Regimen Lab Skincare Encyclopedia ?

Quercetin

V 1.0 last edited 05 May 2022

Ingredient Profile

Common Name: Quercetin
INCI: Quercetin
Source: Citrus, Vegetables, Grains

kligman ingredient evaluation

Penetration:
  • ROS inhibitor
  • NF-kB, IL inhibitor
  • Anti-MMP activity
Biochemical Mechanism: Antioxidant, Anti-inflammatory, Soothing, Barrier Repair, Anti-aging
Level of Evidence: Level B, Good Quality Evidence

Regimen's Take

Quercetin is a multifunctional antioxidant that shows great soothing properties in the skin. We use it in our Vitamin X serum as it has synergistic effect with other antioxidants. Like most antioxidants, it can turn into a pro-oxidant without the support of multiple antioxidants in a formulation. The main drawback to Quercetin is that it is highlighter yellow and it stains your face when used in its pure form.

TLDR

  • It functions as a potent antioxidant with anti-inflammatory, barrier repair and anti-aging properties
  • It has synergistic effects with Ascorbate
  • It also shows great wound repair ability

What is Quercetin?

Quercetin is one of the most abundant and widely distributed natural flavonoids found in fruits and vegetables. It has been shown to exhibit superior antioxidant activity among other flavonoids via scavenging oxygen radicals, protecting lipids against peroxidation, and chelating metal ions. Similar to other plant-derived polyphenolic compounds, its anti-inflammatory action mainly involves the inhibition of cytokine production such as tumor necrosis factor (TNF)-α and interleukins (IL) such as IL-8. It is also reported to contain anti-nociceptive effects that could alleviate inflammatory-related pain. While the powerful cytoprotective effects of quercetin make it a useful active in anti-aging and rejuvenation skincare, a challenge with it in the formulation process is it has poor water solubility, intense colour and skin permeability. Some of the strategies suggested for improving its permeability include the use of prodrugs, liposomes, and novel vesicular systems. 

What are the benefits of Quercetin?

  • Antioxidant
  • Anti-inflammatory
  • Barrier Repair
  • Anti-aging
  • Wound Healing

What is Quercetin's effective concentration?

Quercetin is known for its skin-soothing and anti-inflammatory activity, with a restorative effect that stimulates repair in damaged or irritated skin. For this these reasons, anti-aging and rejuvenation facial creams benefit from the use of quercetin as an active. The topical application of 1% quercetin in a cream-based formula is shown to promote recovery of the skin barrier and normal hydration following UV and chemical-induced skin damage. There are no known adverse effects to the use of topical quercetin as it is still a relatively new active and only a limited number of studies on its skin protective effects is available so far. 

Skin aging is accelerated when damage from chronic inflammation and dryness is left untreated. Flavonoids exhibit potent antioxidant functions, making them common ingredients in cosmetics designed to repair damaged skin from oxidative stress. In 10 minutes to 2 hours following topical treatment of 1% quercetin, a significant improvement in UV and chemical-induced erythema and inflammation was observed. The treatment was also able to stimulate recovery of the skin barrier, prevent water loss, and restore hydration.1 In peroxide-induced skin damage, it is shown to reduce reactive oxygen species (ROS) accumulation, increase cell survival, and promote rejuvenating cellular morphology. While quercetin is not an effective whitening agent, its derivatives (such as glycosides), demonstrate some anti-melanogenesis activity in a dose-dependent manner with no cytotoxicity.2  

Does Quercetin turn into a Pro-oxidant?

