title: In silico target fishing for the potential bioactive components contained in Huanglian Jiedu Tang (HLJDD) and elucidating molecular mechanisms for the treatment of sepsis.
abstract: The present study was designed to target fish for potential bioactive components contained in a Huang Lian Jie Du decoction (HLJDD) and identify the underlying mechanisms of action for the treatment of sepsis at the molecular level. he bioactive components database of HLJDD was constructed and the sepsis-associated targets were comprehensively investigated. The 3D structures of the PAFR and TXA2R proteins were established using the homology modelling (HM) method, and the molecular effects for sepsis treatment were analysed by comparing the bioactive components database and the sepsis targets using computational biology methods. The results of the screening were validated with biological testing against the human oral epidermal carcinoma cell line KB in vitro. We found that multiple bioactive compounds contained in the HLJDD interacted with multiple targets. We also predicted the promising compound leads for sepsis treatment, and the first 28 compounds were characterized. Several compounds, such as berberine, berberrubine and epiberberine, dose-dependently inhibited PGE2 production in human KB cells, and the effects were similar in the presence or absence of TPA. This study demonstrates a novel approach to identifying natural chemical compounds as new leads for the treatment of sepsis.
authors: Food and Drug College, Anhui University of Science and Technology, Fengyang 233100, China; College of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China.
authors: Shi-Tang
authors: ST
authors: Ma
authors: Anhui University of Science and Technology, Huainan 232001, China.
authors: Cheng-Tao
authors: CT
authors: Feng
authors: College of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China.
authors: Guo-Liang
authors: GL
authors: Dai
authors: Food and Drug College, Anhui University of Science and Technology, Fengyang 233100, China.
authors: Yue
authors: Y
authors: Song
authors: Food and Drug College, Anhui University of Science and Technology, Fengyang 233100, China.
authors: Guo-Liang
authors: GL
authors: Zhou
authors: Food and Drug College, Anhui University of Science and Technology, Fengyang 233100, China.
authors: Xiao-Lin
authors: XL
authors: Zhang
authors: Food and Drug College, Anhui University of Science and Technology, Fengyang 233100, China.
authors: Cheng-Gui
authors: CG
authors: Miao
authors: Food and Drug College, Anhui University of Science and Technology, Fengyang 233100, China. Electronic address: yhz_1230@163.com.
authors: Hao
authors: H
authors: Yu
authors: College of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China. Electronic address: nothingchina@126.com.
authors: Wen-Zheng
authors: WZ
authors: Ju
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001599:Berberine / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D015232:Dinoprostone / Q000096:biosynthesis; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007624:KB Cells; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000187:drug effects; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000493:pharmacokinetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004365:Drugs, Chinese Herbal; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D044244:Receptors, Thromboxane A2, Prostaglandin H2; C061676:oren gedoku to; C039351:platelet activating factor receptor; D001599:Berberine; C115958:berberrubine; C061432:epiberberine; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate
keywords: In silico target fishing; Natural products; PGE(2) inhibition; Sepsis target