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It is well known that when lactating livestock eat avocado (Persea americana) leaves they may develop non-infectious mastitis and agalactia. This is associated with extensive coagulation necrosis of the secretory acinar epithelium and interstitial oedema, congestion, and haemorrhage. Similar lesions have been produced in mammary glands of lactating mice fed a diet containing a small percentage of freeze-dried avocado leaf. Tests using these animals have been used to isolate the active principle, termed "persin," from avocado leaves. The purified persin was examined using IR, NMR, and UV spectroscopy and mass spectrometry, and identified as (Z,Z)-1-(acetyloxy)-2-hydroxy-12,15-heneicosadien-4-one. Persin has previously been isolated from avocado leaves and shown to have antifungal properties and to be toxic to silkworms. Our tests have shown that persin at the dose rate of 60-100 mg/kg has the same effect on mammary glands in lactating mice as leaves from avocado. Enantioselective syntheses of the R and the S isomers of persin and related derivatives were carried out. These compounds were tested for activity required to induce widespread lactating mammary gland necrosis in mice, and only the R isomer was found active. At doses of persin above 100 mg/kg necrosis of myocardial fibres may occur and hydrothorax may be present in severely affected animals. The mechanism of action of persin on both the mammary gland and the myocardium remain to be resolved.

Phytochemicals have provided an abundant and effective source of therapeutics for the treatment of cancer. Here we describe the characterization of a novel plant toxin, persin, with in vivo activity in the mammary gland and a p53-, estrogen receptor -, and Bcl-2-independent mode of action. Persin was previously identified from avocado leaves as the toxic principle responsible for mammary gland -specific necrosis and apoptosis in lactating livestock. Here we used a lactating mouse model to confirm that persin has a similar cytotoxicity for the lactating mammary epithelium. Further in vitro studies in a panel of human breast cancer cell lines show that persin selectively induces a G 2 -M cell cycle arrest and caspase-dependent apoptosis in sensitive cells. The latter is dependent on expression of the BH3-only protein Bim. Bim is a sensor of cytoskeletal integrity, and there is evidence that persin acts as a microtubule-stabilizing agent. Due to the unique structure of the compound, persin could represent a novel class of microtubule-targeting agent with potential specificity for breast cancers. [Mol Cancer Ther 2006;5(9):2300 -9]

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This paper describes the isolation and structure elucidation of two toxic tannins, named a-and ppunicalagin, from Terminalia oblongata, an Australian tree. Techniques used in the structure determination included Fast Atom Bombardment (FAB) mass spectrometry, and one-and twodimensional N M R, UV, and I R spectroscopy. A number of microscale derivatisations were performed, followed by FAB analysis.Methylation.-Component B (0.1 mg) was dissolved in diethyl ether (1 ml). A solution of diazomethane in diethyl ether Paper 0/00673D

Regular ingestion of Eupatorium adenophorum [Ageratina adenophora (Spreng.)] or Crofton weed causes chronic pulmonary disease in horses mainly in Australia, New Zealand, and the Himalayas. The disease is characterized by pulmonary interstitial fibrosis, emphysema, alveolar epithelisation and reduced tolerance to exercise. Horses apparently are the only animals affected and there are numerous reports of farms losing all their horses. The disorder was produced experimentally in horse feeding trials, and it was shown that characteristic lesions occurred in the lungs. In studies with laboratory animals, mice were shown to be suitable test animals, but in this species lesions occur in the liver rather than the lungs. The hepatic injury in these animals is characterized by multiple areas of focal necrosis of the parenchyma associated with degeneration and loss of the epithelium lining the small bile ducts. The active principle 9-oxo-10,11 dehydroagerophorone responsible for these lesions in mice has been isolated from E. adenophorum. Although the compound has been shown to exhibit toxicity to larvae of invertebrate species, no mammalian toxicity studies have been previously reported involving the isolated toxin. The mechanism of the toxic effect of the compound as well as its possible relevance to the respiratory disease in the horse remain to be investigated.

Terminalia oblongata (yellow wood) is a small deciduous tree growing over an area of central Queensland that supports a large proportion of this state's cattle population. Cattle and sheep that consume yellow wood leaves are poisoned and die. Severe losses of these animals can occur, and this problem is considered the main cause of economic loss to the cattle industry in the area apart from drought. A new toxic condensed tannin, terminalin was isolated from Terminalia oblongata. Its structure was deduced following NMR, IR, UV, MS analyses and in the knowledge that these data show good correlations to those obtained from the related punicalagin molecule which is present in the plant. Terminalin has a high toxicity (20 mg/kg) to white Quackenbush male mice and produces a vascular renal necrosis with slight liver necrosis, unlike punicalagin, which produces liver lesions but not kidney lesions. Similar results were obtained with sheep. A most interesting aspect is that there are two different specific toxins in the plant.

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