Envenomations due to snake bites are commonly treated by parenteral administration of horse or sheep-derived polyclonal antivenoms aimed at the neutralization of toxins. However, despite the widespread success of this therapy, it is still important to search for different venom inhibitors, either synthetic or natural, that could complement or substitute for the action of antivenoms. Several plants have been utilized in folk medicine as antiophidian. However, only a few species have been scientifically investigated and still less had their active components isolated and characterized both structurally and functionally. This article presents a review of plants showing neutralizing properties against snake venoms which were assayed in research laboratories, correlating them with ethnopharmacological studies, as (i) the part of the plant used as antidote, (ii) its respective genus and family and (iii) inhibition of the main pharmacological, toxic and enzymatic activities of snake venoms and isolated toxins. Protective activity of many of these plants against the lethal action of snake venoms has been confirmed by biological assays. Compounds in all of them belong to chemical classes capable of interacting with macromolecular targets (enzymes or receptors). Popular culture can often help to guide scientific studies. In addition, biotechnological application of these inhibitors, as helpful alternative or supplemental treatments to serum therapy, and also as important models for synthesis of new drugs of medical interest, needs to be better oriented and scientifically explored.

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Abstract:We genetically modified Eclipta alba using Agrobacterium rhizogenes LBA 9402, with the aim of producing secondary metabolites with pharmacological properties against phospholipase A 2 and the myotoxic activities of snake venom. Extracts from in natura aerial parts and roots, both native and genetically modified ( in vitro ), were prepared and analysed by high-performance liquid chromatography. In natura materials showed the coumestan wedelolactone at higher concentration in the aerial parts, while demethylwedelolactone appeared at higher concentration in roots. Among the modified roots, clone 19 showed higher concentrations of these coumestans. Our results show that the in natura extracts of plants collected from Botucatu and Ribeirão Preto were efficient in inhibiting snake venom phospholipase A 2 activity. Regarding in vitro material, the best effect against Crotalus durissus terrificus venom was that of clone 19. Clone 19 and isolated coumestans (wedelolactone and demethylwedelolactone) inhibited the myotoxic activity induced by basic phospholipases A 2 isolated from the venoms of Crotalus durissus terrificus (CB) and Bothrops jararacussu (BthTX-I and II). The search for antivenom is justified by the need of finding active principles that are more efficient in neutralizing snake venoms and also as an attempt to complement serum therapy.Eclipta alba (L.) Hassk. (syn. Eclipta prostrata ), popularly known as dye weed and belonging to the Asteraceae family, is an annual herbaceous species [1]. Native to Brazil and other tropical and subtropical regions, this plant is a source of several secondary metabolites, such as polypeptides, polyacethylenes and triterpenes [2], flavonoids, phytosterols and coumestans [3].Coumestans represent an important class of natural oxygenated aromatic products, including wedelolactone and its demethylated form, demethylwedelolactone, both responsible for the main medicinal effects of Eclipta , such as its anti-hepatotoxic, anti-hypertensive, antitumor, antiphospholipase A 2 and antidote activities against snake venoms [2,4 -7].With the development of in vitro plant tissue cultures, it is possible to produce viable, economically valuable compounds [8]. Among the procedures for tissue culture, those for genetically modified plants have developed significantly, and the obtainment of transgenic plants is made by indirect modifications with a biological vector, such as Agrobacterium [9].Hundreds of plants have been related with anti-snake venom action, but only a few have been scientifically investigated [5][6][7] [11]. More recently, the potential antivenom property of wedelolactone against Calloselasma rhodostoma venom (by neutralizing isolated phospholipases A 2 and venom lethality) has been observed [12]. In this study, E. alba was genetically modified, aiming at the production of secondary metabolites of pharmacological interest, which were assayed against phospholipase A 2 and myotoxic activities of snake venoms and isolated toxins. Materials and MethodsAnimals, venoms and t...

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Medicinal plants are still the major source of therapies for several illnesses and only part of the herbal products originates from cultivated biomass. Wild harvests represent the major supply for therapies, and such practices threaten species diversity as well as the quality and safety of the final products. This work intends to show the relevance of developing medicinal plants into crops and the use of micropropagation as technique to mass produce high-demand biomass, thus solving the supply issues of therapeutic natural substances. Herein, the review includes examples of in vitro procedures and their role in the crop development of pharmaceuticals, phytomedicinals, and functional foods. Additionally, it describes the production of high-yielding genotypes, uniform clones from highly heterozygous plants, and the identification of elite phenotypes using bioassays as a selection tool. Finally, we explore the significance of micropropagation techniques for the following: a) pharmaceutical crops for production of small therapeutic molecules (STM), b) phytomedicinal crops for production of standardized therapeutic natural products, and c) the micropropagation of plants for the production of large therapeutic molecules (LTM) including fructooligosaccharides classified as prebiotic and functional food crops.

Snakebites comprise a serious health problem in several countries due to their global incidence, which exceeds 2.5 million per year, and the elevated number of victim fatalities. To counteract envenomations, antivenoms have been used regularly for more than a century. Apart from side effects including anaphylactic reactions, antivenoms are not able to efficiently neutralize local tissue damage, which contributes to increasing the severity and morbidity observed in patients. This fact, in turn, may be responsible for economic hardship, particularly in rural populations of developing countries. In the present work, we evaluated the antiophidian properties of 12 Brazilian plant extracts against the hemolytic, coagulant, hemorrhagic and proteolytic effects of Lachesis muta venom. Taken together, our data revealed that most of these aqueous products were capable of inhibiting those activities at different levels, except for Sapindus saponaria extract. In contrast, Stryphnodendron barbatiman extract completely neutralized all the analyzed biological activities. Thus, we may conclude that Brazilian flora may also be useful against L. muta accidents.

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