Natural product-derived (exercise mementics) therapy for Metabolic disease: Angelica sinensis increases PPARδ levels, inhibits glucose catabolism, preserves glucose levels, stimulates FA catabolism, delays the onset of hypoglycemia and boosts endurance exercise via down regulation of its target gene, 19/May/2017, 12.00 am

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Introduction: What they say

A study from the Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA shows that “PPARδ Promotes Running Endurance by Preserving Glucose.” This research paper was published, in the 2 May 2017 issue of the journal “Cell Metabolism” [One of the best research journals in Metabolism with an I.Fs of 30.357], by Prof.Ronald M. Evans, Weiwei Fan and others.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Natural product-derived (exercise mementics) therapy for Metabolic disease: Angelica sinensis increases PPARδ levels, inhibits glucose catabolism, preserves glucose levels, stimulates FA catabolism, delays the onset of hypoglycemia and boosts endurance exercise via down regulation of its target gene


From the Significance of the study to Public health relevance:

Given that: (1) metabolic disease is the principal cause for a number of human diseases; (2) metabolic disease approximately affects more than 60% of population older than 50 years; (3) metabolic disease affects 30-32% of adult population worldwide; (4) metabolic disease is characterized by abdominal (central) obesity, increased blood pressure, large increase in fasting plasma glucose, high serum triglycerides, low high-density lipoprotein (HDL) levels and high low-density lipoprotein (LDL) levels; (5) prolonged uncontrolled metabolic disease may result in atherosclerosis, diabetes, hypertension, cardiovascular disease etc., (6) the raise of death rate, due to metabolic disease, has increased considerably in the last few decades; (7) 13% of cardiovascular disease occur due to uncontrolled high blood pressure; (8) in India, in 2004, 14.6 lakhs deaths (14% of total deaths) were due to ischemic heart disease; (9) 85% of people over 80 years are susceptible to cardiovascular diseases; (10) the global economic cost spent in the treatment of metabolic disease is enormous; and (11) the death due to cardiovascular disease is higher in low-to-middle income countries compared to developed countries, there is an urgent need to find: (i) a cure to metabolic diseases leading to a number of health complications, as mentioned above; (ii) a way to induce exercise endurance in older people; (iii) a cheaper alternative to the existing expensive drugs; and (iv) a side-effect-free Natural product-based drug that alleviates metabolic disease, dystrophies, and boosts exercise performance in older individuals.


What is known?

Prof. Ronald M. Evans’s research team has recently shown that increased expression of PPARδ: (1) by exercise mimetics promotes endurance; (2) increases running time significantly; (3) decreases the expression of genes involved in glucose uptake, glycolysis, and mitochondrial pyruvate entry such as Hk2, Gck, and mitochondrial pyruvate carrier (Mcp1); (4) increases mitochondrial gatekeeper genes Cpt1b and Pdk4; (5) up regulates genes involved in FA transport, FA oxidation, lipogenesis, and gluconeogenesis; (6) increases FA catabolism, decreases glycolysis and preserves systemic glucose; and (7) promotes endurance.


From Research findings to Therapeutic opportunity:

A few studies suggests that Angelica sinensis ameliorates metabolic diseases. However, the mechanistic basis of which remains largely unclear.

This study suggests a natural product-based therapy to increase exercise endurance; and alleviate metabolic disease.

Angelica sinensis extract, by increasing the expression of its target gene, it may increase the expression of PPARδ and its down stream target genes. Thereby, it may: (1) decrease the expression of genes involved in glucose uptake and transport metabolism such as Hk2, Gck, and Mcp1; (2) increase the expression of mitochondrial gatekeeper genes Cpt1b and Pdk4; (3) increase the expression of genes that govern FA transport, FA oxidation, lipogenesis, and gluconeogenesis; (4) increase decrease glycolysis and preserve systemic glucose in muscle; and (5) promote endurance. Thus, pharmacological formulations encompassing Angelica sinensis extract  or an active compound isolated from it, either alone or in combination with other drugs,” may be used to treat metabolic disease, dystrophies, and to boost exercise/athletic performance (fig 1). 

Figure1. Mechanistic insights into how Angelica sinensis increases PPARδ levels, decreases glycolysis, preserves systemic glucose levels and promotes endurance.


Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Amount: $ 500#

Undisclosed mechanistic information: How Angelica sinensis  increases PPARδ levels, decreases glycolysis, preserves systemic glucose levels and promotes endurance.
# Research cooperation

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References:

Web: http://genomediscovery.org or http://newbioideas.com

Citation: Boominathan, L., Natural product-derived (exercise mementics) therapy for Metabolic disease: Angelica sinensis increases PPARδ levels, inhibits glucose catabolism, preserves glucose levels, stimulates FA catabolism, delays the onset of hypoglycemia and boosts endurance exercise via down regulation of its target gene, 19/May/2017, 12.00 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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