New and Future Animal Testing Research on Herbal Antivenoms

My research in Early Tantric Medicine focused on early medieval religious systems designed to counter snakebite envenomation. The same texts also prescribed particular herbs reputed to have antivenom properties—a much more realistic proposal from a rationalist point of view. The past few decades has seen a proliferation of scientific evaluations of plants traditionally used for curing envenomation. Scores of studies have highlighted the venom-neutralizing potential of chemical compounds that occur naturally in ethno-medically significant plants.

Here I want to highlight a research paper by a promising undergraduate named Naryan Dahlstrom, who took my seminar “Traditional Indian Medicine” this Fall. Dalhstrom’s investigations focused on the manner in which the herbal antivenom is prepared in the laboratory: did researchers follow the recipes of ancient texts or oral tradition, preparing the plant parts by grinding, boiling, or fashioning of a poultice? Or did they follow the route of modern pharmacology, seeking to isolate the active chemical components, or at least standardize the herb through hydro-alcoholic preparations? It would be logical for someone investigating traditional remedies to prepare the plant in the traditional method. However, Dahlstrom found that almost all studies she consulted used hydro-alcoholic extracts, which often take longer to prepare than traditional methods.

Dahlstrom highlighted some studies that bypassed traditional medicine entirely, instead experimenting with plant sources of compounds that are believed to be able to neutralize common components of venoms, such as the phospholipase A2 (PLA2) enzyme that degrades the membranes of cells, killing them. One such study conducted in 2018 by Egyptian researcher Azza M.Abdel-Aty, et al., found that a tiny amount (20 μg) of an extract of something as common as mango kernels could effectively inhibit the effect of up to two lethal doses of venom in mice. Dahlstrom notes that they chose mango kernel for the experiment not on the basis of traditional use, but because it is known to contain compounds that would potentially counteract PLA2. Given the potency of this natural plant material prepared in this way, Dahlstrom asks whether the effect might be the same or even more effective if prepared in a manner prescribed by traditional medicine.

Another study that Dahlstrom reviewed, by Kumarappan et al., 2011 (the name of the principal investigator is misspelled by the journal as Kumarapppan), also used alcohol-extractions methods, but used plants recognized in the traditional Indian science of Ayurveda as having anti-snakevenom properties. Each of the four plant extracts used showed varying ability to neutralize venom, with one, Gloriosa superba, showing the most effectiveness by saving the lives of nine out the ten laboratory mice injected with a lethal dose of the venom of the black-necked spitting cobra. Dahlstrom again rightly questions the wisdom of only testing these traditional remedies with alcohol extracts—might the traditional methods of preparations handed down over centuries alter or preserve the chemical constituents of the plant material and potentially lead to even more effective remedies? In this study the researchers use of a venom from a species of cobra not found in South Asia raises the question of whether the results would be the same for Indian cobra venom—the specific antagonist that the traditional remedy is reputed to counter.

Dahlstrom was unable to locate studies testing traditional remedies for snakebite that were prepared in the traditional way. However, she did find a study testing a traditional Amazonian medicine for the notorious fer-de-lance viper (Bothrops atrox) by comparing the effectiveness of the traditional method of preparation to that of the standard scientific alcohol extraction (Moura et al., 2015). In brief, this study found that traditional tea-extract of the leaves and bark were more effective at neutralizing fer-de-lance venom in mice than the hydroalcholic preparations.

These studies and dozens of others suggest the great potential that traditional medicine holds for future development of plant-based antivenoms. Modern snake antivenom serum (ASV) is expensive and difficult to prepare, and its distribution often does not reach far-flung rural areas in developing countries that need it the most. As I described briefly in Early Tantric Medicine on the basis of publications of the World Health Organization, ASV is also often highly allergenic, and can itself cause potentially deadly adverse reactions (serum-sickness) when not properly prepared and administered in a well-equipped clinic staffed with highly trained doctors. Less allerginic alternatives based on free locally-available plants might be a valuable life-saving alternative for some rural communities and deserves much more attention from scientists and, in the future, policy-makers.