Most antioxidants can turn into a pro-oxidant but it is pronounced with Quercetin. When Quercetin gets oxidized, it turns into O-semiquinone (OQ) which gets further oxidized to O-quinone/quinone methide (OQQ). OQQs can react with protein thiols and can lead to further damage. Luckily, if formulated properly, Quercetin can be recycled through several ways. 1) Combining it with Ascorbic acid can recycle OQQ back to OQ back to Quercetin. 2) NADH can also recycle OQ back to Quercetin. Finally 3) Glutathione that is present in the skin can react with OQQ to form Gluthionylquercetin which has some antioxidant property as well. This phenomenon highlights the need for antioxidants to be formulated in a system that supports recycling of antioxidants, preventing them from becoming pro-oxidants. 12-16

Formulation Considerations

Each cosmetic formulation is designed to target specific needs through a combination of ingredients that could either work synergistically to enhance each other’s benefits, promote better skin permeability, or help maintain chemical stability. Ceramides are long-chain fatty acids that are important for keeping the skin barrier intact, and the skin permeability of quercetin (and other water-insoluble antioxidants) can be enhanced by combining with these fatty acids in the ceramide liposomes-in-hydrogel delivery system.3 Compounds such as avobenzone and octinoxate that are found in broad-spectrum sunscreens may also benefit from formulation with quercetin as it has photostability properties to help prevent their degradation.4 It is shown that quercetin is much more effective as a stabilizer than vitamin E and octocrylene. There is no known cross-reactivity between quercetin and other actives that are commonly found in cosmetic formulations.

How does Quercetin work?

Quercetin is classified as a flavonol, one of the subclasses of flavonoids. It has a polyphenol structure with a hydroxyl (OH) group at positions 3, 5, 7, 3’, and 4’. The aglycone form of quercetin, which lacks an attached sugar, has poor solubility in water but favorable solubility in alcohols and lipids. Meanwhile, quercetin derivatives such as glycosides that have a sugar in replacement of one of the OH groups, usually at position 3, are water soluble. This can directly influence the skin absorption and in vivo effects of the ingredient. 

How does it work as anti-inflammatory active?

Quercetin and its derivatives are naturally occurring phytochemicals with promising bioactive effects. It has a versatile role in the skin and body as it possesses biological activities that target different mechanisms to combat damage from both intrinsic and extrinsic factors. The major role it has in skincare is anti-aging through its antioxidant and anti-inflammatory properties. It has potent effects to protect our skin from premature aging, making it a superior active in restorative skincare. In cell models, quercetin is shown to inhibit lipopolysaccharide (LPS)-induced TNF-α and IL-8 expression, and the production of pro-inflammatory enzymes cyclooxygenase (COX) and lipoxygenase (LOX).9 In another skin model, skin cultures exposed to the acne-causing bacteria Propionibacterium acnes showed marked inflammation as measured by the increase in pro-inflammatory cytokines IL-6 and IL-8. Quercetin significantly decreased both IL-6 and IL-8 even in very low concentrations.11

Adapted from: Lim, H., Kang, S., Song, Y., Jeon, Y., & Jin, J. (2021). Inhibitory Effect of Quercetin on Propionibacterium acnes-induced Skin Inflammation. International Immunopharmacology96, 107557. https://doi.org/10.1016/j.intimp.2021.107557

In UV-induced skin damage, it demonstrates protective effects by inhibition of metalloproteinase-1 (MMP-1), a protease enzyme that breaks down collagen, and downregulation of MMP-1 expression by preventing AP-1 activation. It interferes with several signal transduction pathways to stimulate NF-κB antagonist activity, and the blockage of cytokine-mediated induction of inflammatory cascades and IL-1-stimulated IL-6 production from human mast cells. 

How does it work as an antioxidant?

The immunomodulatory activity of quercetin in murine models also includes the inhibition of TNF-α expression and activity, as well as nitric oxide production and downregulation of nitric oxide synthase. In acute inflammation, quercetin functions in a dose-dependent manner to suppress leukocyte recruitment, decrease lipid peroxidation and chemokine and ROS levels, and increase antioxidant enzyme activity. It interferes with the production and balance of pro-inflammatory cytokines such as TNF-α and IL-17, and anti-inflammatory cytokines such as IL-10.9 It universally suppresses the accumulation and activation of immune cells by reducing oxidative stress and NF-κB activity to prevent chronic inflammation. It also has shown a synergistic effect with Vitamin C as ascorbate is able to recycle quercetin, thus, increasing its efficacy.5 Its wound-healing effects have also been extensively investigated.6  

How does it work as an anti-aging agent?

