|
| Herbs in the Management of Hyperglycemia in Diabetes. Importance of
Screening Methods in the Identification of Phyto Anti-Hyperglycemic Principles |
| Bassa V. Babu1*, Vipin Kumar Chaturvedi1 and Rao M. Uppu1,2 |
| 1Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA |
| 2Department of Environmental Toxicology and the Health Research Center, Southern University and A&M College, USA |
| *Corresponding author: |
Bassa V. Babu
Laboratory of Autoimmunity
Torrey Pines
Institute for Molecular Studies
San Diego, CA 92121, USA
Tel: +16199488494
E-mail: bbassa9823@aol.com |
|
| |
| Received September 01, 2012; Accepted September 10, 2012; Published September 15, 2012 |
| |
| Citation: Babu BV, Chaturvedi VK, Uppu RM (2012) Herbs in the Management of
Hyperglycemia in Diabetes. Importance of Screening Methods in the Identification of
Phyto Anti-Hyperglycemic Principles. J Diabetes Metab 3: e110. doi:10.4172/2155-6156.1000e110 |
| |
| Copyright: © 2012 Babu BV, et al. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited. |
| |
| It is common knowledge that normal glucose regulation is impaired
in diabetes mellitus. The two major classes are type 1 or insulin
dependent, and type 2 or non-insulin dependent diabetes mellitus.
Where in type 1 diabetes there is almost complete destruction/loss
of insulin producing cells resulting in glucose starvation in skeletal
muscle, in type 2 diabetes the major manifestations are insensitivity of
the pancreatic beta cells to glucose stimulated insulin release and the
impairment of skeletal muscle cells to insulin stimulated glucose entry
(insulin resistance). |
| |
| Over the years many natural products, especially plant derived have
been used in the traditional medicine for the treatment of diabetes.
Apart from their empirical value, the scientific basis for investigating
the Nature’s inventory of chemical compounds for an anti-diabetic
principle forms an interesting inquiry. Insulin is released from the
beta cells of pancreas in response to rising glucose in the bloodstream.
Interestingly, although glucose is a potent natural stimulator of insulin
release from the pancreatic beta cells, there is no evidence to show that
primitive man consumed bolus meals comprising of carbohydrates in
abundant quantities, to raise the blood glucose levels high enough (180
mg/dL) to stimulate insulin release from the pancreas. Furthermore,
nature is also rich in chemical compounds that are structurally similar
to glucose. The insulino tropic activities of sulfonylureas which have
structural similarities with glucose support this line of thinking. Of
late, incretins and incretin mimetics have been used for the treatment
of diabetes. Incretins like glucagon like peptie-1 (GLP-1) and gastric
inhibitory polypeptide (GIP) are gut hormones released in response
to ingestion of food. These are short lived as they are immediately
acted upon by dipeptidyl peptidase-4 (DPP-4). Apart from modifying
the peptide for a longer duration of action, inhibitors of DPP-4 are in
clinical use as antidiabetics. The search for natural inhibitors of DPP-
4 in some of the plants and their products used for glycemic control
therefore would merit attention. |
| |
| Among plant based antidiabetic principles, Panax ginseng, the
Asian vegetable bitter melon, Gymnema sylvestre, Fenugreek and Tian
Hua Fen (trichosanthes root) are known to contain factors that lower
blood sugar levels in diabetics. Interestingly, the parent compound of
biguanides used in the treatment of insulin resistance was originally
isolated from a plant source (French lilac) [1]. |
| |
| Lately, several laboratories across the world are engaged in the
screening of herbs for their antidiabetic properties using modern
methods of detection [2-6]. Animal models of both type 1 diabetes
with chemically ablated pancreas (using alloxan, or streptozotocin)
and models of type 2 diabetes like Ob/Ob mouse, Zucker diabetic rats,
and in vitro cultures of pancreatic beta cells are used in the bioassay
for anti-hyperglycemic activity. Since widely varying physiological
mechanisms can produce hyperglycemia as an end result, proper
selection of screening methods are critical in identifying and purifying
naturally occurring antidiabetic principles. One bioassay developed
by us involved alloxan-recovered rabbits. Rabbits are susceptible
to alloxan to varying degrees and some of them quickly recover
after initially exhibiting fasting hyperglycemia in the days following the administration of alloxan (Figures 1A and 1B). These animals
designated as alloxan-recovered rabbits still remain less tolerant to
glucose. Thus oral glucose (3 g/kg bdwt) tolerance tests in these animals
provide a wide range of peak values to use as a sensitive test for the
identification of hypoglycemic properties present in the herbal extracts
[7] (Figures 1A and 1B). Cultures of immortalized pancreatic beta
cells (e.g., Hit T-15) currently available through the ATCC are ideal
in identifying insulino tropic compounds. Interestingly, one partially
purified herbal extract that dramatically improved glucose tolerance in
alloxan-recovered rabbits, strongly inhibited insulin secretion in the in
vitro cultures of pancreatic beta cells [2] (Figure 1C). This observation
underscores the importance of employing more than one test method
in the screening of herbal extracts for their anti-hyperglycemic activity.
