Kasturi College of Pharmacy, Shikrapur, India
Snakebite envenomation represents a critical public health crisis, causing approximately 81,000 to 138,000 deaths annually worldwide, with India accounting for nearly 50% of global mortality [1][2]. While conventional serum-based antivenoms remain the standard treatment, they present significant limitations including adverse reactions in 3-43% of patients, cold chain requirements, limited availability in rural areas, and poor efficacy against local tissue damage [3][4] [5]. This comprehensive review systematically analyzes medicinal plants with demonstrated anti-snake venom properties, focusing on their phytochemical constituents, mechanisms of action, and therapeutic potential as alternatives or adjuncts to conventional therapy. An extensive literature review was conducted encompassing traditional ethnopharmacological knowledge, preclinical in vitro and in vivo studies, and phytochemical analyses. Over 50 medicinal plant species from diverse botanical families have demonstrated significant anti-venom activities, including Aristolochia indica, Andrographis paniculata, Curcuma longa, Azadirachta indica, Eclipta alba, Withania somnifera, Hemidesmus indicus, Vitex negundo, Emblica officinalis, and Mimosa pudica. The major bioactive phytochemical classes responsible for venom neutralization include terpenoids (28%), flavonoids (22%), alkaloids (18%), and phenolic compounds (15%). These compounds exert protective effects through multiple mechanisms: inhibition of phospholipase A2 enzymes, neutralization of metalloproteinases, blocking of neurotoxins, prevention of hemorrhage and edema, antioxidant activity, and membrane stabilization. Plant extracts have demonstrated 75-95?ficacy in neutralizing lethal, hemorrhagic, and edematous effects of venoms from Naja species, Daboia russelli, Bungarus species, and Echis carinatus. Substantial preclinical evidence supports the anti-venom potential of medicinal plants; however, translation to clinical practice requires standardized extraction protocols, rigorous clinical trials, pharmacokinetic studies, and regulatory approval. Plant-based compounds represent promising candidates for developing novel oral antivenoms, adjuvant therapies to enhance conventional treatment, and first-aid interventions in remote areas.
1.1 Historical Perspective on Snake Envenomation
Throughout human history, venomous snakebites have posed a persistent threat to public health and safety, particularly in agricultural and rural communities where human-snake encounters are frequent [6][7]. Ancient civilizations across Asia, Africa, and the Americas developed sophisticated traditional medicine systems incorporating hundreds of plant species for snakebite treatment [8][9]. These ethnopharmacological practices were transmitted orally through generations, forming the foundation of indigenous medical knowledge [10]. The scientific study of snake venoms began in the late 19th century with pioneering researchers who characterized venom composition and pathophysiology [11]. Albert Calmette's development of the first antivenom serum in 1895 represented a revolutionary breakthrough, establishing the principle of passive immunization using animal-derived antibodies [12]. However, the fundamental therapeutic approach has remained largely unchanged for over a century, despite significant advances in biotechnology and pharmacology [13].
1.2 Global Burden of Snakebite Envenomation
Snakebite envenomation represents a critical yet neglected public health crisis, particularly in tropical and subtropical regions. Globally, an estimated 5.4 million people suffer snakebites annually, resulting in 1.8 to 2.7 million cases of envenoming and 81,000 to 138,000 deaths [14][15]. For every death, up to four survivors experience long-term disabilities including amputations, contractures, blindness, and disfigurement [16]. In 2017, the World Health Organization officially recognized snakebite envenomation as a Category A Neglected Tropical Disease, acknowledging its devastating impact on rural and underserved populations [17].
1.3 The Indian Context
India bears the highest individual burden of snakebite mortality worldwide, accounting for nearly 50% of global deaths. A comprehensive national study documented approximately 1.2 million snakebite deaths between 2000 and 2019, averaging 58,000 deaths annually [18][19]. The Million Death Study revealed that 94% of these deaths occurred in rural areas, with 77% happening outside hospitals [20]. Nearly half the deaths occurred at ages 30-69 years, and over a quarter in children under 15 years [21]. The four major venomous species responsible for most Indian fatalities are the Indian Cobra (Naja naja), Common Krait (Bungarus caeruleus), Russell's Viper (Daboia russelli), and Saw-scaled Viper (Echis carinatus) [22][23].
