The Chinese herbal formula Free and Easy Wanderer ameliorates oxidative stress through KEAP1-NRF2/HO-1 pathway.

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.

Identification of NF-κB as Determinant of Posttraumatic Stress Disorder and Its Inhibition by the Chinese Herbal Remedy Free and Easy Wanderer.

Posttraumatic stress disorder (PTSD) is a mental disorder developing after exposure to traumatic events. Although psychotherapy reveals some therapeutic effectiveness, clinically sustainable cure is still uncertain. Some Chinese herbal formulae are reported to work well clinically against mental diseases in Asian countries, but the safety and their mode of action are still unclear. In this study, we investigated the mechanisms of Chinese remedy free and easy wanderer (FAEW) on PTSD. We used a reverse pharmacology approach combining clinical data to search for mechanisms of PTSD with subsequent in vitro verification and bioinformatics techniques as follows: (1) by analyzing microarray-based transcriptome-wide mRNA expression profiling of PTSD patients; (2) by investigating the effect of FAEW and the antidepressant control drug fluoxetine on the transcription factor NF-κB using reporter cell assays and western blotting; (3) by performing molecular docking and literature data mining based on phytochemical constituents of FAEW. The results suggest an involvement of inflammatory processes mediated through NF-κB in the progression of PTSD. FAEW was non-cytotoxic in vitro and inhibited NF-κB activity and p65 protein expression. FAEW's anti-inflammatory compounds, i.e., paeoniflorin, isoliquiritin, isoliquiritin apioside and ononin were evaluated for binding to IκK and p65-RelA in a molecular docking approach. Paeoniflorin, albiflorin, baicalin, isoliquiritin and liquiritin have been reported to relieve depression in vivo or in clinical trials, which might be the active ingredients for FAEW against PTSD.

Targeting epidermal growth factor receptors and downstream signaling pathways in cancer by phytochemicals.

Epidermal growth factor receptors (EGFR, HER2, HER3) activate signal transduction pathways involved in cancer proliferation, apoptosis, differentiation, metastasis, and angiogenesis. Their overexpression and activation are associated with unfavorable prognosis of cancer patients. Therefore, they are attractive targets for cancer therapy. Due to the development of drug resistance, therapeutic monoclonal antibodies and synthetic small molecule tyrosine kinase inhibitors directed against EGFR family members may fail with fatal consequences for cancer patients. Medicinal plants raised considerable interest during the past years as valuable resources to develop novel treatment therapies targeting epidermal growth factor receptors and their downstream signal transduction pathways. The present review gives an overview of isolated phytochemicals that inhibit these signaling routes. Inhibitors have been described that down-regulate the mRNA or protein expression of EGFR, HER2, or HER3 or inhibit the phosphorylation of these receptors and/or their downstream signaling kinases. Remarkably, a wealth of in vivo experiments complemented in vitro data, indicating that natural products are also active in living animals bringing this research concept closer to clinical applicability. The combination of receptor-inhibiting natural product with standard anticancer drugs frequently caused increased or even synergistic tumor inhibition in vitro and in vivo. It deserves further evaluation, if and how epidermal growth factor receptor-targeting natural products can be integrated into clinical oncology as well as to define their role for more tumor-specific and individualized tumor therapies.

Posttraumatic stress disorder among earthquake survivors of the Wenchuan area (Sichuan, China).

BACKGROUND: On May 12, 2008, an earthquake with a power of 8.0 M on the Richter scale occurred in the Wenchuan County of Sichuan Province in southwest China, which was unprecedented in magnitude and aftermath. Approximately 70,000 people were killed and nearly 20,000 went missing. The earthquake caused a wide number of mental and physical health outcomes among survivors, and posttraumatic stress disorder (PTSD) was one of the most commonly studied. METHODS: We conducted a systematic overview to assess research achievements about PTSD in the past 6 years after the Wenchuan earthquake, including symptoms and risk factors about PTSD among Wenchuan earthquake survivors, as well as research developments in genetics, molecular biology, and treatment of PTSD. RESULTS: The large body of research conducted after the Wenchuan earthquake suggests that the burden of PTSD among persons with high exposure was substantial. Adolescents and adults were among the most studied populations with high prevalence rates. Phytotherapy with Chinese herbs as well as acupuncture were rarely studied as of yet, although published data indicated promising therapy effects. Genome-wide microarray technologies are widely used in experimental mice and rat models to study PTSD mechanisms as well as in patients suffering from PTSD and other psychosomatic disorders to search for novel biomarkers and to monitor the effectiveness of treatment interventions. CONCLUSIONS: Using genomic and transcriptomic technologies, our future research will focus on the efficacy and safety of Chinese medicine to find potential interventions and effective treatments of PTSD.