Complement Factor D (CFD) bound by Saikosaponin D (SSD) extracted from Bupleuri Radix might drive the anti-depression network to function

Bupleuri Radix, a famous Chinese herbal medicine called Chai-Hu, has been widely used to treat depression like syndromes over a long history. Although associated clinical evidences has been accumulated and studied, its molecule level therapeutic mechanism is still obscure which blocks the understanding and new drug discovery against major depression. In this study, focused on the active compounds extracted from Bupleuri Radix reported with anti-depression effects, target proteins were determined. Following these targeted proteins, protein-protein regulating network towards proteins participated in the anti-depression processes e.g. serotonin secretion and positive regulation of dopamine secretion was constructed. As a result, together with other 12 regulated proteins, targeted protein of Complement Factor D (CFD) which is bound with Saikosaponin D (SSD) was recognized as a candidate biomarker driving the anti-depression network to function. The primary results were also validated with bioinformatics tools (e.g. DAVID and PANTHER) and PubMed collected literatures.

[1]  Xin Yi,et al.  CXCL12 inhibits cortical neuron apoptosis by increasing the ratio of Bcl-2/Bax after traumatic brain injury , 2014, The International journal of neuroscience.

[2]  J. Lile,et al.  GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. , 1993, Science.

[3]  John P. Overington,et al.  ChEMBL: a large-scale bioactivity database for drug discovery , 2011, Nucleic Acids Res..

[4]  Yi Ai,et al.  Dopamine Neuron Stimulating Actions of a GDNF Propeptide , 2010, PloS one.

[5]  A. Carvalho,et al.  Role of trophic factors GDNF, IGF-1 and VEGF in major depressive disorder: A comprehensive review of human studies. , 2016, Journal of affective disorders.

[6]  Fang Wang,et al.  Antidepressant-like effects of Xiaochaihutang in a rat model of chronic unpredictable mild stress. , 2014, Journal of ethnopharmacology.

[7]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[8]  Elisabet Englund,et al.  Inhibition of CXCL12 Signaling Attenuates the Postischemic Immune Response and Improves Functional Recovery after Stroke , 2013, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[9]  Damian Szklarczyk,et al.  STITCH 5: augmenting protein–chemical interaction networks with tissue and affinity data , 2015, Nucleic Acids Res..

[10]  Michael K. Gilson,et al.  BindingDB in 2015: A public database for medicinal chemistry, computational chemistry and systems pharmacology , 2015, Nucleic Acids Res..

[11]  David Liu,et al.  DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis , 2007, BMC Bioinformatics.

[12]  G. Turecki,et al.  MicroRNA regulation of central glial cell line-derived neurotrophic factor (GDNF) signalling in depression , 2015, Translational Psychiatry.

[13]  B E Read,et al.  THE CHINESE PHARMACOPOEIA. , 1930, Canadian Medical Association journal.

[14]  D F Swaab,et al.  Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression. , 1995, The American journal of psychiatry.

[15]  Jin-Hee Seo,et al.  Stress-Induced Depression Is Alleviated by Aerobic Exercise Through Up-Regulation of 5-Hydroxytryptamine 1A Receptors in Rats , 2015, International neurourology journal.

[16]  Qi Chang,et al.  Neuroprotective effects of total saikosaponins of Bupleurum yinchowense on corticosterone-induced apoptosis in PC12 cells. , 2013, Journal of ethnopharmacology.

[17]  Ying Peng,et al.  Separation and identification of multiple constituents in Xiao Chai Hu Decoction (Sho-saiko-to) by bioactivity-guided fractionation combined with LC-ESI-QTOFMS/MS. , 2015, Biomedical chromatography : BMC.

[18]  Feng Qin,et al.  Chaihu-Shugan-San, an oriental herbal preparation, for the treatment of chronic gastritis: a meta-analysis of randomized controlled trials. , 2013, Journal of ethnopharmacology.

[19]  Jia-Xu Chen,et al.  Effects of chai hu (radix burpleuri) containing formulation on plasma beta-endorphin, epinephrine and dopamine on patients. , 2005, The American journal of Chinese medicine.

[20]  Anushya Muruganujan,et al.  Large-scale gene function analysis with the PANTHER classification system , 2013, Nature Protocols.

[21]  Tanya Z. Berardini,et al.  The Gene Ontology (GO) Cellular Component Ontology: integration with SAO (Subcellular Anatomy Ontology) and other recent developments , 2013, J. Biomed. Semant..

[22]  X. Ou,et al.  Monoamine oxidases in major depressive disorder and alcoholism. , 2012, Drug discoveries & therapeutics.

[23]  S. Heinisch,et al.  SDF-1α/CXCL12 enhances GABA and glutamate synaptic activity at serotonin neurons in the rat dorsal raphe nucleus , 2010, Neuropharmacology.

[24]  Davide Heller,et al.  STRING v10: protein–protein interaction networks, integrated over the tree of life , 2014, Nucleic Acids Res..