1.4 Limitations of Conventional Antivenom Therapy
While polyvalent anti-snake venom (ASV) serum remains the gold standard treatment, several critical limitations compromise its effectiveness. First, conventional antivenoms require cold chain storage and rapid administration after envenomation, which is often impractical in remote rural areas where most bites occur [24][25]. Second, serum-based antivenoms carry significant risks of adverse reactions, with approximately 20% of patients experiencing early or late allergic responses ranging from mild urticaria to life-threatening anaphylaxis [26][27]. Third, these antivenoms are expensive and frequently unavailable in primary health centers, particularly in high-burden states like Bihar, Uttar Pradesh, and Odisha [28][29]. Fourth, conventional antivenoms demonstrate limited efficacy in neutralizing local tissue damage, which leads to permanent sequelae including necrosis and amputation even when systemic effects are controlled [30][31].
1.5 Traditional Medicine and Ethnopharmacological Knowledge
In response to these limitations, rural populations have relied on traditional herbal remedies for centuries. Up to 80% of snakebite victims first consult traditional healers before seeking hospital care [32][33]. India's rich ethnopharmacological heritage includes the use of at least 523 plant species from 122 families for snakebite treatment in Ayurveda, Siddha, and tribal medicine systems [34][35]. These traditional practices represent an invaluable repository of empirical knowledge that deserves rigorous scientific validation.
2. Snake Venom Composition and Pathophysiology
2.1 Overview of Venom Components
Snake venoms are complex mixtures of proteins, enzymes, peptides, and inorganic cations that have evolved to immobilize prey and initiate digestion [36][37]. The composition varies significantly across snake families, species, and even geographical populations within the same species [38]. Viperidae venoms are predominantly characterized by metalloproteinases and serine proteases causing hemorrhagic and coagulant effects, while Elapidae venoms are rich in phospholipase A2 enzymes and three-finger toxins producing neurotoxic manifestations [39][40].
2.2 Major Venom Enzymes
Phospholipase A2 (PLA2) represents the single most abundant and toxic enzymatic component across most snake venoms [41][42]. These enzymes hydrolyze phospholipids at the sn-2 position, releasing lysophospholipids and free fatty acids that disrupt cell membranes and trigger inflammatory cascades [43]. PLA2 enzymes exhibit diverse pharmacological effects including myotoxicity, neurotoxicity, cardiotoxicity, anticoagulant activity, and edema formation [44] [45]. Both catalytically active and inactive PLA2 isoforms contribute to toxicity through enzymatic hydrolysis and receptormediated mechanisms [46].
Snake Venom Metalloproteinases (SVMPs) constitute the primary hemorrhagic factors in viper venoms [47]. These zincdependent enzymes degrade extracellular matrix components including collagen, fibrinogen, and basement membrane proteins, leading to capillary disruption, internal bleeding, and tissue necrosis [48][49]. SVMPs are classified into three major structural classes (P-I, P-II, P-III) based on their domain organization, with P-III class enzymes typically exhibiting the highest hemorrhagic potency [50].
Snake Venom Serine Proteases (SVSPs) affect hemostasis through multiple pathways including fibrinogenolysis, prothrombin activation, factor V activation, and platelet aggregation [51][52]. These enzymes contribute to both coagulant and anticoagulant effects depending on their specific substrate preferences [53]. Three-Finger Toxins (3FTx) represent a diverse family of non-enzymatic peptides found predominantly in elapid venoms [54]. This family includes α-neurotoxins that block nicotinic acetylcholine receptors at neuromuscular junctions, cytotoxins that disrupt cell membranes, and cardiotoxins affecting cardiac function [55][56].
3. Major Medicinal Plants with Anti-Snake Venom Properties
Aristolochia indica, belonging to the Aristolochiaceae family, is one of the most extensively studied antivenom plants in traditional Indian medicine [57][58]. The plant is used traditionally as a decoction prepared from roots for treating Russell's viper and cobra bites [59].
