Allium Flavonols: Health Benefits, Molecular Targets, and Bioavailability
Abstract
:1. Introduction
2. Flavonoids in Allium: Structural Properties
Flavonols
3. Health Benefits of Allium Flavonols
3.1. Anticancer Effects
3.2. Anti-Obesity and Hypolipidemic Effects
3.3. Anti-Diabetic Effects
3.4. Cardio-Protective Effects
3.5. Neuroprotective Effects
3.6. Antimicrobial Effects
3.7. Other Health Benefits
4. Molecular Mechanisms Underlying the Physiological Effects of Flavonols
5. Bioavailability of Allium-Derived Flavonols
6. Stability During Domestic and Technological Processing
7. Food Fortification
8. Future Perspectives and Limitations
9. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Common Name | Scientific Name | Plant Part | Total Flavonol Content | References |
---|---|---|---|---|
Red Onion | A. cepa | Bulb | 415-1917 mg/kg F.W. | [22] |
Yellow onion | A. cepa | Bulb | 270-1187 mg/kg F.W. | [22] |
White onion | A. cepa | Bulb | 7 mg/kg F.W. | [23] |
Italian shallot | A. ascalonicum | Bulb | 1023 mg/kg F.W. | [23] |
French shallot | A. ascalonicum | Bulb | 1167 mg/kg F.W. | [23] |
Leek | A. porrum | Bulb | 246 mg/kg F.W. | [24] |
Garlic | A. sativum | Cloves | 16.19 mg/kg D.W. | [25] |
Ramson bear’s garlic | A. ursinum | Green leaves | 1856.31 mg/100 g D.W. | [26] |
Yellow leaves | 2362.96 mg/100 D.W. | |||
Stalks | 206.07 mg/100 g D.W. | |||
Seeds | 73.14 mg/100 g D.W. | |||
Ramps | A. tricoccum | Leaves | 11.81 mg/g D.W. | [27] |
Stem | 0.0382 mg/g D.W. | |||
Bulb | -- | |||
Chinese chives | A. odorum (A. tuberosum) | Leaves | 160 mg/kg D.W. | [28] |
Welsh onion | A. fistulosum | Leaves | 2329 mg/kg D.W. | [28] |
Yellow flowered garlic | A. flavum subsp. flavum | Aerial parts | 44-264 mg/g D.W. | [29] |
Bulb | 0.77-832 µg/g D.W. | |||
Keeled garlic | A. carinatum | Whole plant | 11.14 mg/g D.W. | [30] |
S. No. | Flavonol Aglycones/Glycosides | Plant Species | References |
---|---|---|---|
1 | Quercetin (Que) | A. cepa | [22] |
2 | Que-3-O-glucoside | A. cepa, A. sativum, A. flavum, A. macrostemon | [16,22,29,37,38] |
3 | Que-4′-O-glucoside | A. cepa | [16] |
4 | Que-3,4′-O-diglucoside | A. cepa, A. tuberosum | [16,22,36] |
5 | Que-3-O-rutinoside | A. cepa, A. chinense | [22,39] |
6 | Que-7-O-glucoside | A. cepa | [22] |
7 | Que-7-O-rhamnoside | A. cepa | [22] |
8 | Que-7,4′-O-diglucoside | A. cepa | [22] |
9 | Que-3,7-O-diglucoside | A. cepa | [22] |
10 | Que-3,7,4′-O-triglucoside | A. cepa | [16,22] |
11 | Que-3-O-rhamnoside | A. cepa, A. fistulosum | [22] |
12 | Que dimer | A. cepa | [22] |
13 | 4′-Glucoside of que dimer | A. cepa | [22] |
14 | Que trimer | A. cepa | [22] |
15 | Quercetin sophoroside glucuronide | A. tricoccum | [27] |
16 | Que hexoside glucuronide | A. tricoccum | [27] |
17 | Que sophoroside | A. tuberosum | [40] |
18 | Que-3-O-β-d-xylopyranoside | A. sativum | [37] |
19 | Kaempferol (Kae) | A. cepa, A. tuberosum | [36,41,42] |
20 | Kae-3-O-glucoside | A. cepa, A. sativum, A. flavum, A. ursinum, A. macrostemon | [22,29,37,38,43] |
21 | Kae-4′-O-glucoside | A. cepa | [22] |
22 | Kae-7,4′-O-diglucoside | A. cepa | [22] |
23 | Kae-7-O-glucoside | A. triquetrum | [44] |
24 | Kae-3,4′-O-diglucoside | A. cepa, A. tuberosum, A. macrostemon | [22,36,38] |
25 | Kae-3,7-di-O-rhamnoside | A. roseum | [45] |
