In silico Analysis of Berberine as a Potential Therapeutic Approach for Various Signalling Pathways Linked to Androgenetic Alopecia

Background: Alopecia is defined by a loss of hair density and is often considered a symptom of multiple illnesses, such as infection and inflammation. Objective: The molecular mechanisms underlying the hair-promoting effects include inhibition of 5α-reductase activity, reducing the binding affinity of Dihydrotestosterone (DHT) to androgen receptors, and decreasing/down-regulating TGF-β2 activity, which have a suggestive role in androgenetic alopecia. Finasteride and minoxidil are the approved non-surgical treatment alternatives for hair loss, but they cause side effects in patients. Therefore, bioactive phytoconstituents with multiple targets can be used to find novel, secure, and efficacious hair-promoting medicinal products. Methods: This study has carried out the in silico evaluation of berberine using various software. To find possible interactions between the 5α-reductase enzyme and Transforming Growth Factor-- beta 2 (TGF-β2), a critical protein involved in the human hair development cycle, computer-aided drug discovery was employed. Results: According to in silico studies, berberine has been found to bind well to the 4K7a and 6M2N binding sites. The drug has been found to adhere to Lipinski's rule of five, and its pharmacokinetic characteristics were noteworthy. Drug-likeness and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties showed appreciable results. Furthermore, berberine showed docking scores of -8.4 (5α-reductase) and -7.1 (TGF-β2), which were significantly better than minoxidil (-4.8, -3.2). In general, the drug exhibited improved binding interactions, and the possible toxicity investigations provided very little basis for risk prediction. Conclusion: The current protocol has offered experimental support for berberine's possible therapeutic use in reducing male pattern baldness. Therefore, it can be a possible target for the therapy of androgenetic alopecia through the regulation of TGF-β2 and 5α-reductase activity.