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MEGAL

Tue, 2025-02-11 18:32 — Gergana Vasileva

MEGAL - Method for extraction of galanthamine from an innovative raw material. Funded by: European Union – NextGenerationEU, A recovery and resilience mechanism for the implementation of an investment under C2I2 "Increasing the innovation capacity of the Bulgarian Academy of Sciences (BAS) in the field of green and digital technologies" in the Recovery and Resilience Plan (contract №ПВУ–67,16.12.2024/BG-RRP-2.017-0021-C01/). Project coordinator: prof. Strahil Berkov, PhD.

 

DURATION OF THE PROJECT:

16 December 2024 – 30 May 2026

 

RELEVANCE OF THE PROJECT:

Galantamine is a natural product, an alkaloid obtained from plants of the subfamily Amaryllidoideae, and is one of three (along with donepezil and rivastigmine) acetylcholinesterase inhibitors approved by the FDA for the treatment of symptoms in people suffering from Alzheimer's disease. Today, over 45 million people are affected by this disease (mostly adults), and this number is expected to double in the next 20 years.

Studies on galantamine for the treatment of neurodegenerative diseases, including polio, started in Bulgaria in the 1960s with the work of Dr. Paskov. Initially, in Bulgaria galanthamine was extracted from the common snowdrop (Galanthus nivalis) and later from the larger summer snowflake (Leucojum aestivum), for which no agrotechnology of industrial cultivation has been created. As a result of the overuse of natural L. aestivum fields, the species is endangered and is included in the Red Data Book of the Republic of Bulgaria, and its collection is possible only with a permit.

The limited and unsustainable extraction of raw material from L. aestivum, unsatisfactory galantamine yields and the growing demands for it have led Bulgarian producers to rapidly lose their leading positions on the international market. In Western Europe, galantamine is extracted from Narcissus pseudonarcissus cv. Carlton, and in China – from species of the genus Lycoris cultivated on an industrial scale.

In recent years, a team of scientists from Bulgaria and Spain has been working on the introduction of a new source of galantamine – Hippeastrum papilio (Ravena) van Scheepen, which significantly surpasses other species in size and galantamine content. Effective methods for propagation, cultivation and sustainable biomass production have been developed for this species, but no efficient technologies for galantamine extraction have been developed.

The MEGAL project intends to achieve the extraction of galantamine from cultivated Hippeastrum papilio plants. This process will eliminate the exploitation of natural fields of the endangered medicinal plant Leucojum aestivum in Bulgaria. This will directly lead to a reduction in anthropogenic pressure on its populations and will have a positive impact on environmental protection. An additional benefit for the environment will be achieved by the reduction in organic solvent usage during the extraction of galantamine within the project in accordance with the principle of Do No Significant Harm.

 

AIMS OF THE PROJECT:

Primary objective: to validate and establish an efficient method for the extraction and purification of galantamine from an innovative raw material, Hippeastrum papilio bulbs and leaves.
Secondary aims: related to the sustainability of the project; creation of innovative technologies for obtaining raw materials for medicines; implementation of innovative raw materials leading to a reduction in anthropogenic pressure on natural plant populations; cooperation with business and sharing of scientific knowledge to improve the ecosystem for scientific research and innovation.
 
 
 
 
THE FOLLOWING TASKS HAVE BEEN COMPLETED DURING THE PROJECT:
  • galanthamine yields in the primary extract and the isolation of a galanthamine-rich alkaloid fraction were optimized;
  • chromatographic protocols for qualitative and quantitative control of the plant raw material, primary extract and final product were validated;
  • secondary alkaloids accompanying galanthamine were isolated as standard compounds;
  • the plant raw material was successfully genetically barcoded;
  • an efficient and reproducible protocol for the isolation of galanthamine was developed; this protocol is in accordance with the principles of green chemistry and was successfully upscaled and validated in laboratory conditions;
  • the extraction method for galanthamine was synchronized with the requirements for a sustainable economy established by the European union.

 

DISSEMINATION OF RESULTS ACHIEVED DURING THE PROJECT:

Denev R., Berkov S. (2026) A fast and simple method for GC–MS quantification of galanthamine in Hippeastrum papilio (Ravena) Van Sheepen and assessment of its alkaloid fractions. Journal of Chromatography A, Vol. 1774, article 466902. doi: 10.1016/j.chroma.2026.466902. https://www.sciencedirect.com/science/article/pii/S0021967326002323

Denev R., Sidjimova B., Platicanov S., Tallini L., Torras-Claveria L., Berkov S., Development and validation of a GC–MS method for determination of galanthamine and haemanthamine in Hippeastrum papilio. 6th International Conference on Natural Products Utilization: from Plants to Pharmacy Shelf (27-30 May, 2025), Bansko (Bulgaria).

Berkov S., Denev R., Sidjimova B., Georgiev B., Nikolova M., Dimitrova D., Titorenkov V., Ivanova T., Kiselova I., Vladimirov V. Method for extraction of galanthamine- and haemanthamine-rich alkaloid fraction from Hippeastrum papilio (Ravenna) Van Scheepen. Patent proposal deposited in the Patent Office (BG/P/2026/114385, date of application 4 June 2026).



by Dr. Radut.