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Bioactivity of compounds derived from Amaryllicaea (Daffodil)

People Involved

Sarah Walsh

Project Description

Heart Failure (HF) is a long-term complication of cardiovascular (high blood pressure and heart attack) and cardiovascular-related (obesity and metabolic syndrome) disorders and of drug-induced cardiotoxicity. HF is characterised by thickening (hypertrophy) and stiffening (fibrosis) of the walls of the heart, leading to reduced cardiac function and increased morbidity. Agroceutical Products Ltd (APL) produces sustainable quantities of the naturally derived alkaloid galanthamine from daffodils, which is a key active pharmaceutical used for the treatment of Alzheimer’s disease. Daffodils contain an abundance of other alkaloid compounds, some of which (e.g. narciclasine and haemanthamine) APL can extract alongside galanthamine. There is emerging evidence that some of these alkaloids may target cellular events in the heart cell (cardiomyocyte) to interrupt the HF-associated structural changes, and thus have the potential for development as novel therapeutics in the prevention of HF. This project will involve testing three alkaloids extracted from daffodils in cell-based cardiomyocyte models that mimic the different stimuli for cardiac hypertrophy (high glucose, oxidative stress and doxorubicin), to determine their potential as anti-hypertrophic/anti-fibrotic molecules, and by measuring multiple cellular signalling pathways we will gain insight into cellular mechanism of action. This will provide essential “proof of concept” data that will identify the most efficacious compounds, inform the refinement of extraction methods to isolate different alkaloids, and potentially identify what structure-activity relationships may exist between alkaloids. This will inform APL as to which alkaloids have the potential to bring added value to their current production stream which will, in turn maximise the commercial potential for their products.

Status Project Live
Funder(s) Industrial Biotechnology Innovation Centre
Value £39,958.00
Project Dates Feb 1, 2021 - Jan 31, 2022
Partner Organisations Agroceutical Products Ltd

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