TABLE 1.
Summary of in vitro studies investigating the effects of resveratrol on wound healing, scarring, and photo‐aging
| Study topic | Author, year | Cohort | Test substance | Setting | Effects |
|---|---|---|---|---|---|
| Wound healing | Brakenhielm et al (2001) 32 | Bovine capillary endothelial cells, chick chorioallantoic membrane | 1–100 μg RES discs |
Effect of RES on fibroblast growth factor 2 (FGF‐2)‐induced activation of mitogen‐activated protein kinases in bovine capillary endothelial cells; effect of RES in porcine aortic endothelial cell lines; antiangiogenic activity of RES in chick chorioallantoic membrane (1–100 μg per disc.) Parameters evaluated: FGF‐2 and vascular endothelial growth factor (VEGF) receptor‐mediated endothelial cell growth and chemotaxis |
RES inhibits FGF‐2 and VEGF receptor‐mediated endothelial cell growth and chemotaxis. Dose‐dependent inhibitory effect on angiogenesis of RES. |
| Khanna et al (2001) 33 | Human keratinocytes (line HaCaT) | GSPE (grape seed proanthocyanidin extract) containing 5000 ppm trans‐RES |
Keratinocytes treated with GSPE; washed with GSPE‐free medium before, then challenged with H2O2 (hydrogen peroxide) or TNF‐α Parameters evaluated: VEGF |
Treatment with GSPE upregulated H2O2 and TNF‐α induced VEGF expression and release | |
| Chan et al (2002) 34 | Bacteria and dermatophytes | 3.12, 6.25, 12.5, 25, 20, 100 μg/mL RES | Susceptibility testing of bacteria (Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa) and dermatophytes (Trichophyton mentagrophytes, Trichophyton tonsurans, Trichophyton rubrum, Epidermophyton floccosum, Microsporum gypseum) in control medium, dimethyl sulphoxide solvent, and RES. | RES inhibited the growth of bacteria and dermatophytes in a dose‐dependent manner. Higher RES concentration resulted in better growth inhibition of bacteria and dermatophytes. | |
| Pastore et al. (2013) 35 | Human epidermal keratinocytes (HEK) | 50 μM RES |
HEK from 4 healthy donors: verbascoside (control), RES 50 μM Parameters evaluated: IL‐8 expression, extracellular‐signal regulated kinase (ERK), p65, c‐Fos, epidermal growth factor receptor (EGFR), NHEK proliferation |
IL‐8 overexpression, ERK phosphorylation was transiently inhibited, enhanced p65 and EGFR phosphorylation, c‐Fos upregulation, NHEK proliferation inhibited | |
| Eroğlu et al (2014) 36 | Normal skin‐derived fibroblasts (NSFBs); | RES loaded into microparticles consisting of dipalmitoylphosphatidylcholine and hyaluronic acid | Cell culture of NSFBs: RES‐loaded microparticles Parameters evaluated: cellular proliferation (CP), total glutathione (GSH), oxidised glutathione (GSSG), glutathione peroxidase (GPx), malondialdehyde (MDA), superoxide dismutase (SOD) | RES‐loaded microparticles increased CP, decreased oxidation in cells by GSH/GSSHG ratio reduction. No effect of RES in GPx, MDA, and SOD. | |
|
Abbas et al (2019) 37 |
Human fibroblasts | Flavonoids (chrysin, naringenin, RES) with β‐sitosterol |
Scratch‐wound migration assay: Parameters evaluated: closure rate, cytotoxicity, fibroblasts migration |
β‐sitosterol combined with RES and β‐sitosterol combined with naringenin achieved the best closure rates. No toxic effect on fibroblasts was detected. | |
| Comotto et al (2019) 38 | Human keratinocytes | Alginate dressings with natural antioxidants (curcumin; RES) |
Determination of the optimal concentration of the active compounds Parameters evaluated: release rate, cellular growth, bacterial growth |
Release rate: burst release followed by a gradual release; 300 μg/mL of RES did not induce any toxicity; curcumin and RES showed an improved cell viability; curcumin was superior regarding anti‐microbial properties | |
| Meng et al (2019) 39 | Human adipose stem cells | Bacterial cellulose conjugated with RES, collagen conjugated with RES |
In vitro biocompatibility: adipose stem cells were cultured in keratinocyte serum‐free medium with foetal bovine serum. Examination of the samples by immunocytochemical staining. |
RES‐conjugated bacterial cellulose created a biocompatible environment for stem cell attachment and cell growth. | |
| Huang et al (2019) 40 | Human umbilical vein endothelial cells (HUVECs) | 10 μM RES |
HUVECs in high glucose medium (HGM), HGM + 10 μM RES, normal glucose medium (NGM), NGM + 10 μM RES Parameters evaluated: CP, cell migration, apoptosis |
RES treatment increased hyperglycemia‐impaired endothelial CP. HGM induced cell migration and apoptosis alleviated by RES |
|
| Kaleci et al (2020) 41 | 3 T3 Swiss Albinofibroblasts | 1, 5, and 10 μM RES in combination with 500 μM H2O2 |
Fibroblasts, 4 groups: control group, 500 μM H2O2, RES, 500 μM, H2O2 + RES group Parameters evaluated: CP, OS (oxidative stress) level, collagen‐I‐expression, cell migration |
