Introduction

A large group of phenolic or polyphenol compounds can be defined as flavonoids with one or more aromatic rings along with at least one hydroxyl group, as well as specific additional functional groups [1]. Flavonoids have been recognized in plants for a long time and their function as plant pigments, particularly the anthocyanins, has been the driving force for their early studies [2]. Flavonoids were first isolated in the 1930s from citrus and were initially misclassified as vitamins [3]. Up until the early 1960s, researchers largely considered them mere by-products of plant cell metabolism. However, the application of advanced spectroscopy and analytical techniques, such as nuclear magnetic resonance (NMR) and gas-liquid chromatography (GLC), enabled accurate structural determination, leading to a new appreciation for flavonoids as vital metabolites with significant human health benefits [4]. Since then, an estimated 10,000 or more flavonoid derivatives have been reported. This vast structural diversity is generated by various modification reactions, such as O-methylation catalysed by O-methyltransferases, critically affecting the compound's solubility and bioavailability, factors highly relevant to ADMET studies [5].

Flavonoids perform essential functions in plants, contributing to growth, structure and environmental stress response. Beyond protecting against UV radiation and soil metal toxicity, they are key mediators in the plant's interaction with its ecosystem [6,7]. For instance, their vibrant colours attract pollinators (insects and birds), aiding seed dispersal. The characteristic colours of flavonoids also make it possible for their widespread use in food as a natural colorant, as well as in cosmetics and skincare products [8,9]. The in vivo biological activity of flavonoids is influenced by their chemical structure, specifically their degree of hydroxylation, substitution patterns, conjugation and polymerization [10]. Extensive in vivo and in vitro studies of flavonoids indicated that they have various bioactivities, including antioxidant, cytotoxic, anticancer, anti-inflammatory, antiviral, antibacterial, anti-allergic, antiplatelet, cardioprotective, hepatoprotective, neuroprotective, antimalarial and antiparasitic effects [11-13]. While previous reviews have catalogued the general classes of flavonoids and their bioactivities, this review also examines how these plant-based survival tools translate into potent therapeutic agents for human health and the breakthrough in the de novo production.