Therefore it is very important to design studies that combine in vivo
methods with in vitro techniques for gaining a better insight into the
actions of naturally occurring anti-hyperglycemic compounds. |
| |
|
Figure 1: (A) Glucose tolerance in alloxan-recovered rabbits treated with tolbutamide. Alloxan-recovered rabbits, after an overnight fasting, were orally administered
tolbutamide (1 g/kg bdwt). Glucose (3 g/kg bdwt) was administered orally 90 min later. Blood samples were drawn from the marginal ear vein at various intervals as
shown and serum glucose concentration was determined by a glucose-oxidase method.
(B) Glucose tolerance in alloxan-recovered rabbits treated with the bark extract (silica gel chromatographic fraction) of Ficus bengalensis. Alloxan-recovered rabbits,
after an overnight fasting, were orally administered with the bark extract (1 g/kg bdwt). Glucose (3 g/kg bdwt) was administered orally 90 min later. Blood samples
were drawn and analyzed for serum glucose as described in A.
(C) Insulin content of the culture media in which pancreatic beta cells were exposed to: a: none (control); b: DMSO (10 μL/mL); c: glybenclamide (1 mg/mL); and d: fenugreek protodioscin enriched fraction (FPEF; 1 mg/mL). Pancreatic beta cells were grown in 12-well cluster dishes to 60% confluence and then treated with
various agents (a-d) in high glucose DMEM medium for 30 min. The insulin content of the medium was determined using an ELISA kit from Crystal Chem (Downers
Grove, IL). Data points in A-C represent values of mean ± SEM (A and B) or mean ± SD (n=3; C). In Figure 1C, *p<0.01 and **p<0.05 for DMSO vs. glybenclamideand
FPEF treatments (respectively). With regard to (a) untreated controls, the treatments with (c) glybenclamide and (d) FPEF are significant at p<0.05. |
|
| |
| Acknowledgements |
| |
| This publication was supported in part by National Institutes of Health (NIH)
grant No. P20RR16456 and US Department of Education (ED) grant PO31B040030.
The contents of this publication are solely the responsibility of authors and do not
necessarily represent the official views of the NIH or USED. |
| |
|
| References |
| |
- Cusi K, DeFronzo RA (1988) Metformin: a review of its metabolic effects. Diabetes Rev 6: 89-131.
- Babu BV (2003) Antitumor agents. US Patent 6,660, 309.
- Poudyal H, Campbell F, Brown L (2010) Olive leaf extract attenuates cardiac, hepatic, and metabolic changes in highcarbohydrate–high fat-fed rats. J Nutr 140: 946-953.
- Gireesh G, Thomas SK, Joseph B, Paulose CS (2009) Antihyperglycemic and insulin secretory activity of Costus pictus leaf extract in streptozotocin induced diabetic rats and in in vitro pancreatic islet culture. J Ethnopharmacol 123: 470-474.
- Hannan JM, Marenah L, Ali L, Rokeya B, Flatt PR, et al. (2006) Ocimum sanctum leaf extracts stimulate insulin secretion from perfused pancreas, isolated islets and clonal pancreatic beta-cells. J Endocrinol 189: 127-136.
- El Aoufi S, Gendre P, Sennoune SR, Rigoard P, Maixent JM, et al. (2007) A high calorie diet induces type 2 diabetes in the desert sand rat (Psammomys obesus), Cell Mol Biol(Noisy-le-grand) 53: OL943-OL953.
- (1985) The hypoglycemic activity of Ficusbengalensis.
|
| |
| |
|
|
|
This article |
DOWNLOAD |
|
CONTRIBUTE |
|
SHARE |
|
EXPLORE |
|
 |
 |
| |
|
| |
| |
| |
|
Untitled Document
|
|
|
|
|
