabetic rats. Journal of pharmacological Sciences. (In
press).
CONFERENCE PRESENTATIONS (Published Abstracts)
S. R. Foster (Author & Presenter), R. L. Alexander Lindo, L. L Dilworth, J. Bustamante, F. O. Omoruyi. (2016). Anti-
diabetic properties of combined inositol hexakisphosphate (IP6) and inositol in streptozotocin-induced type 2 diabetes
mellitus Sprague-Dawley rats. American Association for Clinical Chemistry (AACC) Annual meeting abstracts, B-003.
Pp 28.
S Foster (Author & Presenter), F Omoruyi, L Dilworth, J Bustamante and R Alexander-Lindo. (2016). The effect of
inositol hexakisphosphate (IP6) and inositol combination on renal and hepatic function and antioxidant status in
streptozotocin-induced type 2 diabetes mellitus Sprague-Dawley rats. West Indian Medical Journal, 65 (1):34.
SR Foster (Author & Presenter), LL Dilworth, FO Omoruyi, J Bustamante and R Alexander-Lindo. (2015). Inositol
and Inositol Hexakisphosphate (IP6) Combination lowers fluid and food intake in Type 2 Diabetes Mellitus Sprague-
Dawley rats. West Indian Medical Journal, 64(4):26. Oral presentation delivered at the Faculty of Medical Sciences
Conference. 24th Annual Research Conference and Workshop on Cancer, a Growing Public Health Priority in the
Caribbean. The University of the West Indies, Mona, Kingston, Jamaica.
Foster, S. (Author & Presenter), Alexander-Lindo, R., Omoruyi, R., Bustamante, J. and Dilworth, L. (2015). The Effect
of inositol and inositol hexakisphosphate (IP6) combination on blood glucose concentration and lipid metabolism in
type 2 diabetes mellitus Sprague-Dawley rats. West Indian Medical Journal, 64 (1):37.
AWARDS AND HONORS
Best Poster Presentation Award, University Diabetes Outreach Programme (UDOP)
Conference (2015)
Best Poster Presentation Award, University Diabetes Outreach Programme (UDOP)
Conference (2016)
The University of the West Indies Postgraduate Scholarship (2013 - 2015)
Department of Basic Medical Sciences Postgraduate Award (2012-2013 & 2015-2017)
The University of the West Indies Dean’s list Award 2010-2011
M and M Jamaica Limited Scholarship (2009-2010)
Acknowledgements
My supervisors: Dr. Lisa Lindo & Dr. Lowell Dilworth
Dr. Felix Omouryi & Dr. Juan Bustamante (Texas A&M university)
Dr. Rory Thompson (Pathologist)
Office of Graduate Studies and Research
The University of the West Indies
Texas A & M University (Corpus Christi and Kingsville)
Marshall Arts Solutions - Gawaine Marshall
Scientific Research Council
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Thank you