Quercetin has skin-soothing and restorative effects that stimulate repair in damaged and aging skin by promoting recovery of the skin barrier, restoring normal hydration level, and preventing moisture loss from UV and chemical exposure. Its antioxidant properties protect the skin from damage due to chronic oxidative stress, increasing cellular survival.10 Aside from its anti-MMP activity, it has senolytic effects and is able to stimulate rejuvenating cellular morphology.8 Some studies suggest quercetin glycosides may contain anti-melanogenesis activity, thus, potential as a whitening agent to treat dark, aging spots.2

Clinical trials 

Actives

Conclusion 

Source

2 μg/mL QUER


0.5, 2, and 5 μg/mL QU-CAP

Objective: To investigate the influence of quercetin and its derivative on cytoprotective and antioxidant activity in fibroblasts

Subjects: Cell culture (HFL-1 primary human fibroblasts)

Methods: The cells were treated for 24 hours with 2 μg/mL quercetin (QUER), or 0.5, 2, 5 μg/mL quercetin caprylate (QU-CAP), a derivative of QUER. The cells treated with diluent were part of the control group. A fluorescent dye was added to the cell cultures with the compounds for the detection of reactive oxygen species (ROS). In a separate set of cultures with the same concentrations of QUER and QU-CAP, ROS and oxidized protein levels were measured after incubation with 300 μM hydrogen peroxide. 

Results: A reduction in the levels of ROS and oxidized proteins was observed after QUER and QU-CAP treatment, as compared to the control.

Conclusions: QUER and QU-CAP exhibit cytoprotective properties against hydrogen peroxide-induced oxidative stress. 

Chondrogianni N, Kapeta S, Chinou I, Vassilatou K, Papassideri I, Gonos ES. (2010). Anti-ageing and rejuventating effects of quercetin. Exp Gerontol. 45(10): 763-771. doi: 10.1016/j.exger.2010.07.001

2 μg/mL QUER


0.5, 2, and 5 μg/mL QU-CAP

Objective: To investigate the influence of QUER and QU-CAP on cell survival in fibroblasts

Subjects: Cell culture (HFL-1 primary human fibroblasts)

Methods: The cells were treated with 2 μg/mL QUER, or 0.5, 2, 5 μg/mL QU-CAP for 24 hours, and then with 300 μM hydrogen peroxide for 2.5 hours. After 5 days of recovery, the number of cells in each culture was enumerated.  

Results: The survival rate in the treated cells with QUER and QU-CAP ranged from 5.4% to 7.5%, compared to the control (diluent treatment). 

Conclusions: QUER and QU-CAP exhibit cytoprotective properties against hydrogen peroxide-induced oxidative stress.

2 μg/mL QUER


0.5, 2, and 5 μg/mL QU-CAP

Objective: To investigate the influence of QUER and QU-CAP on cellular lifespan, and rejuvenating effect in fibroblasts

Subjects: Cell culture (HFL-1 primary human fibroblasts)

Methods: The cells were treated with 2 μg/mL QUER, or 0.5, 2, 5 μg/mL QU-CAP until senescence. β-galactosidase activity was measured at the end of the treatment period to assess the rejuvenation effect of QUER and QU-CAP. 

Results: All concentrations of QUER and QU-CAP produced much higher cellular proliferation rates, as compared to the untreated control. Treated cells also had more elongated phenotype and lower percentage of β-galactosidase staining, which are linked to rejuvenating effects.  

