Abstract
Background
Despite global economic growth and health care and education improvements, the global birth rate has remained negative. How to increase fertility has become a common global challenge. Fertility-boosting No. 1 Tang (FB1T) and Fertility-preserving Tang (FPT) are clinically effective prescriptions of traditional Chinese medicine, which play important roles in improving the sperm quality of boys and the embryo loading rate of women to the process of fertilization of sperms and eggs, but the mechanism of their action is still unclear.
Methods
For insight into the molecular mechanism of FB1T and FPT in reproduction, we used a network pharmacology approach to analyze it with recurrent miscarriage (RM) as the disease representative. Then, we analyzed the potential protein targets signaling pathways looking for therapeutic mechanisms between FB1T and FPT and RSA by drug-target network respectively. Finally, AutoDock Vina was selected for molecular docking validation.
Results
From the OMIM, DisGeNET, and GeneCards databases, we identified 1933 targets for Recurrent Miscarriage (RM). Post-ADME screening, 96 active components and 467 targets in FB1T, along with 137 active components and 327 targets in FPT were recognized. A total of 286 active component targets in FB1T and 230 in FPT overlapped with RM targets. PPI analysis revealed top targets like TNF, AKT1, IL6, TP53, IL1B, ESR1, STAT3, EGFR, CASP3, JUN, CTNNB1, and MMP9. These targets are associated with 124 and 99 signalling pathways in FB1T and FPT respectively, including the AGE-RAGE signaling pathway and chemical carcinogenesis-receptor activation. Quercetin, kaempferol, and luteolin were identified as the primary active components in both FB1T and FPT for RM treatment. We hypothesize FB1T and FPT may activate NF-kB through the AGE-RAGE signaling pathway, inhibiting pro-inflammatory cytokines such as IL-1β, IL-6, and TNFα, thereby offering therapeutic benefits for RM. Molecular docking further verified that quercetin, kaempferol, and luteolin have strong binding activities with proteins involved in the AGE-RAGE signaling pathway.
Conclusions
The material basis of FB1T and FPT for the treatment of RM is quercetin, kaempferol, and luteolin. The mechanism may be to enhance oxidative stress resistance and improve anxiety and ovarian function by inhibiting the AGE-RAGE signaling pathway for the treatment of RM.