A recent study from the Yonsei University College of Medicine, Seoul, Korea shows that Sestrin2 suppresses Sepsis by inducing mitophagy and inhibiting NLRP3 activation. This study was published in the 2 August 2016 issue of the Journal “Autophagy” [the number one journal in autophagy with an impact factor of 10+] by Drs. Yoon JH, Kim MJ and others.
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Natural product Antisepsis therapy: Epigallocatechin gallate, one of the components in green tea, increases Sestrin2 expression, inhibits NLRP3 inflammasome activation, and pro-inflammatory cytokines secretion, induces mitophagy in macrophages, and clears damaged mitochondria via autophagic machinery, and protects the host from sepsis via up- regulation of its target gene
Given that: (1) molecular pathways and the mechanism of development of Sepsis is far from understood; (2) nearly 180 lakhs of people are affected by Sepsis each year globally; (3) the risk of death from Sepsis is anywhere from alarming 30% to 80%; (4) millions of deaths occur due to Sepsis each year globally; (5) Sepsis is the tenth leading cause of death globally; (6) Sepsis is the second-leading cause of death in non-coronary intensive care unit patients; (7) global economic cost spent in the treatment of Sepsis is little more than 2 billion US dollars each year; & (8) more than 90% of cases are registered in developing countries—that cannot afford high-cost treatment —compared to developed countries, there is an urgent need to find: (i) a way to inhibit Sepsis-causing agents that promote activation of inflammasomes, and aberrant secretion of pro-inflammatory mediators; (ii) a cheaper alternative to the existing expensive drugs; and (iii) a side-effect-free-Natural product-based drug.
This study suggests a natural product-based therapy for Sepsis. Epigallocatechin gallate, by increasing the expression of its target gene, it may: (1) increase the expression of Sestrin-2; (2) decrease NLRP3 (NLR family, pyrin domain containing 3) inflammasome activation and pro-inflammatory mediators secretion; (3) promote perinuclear clustering and clearance of damaged mitochondria through induction of (a) SQSTM1 (Sequestosome 1) aggregation on the mitochondrial surface; (b) ULK1 (unc-51 like kinase 1) protein levels; and (c) mitophagy. Thereby, it may promote immunological homeostasis and protect the host from Sepsis. Together, pharmacological formulations encompassing “Epigallocatechin gallate or its analog“ may be used to (1) enhance innate immunity against bacterial infections; and (2) treat Sepsis.
Idea Proposed/Formulated by: Dr L Boominathan Ph.D.
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Citation: Boominathan, Natural product Antisepsis therapy: Epigallocatechin gallate, one of the components in green tea, increases Sestrin2 expression, inhibits NLRP3 inflammasome activation, and pro-inflammatory cytokines secretion, induces mitophagy in macrophages, and clears damaged mitochondria via autophagic machinery, and protects the host from sepsis via up- regulation of its target gene, 20/October/2016, 10.05 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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Undisclosed information: How Epigallocatechin gallate: (1) increases the expression of Sestrin-2 ; and (2) enhances innate immunity against bacterial infection and Sepsis.