Swainsonine

Developmental and loco-like effects of a swainsonine-induced inhibition of alpha-mannosidase in the honey bee, Apis mellifera.[Pubmed:28321369]

PeerJ. 2017 Mar 16;5:e3109.

BACKGROUND: Deficiencies in lysosomal a-mannosidase (LAM) activity in animals, caused either by mutations or by consuming toxic alkaloids, lead to severe phenotypic and behavioural consequences. Yet, epialleles adversely affecting LAM expression exist in the honey bee population suggesting that they might be beneficial in certain contexts and cannot be eliminated by natural selection. METHODS: We have used a combination of enzymology, molecular biology and metabolomics to characterise the catalytic properties of honey bee LAM (AmLAM) and then used an indolizidine alkaloid Swainsonine to inhibit its activity in vitro and in vivo. RESULTS: We show that AmLAM is inhibited in vitro by Swainsonine albeit at slightly higher concentrations than in other animals. Dietary exposure of growing larvae to Swainsonine leads to pronounced metabolic changes affecting not only saccharides, but also amino acids, polyols and polyamines. Interestingly, the abundance of two fatty acids implicated in epigenetic regulation is significantly reduced in treated individuals. Additionally, swainsonie causes loco-like symptoms, increased mortality and a subtle decrease in the rate of larval growth resulting in a subsequent developmental delay in pupal metamorphosis. DISCUSSION: We consider our findings in the context of cellular LAM function, larval development, environmental toxicity and colony-level impacts. The observed developmental heterochrony in Swainsonine-treated larvae with lower LAM activity offer a plausible explanation for the existence of epialleles with impaired LAM expression. Individuals carrying such epialleles provide an additional level of epigenetic diversity that could be beneficial for the functioning of a colony whereby more flexibility in timing of adult emergence might be useful for task allocation.

A Screen for Swainsonine in Select North American Astragalus Species.[Pubmed:28155255]

Chem Biodivers. 2017 Apr;14(4).

Swainsonine is found in several plant species worldwide, and causes severe toxicosis in livestock grazing these plants, leading to a chronic condition characterized by weight loss, altered behavior, depression, decreased libido, infertility, and death. Swainsonine has been detected in 13 North American Astragalus species of which eight belong to taxa in four taxonomic sections, the Densifolii, Diphysi, Inflati, and Trichopodi. These sections belong to two larger groups representing several morphologically related species, the Pacific Piptolobi and the small-flowered Piptolobi. The objective of this study was to screen the other 31 species for Swainsonine in sections Densifolii, Diphysi, Inflati, and Trichopodi previously not known to contain Swainsonine. Furthermore, to broaden the scope further, 21 species within the 8 sections of the Pacific Piptolobi and the small flowered Piptolobi were screened for Swainsonine. Swainsonine was detected for the first time in 36 Astragalus taxa representing 29 species using liquid and gas chromatography coupled with mass spectrometry. Several taxonomic sections were highly enriched in species that contain Swainsonine while others were not. A systematic examination for Swainsonine in these species will provide important information on the toxic risk of these species and may be a valuable reference for diagnosticians and land managers.

Effects of Elevated CO2 on the Swainsonine Chemotypes of Astragalus lentiginosus and Astragalus mollissimus.[Pubmed:28190150]

J Chem Ecol. 2017 Mar;43(3):307-316.

Rapid changes in the Earth's atmosphere and climate associated with human activity can have significant impacts on agriculture including livestock production. CO2 concentration has risen from the industrial revolution to the current time, and is expected to continue to rise. Climatic changes alter physiological processes, growth, and development in numerous plant species, potentially changing concentrations of plant secondary compounds. These physiological changes may influence plant population density, growth, fitness, and toxin concentrations and thus influence the risk of toxic plants to grazing livestock. Locoweeds, Swainsonine-containing Astragalus species, are one group of plants that may be influenced by climate change. We evaluated how two different Swainsonine-containing Astragalus species responded to elevated CO2 concentrations. Measurements of biomass, crude protein, water soluble carbohydrates and Swainsonine concentrations were measured in two chemotypes (positive and negative for Swainsonine) of each species after growth at CO2 levels near present day and at projected future concentrations. Biomass and water soluble carbohydrate concentrations responded positively while crude protein concentrations responded negatively to elevated CO2 in the two species. Swainsonine concentrations were not strongly affected by elevated CO2 in the two species. In the different chemotypes, biomass responded negatively and crude protein concentrations responded positively in the Swainsonine-positive plants compared to the Swainsonine-negative plants. Ultimately, changes in CO2 and endophyte status will likely alter multiple physiological responses in toxic plants such as locoweed, but it is difficult to predict how these changes will impact plant herbivore interactions.

