Epigenetics is defined as heritable alterations of gene expression without altering DNA sequences, leading to the occurrence of new phenotypes. Epigenetic modifications of DNA, histone, chromatin, and miRNA modulate gene transcription and expression, which are deposited by “writer”, “reader”, and “eraser” proteins. Recently, post-translational modifications have been deemed as promising targets in many chronic inflammatory diseases, including but not limited to cancer, fibrosis, inflammatory bowel disease, rheumatic arthritis, and neurodegenerative diseases. Natural compounds, as bioactive ingredients isolated from natural sources (plants, fungi, marine organisms, etc.) have the high potential to be developed as drug candidates. However, the natural and novel epigenetic antagonists/agonists against these diseases are severely lacking, despite several compounds in the clinical trials such as RVX-208, which ascribe to at least two major challenges:

a. Large amounts of new epigenetic modification types have not been found, and the modulation functions of the related target enzymes or effector proteins during the disease progression remain to be studied.
b. Chemical structural types of the existing epigenetic modulators for the treatment of chronic inflammatory diseases are sole and limited, urgently demanding the discovery of novel, safer, and more effective compounds with scaffold diversity, especially from the natural resource.

This Topic focuses on the discovery of novel natural antagonists/agonists and epigenetic modifications/targets in chronic inflammatory-related diseases. The detailed pharmacological mechanism of compounds at the animal level or the combination of theoretical and experimental methods are encouraged. Submissions (Editorials, Reviews, Concepts, Notes, Perspectives, Original Research, Book Reviews, etc.) are welcome in (but not limited to) the following topics:
• Discovery of natural small-molecule compounds targeting epigenetic proteins for treating chronic inflammatory diseases above.
• Identification of novel inflammation-related epigenetic modification types (or targets) and their biological function.
• Natural epigenetic modulators combined with chemical drugs in chronic inflammatory diseases.
• Natural epigenetic modulators combined with immune checkpoint therapy in cancer progression and metastasis.
• Structural modifications of natural compounds for improving their epigenetic functions.

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