Galantamine Quantity and Alkaloid Profile in the Bulbs of Narcissus tazetta and daffodil cultivars (Amaryllidaceae) Grown in Israel.

Alkaloids produced by the bulbs of the Amaryllidaceae are a source of pharmaceutical compounds. The main alkaloid, galantamine, is a reversible acetylcholinesterase inhibitor and allosteric nicotinic receptor modulator, which slows cognitive and functional decline in mild to moderate dementia due to Alzheimer's disease. Having a complex stereochemistry, the organic synthesis of galantamine for pharmaceutical uses is highly challenging and not always economically viable, and it is therefore isolated from Amaryllidaceae bulbs. In the present study, galantamine was extracted and quantified in Narcissus bulbs from five cultivars (cvs.), Fortune, Carlton, Ice Follies, Galilee and Ziva, which were grown in Israel under various conditions. Results show that the cvs. Fortune, Carlton and Ice Follies bulbs contained 285 ± 47, 452 ± 73 and 69 ± 17 µg g-1 galantamine, respectively, while the Galilee and Ziva bulbs contained relatively low concentrations of galantamine (1-20 µg g-1). Irrigation levels and pruning conditions did not affect the galantamine contents. Additionally, the alkaloids profile of the five cvs. was analyzed and characterized using LC-MS/MS showing that galantamine-type alkaloids were mainly detected in the Fortune and Carlton bulbs, lycorine-type alkaloids were mainly detected at the Galilee and Ziva bulbs and vittatine-type alkaloids were mainly detected in the Ice Follies bulbs. The present research is the first to characterize the alkaloids profile in the Narcissus bulbs of Galilee and Ziva, indigenous cvs. grown in Israel. The antiviral and anticancer alkaloids lycorine and lycorinine were the main alkaloids detected in the bulbs of those cultivars.

High levels of LINE-1 transposable elements expressed in Kaposi's sarcoma-associated herpesvirus-related primary effusion lymphoma.

Kaposi's sarcoma-associated herpesvirus (KSHV, HHV-8) is a gamma herpesvirus associated with several human malignancies. Transposable elements (TEs) are ubiquitous in eukaryotic genomes, occupying about 45% of the human genome. TEs have been linked with a variety of disorders and malignancies, though the precise nature of their contribution to many of them has yet to be elucidated. Global transcriptome analysis for differentially expressed TEs in KSHV-associated primary effusion lymphoma (PEL) cells (BCBL1 and BC3) revealed large number of differentially expressed TEs. These differentially expressed TEs include LTR transposons, long interspersed nuclear elements (LINEs), and short interspersed nuclear elements (SINEs). Further analysis of LINE-1 (L1) elements revealed expression upregulation, hypo-methylation, and transition into open chromatin in PEL. In agreement with high L1 expression, PEL cells express ORF1 protein and possess high reverse transcriptase (RT)-activity. Interestingly, inhibition of this RT-activity suppressed PEL cell growth. Collectively, we identified high expression of TEs, and specifically of L1 as a critical component in the proliferation of PEL cells. This observation is relevant for the treatment of KSHV-associated malignancies since they often develop in AIDS patients that are treated with RT inhibitors with potent inhibition for both HIV and L1 RT activity.