Recent advances in the biosynthesis, structure–activity relationships, formulations, pharmacology, and clinical trials of fisetin

Abstract

Fisetin is one of the most popular flavonoids found in vegetables and fruits with several health benefits such as antidiabetic, anticancer, and anti-inflammatory activities. Biotechnology or chemosynthesis tools were used for the synthesis of fisetin and its analogs to improve their yield and efficacy. Structure activity relationships (SARs) revealed that the aromatic hydroxyl groups especially the 3,4-dihydroxylation at ring B were crucial for fisetin biological activities, whereas substitution of several hydroxyl groups in fisetin appeared to impact its original effects. The ongoing or upcoming clinical trials containing fisetin are applied in drugs and dietary supplements. Noteworthily, fisetin has been successfully incorporated into nutraceuticals in the market. Furthermore, the delivery system of fisetin-loaded nanocochleates showed the best bioavailability compared to other formulations. This review presents the latest research progress of fisetin on its synthesis, structure-activity relationships, pharmacokinetics, biological activities, and underlying mechanisms, bioavailability, delivery systems, and clinical trials to provide a comprehensive insight into the research and application of this valuable natural compound.

Preparation and characterization of garlic polysaccharide-Zn (II) complexes and their bioactivities as a zinc supplement in Zn-deficient mice

“…zinc sulfate and zinc nitrate), with extremely low bioavailability and severe side effects on the gastrointestinal tract; 2) improved inorganic zinc salts (zinc gluconate and zinc citrate), with improved bioavailability and decreased severe side effects, but still affecting gastrointestinal digestion; 3) biological zinc, with significant bioavailability and no toxicity and hazards, including polysaccharide chelated zinc, protein chelated zinc, polypeptide chelated zinc ( Caetano-Silva, Netto, Bertoldo-Pacheco, Alegría, & Cilla, 2021 ). Compared with inorganic zinc, many natural substances may have the potential to be used ( Zhong, Farag, Chen, He, & Xiao, 2022 ), natural polysaccharide-zinc complex has significant advantages as a biological zinc supplement. Prepared Athelia rolfsii exopolysaccharide-zinc complexes were more effective than inorganic and organic zinc supplements in treating zinc deficiency and improving antioxidant activities in vivo ( Dong, Li, & Min, 2018 ).…”

Utilization of Diaphragma juglandis extract as a natural antioxidant for improving the oxidative stability of soybean oil during deep frying

“…The contents of other fractions were low, ranging from 0.27 to 85.46 μg/g dry weight. As common bioactive polyphenols, these compounds are widely found in fruits and vegetables ( Liu et al, 2019 , Zhong et al, 2022 ). Previous studies demonstrated that polyphenols could offer good protection of oils against oxidative degradation during frying and storage ( Li et al, 2021 , Wu et al, 2019 ).…”

Anti-inflammatory activity of flavonols via inhibiting MAPK and NF-κB signaling pathways in RAW264.7 macrophages

“…3 ). The structure-activity relationship (SAR) could reveal the antioxidant characteristics of these structurally related flavonols ( Zhong et al, 2022 ). The anti-oxidant potencies of dietary flavonoids are reported to be closely associated with the site and number of hydroxylations on the A and B rings.…”