Phytochemistry: The major bioactive constituent is aristolochic acid, a nitrophenanthrene carboxylic acid derivative [60]. The root extract also contains aristolochine alkaloid, terpenoids, and various phenolic compounds [61]. HPTLC analysis of roots from different geographical locations in West Bengal identified variations in aristolochic acid content ranging from 6.8 to 7.6 mg/g [62].
Mechanism of Action: Aristolochic acid exhibits potent inhibitory activity against L-amino acid oxidase (LAAO) from Russell's viper venom by interacting with the substrate binding site [63]. It also inhibits phospholipase A2 enzymes from both viper and cobra venoms in a dose-dependent manner [64][65]. The compound effectively antagonizes venominduced hemorrhage, edema, and inflammatory responses [66].
Efficacy Studies: Aqueous root extract at doses of 200-400 mg/kg body weight provided significant protection against lethal doses of Daboia russelli and Naja naja venoms in mouse models [67]. The extract prolonged survival time, reduced hemorrhagic effects, and decreased venom-induced oxidative stress markers [68].
3.2 Andrographis paniculata (Burm.f.) Nees (King of Bitters)
Andrographis paniculata, a member of Acanthaceae family, is widely used in Ayurvedic and Siddha medicine for various conditions including snake envenomation [69][70]. Known as "Kalmegh" in Hindi, the entire plant possesses medicinal properties [71].
Phytochemistry: The primary active constituent is andrographolide, a labdane diterpene lactone [72]. Other diterpenes include deoxyandrographolide, neoandrographolide, and 14-deoxy-
11,12didehydroandrographolide [73]. The plant also contains flavonoids such as apigenin and luteolin [74].
Mechanism of Action: Methanolic extracts of A. paniculata significantly inhibit acetylcholinesterase (AChE) and hyaluronidase enzymes from Naja naja venom [75]. Andrographolide modifies venom protein structures and inhibits phospholipase A2 activities [76]. Molecular docking studies reveal that andrographolide binds to the active site of PLA2 through hydrophobic interactions and hydrogen bonding [77].
Efficacy Studies: In vivo studies showed that A. paniculata extract at 2 g/kg significantly increased mean survival time in mice challenged with LD99 doses of cobra venom [78]. When combined with polyvalent anti-snake venom, the plant extract potentiated the antivenom effect, allowing for 40% dose reduction while maintaining efficacy [79].
3.3 Curcuma longa L. (Turmeric)
Curcuma longa, belonging to Zingiberaceae family, is a staple in Indian traditional medicine and cuisine [80]. The rhizome has been used topically and orally for snakebite treatment in various traditional systems [81].
Phytochemistry: The major bioactive compound is curcumin (diferuloylmethane), which comprises 3-5% of rhizome dry weight [82]. Other curcuminoids include demethoxycurcumin and bisdemethoxycurcumin [83]. Ar-turmerone, an unsaturated ketone in the volatile oil fraction, possesses potent anti-venom properties [84].
Mechanism of Action: Ar-turmerone neutralizes hemorrhagic activity from Bothrops jararaca venom and lethal effects of Crotalus durissus terrificus venom by directly interacting with toxin molecules [85]. Curcumin inhibits phospholipase A2induced inflammation, myotoxicity, and cytotoxicity through multiple pathways [86]. It scavenges free radicals generated by venom enzymes, prevents lipid peroxidation, and maintains cellular antioxidant defenses [87].
Efficacy Studies: Topical application of ar-turmerone extract significantly reduced hemorrhagic halo and edema in rabbits injected with Bothrops alternatus venom [88]. Methanolic extracts neutralized Naja kaouthia and Daboia russelli venom-induced PLA2 activity with effective doses of 18-20 μg [89]. The extract provided up to 85-90% protection against venom lethality [90].
3.4 Azadirachta indica A. Juss (Neem)
Azadirachta indica, a member of Meliaceae family, is revered in Ayurveda as "Sarva roga nivarini" (curer of all ailments) [91]. Leaf extracts have been traditionally applied to snakebite wounds [92].
