Abstract
It is known that quercetin is useful in the treatment of pressure wounds due to its ability to reduce oxygen radicals, but its effect on eyelid wound healing is unclear. In this study, forty male Wistar albino rats weighing 250–300 grams were used to investigate the effect of quercetin on eyelid wound healing. Four groups were created: control group, sham group, incision wound group, and suture + quercetin group. Full-thickness skin excision was performed through a 3–5 mm incision in the superior palpebrae to create a wound. On the 1 third and seventh days, the rats were sacrificed, and blood samples were taken by cardiac puncture for biochemical measurement and tissue samples for histopathological examination from the palpebrae. 2 Inflammatory cells in the quercetin group were significantly lower on day 3 (P < 0.05). Blood levels of IL-1 and TNF-α were significantly lower in the quercetin group compared to other groups (P < 0.05). Also, IL-6 was found to be significantly lower on day 7 in the quercetin group compared to other groups (P < 0.05). The quercetin group was as effective as the sham group in terms of collagen formation on day 3, and the hydroxyproline value was significantly higher. Total oxidant status levels were lower in the quercetin group than in the sham group (P = 0.005). In conclusion, quercetin exhibited anti-inflammatory and antioxidant effects, along with higher collagen accumulation in the eyelid compared to other groups. Our results suggest that quercetin could be a potential therapeutic agent that accelerates wound healing and reduces scar formation in the eyelid.
KEY WORDS: Dermatologic surgery, eyelid surgery, quercetin, wound healing
Introduction
Reactive oxygen species (ROS) play an essential role in the normal wound-healing process. Thus, it is necessary to maintain an ideal balance between low and high ROS levels. New treatments focus on antioxidant products that regulate this balance. In addition to facilitating the adhesion of leukocytes to wounds and the chemotaxis of proinflammatory factors into wounds, ROS have also been shown to inhibit keratinocyte migration and re-epithelialization.[1,2]
It is pertinent to ask whether a model that simulates impaired wound healing can replicate all the complexities associated with the healing process of a human wound.[1,2,3,4] To study the healing process of wounds, pathological problems that are typically chronic in humans must be carefully simulated in animals. This will enable them to survive for an extended period.
The healing process consists of four overlapping stages: proliferation, wound remodelling, hemostasis, and inflammation. There are, however, many chronic wounds, including pressure ulcers, arterial, and venous. They are defined by prolonged inflammation and, as a result, protease, ROS, and high levels of proinflammatory cytokines. During the recovery process for chronic wounds, stalls can occur at any point. This is from the time of their initial presentation to the time when they are close to healing.[5,6,7] The presence of macrophages at higher levels than average in chronic wounds resulted in increased inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α).[8] As part of remodelling, fibroblast proliferation, and migration, this factor contributes to wound healing when released under controlled conditions. ROS production and extracellular matrix degradation are two ways TNF induces chronicity when it is upregulated.[9,10,11,12]
In this study, identifying compounds with antioxidant properties that have been tested for wound healing and reviewing the evidence supporting their effectiveness is a major objective. Gomathi et al. found that a collagen matrix containing quercetin had a greater ability to heal wounds and scavenge free radicals than a collagen matrix at day 7 compared with collagen-treated wounds. Quercetin also resulted in a higher percentage of wound contraction in animals treated with the drug (20 ± 1.77).[13] An animal model was used by Yin G et al. to investigate the novel effects of the topical application of quercetin on pressure ulcers. According to the study, quercetin successfully reduced immune cell infiltration and proinflammatory activity in wounds. The wounds treated with quercetin had nearly closed by day 14, whereas the wounds in the control group had healed only 80% by that day. Thus, it has been determined that quercetin may be an effective treatment for pressure ulcers.[14] This study will examine the effects of quercetin on wound healing in the eyelid, an area that had never been examined prior to this study and has thin skin. At topical application, quercetin has been shown to improve cutaneous wound healing in rats; however, due to its hydrophobic nature and limited skin penetration, it is not an ideal treatment for cutaneous wounds. Therefore, this study was designed to determine whether oral quercetin could promote wound healing.
