Supplementary Material for: Zigui-Changqi decoction against premature ovarian insufficiency by moderating autophagy via EGFR/ERBB2/IL6/AKT1 signals

Background: Autophagy defect has been detected in premature ovarian insufficiency (POI) patients.
Aim: To evaluate the efficacy and explore the mechanism of Zigui-Changqi Decoction (ZCD) in the treatment of POI.
Material and methods: Rat model of POI was established to evaluate the efficacy of ZCD on serum hormone levels, ovarian index, and ovarian cell apoptosis. The effect of ZCD on the autophagy of granulosa cell was assessed. Network pharmacology was used to predict potential targets of ZCD against POI.
Results: ZCD attenuated tripterygium glycosides-induced damage to ovarian tissues in rats by improving ovarian index, moderating serum hormone levels, inhibiting ovarian cell apoptosis, and increasing the number of ovarian stromal cells. ZCD moderated the expression of autophagy-related markers, including BECN1, p62 and LC3. Through network pharmacological analysis, the predicted hub genes were EGFR, ERBB2, AKT1, IL6, PTEN, and TP53. After molecular docking and detection of cell expression levels, EGFR, ERBB2, AKT1, and IL6 were inhibited by ZCD, as well as mTORC1.
Conclusion: ZCD can ameliorate POI, maybe by moderating autophagy via EGFR/ERBB2/IL6/AKT1 signals.