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The Zishen Yutai pills (ZYP), a Chinese medicinal formulation derived from the Qing Dynasty prescription "Shou Tai pills", have been documented to exhibit beneficial effects in clinical observations treating premature ovarian failure (POF). However, the anti-POF effects and its comprehensive systemic mechanism have not yet been clarified.

Therapeutic effects and systemic mechanism of ZYP in POF were evaluated.

After pulverization, sieving, and stirring, ZYP was administered intragastrically to cisplatin-induced POF mice at a dose of 1.95 mg/kg/d for 14 days. The anti-POF effects of ZYP were investigated by assessing the number of ovarian follicles at different developmental stages, as well as measuring serum estradiol (E₂) levels and ovarian-expressed anti-Müllerian hormone (AMH). Reproductive performance and offspring health were evaluated to predict fertility restoration. Furthermore, a combination of proteomic and metabolomic profiling was employed to elucidate the underlying molecular mechanism of ZYP in treating POF. Western blot (WB) analyses and real-time quantitative polymerase chain reaction (RT-qPCR) were conducted to explore the mechanisms through which ZYP exerted its anti-POF effects.

We have demonstrated that oral administration of ZYP reversed the reduction in follicles at different developmental stages and stimulated the expressions of serum E₂ and ovarian-expressed AMH in a cisplatin-induced POF model. Additionally, ZYP ameliorated follicle apoptosis in ovaries affected by cisplatin-induced POF. Furthermore, treatment with ZYP restored the quantity and quality of oocytes, as well as enhanced fertility. Our results revealed 62 differentially expressed proteins (DEPs) through proteomic analyses and identified 26 differentially expressed metabolites (DEMs) through metabolomic analyses. Both DEPs and DEMs were highly enriched in the arachidonic acid (AA) metabolism pathway. ZYP treatment effectively upregulated the protein and mRNA expression of critical targets in AA metabolism and the AKT pathway, including CYP17α1, HSD3β1, LHR, STAR, and AKT, in cisplatin-induced POF mice.

These results indicated that ZYP exerted protective effects against POF and restored fertility from cisplatin-induced apoptosis. ZYP could be a satisfying alternative treating POF.

In modern drug discovery and development, the prodrug approach has become a crucial strategy for enhancing the pharmacokinetic profiles of drugs. A prodrug is a chemical compound, which gets metabolized into a pharmacologically active form (drug) inside the body after its administration. In the current work, we report 'smProdrugs' (http://cheminfolab.in/databases/prodrug/), which is one of the first exclusive databases on small molecule prodrugs. It stores the structures, physicochemical properties and experimental ADMET data manually curated from literature. SmProdrugs lists 626 small molecule prodrugs and their active compounds with the above mentioned experimental data from 1808 research articles and 61 patents have been stored. The information page of each record gives the structures and properties of the prodrug and the active drug side by side which makes it easy for the user to instantly compare them. The structural modifications in the prodrug/active drugs are highlighted in a different colour for easy comparison. Experimental data has been curated from the downloaded PubMed and patent articles and were catalogued in a tabular form with more than 25 fields under sub-sections i) name and structures of the prodrugs and their active compounds, ii) mode of activation of the prodrug and enzyme/biocatalyst involved in the conversion, iii) indications/disease, iv) pharmacological target, v) experimental pharmacokinetic properties such as solubility, absorption, volume of distribution, half-life, clearance etc. and vi) information on the purpose/gain from the prodrug strategies. Considering the ever expanding utility of the prodrug approach smProdrugs will be of great use to the scientific community working on rational design of small molecule prodrugs.