Various foods contain flavonoids, like apples, green leafy vegetables, tea, strawberries, and onions. Quercetin can be found naturally in many fruits, vegetables, and plants. There was a down-regulation of collagen III and smooth muscle actin by quercetin in human keratoconus corneal stromal cells, two key markers of fibrosis in the cornea. Furthermore, we found that quercetin inhibited transforming growth factor-b2 (TGF-b2) expression in the presence and absence of excess lactate. TGF-b signalling has been identified as one of the key players in corneal fibrosis, and several strategies have been proposed to inhibit its activity. It may be possible to inhibit corneal scarring by regulating the expression of TGF-b with quercetin.[15]
Methods and Material
Study design and setting
This experimental study was conducted at the Afyon Kocatepe University Experimental Animal Laboratory from 1st January 2022, to 1st March 2022. Approval for the study protocol was obtained from the Local Ethics Committee for Animal Experiments of Afyon Kocatepe University, Afyonkarahisar, Turkey (Approval No: 49533702/08). All animal procedures adhered to the guidelines outlined in the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health.
Animals
Forty male Wistar albino rats, weighing between 250–300 g and aged 4–6 months, were obtained from the Experimental Animal Production and Research Centre, Afyonkarahisar, Turkey.
Anaesthesia and surgical preparation procedures
Anaesthesia was induced by intramuscular injection of xylazine HCl (13 mg/kg) and ketamine hydrochloride (87 mg/kg). The right eye of each rat was surgically prepared under regional anaesthesia. Following hair removal from the superior palpebra with a razor blade, the right eye was cleaned with povidone iodine.
Standard operating procedures
A solution of quercetin (BLD Pharma, 10 g, 98.24%, SW08-06, Sigma-Aldrich, Shanghai, China) was prepared with distilled water at room temperature and administered to rats in the suture + quercetin group by oral gavage at a dose of 1 mg/kg.
Quality assurance (QA) parameters
Quercetin purity (98.24%) was confirmed by the manufacturer’s certificate. The solution was stored in a light-protected environment at a temperature of −20 degrees Celsius. All preparation and application processes were carried out in accordance with the current good manufacturing practice (GMP) rules.
Experimental groups
Control Group (n = 10): Rats were sacrificed on day 0 with a 150 mg/kg thiopental sodium intracardiac injection. Blood samples were collected by cardiac puncture.
Sham Group (n = 10): Rats underwent a full-thickness skin excision with a 3–5 mm incision in the superior palpebra of the right eye on day 0 under general anaesthesia. On the 3rd and 7th days post-surgery, rats were sacrificed, and blood and tissue samples were collected for analysis.
Incision Wound Group (n = 10): Rats underwent a full-thickness skin excision on day 0. The wound was left open and treated daily with sterile saline. On the 3rd and 7th days post-surgery, rats were sacrificed, and samples were collected.
Suture + Quercetin Group (n = 10): Rats underwent a full-thickness skin excision on day 0. The wound was closed with sutures, and rats received 1 mg/kg quercetin daily via gastric gavage until the end of the study. Samples were collected for analysis.
Outcome measures
Histopathological evaluation of wound healing was performed on tissue samples. Enzyme-linked immunosorbent assay (ELISA) was used to measure TNF-α, S-TNF-lβ, IL-6, and EGF levels in tissue and serum. Hydroxyproline (HYD) levels and total oxidant status (TOS) and total antioxidant status (TAS) were also assessed in tissue and serum samples.
Data analysis
The data analysis was carried out using IBM SPSS statistics version 25.0 software (IBM Corporation, Armonk, NY, US).
An analysis of Shapiro-Wilk and Levene tests was performed to determine whether the standard distribution and variance homogeneity assumptions were met. We expressed data as mean + SD or median (25th–75th) percentiles; whenever possible. One-way ANOVA was used to compare IL-1 and IL-6 levels among study groups, and the Kruskal Wallis test was used to compare HYD and EGF levels. A post-hoc Tukey HSD or Dunn-Bonferroni test was used when P values from one-way ANOVA or Kruskal Wallis test were statistically significant. For the comparison of the continuous variables, the Mann Whitney U test was applied if the parametric test assumptions were not met. Student t-tests were used to compare the mean differences between follow-up times within each group. It was considered statistically significant if the P value was less than 0.05. A Bonferroni correction was applied to every possible multiple comparison to control Type I errors.
