Scorpion Venom: a Poison Or a Medicine-Mini Review
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Indian Journal of Geo Marine Sciences Vol. 47 (04), April 2018, pp. 773-778 Review Article Scorpion venom: A poison or a medicine-mini review Pir Tariq Shah1, Farooq Ali1, Noor-Ul-Huda1, Sadia Qayyum1, Shehzad Ahmed1, Kashif Syed Haleem1, Isfahan Tauseef1, Mujaddad-ur-Rehman2, Azam Hayat2, Attiya Abdul Malik2, Rahdia Ramzan2 & Ibrar Khan1,2* 1Department of Microbiology, Hazara University, 21300 Mansehra, Pakistan 2Department of Microbiology, Abbottabad University of Science & Technology, 2250 Havelian, Pakistan *[E-mail: [email protected] ] Received 16 June 2016 ; revised 27 July 2016 The Scorpion’s venom considered to be highly complex mixture of nucleotides, enzymes, mucoproteins, biogenic amines, salts, as well as peptides and proteins, which have been used in traditional medicine for thousands of years mainly in Asia and Africa. With the significant discoveries in the number of valuable biologically active components of scorpion venom, numerous drug candidates have been found with the potential to encounter many of the emerging global health crisis. This mini-review sheds light on the application of scorpion venoms and toxins as potential novel antibacterial, antifungal and antiviral, especially as anticancer therapeutics. [Keywords: Scorpion venom, Antibacterial, Antifungal, Antiviraland Anticancer Potential.] Introduction Scorpion Venomous animals are famous only for their Scorpions are the predatory arachnids and members adverse effects caused after interaction with humans of the order scorpiones. They have eight legs, a accidently. These creatures transmit variety of narrow, segmented tail curved over the body, with a detrimental toxins with diverse physiological poisonous stinger at the end. Size ranges from 9 mm activities that may either lead to minor symptoms like to 20 cm (Typhlochactas mitchelli and Hadogenes dermatitis and allergic responses or highly severe troglodytes respectively)2. Scorpion’s evolutionary symptoms such as coagulation ailments, disseminated history goes back to the Silurian period 430 million intravascular coagulation and haemorrhage. Other years ago. Taxonomy of all known scorpions complications like respiratory arrest and necrosis may recorded from 1758 to 31st December 1998 contain also occur. Although envenomation effects usually 16 families, 16 subfamilies, 155 genera, 31 subgenera lead to harmful characters, but these venomous (including 10 nominotypical), 1259 species and 356 creatures are pharmacologically rich source of subspecies (including 114 nominotypical)3. Scorpions treasured principles for many scientists. Scientists belongs to; Kingdom Animalia, Phylum Arthropoda, are still exploring these toxins, aiming to develop Subphylum Chelicerata, Class Arachnida, Subclass new useful molecules to diagnose, treat and cure Dromopoda and Order Scorpiones4. Super families; some types of diseases1. Researchers and Buthoidea, Chaeriloidea, Chactoidea, Luroidea, scientists always continue their efforts to explore and Pseudochactoidea, Scorpionoidea4. discover new techniques and approaches for the Scorpion’s venom is one of the most dangerous and welfare of human beings. In ancient era, the venoms life threatening agents causing high number of human and natural toxin of plants, animals, fungi and marine organisms had played a great divesting Table 1 — Comparative antibiotic activity of different venoms role in the mortality and morbidity of human Venomous Antibacterial Antiviral Antifungal Anticancer population. Researchers continue their efforts to Animal activity activity activity activity identify the nature of these toxins. As the chemical Scorpion + + + 16, 19 + + + 28, 30, 32, 33 + + + 16 + + + 13, 36 composition of these toxins is defined by different Snake + + + 37, 38 + + + 39 + + + 40 + + + 36 researchers, these risky toxins are now used directly Spider + + + 41 - - - + + + 42 + + + 43 or indirectly in the drugs for number of diseases Frog and + + + 44, 45 + + + 46 + + + 46 + + + 36 treatments (Table I). Toad 774 INDIAN J. MAR. SCI., VOL. 47, NO. 04, APRIL 2018 deaths. According to the current studies, seven from spine. According to recent study, about 30% of regions of the world are considered at high risk glioma starts progression from brain and spine, while containing; North-Saharan Africa, Near and Middle- 80% leads to malignant brain tumor12. Glioma is East, South Africa, Sahelian Africa, South-India, East highly vascular tumor having the ability to infiltrate, of the Andes, Mexico and South Latin America5, which leads to wide areas necrosis, hypoxia and may comprising 2.3 billion population at risk. Annually cause breakdown of blood-brain barrier (BBB) around more than 1.2 million peoples are stung by scorpions