Introduction: What they say:
A study from Department of Molecular Biology, Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA; and Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA shows that “Phf8 loss confers resistance to depression-like and anxiety-like behaviors in mice.” This research paper was published, in the May 2017 issue of the journal “Nature communications” [One of the best research journals in Metabolism with an I.Fs of ], by Prof.Hochedlinger K, Ryan M. Walsh 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 therapy for anxiety and depression: Nordihydroguaiaretic acid (NDGA), isolated from Larrea tridentata, decreases PHF8 levels, increases the expression of serotonin receptors Htr1a and Htr2a, and promotes resistance to stress-induced -anxiety and -depression via down regulation of its target gene
From the significance of the study to Public health relevance:
Given that: (1) one in three suffer from anxiety-related disorders worldwide; (2) nearly 12% of world population suffer from anxiety-related disorders in any given year; (3) 5-30% of people suffer from anxiety at some point in their lives; (4) 40 million adults in the US suffer from anxiety disorders; (5) nearly $42 billion a year spent in the US to treat anxiety disorders; (6) anxiety and depression are associated with higher rate of morbidity; (7) the percentage of people who suffer from anxiety is more from developed countries than from developing countries, while the opposite is true with depression; and (8) the global economic cost spent in the treatment of anxiety and depression occupies the significant portion of health care bill, there is an urgent need to find: (i) a way to cure long term anxiety and depression that are leading to a number of serious health complications; (ii) a way to induce resilience to anxiety and depression; (iii) a cheaper alternative to the existing expensive drugs; and (iv) a side-effect-free Natural product-based drug that not only alleviates, but also cures anxiety and depression.
What is known?
Mutations in PHF8, a histone demethylase, has been shown to result in cognitive defects and cleft lip/palate. However, its role in other physiological processes remains to be determined.
Prof.Hochedlinger Konrad’s research team has recently shown that knocking out PHF8/JMJD1.2 in mice results in: (1) no cognitive impairment; (2) up regulation of serotonin receptors Htr1a and Htr2; (3) normalization of Serotonin signalling; and (4) resistance to stress-induced anxiety- and depression-like behaviour, suggesting that inhibiting the expression of PHF8 may aid in the treatment of anxiety and depression.
From research findings to Therapeutic opportunity:
This study suggests a natural product-based therapy for anxiety and depression.
Nordihydroguaiaretic acid (NDGA), by increasing the expression of its target gene, it may decrease the expression of PHF8. Thereby, it may: (1) increase the expression of genes involved in serotonin signalling such as Htr1a and Htr2a; (2) normalize serotonin signalling; (3) promote resistance to stress-induced anxiety; and (4) heighten resistance to stress-induced depression-like behaviour. Thus, pharmacological formulations encompassing “Nordihydroguaiaretic acid (NDGA) or its analogues, either alone or in combination with other drugs, may be used to treat anxiety and depression; and promote resistance to depression- and anxiety-like behaviors (fig 1).
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
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Undisclosed mechanistic information: How Nordihydroguaiaretic acid (NDGA) decreases PHF8 levels, and increases serotonin receptors Htr1a and Htr2a levels, and promotes resistance to stress-induced anxiety and depression.
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Citation: Boominathan, L., Natural product-derived therapy for anxiety and depression: Nordihydroguaiaretic acid (NDGA), isolated from Larrea tridentata, decreases PHF8 levels, increases the expression of serotonin receptors Htr1a and Htr2a, and promotes resistance to stress-induced -anxiety and -depression via down regulation of its target gene, 24/November/2017, 10.53 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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