Results
Among the subjects sacrificed on the 3rd day, the IL-1 protection orientation was intentionally different between the groups (P = 0.016) and the situation causing the difference; quercetin group had lower IL-1 levels than the sham group (P = 0.025). Among the subjects sacrificed on the 7th day, there was an external difference by limiting the IL-1 environment (P = 0.017) compared to the groups, and the reason for the difference was that IL-1 was lower than the quercetin standards compared to the incision group (P = 0.017, 0.016). The sham, incision, and quercetin groups contained no difference between the subjects sacrificed on day 3 and those sacrificed on day 7 according to the Bonferroni correction that went beyond IL-1 (P > 0.0167) [see Figure 1 and Table 1].
Figure 1.

Control, sham, insicion, and quercetin IL-1 levels
Table 1.
Biochemical measurements in terms of study groups and follow-up times
| Sham | Incision | Quercetin | P † | |
|---|---|---|---|---|
| IL-1β | ||||
| 3rd day | 7.12±1.42a | 6.97±0.79 | 5.02±0.90a | 0.016 |
| 7th day | 4.98±1.05 | 5.55±1.01b | 3.54±0.80b | 0.017 |
| P‡ | 0.027 | 0.039 | 0.025 | |
| IL-6 | ||||
| 3rd day | 5.44±0.78c | 4.08±0.67c | 4.18±0.57 | 0.013 |
| 7th day | 5.82±1.12a | 4.56±0.80 | 3.42±0.64a | 0.004 |
| P‡ | 0.550 | 0.339 | 0.083 | |
| TNF-α | ||||
| 3rd day | 55.64±4.82 | 54.09±4.52 | 46.56±6.26 | 0.040 |
| 7th day | 48.22±2.59a | 45.37±2.18 | 40.46±3.23a | 0.002 |
| P‡ | 0.016 | 0.005 | 0.089 | |
| HPO | ||||
| 3rd day | 198.23 (184.67–202.87) | 202.54 (195.16–208.06) | 231.23 (198.01–245.61) | 0.208¥ |
| 7th day | 190.11 (185.28–213.30) | 190.76 (183.47–196.17)b | 231.93 (210.12–251.32)b | 0.017¥ |
| P‡ | 0.690¥¥ | 0.056¥¥ | 0.548¥¥ | |
| EGF | ||||
| 3rd day | 96.78 (91.50–102.16) | 95.67 (92.31–101.04) | 96.87 (85.44–113.44) | 0.932¥ |
| 7th day | 97.66 (89.11–117.22) | 90.32 (79.63–91.61) | 100.98 (97.10–116.20) | 0.054¥ |
| P‡ | 0.841¥¥ | 0.056¥¥ | 0.421¥¥ | |
| TAS | ||||
| 3rd day | 10.59±1.15 | 10.89±1.27 | 11.82±1.32 | 0.304 |
| 7th day | 11.26±1.57 | 11.64±0.88 | 13.30±1.56 | 0.082 |
| P‡ | 0.461 | 0.311 | 0.144 | |
| TOS | ||||
| 3rd day | 3.19±0.23 | 3.12±0.16 | 2.90±0.13 | 0.062 |
| 7th day | 3.38±0.26a | 3.21±0.15 | 2.93±0.10a | 0.007 |
| P‡ | 0.250 | 0.353 | 0.648 |
When appropriate, data are presented as mean+SD or median (25th–75th) percentiles. †Based on the Bonferroni correction, P=0.025 was considered statistically significant for comparisons between study groups within each study period. A statistically significant difference was observed between follow-up times within each study group, based upon results from the Bonferroni correction for comparisons between follow-up times within each study group. Statistical analyses include one-way ANOVA, Kruskal Wallis test, Student’s t-test, and Mann Whitney U test. a: Sham vs quercetin (P<0.025), b: Incision vs quercetin (P<0.025), c: Sham vs incision (P=0.020)
The level of IL-6 differs statistically significantly among the subjects sacrificed on the 3rd day (P = 0.013), the situation causing the said difference; there was a significant reduction in IL-6 levels in the incision group compared to the sham group (P = 0.020). Among the subjects sacrificed on the 7th day, there was a statistically significant difference in IL-6 levels according to the groups (P = 0.004). There was a significant difference between the quercetin group and the sham group in terms of IL-6 levels (P = 0.003). Within the sham, incision, and quercetin groups, in terms of statistical significance, there was no difference between the subjects sacrificed on day 3 and those sacrificed on day 7 in terms of IL-6 levels according to Bonferroni correction (P > 0.0167) [see Figure 2 and Table 1].
Figure 2.

