Review Article International Ayurvedic Medical Journal ISSN:2320 5091

A REVIEW ON THE THERAPEUTIC APPLICATIONS OF Dr. Sri Jyothsna P M1, Dr. Santosh Kumar Verma2, Dr. M. Sreevani3, Dr. T. Udaya Kiran4 1,2P.G.Final year, 4PG Reader Department of Shalya, 3P.G.Final year, Department of Ayurveda Samhita & Siddhanta, S.V. Ayurvedic College, Tirupati, Andhra Pradesh, India ABSTRACT have been used since the beginning of civilization starting from the Ancient Egyptian, Indian, Greek and Arab physicians to modern era for various therapeutic purposes. They consist of biologically active compounds in their secretions, especially in their saliva and are hematophagous . As a result of recent researches which had revealed the presence of variety of bioactive peptides and proteins in leech saliva, it has become a new remedy for many chronic and life-threatening abnormalities, such as cardiovascular problems, cancer, metastasis, and infectious diseases. In the 20th century, leech therapy has established itself in plastic and mi- crosurgery as a protective tool against venous congestion and served to salvage the replanted di- gits and flaps. Despite the efficacious properties of leech therapy, complications of leeching are still controversial. Keywords: Hematophagous, Therapeutic purposes, Bioactive peptides, Microsurgery.

INTRODUCTION Hematophagous animals that feed on sion on its prey skin [3,4,5]. blood have been known to overcome blood Leech locality and ecology: clotting by secreting in their salivary gland Leeches can live in a variety of environ- secretion a multitude of biologically active ments, including aquatic and moist terrestri- compounds, especially the anticoagulants al regions. Some species live in freshwater, [1]. Amongst the blood-sucking organisms, estuaries, rivers, ponds, lakes, and sea. Be- leech is a distinct example of an inverte- cause moisture is a very essential factor af- brate, which possesses a highly-developed fecting the terrestrial leech's distribution and mechanism by which they prevents blood behavior, they can be found in a large num- clotting [2]. For various therapeutic purpos- ber in the forests and highlands of North es, the European medicinal leech species, America, Europe, and South-East Asia. Hirudo medicinalis, also known as the heal- Leech and morphology: ing leech was preferred by the majority of Leeches (Euhirudinea) were first named by physicians compared to the American spe- Linnaeus in 1758 AD [3]. The medicinal cies, Hirudo decora, which can suck less leech (Hiruda medicinalis) is a segmented blood due to a smaller and superficial inci- belonging to Phylum: Annelida,

How to cite this URL: Sri Jyothsna P M Et Al: A Review On The Therapeutic Applications Of Leech. International Ayurvedic medical Journal {online} 2016 {cited 2016 July} Available from: http://www.iamj.in/posts/images/upload/3028_3035.pdf Sri Jyothsna P M Et Al: A Review On The Therapeutic Applications Of Leech Class: and Subclass: Hirudinea. In complex deficiency, which often occurs in general, early studies classified leeches into blood nutrition-depending animals [6,7]. 4 subclasses, 3 orders, 10 families, 16 sub- HISTORICAL REVIEW OF LEECH- families, 131 genera and more than 696 spe- ING cies [7]. Recently, taxonomists identified Before the Christian era (BC), medicinal more than 1000 leech species [8]. Leech size leeching was mentioned in the 18th dynasty varies among families and can reach up to Pharaohs paintings (1500 BC). Talmud, Bi- 20 cm in length, in addition to some giant ble, and other Jewish manuscripts outlined species, such as the Amazonian leech, Hae- the medical indications of leeching [13]. mentaria ghilianii, which is about 50 cm in Later, in the middle ages, medics depended length [9]. A classic leech body consists of more on leech therapy, which was pre- many segments divided as two preoral, scribed for a wide range of disorders includ- nonmetameric segments, and 32 postoral ing nervous system diseases, urinary, and metameres (somites). Somites are subdi- reproductive organs diseases, inflammatory vided into 2-16 external annuli, and the an- diseases and eye illnesses [3,14]. nulation pattern can be considered as a diag- By the end of 19th century, leeching gradu- nostic feature for leech genus and species. ally fell into disrepute, and almost stopped Sensory structures, such as eyes, oculiform by the early twentieth because hirudo thera- spots, papillae and sensilla are also used by py did not match the new requirements of taxonomists to identify genus, and species. the modern medical regulations and the The biology of leech feeding: great advancement in all medical fields [3]. Based on feeding habits, leeches are divided In 1981, a foundation for leech breeding de- into two major groups. They are predacious velopment and medicinal leech research was and sanguivorous leeches and both digest established by an American biologist, Roy their food in their intestine. With the help of T. Sawyer [3]. After the recession period of suckers and the biting jaws, leeches are able leech therapy, it has resurged after the mid- to absorb prey blood [10]. It is interesting to 20th century with new applications in many note that leeches generally suck 2-20 ml of medical fields including surgical and recons- blood