OBJECTIVE  To explore the promoting effect of durian shell extract on hair regeneration in depilated mice and its associated molecular mechanism.

METHODS  Male C57BL/6J mice were randomly divided into four groups: The normal group, the control group, the positive control group(minoxidil group), and the durian shell extract group. A depilation model was established in mice by the rosin-paraffin method, and the depilated areas of each group of mice were administered for 21 d. A multi-index evaluation system was used, including the growth score of new hair, hair length, hair weight, and the number of hair follicles, to systematically evaluate the hair growth effect of durian shell extract. At the same time, network pharmacology and molecular docking techniques were used to predict the potential target sites and related signaling pathways of durian shell extract. To verify the prediction results, the expression levels of key target genes and proteins were further detected by quantitative polymerase chain reaction(qPCR) and Western blotting.

RESULTS  The experimental results indicated that the scores of new hair growth, hair length, hair weight and the number of hair follicles in the mice treated with durian shell extract were significantly higher than those in the other groups. The results of network pharmacology and molecular docking showed that multiple compounds in durian shell extract, such as quercetin, rutin and proanthocyanidin B, might act on the main targets including PIK3R1, PIK3CA, STAT3 and ESR1, and participate in the treatment of hair loss by regulating the PI3K-Akt, FoxO and HIF-1 signaling pathway. The qPCR and Western blotting results showed that durian shell extract could significantly increase the mRNA and protein level of ESR1 in the skin tissue of the hair loss area in depilated mice.

CONCLUSION  Durian shell extract can significantly promote hair growth in depilated mice, and its mechanism of action may be achieved by targeting and regulating the expression level of ESR1.