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PubMedDate not supplied

[Recent results on the pharmacodynamics of Strychnos malgaches alkaloids].

Investigation of Strychnos (Loganiaceae) shrubs and trees was initiated by their traditional uses of their inherent poisons on arrows: this led to the discovery of strychnine and curare alkaloids. Subsequently, phytochemical investigation of several Strychnos species has shown great structural diversity of the alkaloid constituent which also display various biological effects, i.e. convulsive and relaxant effects on muscles, and antimicrobial, antitumor and antihypertensive properties. Ethnobotanical field work conducted in different regions of Madagascar revealed that infusion of three Strychnos species, S. mostueoides, S. myrtoides and S. diplotricha, is used in association with subcurative doses of chloroquine to treat chronic malaria. Bioassayfractionation led to the isolation of two major bioactive components, strychnobrasiline and malagashanine. Whereas strychnobrasiline is a previously known chemical compound, malagashanine is the first in a series of a new subtype of Strychnos alkaloids. These two alkaloids are devoid of intrinsic antimalarial effects, both in vitro (IC50 = 73.0 micrograms/ml for strychnobrasiline and 69.1 micrograms/ml for malagashanine) and in vivo (10 mg/kg conferred a 5% suppression of parasitemia). When these alkaloids are combined with chloroquine at doses much lower than required for antiplasmodial effects, they greatly enhance the chloroquine action in a dose dependent manner as seen by the isobologram method. Several minor alkaloids structurally related to malagashanine were also isolated from Madagascan Strychnos. They all enhance, to greater or lesser degrees, the chloroquine effectiveness. Interestingly, there is a positive correlation between the ethnomedical use of the three Strychnos species as chloroquine adjuvants and the chloroquine-potentiating effects of malagashanine and strychnobrasiline isolated from them. After preliminary toxicological studies, infusion of stem barks of S. myrtoides in association with chloroquine was successfully evaluated in a clinical setting. Additional chemical, pharmacological and toxicological work is being conducted on these alkaloids with the aim of developing purified and standardized extracts for clinical trials. These trials will be carried out in the chloroquine-resistant regions of Madagascar which are in need of inexpensive and efficient drugs for the treatment of chloroquine-resistant malaria.

Alkaloids↗
PubMed1998

Cytotoxicities of alkaloids from processed and unprocessed seeds of Strychnos nux-vomica.

AIM: To examine the cytotoxicities of 6 crude Strychnos alkaloid fractions from the seeds of Strychnos nux-vomica unprocessed or processed with various traditional processing methods and 13 pure Strychnos alkaloids from the fractions. METHODS: Using cell culture, their inhibitory effects on Vero cell growth-inhibition assay, and host cell DNA synthesis by [3H]thymidine ([3H]TdR) uptake assay. RESULTS: The IC50 of processed seeds were 155% and 212% of unprocessed ones in cell growth-inhibition assay and in [3H]TdR uptake assay, respectively. The IC50 of 13 compounds were 0.45-0.80 mmol.L-1 and 0.50-12 mmol.L-1, respectively. The processing method with sand bath exhibited a wide safety margin compared with other traditional processing methods or no processing. The isomers of Strychnos alkaloids and their N-oxides showed much lower cytotoxicities among these alkaloids. Isobrucine N-oxide showed the lowest cytotoxicity. The contents of isomers and N-oxides of Strychnos alkaloids were the highest in the sand processing. CONCLUSION: Processing of nux vomica plays a critical role in its toxicity.

Alkaloids↗
PubMed2005

In vitro screening of some Strychnos species for antiplasmodial activity.

The antiplasmodial activity of crude extracts of 19 species of Strychnos (Loganiaceae) was assessed in vitro against a chloroquine-susceptible strain of Plasmodium falciparum. For each species, ethyl acetate (EtOAc) extracts were analysed and, for the most active species, methanolic (MeOH) extracts were also tested. Among them, Strychnos variabilis De Wild. seemed to be very promising (inhibitory concentration 50% (IC50) < 5 microg/ml) whereas two other species, Strychnos gossweileri Exell and Strychnos mellodora S. Moore, could be interesting (IC50 < 15 microg/ml) in further antimalarial studies.

Animals↗
PubMed2005

Physicochemical characterization of the Strychnos alkaloids by capillary zone electrophoresis.

A capillary zone electrophoresis (CZE) method has been developed for investigating the physicochemical characteristics of five Strychnos alkaloids in Strychnos nux-vomica L. Firstly, the dissociation constants of the five Strychnos alkaloids were determined, based on the relation between the effective mobility of the solutes and the buffer pH. The mathematical relationship was strictly deduced from the fundamental electrophoretic theory and the dissociation equilibrium. Secondly, an equation describing the relation between the migration time of alkaloids of similar structure and their molecular weights was developed and used to predict the migration order and to calculate the electrosomotic velocity. The results predicted by the theory agreed with those from experiments.

Alkaloids↗
PubMed2004

[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.

Alkalies↗
PubMed1997

[Determation of strychnine and brucine in Strychnos by HPLC].

