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February 5, 2016
Recent preclinical trial results set the stage for ongoing research potentially benefitting type 2 diabetes and joint health.
Therapeutic Potential against Type 2 Diabetes
A new study published in the Journal of Lipid Research, revealed palm gamma-tocotrienol (γ-T3) retarded inflammation in type 2 diabetes mouse models via inhibition of Nod-like receptor 3 (NLRP3) inflammasome (an intracellular sensor that detects imbalanced intake of nutrient such as excessive fats or glucose).
In the study, 6-week old of male (db/db) mice were fed a standard AIN93G diet devoid of γ-T3 (control) or AIN93G diet containing 0.1 percent (w/w) γ-T3 ( supplied by ExcelVite Inc.) for 8 weeks ad libitum.
When comparing to mice not fed with γ-T3, γ-T3-supplemented mice suppressed NLRP3-inflammasome activity by decreasing NLRP3 protein expression and caspase-1 cleavage. Additionally, γ-T3-supplemented mice showed a significant decrease in fasting glucose levels, improved glucose disposal during glucose tolerance test (GTT), significantly high insulin-positive area per pancreatic islet cells (insulin producing cells), and low level of immune cell infiltration into white adipose tissues, suggesting attenuation of type 2 diabetes progression.
Inflammation is critical to the pathogenesis of type 2 diabetes, while imbalanced intake of nutrient may induce pro-inflammatory cytokines such as NF-κB that could lead to the death of insulin-producing cells. The study demonstrated two identified mechanisms exhibited by γ-T3 in decreasing NLRP3 inflammasome activities.
First, γ-T3 deactivated NF-κB (nuclear factor-κB, a pro-inflammatory mediator) by increasing the expression of A20 (protein that attenuates inflammatory process). Secondly, the presence of γ-T3, together with AMPK (5' AMP-activated protein kinase, enzyme important for cellular energy homeostasis) inhibited activities of caspase-1 (enzyme that involves in programmed cell death).
Collectively, γ-T3 helps to enhance insulin sensitivity in cells, reduces nutritional imbalance-associated inflammation, and inhibits the formation of pro-inflammatory mediators with AMPK, thereby decreasing the risks of developing type 2 diabetes.
“This is the first study to demonstrate that γ-T3 is able to ameliorate type 2 diabetes via the suppression of NLRP3 inflammasome," said CheeYen Lau, ExcelVite nutritionist. “According to the World Health Organization, the prevalence of diabetes was estimated to be 9 percent among adults above 18 years. In other words, almost one out of 10 adults worldwide is diagnosed with diabetes! One effective way to reduce the risks of developing type 2 diabetes is to increase the intake of tocotrienol. As the level of tocotrienols in Western food is only at trace level, it is highly recommended to incorporate palm oil as the main cooking oil or consume tocotrienol dietary supplements to increase their daily dietary intake of tocotrienol."
New Developments in Joint Health
The Journal of Integrative Medicine published pre-clinical data showing anti-inflammatory and analgesic efficacy for UP1304, a composite containing a standardized blend of extracts from the rhizome of Curcuma longa and the root bark of Morus alba (as Romatol™ by Unigen Inc.). The data showed UP1304 performing similarly to the positive control for reducing joint discomfort at two time points when tested in a proven pre-clinical model.
The study authors assessed the analgesic and anti-inflammatory effects of UP1304 on rats with carrageenan-induced paw edema using oral dose ranges of 100 to 400 mg/kg. Ibuprofen, at a dose of 200 mg/kg, was used as a reference compound. In vitro, cyclooxygenase (COX) and lipoxygenase (LOX) inhibition assays were performed to evaluate the degree of inflammation.
Statistically significant improvements in pain resistance and paw edema suppression were observed in animals treated with UP1304, when compared to vehicle-treated rats. Results from the highest dose of UP1304 (400 mg/kg) were similar to those achieved by ibuprofen treatment at 200 mg/kg. In vitro, UP1304 showed dose-dependent inhibition of the enzymatic activities of COX and LOX. A half-maximal inhibitory concentration of 9.6 μg/mL for bradykinin B1 inhibition was calculated for the organic extract of C. longa. Curcumin showed Ki values of 2.73 and 58 μg/mL for bradykinin receptors B1 and B2, respectively.
The data suggested UP1304 acted as a bradykinin receptor B1 and B2 antagonist, and inhibited COX and LOX enzyme activities, thereby making the compound a consideration for further research regarding the management of symptoms associated with arthritis.
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