Background and Purpose Infertility due to age-related uterine dysfunction has become a significant global challenge. Cellular senescence and impaired decidualization in endometrial stromal cells (ESCs) are critical contributors to age-related fertility decline. Chlorogenic acid (CGA), a phenolic compound with proven anti-aging properties, has demonstrated potential therapeutic effects. However, its role in ESC senescence and decidualization remains unclear. Experimental Approach Network pharmacology and molecular docking approaches were employed to identify molecular targets of CGA and interactions among them. In vitro studies using senescent ESCs evaluated the effects CGA on cellular proliferation, senescence markers, mitochondrial biogenesis, and signaling pathways (mTOR/AKT/AMPK/SIRT1). Aged female mice were treated with CGA, and uterine tissues were analyzed histologically and molecularly to assess its anti-aging effects. Key Results CGA enhanced ESC proliferation, reduced senescence markers (P16, P21, SA-β-Gal), and promoted decidualization by increasing PRL, IGFBP1, and FOXO1 expression. CGA also restored mitochondrial biogenesis through the activation of SIRT1, AMPK, and PGC1α. Network pharmacology and docking studies identified mTOR and AKT as key targets, and CGA’s strong binding affinity to mTOR was supported by reduced mTOR phosphorylation in vitro and in vivo. In aged mice, CGA improved uterine morphology, reduced senescence markers, and partially restored reproductive parameters. Conclusions and Implications CGA alleviates senescence and enhances decidualization in ESCs via the mTOR/AKT signaling pathway. These findings suggest CGA as a promising senotherapeutic agent for addressing age-related infertility by improving uterine health and function.

Background and Purpose Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis and limited response to standard therapies like gemcitabine, largely due to drug resistance and tumor microenvironmental barriers. This study aimed to investigate the anticancer potential of Schisandrin B (Sch B), a natural compound derived from Schisandra chinensis, and elucidate its mechanisms of action in PDAC through a network pharmacology-guided approach. Experimental Approach Network pharmacology and molecular docking were employed to predict Sch B targets and binding interactions. In vitro studies using PDAC cell lines evaluated proliferation, apoptosis, mitochondrial dysfunction, calcium dysregulation, and ROS production. The synergistic potential of Sch B with gemcitabine was assessed via Chou-Talalay analysis. In vivo efficacy was tested using a PANC-1 xenograft mouse model. EGFR knockdown experiments further clarified Sch B’s mechanism. Key Results Sch B inhibited PDAC cell proliferation and induced mitochondria-dependent apoptosis via disruption of mitochondrial membrane potential, calcium imbalance, and elevated ROS. Key molecular targets included EGFR, AKT, mTOR, BCL-2, and HSP90. EGFR knockdown enhanced Sch B-induced mitochondrial dysfunction and apoptosis. Sch B exhibited synergistic effects with gemcitabine, enhancing cytotoxicity and mitochondrial stress. Sch B significantly suppressed tumor growth and downregulated EGFR/AKT/mTOR signaling in vivo. Conclusions and Implications Sch B exerts potent anticancer effects in PDAC by targeting the EGFR/AKT/mTOR axis and inducing mitochondrial dysfunction. Its ability to synergize with gemcitabine suggests that Sch B may serve as a promising candidate for combination therapy or as an alternative chemotherapeutic agent in PDAC treatment.

Background and Purpose Infertility due to age-related uterine dysfunction has become a significant global challenge. Cellular senescence and impaired decidualization in endometrial stromal cells (ESCs) are critical contributors to age-related fertility decline. Chlorogenic acid (CGA), a phenolic compound with proven anti-aging properties, has demonstrated potential therapeutic effects. However, its role in ESC senescence and decidualization remains unclear. Experimental Approach Network pharmacology and molecular docking approaches were employed to identify molecular targets of CGA and interactions among them. In vitro studies using senescent ESCs evaluated the effects CGA on cellular proliferation, senescence markers, mitochondrial biogenesis, and signaling pathways (mTOR/AKT/AMPK/SIRT1). Aged female mice were treated with CGA, and uterine tissues were analyzed histologically and molecularly to assess its anti-aging effects. Key Results CGA enhanced ESC proliferation, reduced senescence markers (P16, P21, SA-β-Gal), and promoted decidualization by increasing PRL, IGFBP1, and FOXO1 expression. CGA also restored mitochondrial biogenesis through the activation of SIRT1, AMPK, and PGC1α. Network pharmacology and docking studies identified mTOR and AKT as key targets, and CGA’s strong binding affinity to mTOR was supported by reduced mTOR phosphorylation in vitro and in vivo. In aged mice, CGA improved uterine morphology, reduced senescence markers, and partially restored reproductive parameters. Conclusions and Implications CGA alleviates senescence and enhances decidualization in ESCs via the mTOR/AKT signaling pathway. These findings suggest CGA as a promising senotherapeutic agent for addressing age-related infertility by improving uterine health and function.