This paper describes the determination of strychnine and brucine in the seeds, root, stem and leaves of Strychnos species by HPLC. The analytical column used was ZY110 YNG-C18. The mobile phase was KH2PO4(0.01 mol.L-1)--MeOH(73:27), pH2.5, regulated by 10% H3PO4. Flow rate was 1.0 ml.min-1. The detection wavelength was 264 nm. The linear ranges of strychmine and brucine were 0.18-7.26 micrograms and 0.11-4.32 micrograms, respectively. The recoveries of strychnine and brucine were 98.27% and 98.04%, respectively. The analytical results showed that the contents of strychnine and brucine in samples showed great difference between different species. The contents of strychnine in the seeds of Strychnos wallichiana and S. ignatii were 5.6% and 3.9%, respectively. These results show that the two Strychnos species may be developed as the resources of strychnine.

Chromatography, High Pressure Liquid↗
PubMed2006

Analysis of strychnos alkaloids using electrospray ionization Fourier transform ion cyclotron resonance multi-stage tandem mass spectrometry.

The fragmentations of four strychnos alkaloids have been investigated by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) in the positive ion mode. Experiments using multi-stage tandem mass spectrometry (ESI-FT-ICR-MSn) allowed us to obtain precise elemental compositions of product ions at high mass resolution. The experimental data demonstrated that the nitrogen bridge and the coordinated oxygen atom on the nitrogen bridge in the alkaloid compounds were the active sites in the MS2 fragmentations. The loss of CH3 or the OCH3 group in those alkaloids, which have an OCH3 substituent, was the dominant fragmentation mode in the MS3 fragmentations. Logical fragmentation schemes for strychnos alkaloids have been proposed and these should be useful for the identification of these compounds.

Alkaloids↗
PubMed2004

Analysis of strychnine from detoxified Strychnos nux-vomica [corrected] seeds using liquid chromatography-electrospray mass spectrometry.

The content of strychnine from Strychnos nux-vomica [corrected] seeds was analyzed and compared to processed seeds by the HPLC-ESI/MS method. Using this technique, levels as low as 1 ng of strychnine were detected. In contrast to conventional UV detectors, this method also made it possible to discriminate brucine. This study resulted in finding the content of strychnine in detoxified seeds to be one tenth of unprocessed Strychnos nux-vomica [corrected] seeds.

Plant Extracts↗
PubMed2006

Studies on hepatoprotective and antioxidant actions of Strychnos potatorum Linn. seeds on CCl4-induced acute hepatic injury in experimental rats.

Strychnos potatorum Linn. seeds are used in the Indian traditional system of medicine for the treatment of hepatopathy, nephropathy, gonorrhoea, leucorrhoea, gastropathy, bronchitis, chronic diarrhoea, strangury, renal and vesicle calculi, diabetes and eye diseases. The present study describes the hepatoprotective and antioxidant activities of the seed powder (SPP) and aqueous extract (SPE) of Strychnos potatorum seeds against CCl4-induced acute hepatic injury. Hepatic injury was achieved by injecting 3 ml/kg, s.c. of CCl4 in equal proportion with olive oil. Both SPP and SPE at the doses 100 and 200 mg/kg, p.o. offered significant (p < 0.001) hepatoprotective action by reducing the serum marker enzymes like serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT). They also reduced the elevated levels of ALP and serum bilirubin. Reduced enzymic and nonenzymic antioxidant levels and elevated lipid peroxide levels were restored to normal by administration of SPP and SPE. Histopathological studies further confirmed the hepatoprotective activity of SPP and SPE when compared with the CCl4 treated control groups. The results obtained were compared with Silymarin (50 mg/kg, p.o.), the standard drug. In conclusion, SPE (200 mg/kg, p.o.) showed significant hepatoprotective activity similar to that of the standard drug, Silymarin (50 mg/kg, p.o.).

Animals↗
PubMed2006

The anti-tumor effects of alkaloids from the seeds of Strychnos nux-vomica on HepG2 cells and its possible mechanism.

To screen the anti-tumor effects of the four alkaloids: brucine, strychnine, brucine N-oxide and isostrychnine from the seed of Strychnos nux-vomica, MTT assay was used to examine the growth inhibitory effects of these alkaloids on human hepatoma cell line (HepG2). Brucine, strychnine and isostrychnine revealed significant inhibitory effects against HepG2 cell proliferation, whereas brucine N-oxide didn't have such an effect. In addition, brucine caused HepG2 cell shrinkage, membrane blebbing, apoptotic body formation, all of which are typical characteristics of apoptotic programmed cell death. The results of flow cytometric analysis demonstrated that brucine caused dose-dependent apoptosis of HepG2 cells through cell cycle arrest at G0/G1 phase, thus preventing cells entering S or G2/M phase. Immunoblot results revealed that brucine significantly decreased the protein expression level of cyclooxygenase-2, whereas increased the expression caspase-3 as well as the caspase-3-like protease activity in HepG2 cells, suggesting the involvement of cyclooxygenase-2 and caspase-3 in the pro-apoptotic effects exerted by brucine. Therefore, this paper indicate that the major alkaloids present in the seed of Strychnos nux-vomica are effective against HepG2 cells proliferation, among which brucine proceed HepG2 cells death via apoptosis, probably through the participation of caspase-3 and cyclooxygenase-2.

Alkaloids↗