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Xin Deng,1 Yanmei Liu,1 Xiaoli Zhu,1 Hui Zhu,1 Cheng Huang,1 Yan Hong,1,2 Deling Wu,2 Yanquan Han1– 3 1Grade Three-Level Laboratory of TCM Preparation, State Administration of Traditional Chinese Medicine, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 2Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 3Zhejiang University of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Yan Hong, Email hyan2003@163.com Yanquan Han, Email hyquan2003@163.comAbstract: Momordicae Semen (MS), a traditional Chinese medicine (TCM), is clinically used to disperse stagnation, reduce swelling, detoxify, and treat sores.. However, its therapeutic potential is limited by inherent toxicity and insufficient quality control standards that fail to reflect its therapeutic value. This review comprehensively synthesizes recent advances in MS research, encompassing phytochemistry, pharmacology, toxicology, herbal processing, and clinical applications. Phytochemical studies have identified a diverse range of bioactive compounds in MS, including triterpenoids and saponins, volatile oils, lignans, phenolic acids, flavonoids, steroids, proteins, peptides, and nitrogenous compounds. Pharmacological studies reveal its broad biological activities, such as antitumor, anti-inflammatory, antimicrobial, antiviral, antiulcer, antioxidant, immunomodulatory, hypolipidemic, hypotensive, and neuroprotective activities. Additionally, the applications of MS in TCM formulations and processed products are summarized, and prospects are examined. Furthermore, its potential quality markers (Q-markers) were systematically predicted based on the principles of specificity, measurability, efficacy correlation, traditional property, transfer and traceability, and network pharmacology. Despite these advances, critical challenges remain, including a limited understanding of its toxicological mechanisms, the processing-induced reduction of toxicity, the metabolic pathways of active constituents, and the need for comprehensive quality control standards. Addressing these issues through future research is essential to enhance the clinical utility and therapeutic potential of MS. This review provides a systematic reference and targeted directions for subsequent studies, which is crucial for realizing the safe, effective, and standardized application of MS in clinical practice and pharmaceutical development. Keywords: Momordicae Semen, pharmacology, phytochemistry, toxicology, clinical application, Q-markers |