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We also consider future trends and concerns in this domain. We summarize the bioactive components of EE, including G\u201090, lysenin, lumbrokinase, antimicrobial peptides, earthworm serine protease (ESP), and polyphenols, and detail the antitumor, antithrombotic, antiviral, antibacterial, anti\u2010inflammatory, analgesic, antioxidant, wound\u2010healing, antifibrotic, and hypoglycemic activities and mechanisms of action of EE based on existing in\u00a0vitro and in\u00a0vivo studies. We further propose the potential of EE for clinical translation in anticancer and lipid\u2010modifying therapies, and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance. The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis. Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix. The glycolipoprotein extract G\u201090 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage. Earthworms have evolved a well\u2010developed defense mechanism to fight against microbial infections, and the bioactive agents in EE have shown good antibacterial, fungal, and viral properties in in\u00a0vitro and in\u00a0vivo experiments and can alleviate inflammatory responses caused by infections, effectively reducing pain. Recent studies have also highlighted the role of EE in lowering blood glucose. EE shows high medicinal value and is expected to be a source of many bioactive compounds.<\/jats:p>","DOI":"10.1002\/ame2.12465","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T07:18:54Z","timestamp":1719991134000},"page":"653-672","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Pharmacological effects of bioactive agents in earthworm extract: A comprehensive review"],"prefix":"10.1002","volume":"7","author":[{"given":"Zihan","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Orthopedics Xiangya Hospital, Central South University  Changsha Hunan China"},{"name":"Xiangya School of Medicine Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Xiangya Hospital, Central South University  Changsha Hunan 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