Harnessing plant biotechnology-based strategies for in vitro galanthamine (GAL) biosynthesis: a potent drug against Alzheimer's disease

Key message Galanthamine biosynthesis by plant in vitro systems and its mode of action are reviewed to provide a starting point for scaling-up of the biotechnological production of this valuable medicinal alkaloid. Medicinal plants are important for improving human health and represent an essential pool for the identification of novel pharmacological leads. Plant-derived biomolecules have historically proven their value as a source of therapeutic drugs and hold an important potential for the identification and characterization of novel drug leads. Many different alkaloids possessing a broad range of pharmacological activities have been isolated from plants belonging to the Amaryllidaceae family. Galanthamine (GAL) is a selective, reversible and an Amaryllidaceae-derived acetylcholinesterase inhibitor used for the treatment of Alzheimer's disease (AD) and other neurological diseases. Naturally, the bioavailability of Amaryllidaceae alkaloids including GAL is low. Due to the significantly increased demand of GAL by the pharmaceutical industries and the inadequate availability of natural resources, in vitro culture offers an alternative approach for its sustainable production. Thus, different biotechnological tools can optimize the in vitro GAL biosynthesis for treating AD, such as manipulation of plant growth regulators, photoperiod, elicitors, and bioreactors systems, besides being an environmentally sustainable approach, which protects the native biodiversity in a circular bioeconomy context. In the present review, we highlight the biosynthesis of GAL by plant in vitro systems including its mode of action. This article should also provide a starting point in the scaling-up of the biotechnological production of this valuable alkaloid.