| BackgroundPsoriasis is a common, chronic, inflammatory disease of the skin, whose typical clinical manifestions are increased cellular activity of the epidermis and dilated capillaries of the dermis. Psoriasis is one of the difficult miscellaneous diseases in dermasurgery. Plaque type psoriasis is a refractory type of psoriasis. Clinical practice has proved that Chinese herbal compound (CHM) treatment can achieve good curative effect on psoriasis relying on its overall adjustment function. Based on the in-depth summary of predecessors’experience, long-term clinical validation and repeated screening test, Li Yuanwen professor invented Yangxue Huaban decoction (YXHB) with functions of nourishing blood and detoxification (Yangxue and Jiedu). Preliminary clinical observation of YXHB treatment psoriasis showed that YXHB has a good safety and reliable curative effect. However there is lack of the objective evaluation on the basis of the evidence-based medicine and the mechanism of YXHB treatment psoriasis is unclear.According to systems biology viewpoint, the occurrence and development of diseases are associated with a series of interacting genes or proteins that show the characteristics of complex network. Drug produces the synergistic effect through its effects on the multiple targets in the disease network and thus intervenes to the occurrence and development of the disease. CHM is characterized by multi-component, multi-pathways and multi-targets synergy. Exploring CHM effect mechanism at the molecular network level not only is conducive to more comprehensive and more accurate decryption of CHM integrity effect but also provides new ideas for mechanism study pharmacology of Chinese medicine. Therefore using the molecular network analysis method is expected to explore YXHB mechanism for the treatment of psoriasis.Objective(1) To evaluate the efficacy and safety of YXHB on treatment of plaque type psoriasis.(2) To explore the possible acting targets and molecular network mechanism of Yangxue and Jiedu herbal pairs complex prescription (YJPC) on psoriasis. And thus to promote the clinical application and development of traditional Chinese medicine. Methods(1) Efficacy and safety of YXHBIn this prospective, randomized and control clinical trial of120patients with plaque type psoriasis,80were treated with YXHB and40were treated with Xiaoyin capsule (XYC) for8weeks. The therapeutic outcomes were evaluated by PASI score and clinical symptoms evaluation indicators in traditional Chinese medicine. And the adverse effects were analyzed.(2) Acting targets and molecular network mechanism of YJPCThe effective components of Angelica sinensis (DG), Caulis Spatholobi (JXT), Flos Sophorae (HH) and Rhizoma smilacis glabrae (TFL) were retrievalled from the Grand Dictionary of Chinese Medicine (Second Edition), the human target proteins of those effective components were retrievalled from Pubchem database, and genes related psoriasis were retrievalled from Pubmed gene database. Then the target proteins and genes were respectively uploaded Ingenuity Pathways Analysis (IPA) data analysis platform, constructing the molecular networks and biological pathways of each herb and psoriasis. Finally through the network comparison, acting targets and molecular network mechanism of YJPC were presented visually.Results(1) Efficacy and safety of YXHBEffective rates of YXHB group and XYC group respectively were78.2%and62.2%after treatment and there were no significant differences between the two groups. PASI score and clinical symptoms of YXHB group were significantly alleviated than those of XYC group (P<0.05). In the process of treatment, there were no significant adverse reactions and toxicity in YXHB group and one patient had a transient rash in XYC group.(2) Bioinformatics analysis resultsTarget proteins and genes were searched from corresponding database. The number of target proteins of DG, JXT, HH and TFL respectively is44,41,34and35. Psoriasis related genes are165. The results of biological function, biological pathways and molecular network analysis showed as follows:①each herb corresponds to different diseases; the most relevant disease corresponding to DG, JXT, HH and TFL respectively is nutritional disease, neurological disease, cancer and psychological disorders; Dermatological diseases and conditions are common diseases corresponding to each herb; psoriasis involved biological functions mainly includes inflammatory response, immunological regulation and cell-to-cell signaling and interaction.②ach herb corresponds to different biological pathways; the most relevant biological pathway corresponding to DG, JXT, HH, TFL and psoriasis respectively is aryl hydrocarbon receptor signaling, aryl hydrocarbon receptor signaling, ATM signaling and Gai signaling and dendritic cell maturation.③Molecular networks corresponding to DG, JXT, HH, TFL and psoriasis respectively have5,4,4,2,16sub-network; each network related biological functions are different; DG network functions mainly involve lipid metabolism, molecular transport, small molecule biochemistry, etc.; JXT network functions mainly involve neurological disease, psychological disorders, metabolic disease, etc.; HH network functions mainly involve cell cycle, organismal development, DNA replication, recombination and repair, etc.; TFL network functions mainly involve metabolic disease, neurological disease, organismal injury and abnormalities, etc.; psoriasis network functions mainly involve cell-to-cell signaling and interaction, hematological system development and function, cellular movement etc.Compared biological pathways and molecular networks of each herb with those of psoriasis, the results showed as follows:①the special pathways of DG to psoriasis mainly include renin-angiotensin signaling, IL-6signaling, inhibition of matrix metalloproteases, etc.; the special pathways of JXT to psoriasis include Cdc42signaling and superpathway of citrulline metabolism; the special pathway of HH to psoriasis is FXR/RXR activation; the special pathways of TFL to psoriasis include serotonin receptor signaling and aldosterone signaling in epithelial cells,②the special pathways of DG-JXT herbal pair to psoriasis mainly include endothelin-1signaling, RAR activation, LPS/IL-1mediated inhibition of RXR Function, etc.; the special pathway of HH-TFL herbal pair to psoriasis is G-protein coupled receptor signaling.③the special pathways of DG-JXT and HH-TFL herbal pairs (YJPC) to psoriasis include aryl hydrocarbon receptor signaling, androgen signaling, eNOS signaling and PI3K/AKT signaling.④the special key network target molecules of DG to psoriasis mainly include Hsp27, PARP, PEPCK, etc.; the special key network target molecules of JXT to psoriasis mainly include Gsk3, interferon alpha, NOS2, etc.; the special key network target molecules of HH to psoriasis mainly include NOTCH1, Alpha tubulin, CD3, etc.; the special key network target molecules of TFL to psoriasis include beta arrestin, Gpcr and TNF.⑤the special key network target molecules of DG-JXT herbal pair to psoriasis mainly include IL1, pro-inflammatory cytokine, p38MAPK, etc.; the special key network target molecules of HH-TFL herbal pair to psoriasis mainly include LDL, IFN Beta, glutathione peroxidase, etc. ⑥he special key network target molecules of DG-JXT and HH-TFL herbal pairs (YJPC) to psoriasis include26s proteasome, ERK1/2, NFkB (complex), UBC and Ubiquitin.Conclusion(1) YXHB is effective and safe on treatment of plaque type psoriasis and is worth clinical application.(2) YJPC treats psoriasis by regulating four biological pathways (aryl hydrocarbon receptor signaling, androgen signaling, eNOS signaling and PI3K/AKT signaling) and four network target molecules (Ubiquitin, Proteasome, ERK1/2and NF-κB). Perturbation of the biological pathways and molecules also explain the modern biological mechanisms of plaque type psoriasis Xuezao syndrome.(3) Molecular network analysis technique is an effective method to explore and predict targets and mechanisms of traditional Chinese medicine treating diseases. |
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