A systematic review of the traditional uses, chemistry, and curative aptitude of echinacoside-a phenylethanoid glycoside.

Echinacoside (ECH), a naturally occurring water-soluble phenylethanoid glycoside, is one of the primary bioactive compounds present in several plant species, such as Echinacea, Cistanche, Plantago, Rosa, Buddleja, and Rehmannia. Research has revealed that these plants, rich in ECH, have diverse traditional uses and pharmacological activities, like anti-diabetic, anti-inflammatory, anti-fatigue, anti-allergic, anti-ageing, anti-skin glycation, analgesic, wound healing, and aphrodisiac properties. Among other activities, ophthalmic, haematopoiesis, pulmonary, anti-bacterial, anti-protozoal, anti-fungal, and anti-viral effects of ECH have been reported. Chemically, the compound comprises caffeic acid glycoside containing a trisaccharide that includes two glucose and one rhamnose unit. These units are linked through glycosidic bonds to a caffeic acid and a dihydroxyphenylethanol (hydroxytyrosol) residue, which are connected to the central rhamnose. The biosynthesis of ECH has been reported to start with forming L-phenylalanine and tyrosine precursors via the shikimic acid pathway. The structure-activity relationship of ECH has shown that various functional groups in the structure, particularly phenolic hydroxyl groups, are crucial for antioxidant activities. Similarly, in silico studies have revealed that ECH binds to different receptors, like Kelch-like ECH-associated protein 1 (Keap1), receptor for advanced glycation end products (RAGE), etc., to affect various pharmacological activities. The ECH contents in the reported plants often own these multifaceted properties, highlighting their importance in clinical research. Evident from its therapeutic efficacy, there is a huge potential for a comprehensive understanding of the mechanisms of actions of ECH, which underscores the need for more research in this area. Thus, this review is a compendium of the latest literature to analyse the existing knowledge on ECH, encompassing its distribution, traditional uses, extraction, chemical constituents, biosynthesis, pharmacological activities, structure-activity relationship, and in silico studies, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.