The Therapeutic Effects and Mechanisms of Quercetin on Metabolic Diseases: Pharmacological Data and Clinical Evidence - PubMed (original) (raw)

Review

. 2021 Jun 23:2021:6678662.

doi: 10.1155/2021/6678662. eCollection 2021.

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Review

The Therapeutic Effects and Mechanisms of Quercetin on Metabolic Diseases: Pharmacological Data and Clinical Evidence

Huan Yi et al. Oxid Med Cell Longev. 2021.

Abstract

Metabolic diseases have become major public health issues worldwide. Searching for effective drugs for treating metabolic diseases from natural compounds has attracted increasing attention. Quercetin, an important natural flavonoid, is extensively present in fruits, vegetables, and medicinal plants. Due to its potentially beneficial effects on human health, quercetin has become the focus of medicinal attention. In this review, we provide a timely and comprehensive summary of the pharmacological advances and clinical data of quercetin in the treatment of three metabolic diseases, including diabetes, hyperlipidemia, and nonalcoholic fatty liver disease (NAFLD). Accumulating evidences obtained from animal experiments prove that quercetin has beneficial effects on these three diseases. It can promote insulin secretion, improve insulin resistance, lower blood lipid levels, inhibit inflammation and oxidative stress, alleviate hepatic lipid accumulation, and regulate gut microbiota disorders in animal models. However, human clinical studies on the effects of quercetin in diabetes, hyperlipidemia, and NAFLD remain scarce. More clinical trials with larger sample sizes and longer trial durations are needed to verify its true effectiveness in human subjects. Moreover, another important issue that needs to be resolved in future research is to improve the bioavailability of quercetin. This review may provide valuable information for the basic research, drug development, and clinical application of quercetin in the treatment of metabolic diseases.

Copyright © 2021 Huan Yi et al.

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Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this article.

Figures

Figure 1

Figure 1

The chemical structure of quercetin.

Figure 2

Figure 2

Quercetin can improve diabetes, hyperlipidemia, and NAFLD by modulating the marked targets. ↑ indicates increase and ↓ indicates decrease; → indicates stimulatory effect and ⊣ indicates inhibitory effect. In the upper right corner, a represents the effect of quercetin on diabetes, b represents the effect of quercetin on hyperlipidemia, and c represents the effect of quercetin on NAFLD. ABCA1: ATP-binding cassette transporter A1; Abcg5: ATP-binding cassette subfamily G member 5; Acaca: acetyl-coenzyme A carboxylase α; Akt: protein kinase B; Aldh1b1: aldehyde dehydrogenase 1 family member B1; AMPK: adenosine monophosphate-activated protein kinase; Apoa4: apolipoprotein A-IV; ATF-6_α_: activating transcriptional factor 6_α_; CAT: catalase; CD36: cluster of differentiation 36; cGMP: cyclic 3,5-guanosine monophosphate; CHOP: CCAAT/enhancer-binding protein homologous protein; CYP2E1: cytochrome P450 2E1; eNOS: endothelial nitric oxide synthase; FABP1: fatty acid-binding protein 1; FAS: fatty acid synthase; FAT/CD36: fatty acid translocase CD36; FATP5: fatty acid transport protein 5; FFAs: free fatty acids; FOXA1: forkhead box protein A1; FXR1: farnesoid X receptor 1; FAS: fatty acid synthase; FBPase: fructose-bisphosphatase; Fnta: farnesyltransferase CAAX box α; G6Pase: glucose-6-phosphate; G3PDH: glycerol-3-phosphate dehydrogenase; G6PDH: glucose-6-phosphate dehydrogenase; GCK: glucokinase; GLUT4: glucose transporter type 4; Gpam: glycerol-3-phosphate acyltransferase mitochondrial; GR: glutathione reductase; GRP78: glucose regulated protein 78; GSH: glutathione; GSH-Px: glutathione peroxidase; GST: glutathione-S-transferase; HDL: high-density lipoprotein; Hmgb1: high-mobility group box 1; HMG-CoA reductase: 3-hydroxy-3-methylglutaryl-CoA reductase; Ikk-β: inhibitor κ_B kinase β; IL-1_β: interleukin-1_β_; IL-6: interleukin-6; iNOS: inducible nitric oxide synthase; InsR: insulin receptor; IRE1_α_: inositol-requiring transmembrane kinase/endoribonuclease 1_α_; IRS-1: insulin receptor substrate-1; JNK: c-Jun-NH2 terminal kinase; LDL: low-density lipoprotein; LXR_α_: liver X receptor α; MDA: malondialdehyde; MPO: myeloperoxidase; MSR1: macrophage scavenger receptor 1; NF-κ_B: nuclear factor-κ_B; NO: nitric oxide; NPC1L1: Niemann-Pick C1-like 1; OPN: osteopontin; ox-LDL: oxidized low-density lipoprotein; P38 MAPK: P38 mitogen-activated protein kinases; PEPCK: phosphoenolpyruvate carboxylase; PERK: protein kinase-like endoplasmic reticulum kinase; PI3K: phosphatidyl inositol 3 kinase; Pon1: paraoxonase1; PPAR_α: peroxisome proliferator-activated receptor α; PPAR_γ: peroxisome proliferator-activated receptor γ; Ptgs2: cyclooxygenase-2; PTP-1B: phosphatase-1B; Ser9: phosphorylated glycogen synthase kinase 3_β_; SHP: small heterodimer partner; SIRT1: sirtuin 1; SOCS3: suppressor of cytokine signaling 3; SOD: superoxide dismutase; SREBP-1c: sterol regulatory element-binding protein-1c; TBARS: thiobarbituric acid-reactive substances; TC: total cholesterol; TG: triglyceride; TGR5: Takeda G protein-coupled receptor 5; TLR-4: Toll-like receptor-4; TNFR: tumor necrosis factor receptor; TNF-α: tumor necrosis factor-α; VEGF: vascular endothelial growth factor; VEGFR2: vascular endothelial growth factor receptor 2; VLDL: very low-density lipoprotein; XBP1s: X-box-binding protein 1.

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