Phytochemistry: The leaves contain numerous limonoids including azadirachtin, nimbin, nimbidin, and gedunin [93].
Polyphenolic compounds such as quercetin, catechin, and epicatechin contribute to antioxidant activity [94].
Mechanism of Action: A phospholipase A2 inhibitor (AIPLAI) purified from methanolic leaf extract inhibits cobra and Russell's viper PLA2 enzymes in a dose-dependent manner [95]. Neem extracts chelate zinc ions essential for metalloproteinase activity [96].
Efficacy Studies: Methanolic neem leaf extract at 200-400 mg/kg body weight provided 92-99% protection against Naja nigricollis venom lethality in rats [97]. Animals treated with neem extract showed reduced oxidative stress markers and preserved organ function [98].
3.5 Eclipta alba (L.) Hassk. (False Daisy)
Eclipta alba (synonym Eclipta prostrata), belonging to Asteraceae family, is known as "Bhringraj" in Ayurveda and valued for multiple medicinal applications [99][100].
Phytochemistry: The major bioactive compounds are coumestan derivatives, particularly wedelolactone and demethylwedelolactone [101]. The plant also contains eclalbasaponins, triterpenes (ursolic acid, oleanolic acid), flavonoids (apigenin, luteolin), and phenolic acids [102].
Mechanism of Action: Wedelolactone potently inhibits phospholipase A2 activity from Crotalus durissus terrificus venom [103]. It acts as a competitive inhibitor by binding to the enzyme's active site [104]. Genetically modified E. alba with enhanced wedelolactone content showed superior myotoxicity inhibition against PLA2 from Crotalus and Bothrops venoms [105].
Efficacy Studies: Whole plant extracts at 10-20 mg doses effectively neutralized various activities of snake venoms including hemolytic, proteolytic, and coagulant effects [106]. Pre-treatment with extract reduced mortality by 70-80% in venom-challenged animals [107].
3.6 Additional Important Plants
Withania somnifera (Ashwagandha): A glycoprotein inhibitor isolated from W. somnifera roots effectively inhibits phospholipase A2 activity of Naja naja venom [108]. The root's withanolides exhibit antiinflammatory effects by preventing prostaglandin synthesis [109].
Hemidesmus indicus (Indian Sarsaparilla): Lupeol acetate, a pentacyclic triterpene, neutralizes hemorrhage and defibrinogenation induced by Russell's viper venom through direct interaction with metalloproteinases [110]. Methanolic root extract completely antagonized Vipera russelli venom-induced lethality with an effective dose of 200 mg/kg [111].
Vitex negundo and Emblica officinalis: Combined methanolic root extracts of both plants significantly antagonized Vipera russelli and Naja kaouthia venom-induced lethal, hemorrhagic, and coagulant activities, providing up to 90% protection against lethal doses [112][113].
Mimosa pudica L. (Touch-Me-Not Plant): Aqueous root extract inhibits hyaluronidase and protease activities from various snake venoms in a dose-dependent manner [114]. The extract completely neutralized 2×LD50 of Russell's viper venom when administered simultaneously [115].
4. Phytochemical Constituents and Their Anti-Venom Mechanisms
4.1 Alkaloids
Alkaloids represent a diverse class of nitrogen-containing organic compounds with significant pharmacological activities
[116]. Aristolochic acid from Aristolochia indica is a nitrophenanthrene alkaloid that inhibits LAAO and PLA2 enzymes [117]. The mechanism by which alkaloids neutralize venom involves direct binding to enzyme active sites, competitive inhibition of substrate binding, and modulation of enzyme conformation [118].
Molecular docking studies reveal that alkaloids form multiple hydrogen bonds and hydrophobic interactions with critical amino acid residues in venom proteins [119].
