Use of secoisolariciresinol diglucosides (sdgs) and related compounds for protection against radiation and chemical damage

A technology for ring-opening isolarches and glucosides, which can be applied in the directions of active ingredients of hydroxyl compounds, drug combinations, plant raw materials, etc., can solve problems such as difficulty in finding chemopreventive agents

Inactive Publication Date: 2017-09-12
THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this definition sounds simple, it is difficult to find effective chemopreventive agents
First, the mechanisms by which carcinogens induce cancer often involve multiple mechanisms, making efficacy challenging and requiring agents with multiple activities
Second, since the agent will be used to prevent a small number of tumors in a large number of healthy but at-risk individuals, it must be very nontoxic, well tolerated and affordable

Method used

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  • Use of secoisolariciresinol diglucosides (sdgs) and related compounds for protection against radiation and chemical damage
  • Use of secoisolariciresinol diglucosides (sdgs) and related compounds for protection against radiation and chemical damage
  • Use of secoisolariciresinol diglucosides (sdgs) and related compounds for protection against radiation and chemical damage

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0156] Synthetic (S,S) and (R,R)-seoisolarixin diglucoside (SDG) protects naked plasmid and genomic DNA from γ-irradiation damage

[0157] As a result of nuclear disintegration, three types of radiation are produced, alpha (α) with a positive charge, beta (β) with a negative charge and gamma (γ) with no charge. In the case of gamma-radiation, the electromagnetic waves have a very small wavelength (. OH). These hydroxyl radicals ( . OH) is a major source of ionizing radiation-induced damage to cellular components, including lipids, proteins, and genomic DNA. Hydroxyl radicals produced by gamma radiation ( . OH) cause single-strand and double-strand breaks in DNA. ( . OH) free radicals damage DNA by abstracting H atoms from deoxyribose and purine and pyrimidine bases or adding to the double bonds of the bases. These reactions result in DNA strand breaks.

[0158] Compounds with antioxidant and free radical scavenging properties can act as radioprotectants and prevent radia...

example 2

[0199] Radioprotective properties of lignin secoisolaricidin diglucoside (SDG) in lung cells

[0200] Radiation damage to cells is initiated by the generation of reactive oxygen species (ROS). The spectrum of damage caused by ROS to cellular mechanisms includes lipid peroxidation, DNA-protein cross-linking, base modification, adduct formation and single- and double-strand breaks (DNA SSBs and DSBs). These modifications have been implicated in radiation-induced apoptosis and cell death. Since cellular DNA damage is a known determinant in radiation-induced cell death, significant efforts have been made to identify and develop phenotypes that can protect DNA from radiation by interfering with free radical responses or by modulating radiation-induced apoptosis. Damaged reagents.

[0201] Protection from radiation-induced genotoxicity can be achieved by the presence of antioxidants in the system at the time of exposure. Since antioxidants can be ROS scavengers that interfere wit...

example 3

[0254] Hypochlorite ion scavenging by secoisolaricidin diglucoside (SDG): A novel mechanism by which SDG protects genomic DNA from radiation

[0255] Hypochlorous acid (HOCl), a potent oxidant, is produced by neutrophils through activated myeloperoxidase, which catalyzes the physiologically present chloride ions and hydrogen peroxide (H 2 o 2 ) between the responses. Activated neutrophils produce H 2 o 2 and superoxide anion O 2 · - . At physiological pH, HOCl and hypochlorite ions (ClO - )mixture. HOCl kills microorganisms through oxidative damage. However, excess production is known to cause damage to tissues. Hypochlorite modification of adenine nucleotides leads to the formation of chloramines, which appears to be the main mechanism of neutrophil-mediated toxicity.

[0256] HOCl and its conjugate base ClO - Has been shown to oxidize amino acids, peptides, proteins and lipids, and chlorinate bases in cellular DNA and RNA. HOCl / ClO - The reaction leads to the mo...

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Abstract

The invention provides compositions and methods for radio protection and chemo prevention using therapeutic and prophylactics methods of using (S,S)-SDG (R,R)- SDG, (S,R)-SDG (R,S)-SDG, SDG, SECO, EL, ED, analogs thereof, stereoisomers thereof and other related molecules. In one aspect, the invention relates to a method for protecting a biomolecule(such as genetic material like a nucleic acid, a protein or a lipid), a cell, or a tissue, from radiation damage in a subject in need thereof, the method comprising administering to said subject an effective amount of flaxseed, its bioactive ingredient, degradant or a metabolite thereof.

Description

[0001] government interest [0002] This invention was made with government support under grant numbers R01 (CA133470), 1P30ES013508-02, RC1AI081251, and 5-P30-CA-016520-34S2 awarded by the National Institutes of Health. The government has certain rights in this invention. field of invention [0003] This article provides information on the use of cleaved secoisolarixin diglucoside (SDG), secoisolarixin (SECO), enterediol (ED), enterolactone (EL), their stereoisomers, and their metabolism. Compositions and methods for radiation protection and radiation mitigation and for chemoprevention, such as avoiding carcinogen-induced lung cancer and mesothelioma or avoiding hypochlorite ions, and analogs thereof. Background of the invention [0004] Ionizing radiation produces a wide range of harmful effects in living organisms. Exposure of humans to radiation due to occupational hazards, during diagnostic and therapeutic radiography procedures, when electronic equipment is used, bac...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K36/55
CPCA61K31/05A61K31/09A61K31/7028A61P35/00A61P39/02A61P39/06A61K31/365A61K2300/00
Inventor 迈尔波·赫里斯托费多-所罗米多
Owner THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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