5 μg/mL QUER


5 and 10 μg/mL QU-CAP

Objective: To investigate the whitening effect of QUER and QU-CAP in melanocytes 

Subjects: Cell culture (B10F16 melanocytes)

Methods: The cells were treated with 5 μg/mL QUER, 5 μg/mL QU-CAP, or 10 μg/mL QU-CAP for 72 hours. Proteins were extracted at the end of the 72-hour treatment and assayed to determine whether QUER and QU-CAP had influenced: 1) expression of tyrosinase, an enzyme that catalyzes several steps in melanin biosynthesis; and 2) CT-L proteasome activity (at 24 hours), which is thought to mediate tyrosine degradation.

Results: QUER and QU-CAP reduced the level of tyrosinase expression and stimulated CT-L proteasome activity. 

2 μg/mL QUER


0.5, 2, and 5 μg/mL QU-CAP

Objective: To investigate the effect of QUER and QU-CAP on proteasome activity in HFL-1 cells

Subjects: Cell culture (HFL-1 primary human fibroblasts)

Methods: The cells were treated with 2 μg/mL QUER, or 0.5, 2, 5 μg/mL QU-CAP for 24 hours. CT-L proteasome activity was measured at the end of the treatment. 

Results: CT-L activity was increased by ~2.4 fold (for QUER) and ~1.5 fold (for QU-CAP), compared to the controls which were treated with diluent. The expression of representative CT-L proteasome subunits was also enhanced by QUER and QU-CAP-treated cells. 

Conclusions: QUER and QU-CAP are potential proteasome activators that promote proteasome-mediated tyrosine degradation. This property, in addition to its antioxidant activity and rejuvenating effect suggests the use of QUER and its derivatives in topical anti-aging products.  

Quercevita® 1% cream 

Objective: To evaluate the ability of quercetin to reduce skin inflammation induced by UV radiation, histamine, and chemical irritants 

Subjects: Human (n = 30), healthy individuals, no previous skin damage

Route of Administration: Topical, in vivo

Tested Area: Back

Methods: The back of each subject was divided into 4 quadrants each to be treated with: 1) UVA + UVB radiation; 2) histamine solution through a prick test (back and forearm); 3) 4 patches containing 0.07 to 1 mL of 1% sodium lauryl sulfate (SLS) solution for 24 hours; 4) 4 patches containing 0.07 to 1 mL of 1% glycolic acid (GA) solution for 24 hours. Then, each quadrant was divided into 4 areas and each area was treated with (non-occlusive): 1) negative control (no product); 2) test formula Quercevita® 1% cream, 2 mg/cm2; 3) placebo with the same base as Quercevita® but without quercetin, 2 mg/cm2; 4) positive control containing a topical product Polaramin® without quercetin, 2 mg/cm2. The skin condition in each quadrant was assessed pre- and post-therapeutic treatment. 

Results: UV-induced erythema was decreased by ~10.05% after Quercevita® treatment, and ~14.05% after Polaramin®. After 30 minutes of treatment, Quercevita® was able to reduce the mean wheal diameter from the histamine prick test by 13.25%, while Polaramin® reduced it by ~12.23%. The itching sensation also improved after 10 minutes of application of Quercevita® and Polaramin®. SLS-induced erythema was reduced, and hydration values were increased after treatment with Quercevita® at 2 hours and Polaramin® at 4 hours, with a positive trend over time. These formulations had a similar effect on GA-induced erythema and hydration values. The negative control and placebo had statistically insignificant effect in all quadrants. 

Conclusions: Quercetin has skin protective properties against UV damage, histamine, and chemical irritants by reducing redness, itching, inflammation, restoring the skin barrier, increasing hydration, and minimizing water loss. 

Maramaldi G, Togni S, Pagin I, Giacomelli L, Cattaneo R, Eggenhöffner R, Burastero SE. (2016). Soothing and anti-itch effect of quercetin phytosome in human subjects: a single-blind study. Clin Cosmet Investig Dermtol. 9: 55-62. doi: 10.2147/CCID.S98890

20 μM quercetin

Objective: To investigate the senolytic effects of quercetin 

Subjects: Cell culture (3T3-L1 pre-adipocytes, and mature adipocytes)

Methods: Senescence (and oxidative damage) was induced with hydrogen peroxide at a sub-lethal concentration of 150 μM for 3 hours for 3 consecutive days, and then treated with 20 μM quercetin. The following properties in each cell line were assessed: cytotoxicity, morphology, ROS levels, senescence-associated β-galactosidase (SA-β-gal) staining, and protein expression. 