within 10-30 min, then drop-off spon- titution procedures, vascular diseases, arthri- taneously after being completely engorged tis, migraine [14,15]. In 2004, the Food and with no immediate desire of more feeding Drug Organization (FDA) approved leeches and store the ingested blood for up to 18 for medicinal purposes [14]. months [11,12]. MODERN APPLICATIONS OF Symbiotic bacteria named Aeromonas spe- LEECHING cies, located in the leech's gut, secrete en- Cardiovascular diseases: zymes that help not only in breaking down Leech therapy has established itself as an the components of the ingested blood, but alternative remedy for the treatment of vas- also in producing antibiotics to prevent cular disorders, since leech saliva can tem- blood putrefaction after a long storage pe- porarily improve blood flow and ameliorate riod in leech crop. Furthermore, another pre- connective tissue hyperalgesia[12]. Clinical sumed role of these enzymes is to prevent B studies revealed that it can reduce blood hypercoagulability with an antiinflammatory 3029 www.iamj.in IAMJ: Volume 4; Issue 09; September- 2016 Sri Jyothsna P M Et Al: A Review On The Therapeutic Applications Of Leech effect in patients with thrombophlebitis [20]. Leeches were also used to decongest com- The effectiveness of leech saliva in CVDs is pletely amputated ears [28], to improve the results of specific thrombin inhibitors, blood flow after microsurgery of a severely hirudin, which was first isolated from H. avulsed scalp [26], to prevent flap collapse medicinalis [16,17,18] and was shown to [27] and replantation of amputated facial possess a potent inhibitory effect on both tissues[29], finger tips[30] and penile rep- free and clot-bound thrombin [21,22]. lantation[31]. Noteworthy, hirudin is the only hemato- Cancer and metastasis: phagous -derived anticoagulant which A review was carried out based on some has been approved by FDA for clinical pur- studies, which were oriented towards using poses [19]. Many studies revealed that hiru- leech salivary extract as antimetastatic din is more effective than heparin in pre- agents rather than using it for treating the venting deep venous thrombosis (DVT) and tumor itself. It was reported that the metas- ischemic events in patients with unstable tatic inhibitory activity of leech was due to angina[19]. Hirudin can be used safely in some anticoagulants such as warfarin and patients with platelet abnormalities or hepa- heparin [32]. Later, an antimetastatic and rin-induced thrombocytopenia because it has anticoagulant protein named ghilanten was no immune effects on erythrocytes [22]. For purified from the salivary gland secretion of example, two analogs, lepirudin, and desiru- H. ghilianii [33]. It was reported that ghilan- din have been approved by FDA and are ten could suppress metastasis of melanoma, currently in use under the trade names, Ref- breast cancer, lung cancer, and prostate can- ludan® and Iprivask®, respectively [19]. cer [34]. Another research described a syn- Reconstructive and microsurgery: thetic hirudin preparation as an efficacious Microsurgery is a type of surgical operations metastasis inhibitor of a wide range of ma- carried out using the microinstruments under lignant tumor cells, such as pulmonary car- the microscope aiming to anastomose small cinoma, breast carcinoma, bladder carcino- blood vessels, veins and arteries during the ma, colorectal carcinoma, soft-tissue sarco- replantation of tissues or amputated di- ma, leukemia, and lymphoma [32]. gits[13]. Venous occlusion is a serious threat The Mexican leech officinalis in newly transplanted tissues and may lead was observed to have antimetastatic activity to thrombus formation, stasis, and eventual- because its salivary gland secretion contains ly tissue necrosis. The relieving effect is the a 17-kDa protein, called antistasin, having accumulated result of the leech bite-induced the capability to prevent lung cancer coloni- blood oozing, which is a consequence of zation. In 2010, scientists delineated that a 2 many factors, including bleeding wound, month treatment by topical application of H. secreted bioactive enzyme, anticoagulants, medicinalis can completely cure the local and vasodilators [24]. On the other hand, lumbar pain in patients with advanced stages surgeons who practice plastic operations of renal cancer and leiomyosarcoma [35]. considered leeching as a promising remedy, Diabetes mellitus and its complications: since the Y-shaped wounds caused by leech There are no documented scientific reports bites usually heal without scars or complica- on leech therapy as an antihyperglycemic tions [12]. medication up to now. On the other hand, 3030 www.iamj.in IAMJ: Volume 4; Issue 09; September- 2016 Sri Jyothsna P M Et Al: A Review On The Therapeutic Applications Of Leech leech application has been used traditionally tein had an antibacterial activity against for the treatment of DM complications [37]. some bacterial strains because it can destroy One of the most severe complications of their cellular components [38,39]. DM is the cardiovascular ones. The peri- Moreover, it was reported that the nervous pheral vascular complications in diabetic system of the European leech, H. medicina- patients can lead to less blood flow to the lis, could