Atropa belladonna neurotoxicity: Implications to neurological disorders.

Atropa belladonna, commonly known as belladonna or deadly nightshade, ranks among one of the most poisonous plants in Europe and other parts of the world. The plant contains tropane alkaloids including atropine, scopolamine, and hyoscyamine, which are used as anticholinergics in Food and Drug Administration (FDA) approved drugs and homeopathic remedies. These alkaloids can be very toxic at high dose. The FDA has recently reported that Hyland's baby teething tablets contain inconsistent amounts of Atropa belladonna that may have adverse effects on the nervous system and cause death in children, thus recalled the product in 2017. A greater understanding of the neurotoxicity of Atropa belladonna and its modification of genetic polymorphisms in the nervous system is critical in order to develop better treatment strategies, therapies, regulations, education of at-risk populations, and a more cohesive paradigm for future research. This review offers an integrated view of the homeopathy and neurotoxicity of Atropa belladonna in children, adults, and animal models as well as its implications to neurological disorders. Particular attention is dedicated to the pharmaco/toxicodynamics, pharmaco/toxicokinetics, pathophysiology, epidemiological cases, and animal studies associated with the effects of Atropa belladonna on the nervous system. Additionally, we discuss the influence of active tropane alkaloids in Atropa belladonna and other similar plants on FDA-approved therapeutic drugs for treatment of neurological disorders.

Tósigos y antídotos en la literatura cervantina: sobre los venenos en la España tardorrenacentista / “Tosigos” and antidotes in Cervantine literature: on the poisons in the late Renaissance Spain

Los textos cervantinos constituyen una interesante fuente para el estudio de la sociedad española tardorrenacentista. Nosotros hemos abordado las obras de Cervantes desde la óptica de la toxicología, analizando el uso de agentes tóxicos y venenosos, fundamentalmente alucinógenos y narcóticos en el ámbito de la práctica de la brujería y hechicería (ungüentos de brujas, filtros de amor, pócimas venenosas, etc.), así como las menciones a las hipotéticas sustancias dotadas de acción alexifármaca, como la verbena (Verbena officinalis), el cuerno de unicornio, las piedras bezoares o el castóreo. Las obras cervantinas en las que se hace referencia a estos preparados son las novelas El Quijote, La Galatea, Viaje del Parnaso y cuatro Novelas Ejemplares (La española inglesa, El licenciado Vidriera, El celoso extremeño y El coloquio de los perros), así como en las comedias Pedro de Urdemalas, La entretenida y El laberinto del amor. Entre los agentes tóxicos de origen herbal citados expresamente por Cervantes en el contexto analizado se encuentran el beleño (Hyoscyamus niger / albus), el tabaco (Nicotiana tabacum), la adelfa (Nerium oleander), el tártago (Euphorbia lathyris), el ruibarbo (Rheum officinale, Rumex alpinus) y, de forma enmascarada, el opio (Papaver somniferum). En relación con el resto de preparados dotados de actividad tóxica, Cervantes no identifica sus ingredientes, aunque, a tenor de la sintomatología descrita por el autor, podrían ser plantas de la familia de las solanáceas, como el beleño, el solano, la datura, la belladona o la mandrágora. Con respecto a los tóxicos minerales, únicamente hay referencias a los efectos del mercurio o azogue. El Dioscórides comentado por Andrés Laguna pudo ser la fuente técnica utilizada por Cervantes para documentarse en esta materia (AU)

Cervantine texts are an interesting source for the study of Spanish late Renaissance society. We have studied the works of Cervantes from the toxicology viewpoint, analyzing the use of toxic and poisonous substances, essentially hallucinogenic and narcotic agents in the field of witchcraft and sorcery practice (witches ointments, love filters, poisonous potions, etc.), as well as references to hypothetical substances endowed with alexipharmic action, as the vervain (Verbena officinalis), unicorn horn, bezoar stones or castoreum. Cervantine works which refers to these preparations are the novels Don Quixote, The Galatea, Voyage to Parnassus and four Exemplary Novels (The Spanish-English Lady, The Licentiate of Glass, The Jealous Extremaduran and The Colloquy of the Dogs), as well as the comedies Pedro de Urdemalas, The Amusing Woman and The Labyrinth of Love. Toxic agents of herbal origin mentioned explicitly by Cervantes in the analyzed context include the henbane (Hyoscyamus niger / albus), tobacco (Nicotiana tabacum), oleander (Nerium oleander), spurge (Euphorbia lathyris), rhubarb (Rheum officinale, Rumex alpinus), and masked way, opium (Papaver somniferum). In relation to the rest of preparations endowed with toxic activity, Cervantes does not identify its ingredients, though, within the meaning of the symptoms described by the author, they could be plants of the Solanaceae family, as the henbane, nightshade, jimsonweed, belladonna or mandrake. Concerning toxic minerals, only there are references to the effects of mercury (“azogue”). The Dioscorides commented by Andrés Laguna could be the technical font used by Cervantes to document in this matter (AU)

[Toxicological approach to evaluation of bioavailability of powdered medicinal herbs].

Neurotoxicity manifestations related to the extraction of active ingredients from "natural" powdered Atropa belladonna (NPB) and Leonurus cardiaca (NPL) in gastrointestinal tract and respectively of their bioavailability were studied in mice. The symptoms were compared with action of approved officinal extracts. In response to orally administered NPB suspension mice displayed well-defined symptoms of typical cholinolytic appearance. On p.o. administration NPB appeared approximately twice as active as officinal concentrated extract. Sequential administration of NPB and of neostigmine eliminated CNS toxicity confirming the bioavailability and notable cholinolytic activity of NPB. Behavioral, neurological and autonomic profiles developed in response to elevated p.o. doses of NPL were typical of sedative - hypnotic drugs, while maximum prolongation of barbiturate- induced sleep was achieved when "no-effect" doses of NPL and powdered valerian root suspensions were administered concurrently, demonstrating mutual potentiation of specific activity of these natural (non-processed) powders, and respectively excellent bioavailability of their active principles.