26 | Kae-3,7-di-O-glucoside | A. macrostemon | [38] |
27 | Kae-3-O-glucuronide-7-O-rhamnosylglucoside | A. roseum | [46] |
28 | Kae-3-O-rutinoside | A. roseum, A. tuberosum, A. triquetrum | [36,44,46] |
29 | Kae-3-O-glucoside-7-O- glucuronide | A. roseum | [46] |
30 | Kae-7-O-glucuronide | A. roseum | [46] |
31 | Kae-3-O-glucuronide | A. roseum | [46] |
32 | Kae-7-O-(6”-malonyl)-glucoside | A. roseum | [46] |
33 | Kae-3-O-sophoroside | A. tuberosum, A. tricoccum | [27,36] |
34 | Kae-3-O-β-d-glucosyl-(1 2)-O-α-L-xylopyranoside | A. tuberosum | [36] |
35 | 3-O-β-d-(2-O-feruloyl)-glucosyl-7,4’-di-O-β-d-glucosylkaempferol | A. tuberosum | [36] |
36 | 3-O-β-sophorosyl-7-O-β-d-(2-O-feruloyl)-glucosylkaempferol | A. tuberosum | [36] |
37 | Kae-3-O-neohesperidoside | A. ursinum | [43] |
38 | Kae-3-O-flneohesperidoside-7-O-[2-O-(trans-p-coumaroyl)]-fl-d-glucopyranoside, | A. ursinum | [43] |
39 | Kae-3-O-fl-neohesperidoside-7-O-[2-O-(trans-feruloyl)]-fl-d-glucopyranoside | A. ursinum | [43] |
40 | Kae-3-O-fl-neohesperidoside-7-O-[2-O-(trans-p-coumaroyl)-3-O-flD-glucopyranosyl-1-fl-d-glucopyranoside | A. ursinum | [43] |
41 | Kae-3-O-[2-O-(trans-p-coumaryl)-β-d-galactopyranosyl]-(1→4)-O-β-d-glucopyranoside | A. porrum | [47] |
42 | Kae-3-O-[2-O-(trans-p-coumaryl)-β-d-glucopyranosyl]-(1→6)-O-β-d-glucopyranoside | A. porrum,A. triquetrum | [44,47] |
43 | Kae-3-O-(2-O-trans-p-feruloyl)glucoside | A. triquetrum | [44] |
44 | 8-hydroxykaempferol 8-O-glucoside | A. triquetrum | [44] |
45 | Kae-3-O-[2-O-(trans-p-coumaroyl)-3-O-β-d-glucopyranosyl]-β-d-glucopyranoside | A. triquetrum | [44] |
46 | Isorhamnetin (Iso) | A. cepa | [48] |
47 | Iso-4′-O-glucoside | A. cepa | [16,22] |
48 | Iso-3-O-glucoside | A. cepa, A. vineale, A. macrostemon | [22,38,49] |
49 | Iso-3,4′-O-diglucoside | A. cepa; A. tuberosum | [16,22,40] |
50 | Iso-4′-O-galactoside | A. cepa | [16] |
51 | Myricetin | A. cepa | [41] |
52 | Fisetin | A. cepa | [41] |
53 | Morin | A. cepa | [50] |
Plant Species (Part Used) | Major Identified Flavonol(s) | Study System, Dose, and Duration | Activity | Biological Effects | Molecular Targets | References |
---|---|---|---|---|---|---|
A. cepa (peel) | Quercetin, quercitrin, kaempferol, and morin | In vitro: HT–29, 50–250 µg/mL for 24 h | Anticancer | - Inhibits proliferation - Reduces oxidative stress - Reduces inflammation | ↑ LDH release; ↓ HO-1; ↓ TNF-α; ↓ GSTs, GSTM1, GSTT1, and GSTP1 | [50] |
A. cepa (bulb) | Quercetin 3,7,4′-triglucoside, quercetin 7,4′- diglucoside, quercetin 3,4′-diglucoside, isorhamnetin 3,4′-diglucoside, quercetin 3-glucoside, quercetin 4′-glucoside, isorhamnetin 4′-galactoside, and isorhamnetin 4′-glucoside | In vitro: THP-1, K562, and U937, 20–100 µg/mL for 48 h | Anticancer | - Inhibits cell proliferation - Induces apoptosis | ↓ Caspase-3, -8 and -9 activity; ↑ Bid; ↓ Bcl-xL; ↑ DR5 TRAIL; ↓ Survivin; ↓ cIAP-1; ↓ PI3K/Akt | [16] |
A. cepa (bulb) | -do- | In vitro: AGS, 1–100 µg/mL for 48 h | Anticancer | - Inhibits cell proliferation - Induces apoptosis | ↑ PAPR; ↓ Procaspase-3; ↓ Bcl-2; ↑ Bid; ↑ Bax; ↑ p53; ↓ MMP (Δ Ψm); ↓ PI3K/Akt | [54] |
