In silico prediction of prostaglandin D2 synthase inhibitors from herbal constituents for the treatment of hair loss

Ethnopharmacological relevance 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. Aim of the study 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. Materials and 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.