Control, sham, insicion, and quercetin IL-6 levels
Among the subjects sacrificed for three days, there was no statistically significant difference between the groups regarding TNF-α levels according to Bonferroni correction (P = 0.040). On the other hand, among the subjects who were sacrificed on the 7th day, there was a statistically significant difference in TNF-α levels according to the groups (P = 0.002). TNF-α levels were lower in the quercetin group than in the sham group (P = 0.002). TNF-α levels of the subjects sacrificed on the 7th day were statistically significantly lower than those sacrificed on the 3rd day in the sham group (P = 0.016). TNF-α levels of the subjects sacrificed on the 7th day were statistically significantly lower in the incision group than those sacrificed on the 3rd day (P = 0.005). Finally, TNF-α levels were statistically similar between the subjects sacrificed on day three and those sacrificed on day 7 in the quercetin group (P = 0.089) [see Figure 3 and Table 1].
Figure 3.

Control, sham, insicion, and quercetin TNF-α level
HYD levels did not differ statistically significantly between the groups among the subjects sacrificed on the 3rd day (P = 0.208). However, there was a statistically significant difference in HYD levels among the subjects sacrificed on the 7th day compared to the groups (P = 0.017). HYD levels were higher in the quercetin group compared to the incision group (P = 0.021). Sham, incision, and quercetin groups showed no statistically significant difference in HYD levels between the 3rd and 7th day sacrificed subjects (P > 0.05) [see Table 1].
As a result of the 3rd-day sacrifice, the EGF levels were not statistically significant among the groups (P = 0.932). There was no statistically significant difference in EGF levels among the groups sacrificed on the 7th day (P = 0.054). Within the sham, incision, and quercetin groups, EGF levels did not differ statistically significantly between subjects sacrificed on the 3rd day and those sacrificed on the 7th day (P > 0.05) [see Table 1].
The TAS levels in the three groups did not differ statistically significantly (P = 0.304). TAS levels were not statistically significantly different between groups of subjects sacrificed on the 7th day (P = 0.082). Within the sham, incision, and quercetin groups, there was no statistically significant difference in TAS levels between the subjects sacrificed on the 3rd day and the subjects sacrificed on the 7th day (P > 0.05). [see Figure 4 and Table 1].
Figure 4.

Control, sham, insicion, and quercetin total antioxidant (TAS) levels
The TOS levels among the subjects sacrificed on the 3rd day did not differ statistically significantly between the groups (P = 0.062). A statistically significant difference in TOS levels was observed among the subjects sacrificed on the 7th day (P = 0.007). There was a significant reduction in TOS levels in the quercetin group compared to the sham group (P = 0.005). Within the sham, incision, and quercetin groups, the TOS levels did not differ statistically significantly between the 3rd and 7th day sacrificed subjects (P > 0.05) [see Figure 5 and Table 1].
Figure 5.

Control, sham, insicion, and quercetin total oxidant (TOS) levels
Incision and sham groups, sacrificed on the third day, had significantly greater levels of IL-1 than controls (P < 0.001). The IL-6 levels of the sham, incision, and quercetin groups, sacrificed on the 3rd day, were also statistically significantly higher than the control group (P < 0.001). TNF-α level of the sham group sacrificed on the 3rd day was statistically significantly higher than the control group (P = 0.003). The EGF level of the incision group, which was sacrificed on the 3rd day compared to the control group, was also statistically significantly higher (P = 0.005). There was no statistically significant difference between the control group and the groups sacrificed on the 3rd day in terms of other laboratory measurements, according to Bonferroni correction (P > 0.0083) [see Table 2].
Table 2.