Results: Following hydrogen peroxide-induced senescence in 3T3-L1 and mature adipocytes, an increase in ROS accumulation, and gene expression of SA-β-gal and p21 was observed. In mature adipocytes, the accumulation of ROS from induced oxidative damage produced a phenotype with enhanced expression of TNF-α, IL-6, iNOS, and NF-κB. Treatment with 20 μM quercetin in mature adipocytes significantly reduced the expression of SA-β-gal, p65 and SIRT 1, intracellular accumulation of ROS, inflammatory gene expression of IL-6 and MCP-1, and modulated the expression of miR-155-5p. In 3T3-L1 cells, 20 μM quercetin reduced SA-β-gal activity, ROS accumulation, expression of p65 and pro-inflammatory cytokines IL-6 and MCP-1, and modulated the expression of miR-155-5p, but increased SIRT 1 expression. Senolytic effects were observed in mature adipocytes and pre-adipocytes following treatment with 20 μM quercetin with no cytotoxicity in either cell line.

Conclusions: The results confirmed the senolytic and anti-inflammatory role of quercetin in senescent pre-adipocytes and adipocytes, which may be related to anti-aging effects. 

Zoico E, Nori N, Darra E, Tebon M, Rizzatti V, Policastro G, De Caro A, Rossi AP, Fantin F, Zamboni M. (2021). Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence. Nature. 2021(11): 23237 doi: 10.1038/s41598-021-02544-0


Does Quercetin penetrate the skin?

Despite the diverse benefits of quercetin, a challenge to overcome is its poor skin permeability and water solubility. To enhance skin permeability, quercetin can be encapsulated in ceramide liposomes, which is a phospholipid-based delivery system, and incorporated into a hydrogel base. This is believed to be a potential solution for drug delivery of water-insoluble compounds and enhance transdermal permeation of such antioxidants.3 Topical application of quercetin is considered safe and adverse effects are not reported.

Terminology

Term

Definition

adipocytes

fat cells that primarily compose the adipose tissue

apoptosis

Programmed cell death, a process that is involved in the elimination of damaged cells or cancer cells, and aging

COX-2

Cyclooxygenase-2; an enzyme that is expressed during an inflammatory response

cytokine

A small protein that is secreted during an inflammatory response to facilitate cell signaling and immune function

IL

Interleukin; a cytokine that is secreted during an inflammatory response to signal the migration of immune cells to the site of inflammation 

mast cells

A type of immune cell that contains granules rich in histamine and heparin; these cells go through degranulation to elicit inflammatory actions 

MMPs

Matrix metalloproteinases; protease enzymes that break down collagen and are responsible for tissue repair and remodeling 

NF-κB

Nuclear factor kappa B; a transcription factor that regulates the expression of genes important for cell survival and cytokine production

senolytic 

Ability to induce apoptosis in senescent cells

sirtuins

SIRT; enzymes that regular cellular functions including aging, inflammation, detoxification, metabolism, and circadian rhythm

TNF-α

Tumor necrosis factor alpha; a cytokine produced during inflammation to promote necrosis or apoptosis

References

1

Maramaldi G, Togni S, Pagin I, Giacomelli L, Cattaneo R, Eggenhöffner R, Burastero SE. (2016). Soothing and anti-itch effect of quercetin phytosome in human subjects: a single-blind study. Clin Cosmet Investig Dermtol. 9: 55-62. doi: 10.2147/CCID.S98890

2

Choi MH, Shin HJ. (2016). Anti-Melanogenesis Effect of Quercetin. Cosmetics. 3(8); doi: 10.3390/cosmetics3020018

