Screening Potential Drugs From Nitric Oxide Donors for Treating Alopecia Based on Network Pharmacology and Experimental Validation

Nitric oxide (NO) was previously thought to have a beneficial role in hair growth, but it is unclear whether NO donors can encourage hair development. Therefore, this study aims to systematically investigate the physiological mechanisms underlying the therapeutic effects of NO donors in alopecia. We first screened the chemical targets of seven types of NO donors from DrugBank and SwissTargetPrediction, and further identified the differentially expressed genes (DEGs) of three types of alopecia from the GEO database. Integrated bioinformatic analysis was subsequently performed to comprehensively reveal potential pathways. A total of 339 chemical targets of NO donors were collected and 237, 266, and 1158 DEGs of androgenic alopecia (AGA), alopecia areata (AA) and central centrifugal cicatricial alopecia (CCCA) were identified in this study. We further extracted 20 CCCA-related targets from the intersection of 339 targets and 1158 DEGs of CCCA for the following analysis. Through integrative analysis, we found that hesperidin (HP) may exert dual regulatory effects on apoptosis and senescence pathways in hair follicle cells through its specific interactions with BCL2, MAPK8, MMP13 and AURKB, effectively mitigating hair loss. Overall, our work elucidates the molecular mechanisms of NO donors-mediated hair follicle protection, which could pave the way for future investigations into NO-based interventions and their potential clinical applications.