The comparisons between 3rd-day measurements and the control group
| Control | Sham | Incision | Quercetin | |
|---|---|---|---|---|
| IL-1 | 3.83±0.77 | |||
| 3rd day | 7.12±1.42 | 6.97±0.79 | 5.02±0.90 | |
| P†¶ | <0.001 | <0.001 | 0.019 | |
| IL-6 | 2.65±0.39 | |||
| 3rd day | 5.44±0.78 | 4.08±0.67 | 4.18±0.57 | |
| P†¶ | <0.001 | <0.001 | <0.001 | |
| TNF-α | 45.91±4.97 | |||
| 3rd day | 55.64±4.82 | 54.09±4.52 | 46.56±6.26 | |
| P†¶ | 0.003 | 0.009 | 0.829 | |
| HYD | 190.12 (179.66–202.43) | |||
| 3rd day | 198.23 (184.67–202.87) | 202.54 (195.16–208.06) | 231.23 (198.01–245.61) | |
| P‡¶ | 0.594 | 0.165 | 0.019 | |
| EGF | 87.16 (82.52–93.44) | |||
| 3rd day | 96.78 (91.50–102.16) | 95.67 (92.31–101.04) | 96.87 (85.44–113.44) | |
| P‡¶ | 0.019 | 0.005 | 0.099 | |
| TAS | 11.50±1.01 | |||
| 3rd day | 10.59±1.15 | 10.89±1.27 | 11.82±1.32 | |
| P†¶ | 0.140 | 0.331 | 0.609 | |
| TOS | 2.94±0.36 | |||
| 3rd day | 3.19±0.23 | 3.12±0.16 | 2.90±0.13 | |
| P†¶ | 0.189 | 0.325 | 0.794 |
The data were expressed as mean+SD or median (25th–75th) percentiles, depending on the case. †Student’s t-test, ‡Mann Whitney U test, P=0.0083 according to the Bonferroni correction for comparing the control and experimental groups
The IL-1 levels of the Incision group sacrificed on the 7th day were statistically significantly higher than the control group (P = 0.003). The IL-6 levels of the sham and incision groups, which were sacrificed on the 7th day compared to the control group, were also statistically significantly higher (P = 0.002 and P < 0.001). The HYD level of the quercetin group sacrificed on the 7th day was statistically significantly higher than the control group (P = 0.005). The EGF level of the quercetin group sacrificed on the 7th day was also statistically significantly higher than the control group (P < 0.001). There was no statistically significant difference between the control group and the groups sacrificed on the 7th day in terms of other laboratory measurements, according to Bonferroni correction (P > 0.0083) [see Table 3].
Table 3.
The comparisons between 7th-day measurements and the control group
| Control | Sham | Incision | Quercetin | |
|---|---|---|---|---|
| IL-1 | 3.83±0.77 | |||
| 7th day | 4.98±1.05 | 5.55±1.01 | 3.54±0.80 | |
| P†¶ | 0.031 | 0.003 | 0.509 | |
| IL-6 | 2.65±0.39 | |||
| 7th day | 5.82±1.12 | 4.56±0.80 | 3.42±0.64 | |
| P†¶ | 0.002 | <0.001 | 0.011 | |
| TNF-α | 45.91±4.97 | |||
| 7th day | 48.22±2.59 | 45.37±2.18 | 40.46±3.23 | |
| P†¶ | 0.354 | 0.822 | 0.046 | |
| HYD | 190.12 (179.66–202.43) | |||
| 7th day | 190.11 (185.28–213.30) | 190.76 (183.47–196.17) | 231.93 (210.12–251.32) | |
| P‡¶ | 0.594 | 0.953 | 0.005 | |
| EGF | 87.16 (82.52–93.44) | |||
| 7th day | 97.66 (89.11–117.22) | 90.32 (79.63–91.61) | 100.98 (97.10–116.20) | |
| P‡¶ | 0.028 | 0.768 | <0.001 | |
| TAS | 11.50±1.01 | |||
| 7th day | 11.26±1.57 | 11.64±0.88 | 13.30±1.56 | |
| P†¶ | 0.730 | 0.794 | 0.017 | |
| TOS | 2.94±0.36 | |||
| 7th day | 3.38±0.26 | 3.21±0.15 | 2.93±0.10 | |
| P†¶ | 0.031 | 0.134 | 0.958 |
Where appropriate, data were shown as mean±SD or median (25th–75th) percentiles. †Student’s t-test, ‡Mann Whitney U test. The comparison between the control group, according to the Bonferroni Correction P<0.0083, was considered statistically significant
Pathology results showed that re-epithelialization and neovascularization between days 3 and 7 were significant in all groups (P < 0.05). Inflammatory cells in the quercetin group were significantly lower in day 3 (P < 0.05). The quercetin group was found effective as a sham group at day 3 for collagen formation [see Table 4].
Table 4.
