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ABSTRACT
Snakebites have been declared a neglected health problem that must be considered a national disease of the WHO. Asian countries like India have high snakebite death rates due to short antidotes and poorly equipped doctors. In today's scenario, local resources like herbs need to be used to prepare cheap antidotes and often available to victims. Snake bites should be viewed as an emergency problem and require additional national guidelines, doctor training, expertise, and human concentration for effective and timely treatment—measures to be taken to ensure the availability and mass production of antidotes. Currently available, antidotes have problems with storage, manufacture, and aspects of the results. Attention should be paid to the natural compound Gedunin with antitoxic effects. To determine Gedunin's therapeutic efficacy well-designed clinical research is required. This article emphasizes and proves the therapeutic effectiveness of the herbal plant active ingredient Gedunin against snakebites.
keywords: Gedunin, Plant-based inhibitors, snake venom, antivenom
Summary
Current work is focused on natural snake venom inhibitors that could act as alternatives against snakebites, as currently available antidotes have problems with storage, manufacture, and aspects of the results. Attention should be paid to the natural product Gedunin, which has an antitoxic effect. Well-designed clinical research is required to determine the therapeutic effectiveness of Gedunin. This article aims to highlight and demonstrate the therapeutic effectiveness of the herbal plant ingredient Gedunin against snakebites.

LITERATURE REVIEW
Many secretions produced by the animals have been used to develop new drugs to treat various diseases such as heart attacks and cancer. Snake venoms are one of them that has contributed significantly to the treatment of many ailments. Venomous snakes have a bad rap for their deadly bites. Nevertheless, ever wondered what makes a snakebite so deadly is the venom. Snake venoms are made up of hundreds and thousands of different peptides, enzymes, and toxins, and each snake produces its specific venom. There are two main types of toxins, namely hemotoxins and neurotoxins. Hemotoxins target the circulatory system and prevent clotting compounds from working correctly, which in turn causes uncontrollable bleeding, while neurotoxins are those that target the central nervous system and stop muscle work, which can lead to suffocation. Neurotoxin toxins are particularly deadly because the proteins they contain can disrupt the channels that allow ions to flow through neuron membranes. Interruption of the communication channel can lead to a crash of the entire body and immediate death. Medicines derived from hemotoxins are used to treat heart attacks and blood diseases. These drugs also reduce the incidence of stroke, kidney disease, heart failure, and diabetes. Medicines derived from neurotoxins treat brain injuries, strokes, and diseases such as Alzheimer's and Parkinson's. In India, snake bites have become a public danger. In India, an average of more than 250,000 snakebites is recorded in just one year. The snakes found in India have a great variety of species in length and body weight. Snakes occupied deserts, forests, swampy places, lakes, streams, and rivers in rugged terrain. (1. Saini RK et al., 1984)
1.1 Snake Venom
Snake venoms are secretions from poisonous snakes that are synthesized and stored in the venomous gland of snakes. Glands secrete zootoxin, modifying the parotid gland present on each side of the head, near the eye, encapsulated in a muscular shell. Poison is stored in glands in large alveoli and injected into the body through tubular fangs at the time of the bite. Snake venom is also made up of proteins, enzymes, and peptides that can be harmless if ingested. Some snake venoms are a complex mixture of enzymatic and toxic proteins, including phospholipase A2 (Pla2s), myotoxins, hemorrhagic metalloproteinase, and other proteolytic enzymes, clotting components, cardiotoxins, cytotoxins, and neurotoxins. (2. Leon G et al., 2011)
1.2 Composition of snake venom
Snake venom consists of proteins, enzymes, neurotoxins, coagulants, anticoagulants, and a few substances with a cytotoxic effect. These have an acidic pH value and are water-soluble. Snake venom also contains inorganic cations such as sodium, potassium, magnesium, small amounts of zinc, nickel, cobalt, iron. Snake venom enzymes mainly hydrolyze protein and membrane components, leading to tissue necrosis and blood clotting. (3. Jin H and Varner J., 2011). Snake venom contains a mixture of enzymatic and non-enzymatic proteins that are very effective at immobilizing and digesting prey. It is wrong to say that all snakes are poisonous. The Mode of action of snake venom enzymes is shown in TABLE 1 . Venomous snakes are divided into two groups.
1. ELAPINES: It includes cobra, mamba, coral snakes, and venom is neurotoxic as it paralyzes the airways.
2. TRUE VIPERS AND PIT VIPERS: These are the members of the viperine family, and their venom is hemotoxic, anticoagulant, and necrotizing. e.g ., rattlesnakes, copperhead, Russell viper, and puff adder.
There are currently nearly 20 poisonous enzymes that are present or found in snake venoms in the world. Not that all snake venoms have all 20 enzymes, but mostly 6-12 of those enzymes in their venom. The functions of all poisonous enzymes differ from one another. Some of them are:
Phospholipase A2
ATPase
Hyaluronidase
Collagenase
L – aao
Lipooxygenase
Serine protease
Acetylcholinesterase
Proteinase
Metalloproteinase
5'Nucleotidase