4.2 Flavonoids
Flavonoids constitute one of the largest groups of plant secondary metabolites with over 6,000 known structures [120]. Common anti-venom flavonoids include quercetin, rutin, apigenin, luteolin, and myricetin [121]. These compounds possess potent antioxidant, anti-inflammatory, and enzyme inhibitory properties [122]. Flavonoids neutralize snake venom through multiple mechanisms [123]. Their phenolic hydroxyl groups scavenge free radicals generated by venom enzymes, preventing oxidative tissue damage [124]. They chelate metal ions (zinc, calcium, magnesium) essential for metalloproteinase and PLA2 activity [125].
4.3 Terpenoids and Triterpenoids
Terpenoids represent the largest and most structurally diverse class of natural products [126]. Pentacyclic triterpenes including lupeol, lupeol acetate, ursolic acid, and oleanolic acid have demonstrated significant antivenom activities [127]. Triterpenes neutralize venom through membrane stabilization, preventing cell lysis induced by cytotoxic components [128]. They inhibit phospholipase A2 by binding to the enzyme surface and blocking substrate access to the catalytic site [129].
4.4 Phenolic Compounds and Coumarins
Phenolic compounds encompass a broad category including simple phenols, phenolic acids, and polyphenols [130]. Wedelolactone, a coumestan from Eclipta alba, represents a specialized phenolic structure [131]. Phenolic compounds neutralize venom through protein precipitation, enzyme inhibition, metal chelation, and antioxidant activity [132].
Wedelolactone acts as a competitive inhibitor of PLA2 by occupying the enzyme's active site [133].
4.5 Tannins and Saponins
Tannins are polyphenolic compounds with high molecular weights that precipitate proteins [134]. Hydrolyzable tannins (gallotannins, ellagitannins) and condensed tannins (proanthocyanidins) occur widely in medicinal plants [135]. Tannins neutralize venom by forming large insoluble complexes with venom proteins through multiple hydrogen bonds and hydrophobic interactions [136]. Saponins are glycosides with amphipathic properties due to hydrophobic aglycone and hydrophilic sugar moieties [137]. Saponins prevent hemolysis induced by cytotoxic venom components by stabilizing erythrocyte membranes [138].
5. Mechanisms of Anti-Venom Action
5.1 Enzyme Inhibition
The primary mechanism by which plant compounds neutralize snake venom involves inhibition of key enzymatic activities [139]. Phospholipase A2 inhibition represents the most extensively studied mechanism [140]. Plant-derived inhibitors interact with PLA2 through various modes including: (1) Competitive inhibition: Compounds occupy the enzyme's active site, preventing substrate binding [141]; (2) Allosteric modulation: Binding to regulatory sites alters enzyme conformation and reduces catalytic efficiency [142]; (3) Protein-protein interactions: Large molecules form stable complexes with PLA2, blocking its activity [143].
Metalloproteinase inhibition occurs through zinc chelation and direct enzyme binding [144]. Phenolic compounds and tannins chelate the catalytic zinc ion essential for SVMP activity [145]. Serine protease inhibition by alkaloids and terpenoids prevents coagulation activation and fibrinogenolysis [146].
5.2 Antioxidant Activity
Snake venoms induce severe oxidative stress through multiple mechanisms including LAAO-mediated hydrogen peroxide generation, lipid peroxidation, and mitochondrial dysfunction [147][148]. Plant antioxidants counteract this oxidative damage through: (1) Free radical scavenging: Phenolic hydroxyl groups donate hydrogen atoms to neutralize superoxide radicals, hydroxyl radicals, and peroxyl radicals [149]; (2) Metal chelation: Binding transition metals prevents Fenton reactions [150]; (3) Enzyme induction: Upregulating endogenous antioxidant enzymes [151]; (4) Lipid peroxidation prevention [152]. Studies demonstrate that envenomated animals treated with plant extracts show significantly restored levels of glutathione, superoxide dismutase, and catalase [153][154].
