Unlocking the anticoagulant potential of Barrel Jellyfish tentacle extract
Cnidarians in spite of their toxicity have long been indicated as a potential source of natural bioactive compounds of pharmacological concern useful to develop new drugs or biomedical materials. A number of metabolites, anti-cancer, anti-microbial and anti-oxidant compounds have been isolated in the interest of human health and have been found to be active at the cellular level and this makes them possible sources of new drugs.
Thrombosis and related cardiovascular disorders are major life threatening diseases of mankind. Currently used drugs to counter these disease conditions have various limitations including uncontrolled activity leading to haemorrhage or lower efficacy and sometimes, allergic reactions. These limitations drive the continual and intense efforts to develop new anticoagulants targeting specific coagulation factors. Several snake venom-derived toxins and hematophagous animal toxins have shown strong anticoagulant properties. Many of these toxins can dissolve blood clots at very low dose. Search for the ideal anticoagulant with minimal side effects have become a challenging field for the researchers.
This study was aimed at the assessment of anticoagulant and platelet aggregation inhibiting activities in the tentacle extract of one of the commonly found jellyfish species on the Goan coast i.e. Barrel jellyfish (Rhizostomapulmo). The tentacle extract was capable of inhibiting the blood coagulation cascade at three different levels: 1) Platelet aggregation 2) Fibrinogen digestion 3) Fibrin degradation.
Barrel jellyfish tentacle extract (BJFTE) could digest fibrinogen in dose and time dependent manner. It could digest clots, made with fibrinogen but not the ones made with essentially plasminogen free fibrinogensuggestive of the fact that there is possible correlation between plasminogen and BJFTE with respect to fibrin clot digestion. Fibrinogenolytic and fibrinolytic activities of BJFTE were significantly reduced in presence of EDTA and on pre-exposure to heat, but not on pre-treatment with PMSF. This observation indicated the involvement of thermolabilemetalloproteinases in the above-mentioned activities. BJFTE showed dose and time dependent hemolytic activity against human RBCs. The RBCs on exposure to BJFTE initially showed swelling of the cells followed by gradual crenation. It lacked phospholipase activity and could also inhibit ADP dependent platelet aggregation in a dose dependent manner. BJFTE exhibited strong proteolytic activity on fibrinogen, casein, gelatin and azocaesin, which was significantly lost on treatment with EDTA.
Owing to the highly unstable and aggregation prone nature of the jellyfish proteins, various attempts were made using combinations of purification techniques to purify active protein/peptides from BJFTE. As a result of a combination of ammonium sulphate precipitation and SE-HPLC, a semi-pure anticoagulant fraction was obtained, which showed strong fibrinogenolytic activity but no fibrinolytic activity. A 95 kDa metalloproteinase was identified in this fraction and was named Rhizoprotease. Atomic absorption spectroscopy studies suggested the presence of Zn+2 in BJFTE as well as in the semi-pure fraction containing Rhizoprotease. Protein mass fingerprinting analysis revealed that Rhizoprotease is a novel protein and was found to have similarity with invertebrates like Dinoponera quadriceps (giant ant), Taeniasaginata (beef tapeworm), Helobdellarobusta(freshwater jawless leech), Lepeoptheirussalmonis(hookworm), Ancyclostomaceylanicum(sea louse), Aedesalbopictus (mosquito). All these invertebrates are known to have anticoagulant and antiplatelet activities. These results suggest that Rhizoprotease has some sequences similar to several anticoagulant proteins of invertebrate origins.
This work reveals, for the first time, the anticoagulant potential of jellyfish tentacle extract. It also details a novel anticoagulant metalloproteinases, Rhizoprotease from Rhizostomapulmo. The work presented here increases the bio-discovery potential of jellyfish and provides direction for future research to consider them as a source for designing anticoagulant/antiplatelet/thrombolytic drugs.
Dibakar Chakrabarty, Akriti Rastogi
Birla Institute of Technology and Science, Pilani, K K Birla Goa Campus,
Zuarinagar, Goa 403726, India
Partial purification and identification of a metalloproteinase with anticoagulant activity from Rhizostoma pulmo (Barrel Jellyfish).
Rastogi A, Sarkar A, Chakrabarty D
Toxicon. 2017 Jun 15
|Neutralization assays of biological activities of… The venom of the snakes contains a great diversity of molecules, which are toxic to animals, so that the symptomatologies developed in the victim's body are related to multifactorial and…|
|Farnesoid X receptor and liver X receptor ligands… Platelets play a key role in the prevention of excessive blood loss through the formation of a thrombus at the site of vessel damage. Hyper-reactive platelets lead to unwanted, excessive…|
|Interleukin-18: Critical molecule in promoting… First interleukin was discovered in 1977 from monocyte and termed as interleukin (IL)-1. Interleukins are the secreted proteins that bind to their specific receptors with leukocytes. They are recognized as…|
|Cyagen Biosciences – Helping you choose the right… While many animal models are available “ off the shelf ” through various repositories and collaborations, generation of novel animal models has allowed for more effective studies, not limited by…|
|Milk and beef: Do production enhancing hormones pose… After World War II, a sharp increase in demand for beef and dairy products, coupled with a burgeoning veterinary pharmaceutical industry, led to a number of changes in animal husbandry,…|
|IL-1 Receptor 8: a novel player in immunothrombosis In addition to be a key component of blood hemostasis and coagulation, platelets have recently been implicated in thrombotic events associated with immune dysfunctions or inflammation. Platelets participate to innate…|