RES application showed better CP rates compared to the other groups. Best CP results with 1 μM RES. RES decreased H2O2‐induced high OS. No impact of RES in collagen‐I‐expression or cell migration compared to control group. |
|
| Scarring | Zeng et al (2013) 42 | Hypertrophic scar‐derived fibroblasts (HSFBs) | RES 25, 75, 150, 300 and 400 μM |
Cell culture of HSFBs and NSFBs from two young female donors: control, RES 25 μM, RES 75 μM, RES 150 μM, RES 300 μM, and RES 400 μM over the time (24 h, 48 h and 72 h) Parameters evaluated: cell proliferation (CP), cell cycle progression, apoptosis, hydroxyproline, collagen |
RES suppressed cell growth, arrested cell cycle progression, triggered apoptosis in a dose‐ and time‐dependent manner (increased effect with longer duration and higher concentration). RES downregulated mRNA expression of type I and III procollagen in fibroblasts, resulting in significant decreases in hydroxyproline and collagen |
| Zhai et al (2015) 43 | Human pathologic scar‐derived fibroblasts (PSFBs) | RES 10, 50, and 100 μmol/L |
Cell culture with fibroblast from 20 patients. 4 groups: control, RES 10, RES 50, 100 μmol Parameters evaluated: morphological changes in target cells, CP, TGF‐β1, Smad‐2,3,4,7 |
Apoptotic morphological alterations and reduced CP in RES‐treated pathological scar fibroblasts. Inhibitory effect in CP enhanced with increasing RES concentration. TGF‐β1, Smad‐2,3,4 negatively and Smad‐7 positively correlated with RES concentration. | |
| Bai et al (2016) 44 | HSFBs and NSFBs | RES 2.5, 5, 10, 20, and 40 mM |
Cell culture of HSFBs and NSFBs from 9 patients. SIRT1 upregulation by RES. Parameters evaluated: SIRT1, collagen 1, collagen 3, α‐smooth muscle Actin (α‐SMA), TGF‐β1 |
SIRT1 intensity lower in HSFBs compared to NSFBs. RES down‐regulated mRNA levels of collagen 1, collagen 3, α‐SMA due to upregulation of SIRT1 in a dose‐dependent manner. RES inhibited TGF‐β1‐induced mRNA/protein level increase of collagen 1, collagen 3, and α‐SMA. | |
| Tang et al (2017) 45 | PSFBs and NSFBs | RES 10, 50, and 100 μmol/L |
Cell culture of PSFBs and NSFBs from patients: control, RES 10 μmol/L, RES 50 μmol/L, 100 μmol/L Parameters evaluated: mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (70S6K) |
Strengthened mTOR and 70S6K expression in PSFBs compared to NSFBs. Decreased expression of mTOR and 70S6K in dose‐dependent manner. |
|
| Pang et al (2020) 46 | HSFBs and NSFBs | RES 0, 1, 10, 100 μmol/L |
Cell culture of HSFBs and NSFBs: control, RES 1 μmol/L, RES 10 μmol/L, 100 μmol/L over the time (24, 48, 72 h) Parameters evaluated: cell viability (CV), microRNA‐4654, Rheb, 1A/1B‐light chain (LC3), Beclin 1 |
RES decreased CV in dose‐dependent manner (increased effect with higher concentration). RES upregulated microRNA‐4654 expression level in dose‐dependent manner, thus downregulated Rheb expression level and upregulated autophagy markers LC3 and Beclin 1 |
|
| Photo‐aging | Subedi et al (2017) 47 | NSFBs | RES and RESl‐enriched rice (RR) |
Cell culture with NSFBs from a healthy young male donor UV‐B irradiation and treatment with normal rice, RR and RES afterwards Parameters evaluated: ROS (reactive oxygen species), MMP‐1 (matrix metalloproteinase 1), collagen I |
RR demonstrated the most effective reduction of ROS production compared to normal rice or RES alone. RR induced a downregulation of MMP‐1 (matrix metalloproteinase 1), inhibition of inflammatory cascades, and upregulation of collagen type I. |
| Zhou et al (2018) 48 | Human keratinocytes (HaCaT cell line) | RES (<99%): 2.5, 5, 7.5, and 10 mm |
Cell culture with keratinocytes s, UV‐B irradiation for 5 min at 10 cm below the lamp (irradiation intensity: 0.1 mW/cm2) Parameters evaluated: CV, apoptotic rate |
Dose‐dependent increase of CV of RES pretreated cells and decrease of apoptotic rate. Increase of HSP27 expression resulting in antiapoptotic effects through inhibiting NF‐kB and caspase‐3 activation. |
Abbreviations: α‐SMA, α‐smooth muscle actin; CP, cellular proliferation; CV, cell viability; EGFR, epidermal growth factor receptor; ERK, extracellular‐signal regulated kinase; FGF‐2, fibroblast growth factor 2; GPx, glutathione peroxidase; GSH, total glutathione; GSPE, grape seed proanthocyanidin extract; GSSG, oxidised glutathione; H2O2, hydrogen peroxide; HGM, high glucose medium; HSFBs, hypertrophic scar‐derived fibroblasts; HUVECs, human umbilical vein endothelial cells; LC3, 1A/1B‐light chain; MDA, malondialdehyde; MMP‐1, matrix metalloproteinase 1; NGM, normal glucose medium; NSFBs, normal skin‐derived fibroblasts; OS, oxidative stress; PSFBs, pathologic scar‐derived fibroblasts; RES: resveratrol; ROS, reactive oxygen species (ROS); RR, resveratrol‐enriched rice; SOD, superoxide dismutase; TNF‐α, tumour necrosis factor alpha; VEGF, vascular endothelial growth factor.