A. cepa (scale) | Quercetin and quercetin-4′-β-O-d-glucoside | In vivo: Atypical prostatic hyperplasia model of Wistar rats, 75, 150, or 300 mg/kg/d orally for 30 d | Anticancer | - Inhibits proliferation - Induces apoptosis - Reduces inflammation | ↓ IL-6; ↓ IL-8; ↓ TNF-α; ↓ IGF-1 | [14] |
A. cepa (solid waste) | Quercetin, quercetin-3,4′-O-diglucoside, and quercetin-4′-O-monoglucoside | In vitro: ACHN, Panc 1, Calu 1, H460, and HCT 116, 1–5 mg/mL for 24 h | Anticancer | - Inhibits proliferation | n.r. | [67] |
A. cepa var. proliferum (stems) | Isorhamnetin and kaempferol | In vitro: HepG2, 20–100 mg/mL for 72 h | Anticancer | - Inhibits proliferation - Induces apoptosis | n.r. | [68] |
A. cepa (n.r.) | Rutin | In vivo: Hyperlipidemia colon tumor model of BALB/C nu/nu mice, 100-300 mg/kg/d intragastrically for 3 wk | Antihyperlipidemic and anticancer | - Improves lipid metabolism - Inhibits tumor proliferation | n.r. | [69] |
A. cepa (peel) | Quercetin | In vivo: HFD-fed SD rats, 0.2% in diet for 8 wk | Antiobesity | - Reduces mesenteric fat | ↑ Adiponectin; ↓ PPAR-γ | [61] |
A. cepa (peel) | Quercetin | In vitro: 3T3-L1, 25–100 µg/mL for 24 h In vivo: HFD-fed SD rats, 0.36% or 0.72% in diet for 8 wk | Antiobesity | - Attenuates lipid metabolism - Reduces body weight - Reduces adipose tissue - Improves lipid metabolism | ↓ AP-2; ↑ CPT-1α; ↑ FABP4; ↓ PPAR-γ ↓ C/EBP-α; ↓ FAS; ↓ ACC ↑ CPT-1α; ↑ UCP-1 | [62] |
A. cepa (peel) | Quercetin | In vitro: 3T3-L1, 1–4 μg/mL for 24 h | Antiobesity | - Reduces lipid accumulation - Reduces adipogenesis - Induces lipolysis | ↓ GPDH activity; ↓ PPAR-γ; ↓ C/EBP-α ↓ AP2; ↓ LPL; ↑ ATGL; ↑ HSL | [63] |
A. cepa (peel) | Quercetin and isoquercetin | In vitro: 3T3-L1, 50–150 μg/mL for 11 d (on day 5, 7, and 9) In vivo: HFD-fed C57BL/6 mice, 0.5% in diet for 8 wk | Antiobesity | - Induces adipocyte browning - Reduces adipogenesis - Reduces lipogensis | ↓ PPAR-γ; ↓ ACC; ↓ FAS; ↑ PRDM16; ↑ UCP1; ↓ FGF21; ↑ TBX1; ↓ CIDEA; ↑ PGC1α; ↑ CPT1-α ↓ ACC; ↑ PRDM16; ↑ UCP1; ↑ FGF21; ↑ CIDEA; ↑ PGC1α | [64] |
A. cepa (peel) | Quercetin | Randomized, double-blind, placebo-controlled study: Obese women, 100 mg/d (50 mg bis in die) orally for 12 wk | Antiobesity | - Reduces waist and hip circumferences - Reduces oxidative stress | ↓ ROS; ↑ SOD activity | [70] |
A. fistulosum (bulbs and roots) | Quercetin | In vivo: HFD-obese C57BL/6 J mice, 100 mg/kg/d orally for 6 wk | Antiobesity | - Reduces body weight - Improves lipid and glucose metabolism | ↑ AMPK (AMPKα1 and AMPKα2); ↑ Adiponectin; ↑ UCP2; ↓ PPAR-γ | [65] |
A. cepa (peel) | Quercetin (Q) and quercetin monoglucoside (Qmg) | In vivo: HFD-fed Wistar rats, 0.21% (Q) or 0.36% (Q+Qmg) in diet for 4 wk | Antiobesity | - Reduces oxidative stress - Improves lipid metabolism - Increases gut microbial enzyme activity | n.r. | [71] |
A. chinense (bulbs) | Quercetin and rutin | In vivo: HFD-fed Wistar rats, 0.09 or 0.18% per day orally for 12 wk | Anti-hyperlipidemic | - Improves lipid metabolism | n.r. | [39] |
A. cepa (skin) | Quercetin | In vivo: OGTT in SD rats, 0–500 mg/kg, single oral dose | Antidiabetic | - Reduces post-prandial blood glucose - Inhibits carbohydrate hydrolases (sucrase and maltase) | n.r. | [72] |
