title: In silico prediction of prostaglandin D2 synthase inhibitors from herbal constituents for the treatment of hair loss.
abstract: BACKGROUND
  Many herbal topical formulations have been marketed worldwide to prevent hair loss or promote hair growth. Certain in vivo studies have shown promising results among them; however, the effectiveness of their bioactive constituents remains unknown.
  
  
  OBJECTIVE
  Recently, prostaglandin D2 (PGD2) inhibition has been discovered as a pharmacological mechanism for treating androgenic alopecia (AGA). This present study was aimed to identify prostaglandin D2 synthase (PTGDS) inhibitors in traditional Chinese medicines (TCMs) for treating AGA.
  
  
  METHODS
  In this study, 389 constituents of 12 selected herbs were docked into 6 different crystal structures of PTGDS. The accuracy of the docking methods was successfully validated with experimental data from the ZINC In Man (Zim) database using receiver operating characteristic (ROC) studies. Seven essential drug properties were predicted for topical formulation: skin permeability, sensitisation, irritation, corrosion, mutagenicity, tumorigenicity and reproductive effects.
  
  
  RESULTS
  Many constituents of the twelve herbs were found to have more advanced binding energies than the experimentally proved PTGDS inhibitors, but many of them were indicative of at least one type of skin adverse reactions, and exhibited poor skin permeability.
  
  
  CONCLUSIONS
  Overall, ricinoleic acid, acteoside, amentoflavone, quercetin-3-O-rutinoside and hinokiflavone were predicted to be PTGDS inhibitors with good pharmacokinetic properties and minimal adverse skin reactions. These compounds have the highest potential for further in vitro and in vivo investigation with the aim of developing safe and high-efficacy hair loss treatment.
authors.affiliation: School of Health Sciences, Macao Polytechnic Institute, Macao, China. Electronic address: pedrofong@ipm.edu.mo.
authors.forename: Pedro
authors.initials: P
authors.lastname: Fong
authors.affiliation: School of Health Sciences, Macao Polytechnic Institute, Macao, China.
authors.forename: Henry H Y
authors.initials: HH
authors.lastname: Tong
authors.affiliation: School of Health Sciences, Macao Polytechnic Institute, Macao, China.
authors.forename: Kin H
authors.initials: KH
authors.lastname: Ng
authors.affiliation: School of Health Sciences, Macao Polytechnic Institute, Macao, China.
authors.forename: Cheng K
authors.initials: CK
authors.lastname: Lao
authors.affiliation: School of Health Sciences, Macao Polytechnic Institute, Macao, China.
authors.forename: Chon I
authors.initials: CI
authors.lastname: Chong
authors.affiliation: School of Health Sciences, Macao Polytechnic Institute, Macao, China.
authors.forename: Chi M
authors.initials: CM
authors.lastname: Chao
mesh_terms: D000505:Alopecia / Q000188:drug therapy*; D000818:Animals; D003198:Computer Simulation; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D003879:Dermatologic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors*; D054834:Lipocalins / Q000037:antagonists & inhibitors*; D008516:Medicine, Chinese Traditional; D008954:Models, Biological; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship; D012372:ROC Curve; D012867:Skin / Q000187:drug effects; D012869:Skin Absorption
chemical_list: D016861:Cyclooxygenase Inhibitors; D003879:Dermatologic Agents; D004365:Drugs, Chinese Herbal; D054834:Lipocalins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase
keywords: Androgenic alopecia; Docking; Hair loss; Prostaglandin D2 synthase; Traditional Chinese medicines