3

Park SN, Lee MH, Kim SJ, Yu ER. (2013). Preparation of quercetin and rutin-loaded ceramide liposomes and drug-releaseing effect in liposome-in-hydrogel complex systems. Biochem Biophys Res Commun. 435(5): 361-366. doi: 10.1016/j.bbrc.2019.04.093

4

Scalia S, Mezzena M. (2009). Photostabilization effect of quercetin on the UV filter combination, butyl methoxydibenzoylmethane-octyl methoxycinnamate. Photochem Photobiol. 86(2): 273-278. doi: 10.1111/j.1751-1097.2009.00655

5

Biancatelli R, Berrill M, Catravas JD, Marik PR. (2020). Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19). Front Immunol. https://www.frontiersin.org/articles/10.3389/fimmu.2020.01451/full

6

Salehi B, et. al. (2020). Therapeutic Potential of Quercetin: New Insights and Perspectives for Human Health. ACS Omega. 5(20): 11849-11872. doi: 10.1021/acsomega.0c01818

7

Chondrogianni N, Kapeta S, Chinou I, Vassilatou K, Papassideri I, Gonos ES. (2010). Anti-ageing and rejuventating effects of quercetin. Exp Gerontol. 45(10): 763-771. doi: 10.1016/j.exger.2010.07.001

8

Zoico E, Nori N, Darra E, Tebon M, Rizzatti V, Policastro G, De Caro A, Rossi AP, Fantin F, Zamboni M. (2021). Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence. Nature. 2021(11): 23237 doi: 10.1038/s41598-021-02544-0

9

Li Y, Yao J, Han C, Yang J, Chaudhry MT, Wang S, Liu H, Yin Y. (2016). Quercetin, Inflammation and Immunity. Nutrients. 8(3): 167. doi: 10.3390/nu8030167

10

Yakin G, Lee CK. (2020). The Discovery of Druggable Anti-aging Agents. Annals of Geriatric Medicine and Research. 24(4): 232-242. doi: 10.4235/agmc20.0092

11
Lim, H., Kang, S., Song, Y., Jeon, Y., & Jin, J. (2021). Inhibitory Effect of Quercetin on Propionibacterium acnes-induced Skin Inflammation. International Immunopharmacology96, 107557. https://doi.org/10.1016/j.intimp.2021.107557
12 Murota K, Terao J. Antioxidative flavonoid quercetin: implication of its intestinal absorption and metabolism. Arch Biochem Biophys. (2003) 417:12–7. doi: 10.1016/S0003-9861(03)00284-4
13 Boots AW, Li H, Schins RP, Duffin R, Heemskerk JW, Bast A, et al. The quercetin paradox. Toxicol Appl Pharmacol. (2007) 222:89–96. doi: 10.1016/j.taap.2007.04.004
14 Askari G, Ghiasvand R, Feizi A, Ghanadian SM, Karimian J. The effect of quercetin supplementation on selected markers of inflammation and oxidative stress. J Res Med Sci. (2012) 17:637–41.
15 Boots AW, Kubben N, Haenen GR, Bast A. Oxidized quercetin reacts with thiols rather than with ascorbate: implication for quercetin supplementation. Biochem Biophys Res Commun. (2003) 308:560–5. doi: 10.1016/S0006-291X(03)01438-4
16 Bors W, Michel C, Schikora S. Interaction of flavonoids with ascorbate and determination of their univalent redox potentials: a pulse radiolysis study. Free Radic Biol Med. (1995) 19:45–52. doi: 10.1016/0891-5849(95)00011-L
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The Skincare Encyclopedia aims to improve public understanding of the biology and chemistry of skincare. The Encyclopedia is rooted in core scientific principles and extensive research, in many cases in collaboration with the authors of the original studies referenced. This is a project of Regimen Lab, maintained by a group of multidisciplinary scientists, MDs, and researchers.