NRF2 activator compound, drugs and new application of atractylenolide II

Abstract

The invention discloses an NRF2 activator compound, drugs and new application of atractylenolide II, wherein the NRF2 activator compound is the atractylenolide II; the drugs are drugs for treating and preventing the diseases associated with NRF2 pathway regulation, and comprise the component atractylenolide II; the new application of the atractylenolide II is about the use of the atractylenolide II in preparing drugs or foods for treating or preventing the diseases associated with the NRF2 pathway regulation. Through a lot of exploration and research of the inventors, a plurality of compounds are tested and selected, and it is unexpectedly found that the atractylenolide II can be used as an effective NRF2 inducer. The experiments prove that the atractylenolide II can be used in the drugs for treating or preventing the diseases associated with the NRF2 pathway regulation. Particularly, the cell experiments and the animal experiments prove that the atractylenolide II has inhibitory effect on the growth of breast cancer cells.

Description

technical field [0001] The invention belongs to the field of biochemistry and relates to NRF2 activators. Background technique [0002] The nuclear factor-E2-related factor 2 (NRF2) pathway is one of the key signaling pathways for cancer chemoprevention. In the process of cancer development, the NRF2 pathway is activated by the induction of carcinogens and chemopreventive compounds, thereby inducing the synthesis of phase II detoxification enzymes such as NQO1, γ-GCS, GSTs, HO-1, etc. Oxidation, anti-inflammatory, detoxification and other effects, and then protect cells. A large number of studies have shown that the activation of NRF2 plays an important role in the prevention of various diseases, such as cancer, neurodegenerative diseases, cardiovascular diseases, ischemia, diabetes, pulmonary fibrosis, and inflammation. [0003] As far as cancer is concerned, phase II metabolic enzymes can catalyze the binding or reduction of metabolites produced by phase I metabolic reac...

AI Technical Summary

Problems solved by technology

[0006] 1. The bardoxolone developed by Abbott is considered to be an important regulator of intracellular antioxidants and detoxification enzymes, and can inhibit the main inflammatory gene regulator NFkB. It aims to activate the NRF2 pathway and is developed for the treatment of chronic kidney disease and diabetes , but due to the low specificity and the ability to bind to a variety of proteins, excessive serious adverse events and deaths occurred during the trial, and finally stopped in phase III clinical trials

[0007] 2. Now many studies have also found some NRF2 chemical inducers, such as brusatol, ascorbic acid (ascorbic acid), luteolin (luteolin), ochratoxin A (ochratoxin A), trigonellin (trigonelline), all- trans retinoic acid (all-trans retinoic acid), Sulforaphane (sulforaphane), etc., but their effectiveness is still unsatisfactory and even toxic, and their mechanism of action is not completely clear

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