Prophylactic Neuroprotection of Total Glucosides of Paeoniae Radix Alba against Semen Strychni-Induced Neurotoxicity in Rats: Suppressing Oxidative Stress and Reducing the Absorption of Toxic Components.

Strychnos alkaloids (SAs) are the main toxic constituents in Semen Strychni, a traditional Chinese medicine, which is known for its fatal neurotoxicity. Hence, the present study was carried out to evaluate the neurotoxicity induced by SAs and the pre-protective effects of the total glucosides of Paeoniae Radix Alba (TGP). An SA brain damage model was firstly established. The neurotoxicity induced by SAs and the pre-protective effects of TGP were confirmed by physical and behavioral testing, biochemical assay, and histological examination. Then, a liquid chromatography-tandem mass spectrometry method was developed and validated to investigate the time-course change and distribution of strychnine and brucine (two main SAs) in the brain after oral SA administration with or without TGP pretreatment. Biochemical analysis results indicated that TGP could ameliorate the oxidative stress status caused by SAs. Time-course change and distribution studies demonstrated that strychnine and brucine were rapidly absorbed into the brain, peaked early at 0.5 h, and were mainly located in the hippocampus and cerebellum. TGP showed a pre-protective effect against neurotoxicity by reducing the absorption of toxic alkaloids into the brain. These findings could provide beneficial information in facilitating future studies of Semen Strychni neurotoxicity and developing herbal medicines to alleviate neurotoxicity in the clinic.

Important poisonous plants in tibetan ethnomedicine.

Tibetan ethnomedicine is famous worldwide, both for its high effectiveness and unique cultural background. Many poisonous plants have been widely used to treat disorders in the Tibetan medicinal system. In the present review article, some representative poisonous plant species are introduced in terms of their significance in traditional Tibetan medicinal practices. They are Aconitum pendulum, Strychnos nux-vomica, Datura stramonium and Anisodus tanguticus, for which the toxic chemical constituents, bioactivities and pharmacological functions are reviewed herein. The most important toxins include aconitine, strychnine, scopolamine, and anisodamine. These toxic plants are still currently in use for pain-reduction and other purposes by Tibetan healers after processing.

Pharmacokinetics of brucine after intravenous and oral administration to rats.

The toxicity depending on both dose and administration route is the major obstacle to the development of brucine, a bioactive alkaloid from Semen Strychni. In this study, the apparent partition coefficient and plasma protein binding extent of brucine were determined. In addition, the dose-dependency of the pharmacokinetics of brucine was investigated. Three intravenous (2.5, 5 and 10 mg/kg) and three oral (10, 20 and 40 mg/kg) doses were administered to rats. After intravenous administration, the systemic clearance was reduced and AUC was nonlinearly increased as a function of dose. Upon oral administration, brucine was rapidly absorbed (T(max)<0.5h), which was consistent with previously reported high Caco-2 P(app) values. The increase in AUC was proportional to the increase in dose. The oral bioavailability (F) did not vary with the dose (F=40.31%, 47.15% and 43.02% for 10, 20, 40 mg/kg doses, respectively). However, the dose-proportionality was not observed with C(max). The values of C(max)/Dose were calculated to be 92.92±45.83, 55.73±24.01 and 36.29±22.44 µg/L for 10, 20 and 40 mg/kg, respectively. The results of dose-dependent pharmacokinetic behavior under different administration routes may account for the significantly different toxicities of brucine between intravenous and oral administration.

[Study of toxicology of strychnos].

Because of its officinal value, strychnos is widely used by clinic and individual. Since toxic dose and therapeutic dose are very close, strychnos poisoning cases are frequently reported. In this paper the chemical component, toxic dose, mechanisms of toxicity, poisoning symptom and pathological changes after strychnos poisoning are reviewed.

About the toxicity of some Strychnos species and their alkaloids.

Poisons are widespread in plants and animals and humankind has often tried to turn them to its own advantage. Owing to their poisonous properties, some species of Strychnos genus have been employed mainly in hunting and fishing, as an adjunct to weapons used not only in the search of food and clothes, but also for preventing depredation by wild animals. They have been employed for martial and criminal purposes and also as a means of determining guilt or innocence. By their nature, poisons such as strychnine and curare affect the functioning of the victim's body; this also means that they have been, and are, an important source of pharmacological tools and medicines all over the world. With such potentially dangerous substances, care in medication is essential to avoid complications by overdose. All these points are approached in the present review.