Abstract
Posttraumatic stress disorder (PTSD) gains a lot of attention due to high prevalence and strong psychological upset, but the etiology remains undefined and effective treatment is quite limited. Growing studies demonstrated the involvement of oxidative stress in various psychiatry diseases, suggesting anti-oxidation therapy might be a strategy for PTSD treatment. Free and Easy Wanderer (FAEW) is a poly-herbal drug clinically used in China for hundreds of years in the treatment of psychiatric disorder. We hypothesized that FAEW exerts clinical effects through the activity against oxidative stress with fluoxetine as antidepressant control drug. Our results revealed that FAEW significantly reduced both endogenous and H2O2-induced exogenous ROS levels in the human glioblastoma T98G and neuroblastoma SH-SY5Y cell lines. Transcriptome-wide microarray analysis indicated NRF2/HO-1 as the common target of FAEW and fluoxetine. Western blotting assay proved that the two drugs promoted NRF2 release from KEAP1 in the cytoplasm and translocation to the nuclei in a KEAP1-dependent manner, the expression of the protein HO-1 increased accordingly, suggesting the participation of KEAP1-NRF2/HO-1 pathway. The chemical constituents of FAEW (i.e. paeoniflorin, baicalin) bound to KEAP1 in silico, which hence might be the effective substances of FAEW. In conclusion, FAEW counteracted H2O2-induced oxidative stress through KEAP1-NRF2/HO-1 pathway.
Highlights
Posttraumatic stress disorder (PTSD) may develop after a person is exposed to a traumatic event, characterized by repeatedly experiencing trauma with disturbing recurring flashbacks, avoidance or numbing of memories of the event, and hyper-arousal[1,2,3,4]
Fluoxetine was non-toxic up to 3.1 μg/ml (10 μM) and inhibited T98G cells at higher concentrations (Fig. 1A2). Both Free and easy wanderer (FAEW) and fluoxetine have no cytotoxicity towards SH-SY5Y cell, even at higher concentrations (Fig. 1B1, B2)
Oxidative stress occurs if molecular defense systems fail to counteract oxidation caused by endogenous processes such as the mitochondrial breakdown of glucose for energy supply or by exogenous xenobiotic chemicals, air pollution and diet
Summary
Posttraumatic stress disorder (PTSD) may develop after a person is exposed to a traumatic event, characterized by repeatedly experiencing trauma with disturbing recurring flashbacks, avoidance or numbing of memories of the event, and hyper-arousal[1,2,3,4]. It was first recognized as a distinct disease among US-American Vietnam veterans and becomes popular due to high prevalence, strong psychological upset and difficult prediction. Free and easy wanderer (FAEW) is a poly-herbal preparation It has been long used in China for the treatment of depression, premenstrual dysphoric disorder, climacteric syndrome, and Parkinson’s disease. FAEW has a good reputation in the history of Chinese medicine and shows great potential in the treatment of PTSD, the cellular and molecular modes of action are still not well understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
