American ginseng increases insulin production and prevents beta cells apoptosis in diabetes mellitus
Background
As a devastating illness with significant morbidity and mortality, diabetes mellitus has increased steadily worldwide.
There are mainly 2 types of diabetes:
- Type 1 juvenile diabetes is caused by auto immune disorders leading to extensive destruction of the insulin-producing beta cells in the islets of Langerhans in the pancreas.
- Type 2 adult-onset diabetes is a metabolic disorder , it is characterized by a progressive decline in beta cells function and chronic insulin resistance, its cause remains poorly understood.
All type 1 and some of type 2 diabetic patients require daily insulin shots; either replacement of destroyed beta cells via islets or pancreas transplant is sometimes necessary.
Both types are characterized by progressive beta cells failure and recent treatments are focusing on enhancing endogenous β-cell function and regeneration. Apoptosis is probably the main form of β-cell death in diabetes.
The role of Ginseng
The use of herbal remedies has been on the rise in the western countries in the last years.
Historical treatment of diabetes utilizes traditional medicine and integrates of ginseng root extracts in tonic form into the diet. Ginseng is a medicinal plant widely used for the treatment of various conditions: the pharmacological effects of ginseng have been demonstrated in cancer, diabetes, cardiovascular diseases and have been used for promoting immune function, central nervous system (CNS) function, relieving stress, and for its antioxidant activities.
(Biological activities of ginseng and Its application to human health, 2011)
American ( Panax quinquefolius ) and Asian ginsengs ( Panax ginseng ) stand as the two widely used species of ginseng. According to Chinese medicine theory, the two ginseng types possess different properties and display different effects.
Ginenosides
The main active components in ginseng responsible for ginseng's medical value have been identified as Glycosides, that is a naturally occurring substance consisting of a sugar and non-sugar moiety. Some glycosides belong to a family of compounds named Saponins which produce froth under agitation by reducing water surface tension. A group of saponins in ginseng have been named Ginsenosides.
Almost 50 ginsenosides have been isolated from Asian Ginseng root, and novel structures continue to be identified, particularly from American ginseng and Japanese ginseng as well as their berries.
The ginsenosides are often split into two groups:
-Rb1 group (characterized by the protopanaxadiol presence [figure A]: Rb1, Rb2, Rc and Rd)
-Rg1 group (characterized by the protopanaxatriol presence [figure B]: Rg1, Re, Rf, and Rg2)
American ginseng and diabetes
The structural diversity of ginsenosides may contribute to the multiple pharmacological effects of ginseng, in this essay I focus on the capacity of American ginseng ( Panax quinquefolius ) for increasing insulin production and reducing the death of pancreatic beta cells. Ginsenosides Rb1 and Rg1 seem to have a critical role in these process, indeed Panax quinquefolius has high content of these 2 ginsenosides.
(Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium, 2008, paragraph:_chemestry_)
Panax quinquefolius improves beta cells insulin production (the role of UCP-2)
The inability to produce adequate amounts of insulin is a factor attributed to beta cell dysfunction. Possible causes include a disorder in beta cells preventing the production of insulin and the death of the insulin producing beta cells.
The protein UCP-2 has been found to play a critical role in this process. UCP-2 belongs to a family of anion mitochondrial transporters ( Uncoupling Proteins) linked to negatively regulated metabolism.
An Uncoupling protein is a mitochondrial inner membrane protein that can dissipate the proton gradient between the inner and che outer mithocondrial membrane:
-In a coupled state H+ re-enters the mithocondrial matrix trough ATP-sintase to generate ATP from ADP ( oxidative phosphorilation );
-In a Uncoupled state H+ can transit the membrane via UCPs, thereby resulting in oxidation of glucose without concomitant production of ATP.
The energy that is not used for the production of ATP is dissipated as heat .
In mammals we can recognize 5 types of UCP :
-UCP-1 : expressed in brown adipose tissue (also known as Thermogenina);
-UCP-2 : expressed ubiquitously (including pancreatic cells);
-UCP-3 : mainly presented in skeleton muscle;
-UCP-4 and UCP-5 : expressed in brain.
Pancreatic
cells sense glucose through its metabolism and the resulting increase in the ATP/ADP ratio, which closes the K-ATP channel, causing plasma membrane depolarization, influx of Calcium, and finally insulin secretion.
(Secretion of insulin from beta cells )
It has been proposed that UCP2 limits production of reactive oxygen species (ROS) by decreasing the mitochondrial membrane potential. Given the proton leak activity of UCP2 and its predicted negative effect on ATP synthesis in
cells, UCP2 could be a negative regulator of insulin secretion.
(Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes, 2001 )
Cultured cells induced with IL-1 beta (a cytokine that is able to induce apoptosis in cells) exhibit a much higher level of UCP-2, these cells tend to have lower survival rates. Panax quinquefolius significantly reduces the level of UCP-2 and increases ATP in the mitochondrion.
(American Ginseng Stimulates Insulin Production and Prevents Apoptosis through Regulation of UCP-2 in Cultured β Cells,2006,paragraph:_results_)
Panax quinquefolius protects beta cells from apoptosis
During apoptosis, cells shrink, chromatin condenses, DNA is cleaved into pieces at internucleosomal regions. The cell breaks down into small pieces which are then absorbed by neighboring cells without causing inflammation. A proactive way to increase beta cell viability is to decrease apoptosis level in order to retain the cell population and increase insulin production.
Apoptosis is mediated by many factors, one of which is the Bcl-2 proto-oncogene which protects the cell against apoptosis by preventing activation of the Caspase cascade (Programmed Cell Death-Apoptosis, 2002) . This mechanism involves translocation of cytochrome C from the mitochondrion to activate caspase 9 and then caspase 3, initiating the proteolytic cascade essential for apoptosis.
Some studies suggest that Panax quinquefolius regulates pancreatic beta cell apoptosis through mediating the levels of Bcl-2 and capase-9; in particular the herb significantly up-regulated the levels of Bcl-2 and down-regulated levels of caspase-9 expression.
(American Ginseng Stimulates Insulin Production and Prevents Apoptosis through Regulation of UCP-2 in Cultured β Cells,2006,paragraph:_results_)
This image reassume all the previous pathways nominated :
Conclusions
Therefore from these hypothesis we can evaluate Ginseng as an alternative remedy for the treatment of diabetes mellitus.
Further research is required to fully understand the effects of American ginseng extracts on pancreatic β cells and factors utilized by American ginseng to achieve cell regulation and function.
Moreover in some studies a Ginseng abuse syndrome (Ginseng Abuse Syndrome Problems With the Panacea, 1979) is mentioned : that is a group of symptoms arising from prolonged and excessive ginseng intake. Some of these symptoms have included nausea,headache and dizziness, insomnia, nervousness,and hypertension; isolated cases of diarrhea and fatigue also have been reported in some cases.
On the other hand other studies have demonstrated that prolonged or excessive ginseng consumption involves very low risk to the user.