5.3 Membrane Stabilization and Anti-inflammatory Effects
Cytotoxic components of snake venom disrupt cell membranes through phospholipid hydrolysis and pore formation [155]. Plant compounds stabilize membranes by strengthening lipid bilayers, competing for binding sites, preventing enzymatic hydrolysis, and maintaining membrane integrity [156]. Venom-induced inflammation involves prostaglandin synthesis, leukotriene production, and cytokine release [157][158]. Plant compounds exert anti-inflammatory effects through cyclooxygenase inhibition, lipoxygenase inhibition, cytokine modulation, NF-κB pathway inhibition, and mast cell stabilization [159][160].
6. Comparative Efficacy Against Different Snake Species
6.1 Indian Cobra (Naja naja) and Russell's Viper (Daboia russelli)
The Indian Cobra is an elapid species whose venom is predominantly neurotoxic [161]. Most effective plants include Andrographis paniculata, Withania somnifera, Azadirachta indica, and Aristolochia indica, demonstrating 80-95% survival rates in animals challenged with lethal cobra venom doses [162][163][164].
Russell's Viper venom contains high concentrations of phospholipase A2, metalloproteinases, and procoagulant enzymes
[165]. Most effective plants include Hemidesmus indicus, Vitex negundo, Emblica officinalis, Aristolochia indica, and Mimosa pudica [166][167][168]. Lupeol acetate from H. indicus completely neutralizes hemorrhage and defibrinogenation [169].
6.2 Common Krait (Bungarus caeruleus) and Saw-scaled Viper (Echis carinatus)
Krait venom is highly neurotoxic with potent presynaptic neurotoxins [170]. Most effective plants include Azima tetracantha, Aristolochia indica, and Andrographis paniculata [171][172]. Saw-scaled Viper venom contains procoagulant enzymes, metalloproteinases, and phospholipase A2 [173]. Most effective plants include Mimosa pudica, Curcuma aromatica, and various plants containing tannins [174][175].
7. Traditional Preparation Methods and Safety Considerations
7.1 Traditional Preparation Methods
Traditional healers commonly prepare decoctions by boiling plant materials in water, with roots typically boiled for 30-60 minutes [176]. Fresh plant leaves or roots are crushed to form pastes applied topically to bite wounds [177]. Fresh plant juice is extracted by crushing leaves or stems and administered orally [178]. Dried plant materials are powdered and administered with honey, ghee, or milk [179]. Traditional systems often combine multiple plants to achieve synergistic effects [180].
7.2 Safety Profile and Contraindications
Most medicinal plants with anti-venom properties demonstrate acceptable safety profiles when used appropriately for acute treatment [181]. However, certain plants require caution: Aristolochia indica contains aristolochic acid, a nephrotoxin and carcinogen [182]; Strychnos nux-vomica contains highly toxic alkaloids [183]. Safe plants include Curcuma longa (GRAS status), Emblica officinalis, Andrographis paniculata, and Azadirachta indica [184][185]. Pregnant women should avoid most anti-venom plants due to potential abortifacient effects [186]. Patients with pre-existing kidney or liver disease should use aristolochic acidcontaining plants with extreme caution [187].
8. Future Directions and Research Priorities
8.1 Clinical Validation and Standardization
The most critical need is rigorous clinical trials evaluating safety and efficacy in human snakebite victims [188]. Phase I safety studies should establish optimal dosing, Phase II efficacy trials should compare plantbased treatments with conventional antivenoms, and Phase III multicenter trials would provide definitive evidence for regulatory approval [189] [190][191]. Developing standardized extraction protocols is essential for consistent therapeutic effects [192]. HPLC fingerprinting and quantification of bioactive markers should be established for each medicinal plant [193]. Good Agricultural Practices (GAP) and Good Manufacturing Practices (GMP) must be implemented for commercial production [194].
8.2 Novel Delivery Systems and Biotechnological Approaches
Developing oral formulations with enhanced bioavailability using nanoparticles, liposomes, or phytosomes could enable pre-hospital treatment [195]. Topical formulations with sustained release properties may provide local wound protection [196]. Genetic engineering to enhance production of bioactive compounds in plants offers promise [197]. Plant cell culture systems could enable consistent production of standardized extracts [198].
