Therapeutic potentials of natural products for post-traumatic stress disorder: A focus on epigenetics

Abstract

Post-traumatic stress disorder (PTSD) is a relatively common but complex mental illness with a range of diverse risk factors. Typical symptoms include the re-experience or avoidance of traumatic events, cognitive impairment, and hypervigilance. While the exact pathogenesis of PTSD is unclear, many studies indicate that epigenetic regulation plays a key role in its development. Specifically, numerous studies have indicated that the levels of histone acetylation and methylation, DNA methylation, and noncoding RNA are altered in PTSD patients. Further to this, natural products have been found to achieve epigenetic regulation of PTSD by regulating the expression of epigenetic enzymes, long noncoding RNA (lncRNA), and miRNA, thereby playing a role in improving PTSD symptoms. To date, however, no epigenetic regulation related drugs have been used in the treatment of PTSD. Furthermore, while natural products that can epigenetically regulate PTSD have received increasing levels of attention, there have not yet been any systematic reports on the topic. Here, we summarized the roles and mechanisms of natural products in the epigenetic regulation of PTSD, providing a novel and unique perspective that will help to guide the development and application of new PTSD treatments.

Keywords: DNA methylation; epigenetic regulation; histone modification; natural products; noncoding RNA; post-traumatic stress disorder.

Fig. 1

Therapeutic mechanisms of natural products for PTSD. Natural products can exert epigenetic regulatory effects through histone acetylation, histone methylation, DNA methylation, miRNA, LncRNA, and other therapeutic mechanisms. In addition, abnormal histone acetylation or methylation levels and abnormal gene expression levels can also be rescued through the epigenetic effects of natural products, thus playing a therapeutic role.

Fig. 2

Effects of various natural products on histone acetylation and methylation in PTSD. Histone modification mainly includes histone acetylation, methylation and phosphorylation. Firstly, for histone acetylation, the modification site is mainly at the relatively conserved lysine site of the N terminal of histone, and the process is mainly coordinated by histone acetyltransferase and histone deacetylase. Secondly, the main modification sites of histone methylation are arginine and lysine. In addition, different modifications at different sites also play different effects on transcription and gene expression. Moreover, natural products can exert therapeutic effects by acting on different sites. For example, EGCG can up-regulate the methylation level of H3K27 site and also up-regulate the acetylation level of H3K9 site. In short, different natural products can play different regulatory roles by acting on different sites.

Fig. 3

Effects of various natural products on DNA methylation in PTSD. DNA methylation occurs under the action of DNA methyltransferase, and DNA methylation has multiple sites of action. Reports related to PTSD have shown that BDNF, TNF, AIM2, SKA2, KL and other gene loci have different levels of DNA methylation. In addition, natural products can regulate methylation levels at different sites by affecting the expression of DNA methyltransferase, which in turn affects the expression of related factors such as BDNF or TNF in PTSD patients.

Fig. 4

Various natural products and their effects on noncoding RNA in PTSD. The regulation of non-coding RNA mainly includes the regulation of miRNA and LncRNA. Both affect transcriptional activation and inhibition in different ways of action. A large number of natural products, including RA, GAS, GRg1, GRb1, EGCG, can regulate and change the levels of different types of miRNAs through epigenetic regulation, so as to achieve the purpose of transcriptional activation or inhibition, and then regulate the level of miRNA in PTSD patients. Natural products such as GAS, CUR and OLE can also exert therapeutic effects by regulating LncRNA.

Fig. 5

Chemical sructures of various natural products on histone acetylation and methylation in PTSD.