the tumor. As scorpion venom is concerned, causing more than 3250 deaths5. Chlorotoxin is considered to its component which Scorpion’s venom is a complex mixture of salt, specifically binds to the cell surface of the glioma and proteins, small molecules and peptides6. It also impairs the invading ability of glioma cell. The contains neurotoxic peptides which cause massive chlorotoxin bind specifically to matrix damage to the nervous system of both vertebrates and metalloproteinase-2 (MMP-2) receptor which is invertebrates7. Moreover, it has hyaluronidase, usually not expressed in normal brain cells, but is histamine, mucopolysaccharides, phospholipase, upregulated in glioma and cancer. The MMP-2 plays enzyme inhibitors and serotonin8. Like other an important role in degradation and remodelling of predators, scorpion use these toxins or venoms to the extracellular matrix, thereby helping the normal attack and capture the prey as well as for the tumor cells to penetrate through tissue barriers. While, protection against other invaders9. Taken together, the Chlorotoxin interacts with MMP-2 receptor and these peptides and toxins extracted from scorpions inhibits its enzymatic activity, as well as reduce its and other venomous animals are used as therapeutic expression13. agents10, especially with effective inhibitory effect on The endless battle between humans and multiple steps of HSV-1 life cycle and therefore are microorganisms especially bacteria, fungal, parasites, good candidate for development as virucides and viruses is going on from very past. On one side, (Figure 1). humans design antibiotics against these microbes Scorpion’s venoms and toxins contain variety of and its infections. While, on the other side, peptides and other useful molecules which can be microorganisms resist these antibiotics and fight back. used for the treatment of various diseases. Scorpion The successful use of any therapeutic agent is venom is used for antibodies production in animals compromised by the potential development of like horse and sheep, which are used for the tolerance or resistance to that compound from the neutralisation of the venom hazardous effects on the time it is first employed. This is true for agents used humans11. in the treatment of bacterial, fungal, parasitic, and Brain tumor (glioma) is considered to be the most viral infections and for treatment of chronic diseases common and severe tumor in humans. Since it arises such as cancer and diabetes; it applies to ailments from the glial cells, so called glioma. Its most caused or suffered by any living organisms, including common site is brain, but it may also start progression humans, animals, fish, plants, insects, etc. A wide range of biochemical and physiological mechanisms may be responsible for resistance. In the specific case of antimicrobial agents, the complexity of the processes that contribute to emergence and dissemination of resistance cannot be overemphasized, and the lack of basic knowledge on these topics is one of the primary reasons that there has been so little significant achievement in the effective prevention and control of resistance development14. However, the gradual emergence of populations of antimicrobial-resistant pathogenic bacteria resulting from use, misuse, and abuse of antimicrobials has today become a major global health concern. Thus, urgent measures are required not only to minimize the use of antimicrobials for Fig. 1 — Collection of scorpion venoms34. SHAH et al.: SCORPION VENOM 775 prophylactic and therapeutic purposes but also to look the oral and genital tract22, oral thrush23, nosocomial for alternative strategies for the control of bacterial infections24 etc. According to recent studies, one and infections, in sense of discovering new antimicrobial half million people die every year due to the invasive agents15. fungal infections, out of them, 90% deaths are caused Venom of the Opistophtalmus carinatus, a South by species belong to the four genera: Candida, African scorpion contain two unique pore-forming Aspergillus, Cryptococcus and Pneumocystis25. peptides known as opistoporin 1 and 2. Similarly, the Furthermore, many of the fungal pathogens are also venom of another South African scorpion species shows resistance against multiple antibiotic26, so it is Parabuthus schlechteri also contain a pore-forming needed to develop highly potent and effective drugs peptide known as parabutoporin. During an against these life-threatening fungal pathogens. experiment, these two peptides and two other well- On the other hand, two pore-forming cationic known cytolytic peptides, melittin and mastoparan peptides known as opistoporin 1 and 2, isolated were examined against several Gram positive and from venom of most dangerous species of Gram negative bacteria and it was found that