SECRETIONS OF LEECH As mentioned earlier, scientific research reveals that the beneficial effect of leech therapy occurs viathe blood suction and blood decongestion and injection of a cocktail of several medicinally useful bioactive molecules present. Calculation of Jacquard's coefficient showed that H. medicinalis and H. orientalis are closest to each other in SGS [salivary gland secretions] composition, which is consistent with data in the literature on the phylogenetic relationship between these two species of medicinal leech.[44] The judicious description of Leech salivary gland secretions is as follows: 4.1. Hirudin-In 1950, Fritz Marquardt of Germany isolated a protein from Hirudomedicinalis that he termed ―Hirudin‖ and demonstrated its thrombin inhibitory effect. As a heparin-like substance, it is the most potent known natural inhibitor of thrombin..[43] 4.2. Hyaluronidase- Hyaluronidase is a spreading substance that modifies the permeability of connective tissue,through the hydrolysis of endoglucoronidic linkages of hyaluronic acid - a polysaccharide found in the intercellular ground substance of connective tissue.[34] Hence, hyaluronidase from leech saliva helps increase the spread of all salivary secretions..[44] 4.3.Calin- Calin has a rapid (1-10 min.) effect on collagen that is reflected in its ability to suppress collagen induced platelet aggregation as well as adhesion of platelets to collagen coated micro-carrier beads[45] 4.4 Destabilase- Destabilase possesses glycosidase activity. Destabilase lysozyme is the first invertebrate lysozyme with combined enzymatic and non-enzymatic antibacterial action[46] and it also dissolves blood clots [46] 4.5. Apyrase (adenosine 5‘-diphosphate di-phospho-hydrolase) is a nonspecific inhibitor of platelet aggregation by virtue of its action on adenosine 5‘diphosphate, arachidonic acid, platelet-activating factor (PAF), and epinephrine. Two apyrases (isoenzymes) have been isolated from the saliva of medicinal leeches.[47] An Interdisciplinary Critical Review of Leech Therapy; Evolution, Indications, Salivary Glan…. 14 4.6. Eglin-Eglins (elastase-cathepsin G leech inhibitors) are small proteins present in Hirudomedicinalis that have strong inhibitory activity against chymotrypsin and subtilisin-like serine proteinases acting on non-cationic substrates. One leech contains approximately 20 µg of eglin.[48] 4.7. Bdellins- inhibitors of trypsin, plasmin, and sperm acrosinwere first discovered in 1969. A similar proteinase inhibitor, bdellin B-3, was isolated from extracts of Hirudomedicinalis. Bdellins were named after the Greek word for leech.[49] 4.8. Decorsin- Decorsin is a protein isolated from American medicinal leech Macrobdelladecora. It acts as an antagonist of platelet glycoprotein II b-III a and is a potent inhibitor of platelet aggregation.[50] 4.9. Hirustasin- Hirustasin (Hirudoantistasin) belongs to a class of serine protease inhibitors.It was first isolated from the salivary glands of the Mexican leech, Haementeriaofficinalis, but has recently been prepared from Hirudomedicinalis.[51] 4.10. Piguamerin- Piguamerin is a serine protease inhibitor of plasma kallikrein that has been screened and purified from the Korean leech, Hirudonipponia. The peptide potently inhibits plasma and tissue kallikrein and trypsin[60] 4.11. Gelin- Gelin is a potent thrombin inhibitor analogous to eglin, and is isolated from the saliva of the Hirudinariamanillensis, a leech belonging to the same family as Hirudomedicinalis. Like eglin, gelin inhibits elastase, cathepsin G, and chymotrypsin. [52] 4.12. Gamma-GlutamylTranspeptidase- This compound has been isolated from salivary gland secretion of Hirudomedicinalis.[53] 4.13. Platelet Activating Factor Antagonist (PAFA) and anOrnithine-Rich Peptidehas been isolated from lyophilized dilute leech saliva. It is identified as a phosphoglyceride, which may prove to be an important compound for the treatment of thromboembolic disorders and inflammation. In addition, two specific factor Χa inhibitors from diluted leech saliva have been isolated.[54] 4.14. Vasodilatation Effect-Besides, leech saliva contains acetylcholine, histaminelike vasodilators that prolong bleeding time.[55] 4.15.Fibrolytic Activity: It also