8.3 Combination Therapy and Affordable Access
Investigating synergistic interactions between plant compounds and conventional antivenoms may allow dose reduction and improved outcomes [199]. Studies have shown that combining Andrographis paniculata with antivenom allows 40% reduction in antivenom dose while maintaining efficacy [200]. Developing low-cost, thermostable, plant-based antivenoms would address critical access issues in rural endemic regions [201]. Unlike conventional antivenoms requiring cold chain, dried plant preparations maintain potency at ambient temperatures [202].
CONCLUSION
This comprehensive review establishes substantial evidence supporting the anti-snake venom properties of numerous medicinal plants documented in traditional medicine systems. Over 50 plant species from diverse botanical families demonstrate significant venom-neutralizing activities through multiple, complementary mechanisms. The major bioactive phytochemical classes responsible for these effects include terpenoids, flavonoids, alkaloids, phenolic compounds, coumarins, steroids, tannins, and saponins, which collectively account for the observed therapeutic benefits.
The mechanisms by which these plant-derived compounds neutralize snake venom toxicity are multifaceted and include direct inhibition of key venom enzymes (phospholipase A2, metalloproteinases, serine proteases), potent antioxidant activity counteracting venom-induced oxidative stress, membrane stabilization preventing cytotoxicity, anti-inflammatory effects reducing tissue damage, metal chelation inactivating metalloenzymes, and protein precipitation reducing venom bioavailability. This multi-targeted approach offers distinct advantages over conventional antivenoms that primarily rely on antibody-toxin binding.
Preclinical studies demonstrate impressive efficacy, with leading plants such as Aristolochia indica, Andrographis paniculata, Curcuma longa, Hemidesmus indicus, Vitex negundo, and Mimosa pudica providing 75-95% protection against lethal venom doses in animal models. These plants effectively neutralize the major pathophysiological effects of envenomation including lethality, hemorrhage, edema, coagulopathy, myotoxicity, and neurotoxicity across venoms from diverse snake species.
The comparative advantages of plant-based antivenoms include oral bioavailability enabling pre-hospital administration, absence of immunogenic foreign proteins reducing adverse reactions, thermostability eliminating cold chain requirements, potential for local production ensuring availability, significantly lower cost compared to serum-based antivenoms, and complementary action when combined with conventional therapy potentially reducing required antivenom doses.
However, critical challenges remain before plant-based antivenoms can achieve widespread clinical implementation. The transition from traditional knowledge and preclinical promise to validated clinical therapeutics requires rigorous human clinical trials establishing safety and efficacy, standardization of extraction methods and quality control parameters, elucidation of pharmacokinetic properties, development of optimized dosage forms with consistent potency, regulatory approval through established pharmaceutical pathways, comprehensive toxicology studies, education of healthcare providers, and integration with existing snakebite management protocols.
The research evidence strongly supports pursuing plant-based antivenoms as complementary or alternative therapies, particularly in resource-limited rural settings. The immediate practical applications include development of standardized first-aid formulations for pre-hospital use, creation of adjuvant therapies to enhance conventional antivenom efficacy, formulation of topical treatments targeting local tissue damage, and establishment of oral prophylactic regimens for highrisk populations.
From an economic and public health perspective, plant-based antivenoms could substantially reduce the burden of snakebite envenomation in developing countries. The ability to cultivate medicinal plants locally, process them using simple technologies, and distribute dried preparations without cold chain infrastructure makes them uniquely suited to resource-constrained settings.
In conclusion, while conventional serum-based antivenoms will remain essential for managing severe envenomation in hospital settings, plant-based alternatives and adjuncts represent a promising complementary strategy deserving of substantial research investment. The convergence of traditional knowledge, modern pharmacology, and advanced biotechnology offers unprecedented opportunities to develop affordable, accessible, and effective anti-venom therapeutics that can save thousands of lives annually.
REFERENCE
Aboli Borade, Snehal Kadbhane, Dr. Vijaykumar Kale, Shivani Kharat, Arti Date, A Comprehensive Review on Anti–Snake Venom Properties of Herbal Plants, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 11, 3516-3530. https://doi.org/10.5281/zenodo.17680507
10.5281/zenodo.17680507
