Molecular mechanisms of Chinese herb formula free and easy wanderer in the treatment of mental disorders
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Abstract
Background: Posttraumatic stress disorder (PTSD) is a mental disorder after traumatic events and is characterized by repeated experience of a trauma with disturbing recurring reflections, avoidance or numbing of memories of the event and hyper-arousal. Due to the high prevalence it has attracted much attention in the past years. The etiology is unclear and new treatment methods are urgently required. Various recipes of Chinese herbs are successfully used in Asian countries against mental disorders. For example, Free and Easy Wanderer (FAEW) has been a complex herbal mixture for treating mental disorders in China for centuries, but its mode of action is still unclear. Method: We conducted the following studies to elucidate the mechanisms of FAEW: (1) we have chosen a "reverse pharmacology" approach and initially used clinical data to verify identified potential PTSD mechanisms in subsequent in vitro and in silico studies. For this purpose, microarray-based transcriptome-wide mRNA expression profiles of PTSD patients were analyzed, the effect of FAEW and the clinically established antidepressant fluoxetine on the transcription factor NF-κB using reporter cell assays and Western blotting was investigated. (2) We investigated the neuroprotective effect of FAEW under oxidative stress and the underlying mechanism by microarray and Western blot experiments. (3) We identified various potential drugs by molecular docking and literature research based on the phytochemical components of FAEW. Results: FAEW showed high anti-inflammatory activity by inhibiting NF-κB. PTSD-associated oxidative stress was induced by hydrogen peroxide in the experiment. Here it was shown that FAEW counteracts oxidative stress through KEAP1-NRF2/HO-1 pathway. Paeoniflorin, albiflorin, baicalin, isoliquiritin and liquiritin in silico bound with high affinity to the proteins IκK, p65 and KEAP1. Conclusion: FAEW has a variety of drugs and is active against inflammation by inhibition of NF-κB and against oxidative stress by activation of KEAP1-NRF2/HO-1 signaling pathway, which could be relevant mechanisms of Free and Easy Wanderer in the treatment of mental disorders.
Key words: Free and Easy Wanderer, posttraumatic stress disorder, inflammation, oxidative stress, NF-κB, KEAP1-NRF2/HO-1