Natural product therapy for glucose homeostasis and TIIDM: Methyl 3,5-dicaffeoyl quinate (MDQ), a flavonoid glucoside found in Castor-aralia (kalopanax-pictus), Salicornia herbacea L., Aster oharai and Solidago virga-aurea var. gigantean, increases IKKß and XBP1s activity, decreases the levels of tumor suppressor/stress-responsive proteins, such as PDCD4, and PTEN, reduces ER stress, improves insulin sensitivity, promotes glucose homeostasis and prevents the progression of TIIDM via up regulation of its target gene, 25/November/2015, 10.54 am

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What they say

A study from the Division of Endocrinology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02130, USA; Laboratory of Gene Regulation and Signal
Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA; and Department of Pathology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA shows that “Inflammation Improves Glucose Homeostasis through IKKß-XBP1s Interaction.” This research paper was published in the 3 November 2016 issue of the journal “Cell” [One of the best research journals in General Biology with an I.F of 28.71] by Profs. Ozcan Umut, Karin M, Dr. Liu J, and others.


What we say:

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On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Natural product therapy for glucose homeostasis and TIIDM: Methyl 3,5-dicaffeoyl quinate (MDQ), a flavonoid glucoside found in Castor-aralia (kalopanax-pictus), Salicornia herbacea L., Aster oharai and Solidago virga-aurea var. gigantean, increases IKKß and XBP1s activity, decreases the levels of tumor suppressor/stress-responsive proteins, such as PDCD4, and PTEN, reduces ER stress, improves insulin sensitivity, promotes glucose homeostasis and prevents the progression of TIIDM via up regulation of its target gene


Significance of the study to Public health relevance:

Given that: (1) more than 387 million people worldwide are affected by Diabetes mellitus (DM); (2) Diabetes is going to be one of the top 10 causes of death by 2030; (3) the life-long painful injection/drug treatment is required to treat DM; (3) the global economic cost spent for diabetes treatment in 2014 was little more than 600 billion US dollars, there is an urgent need to find: (i) a way to induce regeneration of adult ß-cells that were lost in DM; (ii) a cheaper alternative to the existing expensive weight-loss drugs; (iii) a side-effect-free natural product-based drug; and (iv) a way to cure, not just treat, diabetes.


What is known?

Prof. Ozcan Umut’s research team has recently shown that IKKß, by phosphorylating spliced form of X-Box Binding Protein 1 (XBP1s), it increases the activity of XBP1s. Thereby, it (1) decreases ER stress; (2) increases insulin sensitivity; and (3) promotes glucose homeostasis. However, the mechanistic basis of its regulation remains largely unclear.


From Research findings to Therapeutic opportunity:

This study suggests a Small-molecule based therapy for TIIDM. Methyl 3,5-dicaffeoyl quinate (MDQ), by increasing the expression of its target gene, it may increase the activity of XBP1s. Thereby, it may: (1) decrease the expression of stress-responsive/pro-apoptotic/tumor suppressive proteins, such as PTEN, PDCD4 etc.,; (2) decrease ER stress; (3) increase insulin sensitivity; and (4) promote glucose homeostasis.

Salicornia herbacea L. Methyl 3,5-dicaffeoyl quinate (MDQ), found in Salicornia herbacea L among others, increases the activity of XBP1s, decreases the expression of stress-responsive proteins, such as PDCD4,  & PTEN, increases insulin sensitivity and promotes glucose homeostasis

aster-oharai-aster_spathulifolius_pdb

Aster oharai

Thus, pharmacological formulations encompassing “Methyl 3,5-dicaffeoyl quinate (MDQ) or its analogues or MDQ with any of the known anti-diabeteic compounds in use may be used to treat TIIDM.


Details of the research findings

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

Amount: $ 300

Undisclosed mechanistic information: How Methyl 3,5-dicaffeoyl quinate (MDQ) or its analogues increases the activity of activity of XBP1s and decreases the expression of PTEN and PDCD4

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References: 

Citation: Boominathan, L.,  Natural product therapy for glucose homeostasis and TIIDM: Methyl 3,5-dicaffeoyl quinate (MDQ), a flavonoid glucoside found in Castor-aralia (kalopanax-pictus), Salicornia herbacea L., Aster oharai and Solidago virga-aurea var. gigantean, increases IKKß and XBP1s activity, decreases the levels of tumor suppressor/stress-responsive proteins, such as PDCD4, and PTEN, reduces ER stress, improves insulin sensitivity, promotes glucose homeostasis and prevents the progression of TIIDM via up regulation of its target gene, 25/November/2015, 10.54 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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