Investigation of the Active Ingredients and Mechanism of Action of YGZ223 in the Treatment of Senile Pruritus Using Network Pharmacology and UPLC-MS

Background/Objective: Senile pruritus (SP) is a prevalent disease that occurs in elderly individuals over the age of 60 and is characterized by the primary symptom of pruritus. The disease's pathogenesis is complex, and clinical practice mainly uses symptomatic treatment drugs. YGZ223 is a traditional Chinese medicine currently in clinical trials for treatment of SP. However, its chemical composition and pharmacological mechanism remain unclear. The purpose of this inquiry is to investigate the workings of YGZ223 in managing SP using network pharmacology, UPLC-MS, and molecular docking. Materials and Method: This investigation employs network pharmacology to anticipate the mode of operation of YGZ223 in alleviating SP, and UPLC-MS is applied to identify the chemical constituents. Molecular docking provides the binding strengths between principal constituents and targets, while animal experiments are performed to validate the antipruritic activity of YGZ223. Results: The compound prescription for SP contains formononetin and erysodienone as effective ingredients. These ingredients have the potential to impact pathways related to cancer, endocrine resistance, and the PI3K/AKT signaling pathway by regulating targets such as AKT1, EGFR, and mTOR. Formononetin and erysodienone have a considerable binding capacity with various targets, the former displaying the strongest binding with AKT1. Animal test results show that the YGZ223 group can significantly reduce the number of tickles in mice compared to the 4-Aminopyridine induced model group, and has a good anti-itch effect. Conclusion: This study demonstrates that YGZ223 has potential anti-SP activity due to multiple constituents, targets, and pathways, and thus lays the groundwork for development of novel therapeutic approaches for SP.