Natural Antidotes Against Snake Venom: A Review Of Medicinal Plant-Based Approaches

Snake envenomation remains a major public health concern, particularly in developing countries such as India, where thousands of deaths and disabilities occur annually. [1]For many decades, antivenom serum has been the primary and most effective specific treatment for snakebite poisoning. [2]Despite its clinical importance, antivenom therapy has certain limitations, including inadequate protection against venom-induced tissue damage, hemorrhage, kidney injury, and local necrosis. In addition, some patients may experience allergic or hypersensitivity reactions following antivenom administration.[3]

India possesses a long history of traditional medicine, with numerous medicinal plants being used by local communities and traditional healers for the management of snakebites. Ethnobotanical records describe a wide range of plant species believed to possess antivenom properties. Although many of these plants are traditionally valued, only a limited number have undergone scientific evaluation, and even fewer have had their bioactive constituents isolated and characterized.[4]

Recent pharmacological investigations have demonstrated that several medicinal plants exhibit the ability to neutralize different toxic effects of snake venoms.[5]This review highlights medicinal plants with experimentally validated anti-snake venom activity and discusses their relevance in relation to traditional ethnopharmacological knowledge.[6] Plant-derived Snake Venom Components and Herbal Approaches to Snakebite Management

Snake venom is a complex mixture of biologically active proteins and enzymes that contribute to various toxic effects in the victim. Major venom constituents include phospholipase A₂ (PLA₂), metalloproteinases, myotoxins, neurotoxins, cardiotoxins, cytotoxins, coagulant factors, and several proteolytic enzymes.[7-8] These components act on different physiological systems, leading to local tissue destruction, disturbances in blood coagulation, neuromuscular dysfunction, and systemic toxicity.

In many rural regions of India and other developing countries, medicinal plants continue to play an important role in the management of snakebite.[9] Traditional healers employ various plant species either individually or in polyherbal formulations to counteract venom-induced effects. Numerous plants have been reported in ethnomedicinal literature as possessing antivenom properties. Therefore, investigation of plant-based remedies has gained considerable attention as a potential complementary approach to conventional antivenom therapy. This review highlights ethnopharmacological evidence and experimental studies related to the use of medicinal plants against snake envenomation.[10]

TYPES OF VENOMOUS SNAKES

The clinical condition resulting from venom injection following a snakebite is known as ophitoxaemia. Globally, approximately 2,500–3,000 snake species have been identified, of which nearly 500 are considered venomous. Classification of snakes is based on several anatomical and biological characteristics, including scale arrangement, dentition, skeletal structure, sensory organs, and other morphological features.[11]

The principal families of venomous snakes include Atractaspididae, Elapidae, Hydrophidae, and Viperidae. In the Indian subcontinent, medically important venomous snakes mainly belong to the families Elapidae, Viperidae, and Hydrophidae. The Elapidae family includes cobras and kraits, whereas the Viperidae family comprises Russell's viper, pit vipers, and saw-scaled vipers. Sea snakes belong to the Hydrophidae family.[12]

Among the venomous snake species found in India, a significant proportion of snakebite-related morbidity and mortality is associated with five medically important species: Ophiophagus hannah (King Cobra), Naja naja (Indian Cobra), Daboia russelii (Russell's Viper), Bungarus caeruleus (Common Krait), and Echis carinatus (Saw-scaled Viper). [13-14]These species are responsible for the majority of serious envenomation cases reported across the country. Therapies may offer a promising complementary or alternative approach to conventional antivenom treatment and warrant further scientific exploration.

CLINICAL MANIFESTATIONS OF SNAKE ENVENOMATION

Snakebite envenomation can result in a wide range of local and systemic complications depending on the species involved and the composition of the venom. Local effects commonly include pain, swelling, blister formation, hemorrhage, edema, and tissue necrosis. Certain viper venoms contain metalloproteinases and procoagulant enzymes that promote bleeding disorders and extensive tissue damage.[13-14]

Envenomation by cobra species may lead to severe local necrosis, hemorrhage, respiratory paralysis, and complement system depletion. These effects are largely attributed to venom components such as phospholipase A₂ and cardiotoxins.[15] Ocular complications, including corneal ulceration and anterior uveitis, have also been reported in some cases.

Venoms of the genus Bothrops are known to induce marked local tissue injury characterized by edema, hemorrhage, proteolysis, and myonecrosis. Muscle destruction is one of the most serious consequences of envenomation and may result in permanent disability or, in severe cases, limb amputation.[16] Myonecrosis may occur directly through the action of myotoxic PLA₂ molecules on muscle cell membranes or indirectly due to ischemia caused by vascular damage induced by hemorrhagic metalloproteinases.[17]

TRADITIONALLY USED PLANTS FOR SNAKEBITE MANAGEMENT

While some of the therapeutic herbs work by stimulating the immune system, the majority of them lessen the symptoms of envenomation. [18]Abutilon indicum leaf paste, Acorus calamus root paste, Adhota vesica bark decoction, Amaranthus viridis root paste, Citrus limon paste, Curcuma longa paste, Dalbergia melanoxylon decoction, Eucalyptus globules juice, Helianthus annuus oil, Mimosa pudica rice water paste, Nerium oleander paste, Nicotiana tobaccum decoction, Piper nigrum paste with ghee, Rauvolfia serpentina paste, Solanum torvum paste, Thymus vulgaris juice, Wedelia calendulae juice, Woodfordia fruticosa paste, Asteraceae, Apocynaceae, Araceae, Fabaceae, Euphorbiaceae, Lamiaceae, Malvaceae, Rubiaceae, and Zingeberaceae were the most notable botanical families with notable anti-ophidic properties, according to a study by that elaborated the cross-cultural comparison of medicinal floras for snake venom.[19]

Chewing leaves or bark, swallowing or injecting plant extracts, and applying a topical therapy to affected areas are just a few of the ways that many plant species have historically been used to detoxify snake venoms. [20]Traditional healers now solely employ pure plant medicines to cure snake envenomation. Particularly, krait and snake bites are treated using extracts from the roots of Abrus precatorius and Azadirachta indica, respectively. The rhizomes of certain curcuma species work well against Thai cobras' neurotoxic effects. Extracts from the stem and bark of Brownea rosademonte and Tabebuia rosea show antihemorrhagic qualities against Bothrops atrox venom.[21]

IDENTIFICATION OF TOXINS AND VENOMS

To select the best course of treatment, it is crucial to identify the venom involved in envenomation as soon as possible. It is challenging and perhaps impracticable to rule out the snake species responsible for envenomation since numerous snake bites have similar clinical signs. Bioassays, immune diffusion, immune electrophoresis, immunofluorescence, hemagglutination, radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) are few analytical methods that are used to detect venom involved in the poisoning.[22] Affinity chromatography and hybridoma technologies have also been employed for diagnostic reasons. Polymerase chain reaction (PCR), surface plasmon resonance (SPR), optical immunoassay (OIA), and venom/antibody micro-array assay have all recently been used for venom detection .

Table 1. Traditional plants used against snakebite (India)