Plant natural products active against snake bite--the molecular approach.

The article surveys the substances identified in plants reputed to neutralize the effects of snake venoms. Protective activity of many of them against the lethal action of the venom of the jararaca (Bothrops jararaca) snake was confirmed by biological assays. It was shown that all belong to chemical classes capable of interacting with macromolecular targets--receptors and enzymes. In a few cases it has been shown that exogenous natural micromolecules can mimic the biological activity of endogenous macromolecules. From the evidence presented, it can be inferred that micromolecules which neutralize the action of snake venoms mechanistically replace endogenous antitoxic serum proteins with venom neutralizing capacity such as produced by some animals.

Action of chlorogenic acid on the complement system.

Previous research on plants used in folk medicine as antidotes against snake-bite revealed some constituents responsible for such protection. Chlorogenic acid (3-0-caffeoyl quinic acid) was one of these substances, studied with more attention. It has been shown that this substance binds to proteins through hydrophobic interactions and hydrogen bonds. This paper shows the preliminary results about the anti-complementary action of chlorogenic acid. Human and guinea pig sera, treated with chlorogenic acid, were added to the hemolytic system (sheep erythrocyte sensitized with hemolysin) to study its effect on the activation of the classical complement pathway. The action on the alternative pathway was studied with human serum treated with chlorogenic acid and zymosan. Our results show that chlorogenic acid presents anti-complementary action at the classical pathway, since the sera are not able to lysis the indicator system. The presence of C3b fragments on the surface of the yeast cells demonstrates that the alternative pathway was not affected.

Triaga Brasilica: renewed interest in a seventeenth-century panacea.

Theriacs (electuaries prepared by mixing extracts of many plants) were known from antiquity until the eighteenth century as remedies for all kinds of envenomation, above all those due to the bites and stings of venomous animals, especially snakes. In colonial Brazil, the 'Brazilian theriac' was developed by Jesuit priests by gradually substituting native plants for components of their European model. Most of these ingredients, mentioned in an old manuscript, can be identified by their common names, which have survived the centuries.

Inhibition of the myotoxic and hemorrhagic activities of crotalid venoms by Eclipta prostrata (Asteraceae) extracts and constituents.

The antimyotoxic and antihemorrhagic effects of Eclipta prostrata (EP) and three of its constituents (wedelolactone, WE; stigmaterol, ST; and sitosterol, SI) were investigated. The myotoxicity of crotalid venoms (Bothrops jararaca, Bothrops jararacussu and Lachesis muta), purified myotoxins (bothropstoxin, BthTX; bothropasin; and crotoxin), and polylysine was quantified in vitro by the release rate of creatine kinase (CK) from rat or mouse extensor digitorum muscles, and in vivo by the plasma CK activity in mice. The in vitro myotoxicity of the crotalid venoms and myotoxins was neutralized by simultaneous exposure of the muscles to an aqueous extract of EP or to WE. ST and SI were less effective than WE, but interacted synergistically with it. Both the EP extract and WE failed to neutralize the in vitro myotoxic effects of polylysine. The in vivo myotoxicity of venoms and myotoxins was neutralized by their preincubation with the EP extract or WE. Intravenous administration of the plant extract or WE attenuated the increase in plasma CK activity induced by subsequent intramuscular injections of the crotalid venoms or the myotoxins. EP and WE inhibited the hemorrhagic effect of B. jararaca venom, as well as the phospholipase A2 activity of crotoxin and the proteolytic activity of B. jararaca venom. The data provide direct evidence for antimyotoxic and antihemorrhagic effects of EP and WE against the crotalid venoms responsible for most cases of envenomation by snakebites in Brazil. These effects are interpreted as consequences of antiproteolytic and antiphospholipase A2 activities of EP and its constituents.

Pharmacological Screening of Plants Recommended by Folk Medicine as Snake Venom Antidotes; IV. Protection against Jararaca Venom by Isolated Constituents1.