Swainsonine-induced lysosomal storage disease in goats caused by the ingestion of Sida rodrigoi Monteiro in North-western Argentina.[Pubmed:28093222]

Toxicon. 2017 Mar 15;128:1-4.

There are numerous poisonous plants that can induce intralysosomal accumulation of glycoproteins and neurologic syndromes. Here we describe for the first time, a disease caused by ingesting Sida rodrigoi Monteiro in goats in North-western Argentina. The animals showed weight loss, indifference to the environment, unsteady gait and ataxia. Histopathologic studies showed vacuolization in cells of various organs, mainly in the CNS. The material deposited in the cells was positive for LCA (Lens culinaris agglutinin), WGA (Triticum vulgaris agglutinin), sWGA (succinyl-Triticum vulgaris agglutinin) and Con-A (Concanavalia ensiformis agglutinin) lectins. Finally, toxic levels of swansonine were identified in the plant. The present investigation allowed to recognize S. rodrigoi Monteiro poisoning as a plant induced alpha-mannosidosis.

Inhibition of the growth of human gastric carcinoma in vivo and in vitro by swainsonine.[Pubmed:17097281]

Phytomedicine. 2007 May;14(5):353-9.

In Europe, Swainsonine has been studied widely for prevention of metastasis and cancer therapy. In order to investigate the effects and mechanisms of Swainsonine on the human gastric carcinoma SGC-7901 cell, we carried out in vivo and in vitro experiments. After treatment with Swainsonine, an effective dose and IC50 value of Swainsonine for SGC-7901 cells were examined by MTT assay. Cell-cycle distribution and apoptotic rates were analyzed using FCM, and [Ca2+]i was measured using LSCM. The expression of p53, c-myc and Bcl-2 were determined using an immunocytochemical method. Simultaneously, 50 mice were divided randomly into five groups. Three groups were administrated Swainsonine at dose of 3, 6 and 12 mg/kg body wt., two control groups were administrated N.S. 20 ml/kg body wt. and 5-Fu 20 mg/kg body wt., respectively, by intraperitoneal injection. The inhibition rate was calculated and pathological sections were observed. The growth of SGC-7901 cell is inhibited by Swainsonine in vitro, with an IC50 value at 24 h of 0.84 microg/ml, and complete inhibition concentration is 6.2 microg/ml. After treatment with Swainsonine at the concentrations of 0.5, 1.5 and 4.5 microg/ml for 24 h, the expression of apoptosis inhibiting gene p53 and bcl-2 decreases, and the apoptotic trigger gene c-myc increases markedly (p<0.05), as well as [Ca2+]i overloading, SGC-7901 cell is induced to apoptosis in the end. It is also found that the percentages of S phase are 38.8%, 39.7% and 29.6%, respectively (20.0% in control group and 23.2% in 5-Fu group). The rates of inhibition were 13.2%, 28.9%, 27.3%, respectively, when the nude mice were administered Swainsonine (p<0.05 or 0.01). The structure of the tumor showed hemorrhage, necrosis and inflammatory cell infiltration. We therefore conclude that Swainsonine could inhibit cell proliferation in vitro and the growth of human gastric carcinoma in vivo. The mechanisms of Swainsonine-induced apoptosis may relate to [Ca2+]i overloading and the expression of apoptosis-related genes.

The potential importance of swainsonine in therapy for cancers and immunology.[Pubmed:1754603]

Pharmacol Ther. 1991;50(3):285-90.

Swainsonine, an indolizidine alkaloid, was initially used in biomedical research as a tool to investigate the biosynthesis and function of asparagine-linked 'complex' type oligosaccharide moieties of glycoproteins. Recently, Swainsonine has generated interest in its potential use as an anticancer agent with reports that it (i) inhibits tumor growth and metastasis, (ii) augments natural killer (NK) and macrophage-mediated tumor cell killing, and (iii) stimulates bone marrow cell proliferation. The antineoplastic activity of Swainsonine can be explained at least in part by augmentation of immune effector mechanisms. The potential application of Swainsonine as an anticancer agent is discussed.