Castanospermine

Two calves given a mean of 16.1 g and 16.4 g ripe Castanospermum australe seeds/kg body weight daily for 13 and 16 days respectively developed haemorrhagic gastroenteritis. The first calf died. The second calf had mild myocardial degeneration and necrosis and mild nephrosis at necropsy. Two calves given a mean of 16.8 g unripe C. australe seeds/kg body weight daily for 18 days remained clinically normal and had mild gastritis at necropsy. The activity of alpha-glucosidase was reduced in the mononuclear cells of peripheral blood and in skeletal muscle. This was attributed to the presence of the indolizidine alkaloid, castanospermine, in the seeds. The toxin causing the gastroenteritis and other lesions is unknown.

During times of pre-European Australia, indigenous people utilized methods of food procurement that resulted in toxic phytochemicals from plants entering their waterholes. This paper focuses on three of these plants, namely the leaves of Acacia colei and Duboisia hopwoodii, which were used by hunters to poison water holes to stun fish or a drinking animal, and the seeds of Castanospermum australe, which were eaten following the leaching of toxins into a running stream. If consumed by humans, the main toxins from these plants--saponins/sesquiterpenes, nicotine/nornicotine, and australine/castanospermine--are fatal. However, it is undetermined whether populations of Cyanobacteria also can be affected. During this study, the previously mentioned plants were administered to populations of the species Anabaena circinalis, Microcystis aeruginosa, and Nodularia spumigena, while mimicking the traditional applications of these plants as closely as possible.

Castanospermine is an indolizidine alkaloid that is found in the seeds of the Australian tree Castanospermum australe. These seeds have been reported to be toxic to animals and to cause severe gastrointestinal upset. In order to determine whether castanospermine is responsible for this toxicity, the alkaloid was injected into young mice or rats, and its effects on various intestinal disaccharidases were determined. Another indolizidine alkaloid, the alpha-mannosidase inhibitor swainsonine, was also tested to compare its effects to those of castanospermine. Castanospermine strongly and rapidly inhibited the activity of the disaccharidases, sucrase, maltase, and trehalase, with sucrase being the most sensitive to inhibition. The loss of activity of these enzymes, especially sucrase, in injected animals appeared to be due to a direct inhibition of enzyme activity, rather than to a change in the structure of the glycan chains of the enzyme, since only minor alterations in carbohydrates were observed.

The antidiabetic actions of Castanospermum australe Cunn., seed (CAS) extract were evaluated in Poloxamer-407 (PX-407) induced T2DM rats. The CAS extract (100 and 150 mg/kg body weight) was administered orally once a day for 5 weeks after the animals were confirmed diabetic. A significant increase in blood glucose, HbA₁c and serum insulin levels were observed in T2DM rats in comparison to citrate control rats. Treatment with CAS extract in T2DM rats reduced the elevated levels of blood glucose, HbA₁c and insulin with significant (p≤0.001) improvement in OGT. The CAS extract treatment also increased (p≤0.001) the K(ITT) and prevented increase in HOMA-R level in T2DM rats. The DPP-IV inhibitory potential of CAS extract showed IC₅₀ value of 13.96 μg/ml whilst the standard Diprotin A displayed the IC₅₀ value of 1.543 μg/ml. Molecular docking of the three reported alkaloids from the seeds of C. australe showed comparable DPP-IV inhibition with berberine.