Fifteen Compounds, isolated from plants reputed as snake venom antidotes, belonging to different classes of natural products, were shown to protect mice to a significant degree against the lethal action of the venom of BOTHROPS JARARACA snakes. Administration was by the oral route, one hour prior to envenomation. The substances are nitrogen-free, low-molecular-weight compounds for which some kind of biodynamic activity has previously been reported. The fact that they are mostly trivial, naturally-occurring compounds should explain why plants used as snake-bite antidotes are so widely distributed over the plant kingdom.

Pharmacological screening of plants recommended by folk medicine as snake venom antidotes; IV. Protection against jararaca venom by isolated constituents.

Fifteen compounds, isolated from plants reputed as snake venom antidotes, belonging to different classes of natural products, were shown to protect mice to a significant degree against the lethal action of the venom of Bothrops jararaca snakes. Administration was by the oral route, one hour prior to envenomation. The substances are nitrogen-free, low-molecular-weight compounds for which some kind of biodynamic activity has previously been reported. The fact that they are mostly trivial, naturally-occurring compounds should explain why plants used as snake-bite antidotes are so widely distributed over the plant kingdom.

Inhibition Of The Myotoxic And Hemorrhagic Activities Of Crotalid Venoms By Eclipta Prostrata Extracts And Constitutents

The antimyotoxic and antihemorrhagic effects of Eclipta prostrata (EP) and three of its constituents (wedelolactone, WE; stigmaterol, ST; and sitosterol, SI) were investigated. The myotoxicity of crotalid venoms (Bothrops jararaca, Bothrops jararacussu and Lachesis muta), purified myotoxins (bothropstoxin, BthTX; bothropasin; and crotoxin), and polylysine was quantified in vitro by the release rate of creatine kinase (CK) from rat or mouse extensor digitorum muscles, and in vivo by the plasma CK activity in mice. The in vitro myotoxicity of the crotalid venoms and myotoxins was neutralized by simultaneous exposure of the muscles to an aqueous extract of EP or to WE. ST and SI were less effective than WE, but interacted synergistically with it. Both the EP extract and WE failed to neutralize the in vitro myotoxic effects of polylysine. The in vivo myotoxicity of venoms and myotoxins was neutralized by their preincubation with the EP extract or WE. Intravenous administration of the plant extract or WE attenuated the increase in plasma CK activity induced by subsequent intramuscular injections of the crotalid venoms or the myotoxins. EP and WE inhibited the hemorrhagic effect of B. jararaca venom, as well as the phospholipase A2 activity of crotoxin and the proteolytic activity of B. jararaca venom. The data provide direct evidence for antimyotoxic and antihemorrhagic effects of EP and WE against the crotalid venoms responsible for most cases of envenomation by snakebites in Brazil. These effects are interpreted as consequences of antiproteolytic and antiphospholipase A2 activities of EP and its constituents.

Plants against snake-bites.

Small molecular weight compounds from Mandevilla velutina and from Eclipta prostata were found to be active against snakebite.

Neutralization of lethal and myotoxic activities of South American rattlesnake venom by extracts and constituents of the plant Eclipta prostrata (Asteraceae).

Ethanolic extracts of the aerial parts of Eclipta prostrata L. (Asteraceae) neutralized the lethal activity of the venom of South American rattlesnake (Crotalus durissus terrificus) when mixed in vitro before i.p. injection into adult Swiss mice. Samples of ethanolic extract corresponding to 1.8 mg of dry extract per animal neutralized up to four lethal doses of the venom (LD50 = 0.08 micrograms venom/g animal). Three substances isolated from the plant--wedelolactone (0.54 mg/animal), sitosterol (2.3 mg/animal) and stigmasterol (2.3 mg/animal)--were able to neutralize three lethal doses of the venom. Aqueous extracts of the plant inhibited the release of creatine kinase from isolated rat muscle exposed to the crude venom. The protection conferred against the myotoxic effects of the venom could be demonstrated also in vivo, when the venom was preincubated with the extract prior to injection into mice.

Chemoprophylactic agent in schistosomiasis: 14,15-epoxygeranylgeraniol.

The occurrence of all-trans (-)-14,15-epoxygeranyl-geraniol in Pterodon pubescens Benth. is established, and its prophylactic activity against infection by Schitsosma mansoni demonstrated. Two other diterpenes present in the oil are inactive.