*P<0,01, a, b, c, d, e: Differences between means with different letters in the same column are significant (P<0.05)
| Groups | Re-epithelialization M±SD | Neovascularization M±SD | Scarve ulcus M±SD | Collagen M±SD | Inflammatory cell M±SD |
|---|---|---|---|---|---|
| Control day 3 | 2,60a±0,82 | 0,00c±0,00 | 0,33de±0,82 | 1,00d±0,00 | 0,33d±0,82 |
| Sham day 3 | 0,33b±0,52 | 0,83b±0,41 | 2,17a±0,41 | 2,00c±0,63 | 2,83a±0,41 |
| Incision day 3 | 0,16b±0,41 | 0,50b±0,55 | 2,33a±0,52 | 1,00d±0,00 | 2,83a±0,41 |
| Incision + quercetin day 3 | 0,60b±0,52 | 0,83b±0,41 | 2,67a±0,52 | 2,17bc±0,75 | 2,50b±0,55 |
| Control day 7 | 3,00a±0,00 | 0,00c±0,00 | 0,00e±0,00 | 2,00c±0,00 | 0,00d±0,00 |
| Sham day 7 | 2,17a±1,33 | 2,67a±0,52 | 1,50b±0,55 | 1,67c±0,52 | 2,00bc±0,00 |
| Incision day 7 | 2,67a±0,52 | 3,00a±0,00 | 0,83cd±0,41 | 2,83a±0,41 | 1,83c±0,41 |
| Incision + quercetin day 7 | 2,50a±0,84 | 2,67a±0,52 | 1,17bc±0,41 | 2,67ab±0,52 | 1,83c±0,41 |
| P | 0,000* | 0,000* | 0,000* | 0,000* | 0,000* |
Discussion
The ROS, also known as reactive oxygen intermediates, are essential for preparing a normal wound-healing response. Consequently, ROS levels must be maintained at a balance between low and high. Some upcoming treatments aim to control this balance by using antioxidant products.[15]
It has been demonstrated in vitro and in vivo that quercetin is a flavanol with potent antioxidant properties, anti-inflammatory properties, and anti-fibrotic properties in various tissues.[16,17] There has been increased interest in using quercetin as a therapeutic in the ocular surface as a treatment for conditions such as neovascularization of the cornea, inflammation, keratoconus, and dry eye.[17]
During the proliferative phase of wound healing, neovascularization, re-epithelialization, and granulation tissue are observed. A period of several weeks may be required to complete this process.[18] In our study, re-epithelialization and neovascularization occurred between days 3 and 7. The day was significant in all groups, as expected in the wound-healing process.
During the inflammatory stage, chemotaxis, an increase in vascular permeability, and hemostasis prevent further damage and closing the wound. A few days are necessary for the inflammatory stage.[18]
In our study, inflammatory cells in the quercetin group were significantly lower in day 3. IL-1 blood levels and TNF-α were significantly lower in the quercetin group than in other groups. Also, IL-6 was found to be significantly lower at day 7 in quercetin group in comparison with other groups. It shows the anti-inflammatory properties of quercetin, which can lead to decreased wound-healing time. Inflammatory cells counts between 3 and 7 were not significant because the inflammatory stage is an early stage of wound healing.
The quercetin group is influential as the sham group at day 3 for collagen formation, and HYD value is significantly higher in blood, supporting collagen production in the early stages of wound healing. Our study revealed that quercetin reduced TOS levels compared to sham. It supports the antioxidant properties of quercetin.
At this stage, quercetin was found to be anti-inflammatory and an antioxidant in our study; however, it should be supported by future studies before using clinical treatments.
There has been evidence in vitro and in vivo that quercetin is potently antioxidant, anti-inflammatory, and antifibrotic in various tissues. In this study, quercetin was investigated for its effects on wound healing in the eyelids, an area that has not been studied before and has fragile skin.
All authors have made significant contributions to this publication in terms of Conception/Design of the Study, Data Collection, Data Analysis/Interpretation, Manuscript Preparation, Critical Revision of the Manuscript, Final Approval and Responsibility, Technical or Material Support, Supervision.
