Leech Therapy (Hirudotherapy): A Comprehensive Systematic Review of Pharmacological Constituents, Mechanisms of Action, Therapeutic Applications, and Safety

Background: Hirudotherapy, the medicinal use of leeches, has evolved from traditional healing practices into a scientifically recognized therapeutic modality. The renewed interest in leech therapy arises from the identification of a wide spectrum of pharmacologically active molecules in leech saliva, many of which exhibit potent anticoagulant, anti-inflammatory, antithrombotic, analgesic, and vasodilatory effects.
Objective: This systematic review aims to critically analyze the pharmacologically active compounds present in leech saliva, their mechanisms of action, preclinical and clinical evidence, pharmacokinetic and pharmacodynamic aspects, safety concerns, and future potential in drug discovery.
Methods: A systematic literature search was performed across PubMed, Scopus, Google Scholar, Experimental, preclinical, and clinical studies relevant to pharmacology were included. Data extraction focused on bioactive molecules, mechanisms, therapeutic outcomes, and adverse effects.
Results: Leech saliva contains over 100 bioactive molecules, including hirudin, calin, destabilase, bdellins, and Eglins. These compounds exert synergistic effects on coagulation pathways, inflammatory mediators, and microcirculatory dynamics. Clinical studies support its use in venous congestion, osteoarthritis, and reconstructive surgery, though standardization remains a challenge.
Conclusion: Leech therapy represents a biologically rich source of pharmacologically valuable compounds. Despite promising evidence, further large-scale, standardized clinical trials and molecular studies are essential for its integration into mainstream pharmacotherapy.

Leech therapy, Hirudotherapy, Hirudin, Anticoagulants, Pharmacology, Bioactive peptides

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