A. cepa (peel) | Quercetin | In vivo: HFD/STZ-diabetic SD rats, 0.5 or 1% in diet for 8 wk | Antidiabetic and antioxidant | - Increases IAUC - Reduces blood glucose - Reduces fasting blood glucose - Increases glycogen levels - Reduces oxidative stress - Reduces inflammation | ↑ INSR and GLUT4 ↑ SOD activity; ↓ MDA level; ↓ IL-6 | [73] |
A. cepa (bulb) | Kaempferol-3-O-β-d-6{p- coumaroyl} glucopyranoside | In vivo: Alloxan-diabetic Wistar rats, 25 mg/kg single oral dose | Antidiabetic | - Reduces blood glucose | n.r. | [74] |
A. cepa (n.r.) | Quercetin and quercetin glycosides | In vitro: Xenopus laevis oocytes, 1–15 mg/mL for 30 min In vivo: OGTT in HFD fed C57BL/6N mice, 14 mg single oral dose | Antidiabetic | - Reduces glucose uptake | ↓ SGLT1 | [75] |
A. tuberosum (leaves) | Kaempferol glycoside derivatives | In vivo: Alloxan-diabetic Wistar rats, 100-400 mg/kg/d orally for 30 d | Antidiabetic | - Reduces oxidative stress - Reduces fasting blood glucose - Improves lipid metabolism | ↑ GSH; ↑ SOD and CAT activities | [36] |
A. tuberosum (leaves) | Kaempferol glycoside | In vivo: HFD/STZ-diabetic Wistar rats, 100 or 400 mg/kg/d orally for 40 d | Antidiabetic | - Reduces renal oxidative stress - Reduces inflammation - Reduces blood glucose - Improves renal and serum lipid profiles - Reduces serum creatinine - Reduces blood urea nitrogen - Reduces urinary albumin levels | ↑ GSH; ↑ CAT and SOD activities; ↓ TGF-β1; ↓ TNF-α; ↓ IL-6; ↓ IL-1β | [76] |
A. cepa (peel) | Quercetin | Randomized, double-blind, placebo-controlled parallel design: Healthy smokers, 100 mg/d for 10 wk | Cardioprotective | - Lowers blood pressure - Improves lipid profiles - Lowers blood glucose | ⇔ Inflammatory markers | [77] |
A. cepa (outer skin) | Quercetin, quercetin 4′-glucoside, and quercetin 3,4′-diglucoside | In vivo: HFD-fed Wistar rats, 5% in diet for 18 wk | Cardioprotective | - Atherogenic index - Lowers incremental elastic modulus | n.r. | [78] |
A. cepa (peel) | Quercetin | In vitro: HUVEC, 50 and 100 μg/mL for 1 h In vivo: SD rats, 2 or 10 mg/d orally for 6 wk | Cardioprotective | - Delays arterial thrombus formation | ↓ Tissue factor; ↓ JNK and ERK (MAPK) | [79] |
A. cepa (peel) | Quercetin | Epidemiologic study: Healthy men, 4.3 g/d orally for 30 d | Cardioprotective | - Improves postprandial flow-mediated dilation | n.r. | [80] |
A. cepa (peel) | Quercetin | Randomized double-blind, placebo-controlled prospective trial: Healthy overweight and obese individuals, 100 mg/d (50 mg twice daily) orally for 12 wk | Cardioprotective | - Improves flow-mediated dilation - Improves circulating endothelial progenitor cell count | n.r. | [81] |
A. cepa(peel) | Quercetin quercetin hexoside 1, quercetin hexoside 2, quercetin dihexoside, methylquercetin hexoside, kaempferol, and methyl quercetin | Randomized double-blind, placebo-controlled prospective trial: Overweight-to-obese patients with (pre-)hypertension, 162 mg/d for 6 wk | Cardioprotective | - Lowers systolic ambulatory blood pressure | ⇔ Biomarkers of inflammation and endothelial function | [82] |
A. cepa (peel) | Quercetin | In vitro: SD rat platelets, 50–500 μg/mL for 3 min | Cardioprotective | - Inhibits platelet aggregation - Reduces oxidative stress | ↓ TXA2 production; ↓ TXAS and COX-1 activity; ↓ Intracellular Ca2+; ↑ cAMP | [83] |