Conclusion
In our study, quercetin was found to be anti-inflammatory and antioxidant. These properties can lead to decrease wound-healing time. Also, quercetin healed wounds and scavenged free radicals effectively.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
References
- 1.Bernstein EF. Reactive oxygen species activate the human elastin promoter in a transgenic model of cutaneous photoaging. Dermatol Surg. 2002;28:132–5. doi: 10.1046/j.1524-4725.2002.00328.x. [DOI] [PubMed] [Google Scholar]
- 2.Ponugoti B, Xu F, Zhang C, Tian C, Pacios S, Graves DT. FOXO1 promotes wound healing through the up-regulation of TGF-?1 and prevention of oxidative stress. J Cell Biol. 2013;203:327–43. doi: 10.1083/jcb.201305074. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Gottrup F, Agren MS, Karlsmark T. Models for use in wound healing research: A survey focusing on in vitro and in vivo adult soft tissue. Wound Repair Regen. 2000;8:83–96. doi: 10.1046/j.1524-475x.2000.00083.x. [DOI] [PubMed] [Google Scholar]
- 4.Mogford JE, Mustoe TA. Experimental models of wound healing. In: Falanga V, editor. Cutaneous Wound Healing. London: Martin Dunitz; 2001. pp. 109–22. [Google Scholar]
- 5.Starace M, Orioni G, Alessandrini A, Bruni F, Baraldi C, Misciali C, et al. Digital ulcers: Multidisciplinary approach and dermatological management. Dermatol Pract Concept. 2023;13:e2023019. doi: 10.5826/dpc.1301a19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Raffetto JD. The definition of the venous ulcer. J Vasc Surg. 2010;52((5 Suppl)):46S–49S. doi: 10.1016/j.jvs.2010.05.124. [DOI] [PubMed] [Google Scholar]
- 7.Kant V, Jangir BL, Sharma M, Kumar V, Joshi VG. Topical application of quercetin improves wound repair and regeneration in diabetic rats. Immunopharmacol Immunotoxicol. 2021;43:536–53. doi: 10.1080/08923973.2021.1950758. [DOI] [PubMed] [Google Scholar]
- 8.Xu F, Zhang C, Graves DT. Abnormal cell responses and role of TNF-? in impaired diabetic wound healing. Biomed Res Int. 2013;2013:754802. doi: 10.1155/2013/754802. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Liu R, Bal HS, Desta T, Behl Y, Graves DT. Tumor necrosis factor-alpha mediates diabetes-enhanced apoptosis of matrix-producing cells and impairs diabetic healing. Am J Pathol. 2006;168:757–64. doi: 10.2353/ajpath.2006.050907. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Han YP, Tuan TL, Wu H, Hughes M, Garner WL. TNF-alpha stimulates activation of pro-MMP2 in human skin through NF-(kappa) B mediated induction of MT1-MMP. J Cell Sci. 2001;114:131–9. doi: 10.1242/jcs.114.1.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Khanna S, Biswas S, Shang Y, Collard E, Azad A, Kauh C, et al. Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice. PLoS One. 2010;5:e9539. doi: 10.1371/journal.pone.0009539. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Kasiewicz LN, Whitehead KA. Lipid nanoparticles silence tumor necrosis factor ? to improve wound healing in diabetic mice. Bioeng Transl Med. 2018;4:75–82. doi: 10.1002/btm2.10123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Gomathi K, Gopinath D, Rafiuddin Ahmed M, Jayakumar R. Quercetin incorporated collagen matrices for dermal wound healing processes in rat. Biomaterials. 2003;24:2767–72. doi: 10.1016/s0142-9612(03)00059-0. [DOI] [PubMed] [Google Scholar]
- 14.Yin G, Wang Z, Wang Z, Wang X. Topical application of quercetin improves wound healing in pressure ulcer lesions. Exp Dermatol. 2018;27:779–86. doi: 10.1111/exd.13679. [DOI] [PubMed] [Google Scholar]
- 15.McKay TB, Karamichos D. Quercetin and the ocular surface: What we know and where we are going. Exp Biol Med (Maywood) 2017;242:565–72. doi: 10.1177/1535370216685187. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Cheng J, Luo XQ, Chen FS. Quercetin attenuates lipopolysaccharide-mediated inflammatory injury in human nasal epithelial cells via regulating miR-21/DMBT1/NF-?B axis. Immunopharmacol Immunotoxicol. 2022;44:7–16. doi: 10.1080/08923973.2021.1988963. [DOI] [PubMed] [Google Scholar]
- 17.Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: Mechanisms, signalling, and translation. Sci Transl Med. 2014;6:265sr6. doi: 10.1126/scitranslmed.3009337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Wallace HA, Basehore BM, Zito PM. StatPearls. Treasure Island (FL): StatPearls Publishing; 2022. Wound healing phases. [PubMed] [Google Scholar]
