Contents lists available at ScienceDirect Phytochemistry journal homepage: www.elsevier.com/locate/phytochem Review An insight into the health-promoting effects of taxifolin (dihydroquercetin) Christudas Sunil, Baojun Xu * Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, China ARTICLE INFO Keywords: Flavonoids Taxifolin Dihydroquercetin ABSTRACT Taxifolin (3,5,7,3,4-pentahydroxy flavanone or dihydroquercetin) is a flavonoid commonly found in onion, milk thistle, French maritime pine bark and Douglas fir bark. It is also used in various commercial preparations like Legalon™, Pycnogenol ® , and Venoruton ® . This review focuses on taxifolin’s biological activities and related molecular mechanisms. Published literatures were gathered from the scientific databases like PubMed, SciFinder, ScienceDirect, Wiley Online Library, Google Scholar, and Web of Science up to January 2019. Taxifolin showed promising pharmacological activities in the management of inflammation, tumors, microbial infections, oxidative stress, cardiovascular, and liver disorders. The anti-cancer activity was more prominent than other activities evaluated using different in vitro and in vivo models. Further research on the pharmaco- kinetics, in-depth molecular mechanisms, and safety profile using well-designed randomized clinical studies are suggested to develop a drug for human use. 1. Introduction Taxifolin (3,5,7,3,4-pentahydroxy flavanone or dihydroquercetin) is a flavonoid commonly found in milk thistle (Wallace et al., 2005), onions (Slimestad et al., 2007), Douglas fir bark (Kiehlmann and Edmond, 1995) and French maritime pine bark (Rohdewald, 2002). It is also commonly found in many plants. As a single compound it is used rarely but it is found in different preparations like silymarin (Legalon™), Pycnogenol ® and Venoruton ® (Blumenthal and Busse, 1998) along with silybin A, silybin B, isosilybin A, isosilybin B, silychristin, isosilychristin and silydianin (Ding et al., 2001). Taxifolin is an important component of dietary supplements and used as functional food having rich anti- oxidant. It was first isolated from Douglas fir bark (Pseudotsuga taxifolia (Lindl.) Britton) and later Dahurian and Siberian larch (Larix sibirica Ledeb. and Larix gmelinii (Rupr.) Kuzen.), syn Larix dahurica Turcz. ex Trautv. (Pinaceae) (Pew, 1948). It exists in both trans - and cis - forms (Nifant'ev et al., 2006), soluble in water-alcohol solutions and polar solvents. (+) trans-Dihydroquercetin oxidizes more actively, donates hydrogen atoms and form the oxidation product quercetin (2-(3,4-di- hydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4- one) (Rogozhin and Peretolchin, 2009). The structure-activity relationship of both com- pounds differs in the presence/absence of a C2, C3-double bond in the C-ring (Silva et al., 2002). As a therapeutic agent, taxifolin attracts more and more interest to the researchers. Thereby this review aims to summarize the various pharmacological effects with their mechanism of action (Table 1). https://doi.org/10.1016/j.phytochem.2019.112066 Received 1 May 2019; Received in revised form 7 July 2019; Accepted 11 July 2019 Abbreviations: ABTS, 2,2′-azino-di-(3-ethylbenzthiazoline sulfonic acid); ACAT, Acyl CoA: cholesterol acyltransferase; ActD, Actinomycin D; AKT, AKT, serine/ threonine kinase 1; Akt, Protein kinase B; ARE, Antioxidant –response element; BACE1, β-site APP cleaving enzyme 1; C99, C-terminal fragment β; CDKs, Cyclin- dependent kinases; CHOP, C/EBP homologous protein; COX, Cyclooxygenase; DGAT, Diacylglycerol acyltransferase; DMPD, N,N-dimethyl-ρ-phenylenediamine; DPPH, 2,2-diphenyl-1-picrylhydrazyl; EGFR, Epidermal growth factor receptor; eIf2α, The α subunit of eukaryotic initiation factor 2; ER, Endoplasmic reticulum; EWS, Ewing's sarcoma; GCLM, glutamate–cysteine ligase modifier; GRP78, Glucose-regulated protein 78 kDa; GSTA2, Glutathione S-transferase A2; GSTM1, Glutathione S-transferase M1; HDL, High-density lipoprotein; HMG-CoA reductase, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase; HO-1, Heme oxygenase-1; ICAM-1, Intercellular adhesion molecule-1; IFN-γ, Interferon gamma; IL, Interleukin; iNOS, Inducible-nitric oxide synthase; JAK2, Janus kinase; JNK, c-JunN- terminal kinase; Keap1, Kelch-like ECH-associating protein 1; LDL, Low-density lipoprotein; MIC, Minimum inhibitory concentration; MPO, Myeloperoxidase; MTP, Microsomal triglyceride transfer protein; NF-κB, Nuclear factor-kappa B; NQO1, NAD(P)H quinine oxidoreductase 1; Nrf2, NF-E2 p45-related factor 2; PARP, Poly (ADP-ribose) polymerase; PERK, Pancreatic ER kinase-like; PGE2, Prostaglandin E2; PI3K, Phosphoinositide 3-kinase; RANKL, Receptor activator of nuclear factor-;κB ligand; ROS, Reactive oxygen species; SIRT1, Sirtuin 1; SKP-;2, S-;phase kinase associated protein 2; SOD2, Superoxide Dismutase 2; STAT3, Signal transducer and activator of transcription 3; SUV, Solar-UV; TG, Triglycerides; TNF-α, Tumor necrosis factor-alpha; TXNRD1, Thioredoxin reductase 1 * Corresponding author. 2000, Jintong Road, Tangjiawan, Zhuhai, Guangdong, 519087, China. E-mail address: baojunxu@uic.edu.hk (B. Xu). Phytochemistry 166 (2019) 112066 0031-9422/ © 2019 Elsevier Ltd. All rights reserved. T