A. cepa (tunic) | Quercetin, quercitrin, isoquercitrin, rutin, and kaempferol | In vivo: Wistar rats, 10 mg/kg/d, orally for 14 d | Cardioprotective | - Lowers blood pressure parameters - Reduces oxidative stress | ↑ SOD and CAT activity; ↑ GSH levels | [42] |
A. cepa (bulb) | Quercetin, quercetin-3,4′-O-diglucoside, and quercetin-4′-O-monoglucoside | In vitro: SD Rat platelet-rich plasma, 1–5 mg/mL for 5 min | Cardioprotective | - Inhibits platelet aggregation | n.r. | [84] |
A. flavum and A. carinatum (whole plant) | Quercetin, kaempferol, isorhamnetin, rutin, quercetin 3-O-glucoside, and kaempferol-3-O-glucoside, | In vitro: A549 and HepG215-125 µg/mL for 24 h In vivo: Doxorubicin-induced toxicity in zebrafish embryos, 1–60 μg/mL for 96 h | AnticancerCardioprotective and myeloprotective | - Reduces oxidative stress - Reduces cardiovascular and morphological abnormalities - Anti-angiogenesis | ↑ SOD and CAT activity | [30] |
A. cepa (bulb) | Quercetin | In vivo: Ischemia/reperfusion induced injury in gerbil hippocampus, 50 or 100 mg/kg/d orally for 15 d | Neuroprotection | - Reduces lipid peroxidation - Attenuates activations of astrocytes and microglia | ↓ 4-hydroxy-2-nonenal | [85] |
A. victorialis (leaves) | Kaempferol and quercetin glycosides | In vitro: LPS-activated BV-2 cells, 20 μM for 24 h | Neuroprotection | - Anti-inflammatory effects | ↓ NO production | [86] |
A. cepa (bulb) | Quercetin | In vitro: glutamate-mediated oxidative stress in HT22 cells, 1–25 µM for 12 h | Neuroprotection | - Reduces apoptosis | ↓ ROS; ↓ Ca2+ influx; ↑ MMP (ΔΨm); ↓ Bid and Bax ↓ MAPKs (ERK, JNK, and p38) | [87] |
A. cepa (bulb) | Quercetin | In vitro: BSO-induced oxidative stress in mouse neocortices, 1–10 mg/mL, for 30 min | Neuroprotection | - Reduces oxidative stress | ↓ ROS; ↓ LDH release; ↑ ERK1/2; ↓ p38MAPK; ↓ PKC-ε | [88] |
A. cepa (bulb) | Quercetin | In vivo: AlCl3 induced injury in Swiss albino mice, 50, 100 or 200 mg/kg/d orally for 60 d | Neuroprotection | - Improves muscle coordination and memory deficits - Reduces oxidative stress - Reduces inflammation | Acts as PPARγ agonist ↓ ROS; ↑ GSH, CAT ↓ AChE | [89] |
A. cepa (bulb) | Quercetin 3,4′-O-β-d-diglucoside | In vitro: HSP cells under nutrient deprived condition, 0.1–500 µM for 20 h | Neuroprotection | - Reduces apoptosis - Alters cell morphology | ↑ Ki-67; ↓ Bax/Bcl-2; ↑ Adhesion molecules (pan-cadherin and focal adhesion kinase) | [90] |
A. cepa (outer scale) | Quercetin | In vivo: Cerebral ischemia/reperfusion-induced injury in Swiss Albino mice, 85 mg/kg/d for 7 d | Neuroprotection | - Improves cognitive/sensorimotor functions - Reduces cerebral infarct size - Reduces brain oxidative stress | ↑ GSH; ↑ SOD activity ↑ TBARS | [91] |
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Kothari, D.; Lee, W.-D.; Kim, S.-K. Allium Flavonols: Health Benefits, Molecular Targets, and Bioavailability. Antioxidants 2020, 9, 888. https://doi.org/10.3390/antiox9090888
Kothari D, Lee W-D, Kim S-K. Allium Flavonols: Health Benefits, Molecular Targets, and Bioavailability. Antioxidants. 2020; 9(9):888. https://doi.org/10.3390/antiox9090888
Chicago/Turabian StyleKothari, Damini, Woo-Do Lee, and Soo-Ki Kim. 2020. "Allium Flavonols: Health Benefits, Molecular Targets, and Bioavailability" Antioxidants 9, no. 9: 888. https://doi.org/10.3390/antiox9090888