1.3 Antivenom

Currently, the only treatment available for snakebite is the use of antivenom. Albert Calmette developed the first antidote against Indian cobra (well, well). Antivenom can be made by immunizing mammals such as horses, goats, rabbits with particular snake venom, and the specific immunoglobins are then isolated from blood. The affected animal produces antibodies as part of the immune response against the active poison molecule; these antibodies are harvested and used against poisoning. Among two types of anti-poisons: Monovalent is species-specific, while polyvalent is effective against several species. (4th Lake S, 2004)
1.4 Side effects of Anti-venom:
Side effects of antivenom therapy are anaphylactic reactions. E.g.
Swallowing and breathing difficulty
Swelling of eyes and face
Serum sickness
Rashes and itching
Joint inflammation
(9. MayaDevi C, et al.,2002)


ANTIVENOM AND ISSUES :
Today, ASV is the most effective antidote to snake venom and consists of Fab fragments of purified IgG from horse or sheep plasma or serum that has been immunized with snake venom. It can be monovalent like CROFAB, which works against the poison of rattlesnakes, copperhead, and cottonmouth. If polyvalent, i. H. ASV, it can be used against different species such as Russell viper, common cobra, common krait, saw-scaled viper. (10th Whitaker R and Whitaker S, 2012)
The use of ASV is not as every day as the availability and less, and the specific activity of the species, storage problems contribute to the lower use of this anti-poison. The main problem with immunotherapy is specificity as there is a great deal of variation between species and geographic areas that restrict the use of certain ASVs. in addition, it cannot be raised against all species and subspecies due to a lack of knowledge of the geographical diversity of poisonous snakes aside from the above issues, marketing, production, and delivery are also an issue. Since ASV is time-consuming to manufacture, you need ideal storage facilities. These can be made in lyophilized form, but the process is too costly, and the likelihood of Physico-chemical changes is higher, so monovalent ASV is not made in India (11th Simpson ID and Jacobsen IM 2009). Other drawbacks can include fatal anaphylaxis, serum sickness, and sometimes offspring reactions.
2.1 HERBAL AS A CHOICE :
Plants can be a source of various plant flavonoids, triterpenoids, tertraterpenoids such as Gedunin, effective against snake venom (12. Gupta YK and Peshin SS 2012) shown in TABLE 2 & 3. There are various plants that traditional healers use, and these can be obtained from plant sap, roots, leaves—moreover, given in the form of powders, pills, pastes. Plant-based compounds can act as inhibitors which are shown in TABLE 4 & 5. These can be useful in remote areas in India and other parts of the world.

2.2 Azadirachta. Indica :
It is commonly known as neem and has been known for its medicinal properties in India for more than 2000 years. It belongs to the Meliaceae family. Neem extracts are abundant in more than 300 active ingredients, such as phenol, alkaloids, triterpenoids, tetraterpenoids, alkaloids. Moreover, Gedunin, the most common alkaloids, and terpenes have been reported to show anti-PLA activity against snake venom [62].
CONCLUSION :
Snake bites should be viewed as an emergency problem and require a change in national guidelines, training of doctors, knowledge, and people's awareness for effective and timely treatment. Measures should be taken to ensure the availability and mass production of antidotes. Because currently available antidotes have problems with storage, production, and side effects. Attention should be paid to the natural product Gedunin with an antidote effect. Well-designed scientific studies are required to demonstrate the therapeutic effectiveness of Gedunin.
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(1Aquaculture Biotechnology Division, OIE Reference Laboratory for WTD, Department of Zoology, C. Abdul Hakeem College, Melvisharam, Vellore District, Tamil Nadu, India.)
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B KCDukkaa 2014 Department of Computational Science and Engineering, North Carolina A&T State University, Greensboro, NC, 27411, USA
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Roman A. Laskowskia Department of Crystallography, Birkbeck College, University of London, Malet Street, London WC1E 7HX, UK
Mukherjee AK, Doley R, Saikia D,2008, Isolation of a snake venom phospholipase A2 (PLA2) inhibitor (AIPLAI) from leaves of Azadirachta indica (Neem): Mechanism of PLA2 inhibition by AIPLAI in vitro condition. Toxicon;51(8):1548–53.
TABLE LEGENDS :
TABLE 1: Snake venom enzymes with their Mode of action
TABLE 2 : List of plants with their bio-active medicinal compounds
TABLE 3 : Reported activities of plants bio-active compounds
TABLE 4 : Snake venom Enzymes and their inhibitors
TABLE 5 : Natural bio-active inhibitor compounds against snake venom enzyme activity



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