initiate an antimicrobial response distal parts of the body resulting in ischemic after injury by signaling the synthesis of An- diseases like gangrene. The wild leech spe- timicrobial proteins (AMPs) [40]. Three dif- cies Whitmania pigra (Family: Hirudinidae) ferent peptides with antibacterial activities has been used by the traditional Chinese the- were identified. Hm-lumbricin and neuro- rapists to augment blood flow to the distal macin were isolated from neurons and mi- parts of the body and to alleviate coagula- croglial cells while peptide B was found in tion disorders. leech body fluids [41]. Recently, it was re- Diabetic patients are at a high-risk of myo- ported that leech species of the family Hiru- cardial infarction, which is the main death- dinidae had a high antibacterial activity causing reason in type 2 DM [36]. First of against Shewanella and Aerococcus viridans all, hirudin plays an essential role in pre- while a lower activity was observed against venting clotting process because of its abili- Escherichia coli, Salmonella typhi and Sta- ty to bind thrombin and consequently sup- phylococcus aureus. press thrombin-mediated conversion of fi- Arthritis and analgesic: brinogen into fibrin enabling it to be effica- The painkiller effects of leech application cious for the relieving of ischemic events were ascertained in many trials on patients [19]. Calin, isolated from H. medicinalis, with osteoarthritis who claimed that leech- has been proven to obstruct the formation of ing was more relieving than topical diclofe- thrombi as described above [23]. By the year nac with no adverse effects [42]. Likewise, 2002, an official center for leech therapy some studies proved that hirudin can reduce was opened, which has been during a short synovial inflammation in arthritis patients period of time an international center for by inhibiting DING protein, a derivative of DM treatment by leeches [37]. synovial stimulatory protein acting as au- Infectious diseases: toantigen in rheumatoid arthritis patients The continuously increasing rates of infec- [43]. tious diseases led to a higher usage of the Another clinical trial on patients with ad- commercially available antibiotics, which vanced osteoarthritis at the knee proved that resulted in a new challenging phenomenon leech therapy could effectively reduce the known as resistance to antimicrobial agents. need for analgesic intake. It has been out- For instance, some reported that leech thera- lined that a double treatment regimen at a 4- py was used by traditional dentists as a re- week interval exhibited a longer term reliev- medy for dental infections such as periodon- ing and a better physical activity than a sin- titis and alveolar abscesses [15]. A protein gle treatment course [44]. Other reports in- named destabilize with a lysozyme-like ac- dicated leech therapy as an analgesic for ili- tivity had been isolated from the medicinal osacral joints pain and cervicobrachialgia leech extract. It was reported that this pro- syndrome [12]. 3031 www.iamj.in IAMJ: Volume 4; Issue 09; September- 2016 Sri Jyothsna P M Et Al: A Review On The Therapeutic Applications Of Leech OTHER APPLICATIONS OF LEECH- tes are also reported as post leeching com- ING plications [25]. Dentistry: CONCLUSION Although, the benefits of leeching in denti- To conclude, leeching was a popular thera- stry have not been established yet, many re- peutic practice throughout the ages for a ports mentioned leech application in dental wide range of diseases and it was applied as abnormalities [15]. The bloodletting by an unscientific home remedy by traditional leeches was reported to be considerably suc- therapists. Nowadays, leech came back to cessful in the management of severe post- the contemporary medicine with fewer ap- operation macroglossia cases when the plications, which were proven and supported common treatment method was not satisfac- by a huge number of scientific studies and tory [45]. Other case reports described the case reports. Leech therapy in the field of use of the medicinal leech in the treatment plastic and reconstructive surgery is ex- of sublingual hematoma and massive lingual pected to be of paramount importance due to hematoma [46,47]. the ease of leech application and reduced Audiology and ear abnormalities: side-effects. Hence, more efforts should be It was reported that leeches and their sali- undertaken to optimize this utilization. More vary secretion were successfully used for the investigations are required to assess leech treatment of tinnitus, acute and chronic otitis efficacy and safety in the treatment of DM [48]. Leeching has been applied in sudden and cancer. hearing loss. Despite the unexplained rea- REFERENCES sons of tinnitus, leeches were proven to be 1. Koh CY, Kini RM. Anticoagulants from of great benefits in the treatment of this dis- hematophagous animals. Expert Rev order [12]. Hematol. 2008;1:135–9. [PubMed] Skin disorders: 2. 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Tirupati, Andhra Pradesh, India Assessment of leech therapy for knee os- Email: [email protected] teoarthritis: A randomized study. Acta Orthop. 2008;79:235–43. [PubMed] Source of Support: Nil Conflict of Interest: None Declared

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