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Background:
Systematic Review

Berry Fruit Extracts as Topical Cosmeceuticals for Skin Health Applications: A Systematic Review

by
Filipe Silveira Azevedo
1,
Allan Rodrigues Pires
1,
Mary Ann Lila
2,
Giuseppe Valacchi
3,4,5,
Roberta Targino Hoskin
2,6,
Mariaurea Matias Sarandy
1,3,
Rômulo Dias Novaes
7 and
Reggiani Vilela Goncalves
1,3,8,*
1
Cellular and Structural Biology Graduate Program, Federal University of Viçosa, Viçosa 36570-000, MG, Brazil
2
Department of Food, Bioprocessing and Nutrition Sciences, Plants for Human Health Institute, NC State University, Kannapolis, NC 28081, USA
3
Department of Animal Sciences, Plants for Human Health Institute, North Carolina State University, Kannapolis, NC 28081, USA
4
Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy
5
Department of Food and Nutrition, Kyung Hee University, Seoul 02447, Republic of Korea
6
Department of Chemical Engineering, Federal University of Rio Grande do Norte, Natal 59078-970, RN, Brazil
7
Department of Structural Biology, Biomedical Science Institute, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
8
Department of Animal Biology, Federal University of Viçosa, Viçosa 36570-000, MG, Brazil
*
Author to whom correspondence should be addressed.
Cosmetics 2025, 12(3), 87; https://doi.org/10.3390/cosmetics12030087
Submission received: 20 March 2025 / Revised: 16 April 2025 / Accepted: 18 April 2025 / Published: 23 April 2025
(This article belongs to the Special Issue Feature Papers in Cosmetics in 2025)
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Versions Notes

Abstract

:
Berries are a popular source of natural bioactive compounds with distinctive aspects and sensory attributes. In this review, the term “berry” refers to generally round, small, colorful, and juicy fruits with English common names ending in “berry”. They have high phenolic content, which has been linked to their health-relevant properties. To gather information on the potential of berries for treating skin inflammatory diseases, this systematic review was conducted following PRISMA guidelines (PROSPERO registration number CRD 42024549567), based on studies from PubMed, Scopus, Web of Science, and Embase. It focused on preclinical murine model studies, with bias and methodological quality assessed using SYRCLE’s RoB tool. Studies showed evidence that berries have anti-inflammatory and antioxidant properties due to compounds like anthocyanins, cyanidins, polyphenols, and catechins. Berry exposure reduced oxidative stress markers, such as malondialdehyde, carbonylated proteins, nitric oxide, 8-OHdG, and pyrimidine dimers. This stress reduction was associated with NF-κB and COX-2 pathway downregulation, lower IL-6, IL-1β, TNF-α, and MAPK, and increased IL-10. Morphological outcomes included increased collagen, elastin, glycosaminoglycans, and proteoglycans and reduced metalloproteinases. Bias analysis revealed a low risk, suggesting reliable studies. Berry treatments improved wound healing and extracellular matrix (ECM) production, supporting their potential in pharmaceutical topical formulation.

Graphical Abstract

1. Introduction

Nature-inspired skin care products are now an increasing market trend. The global natural cosmetics market was valued at USD 31.84 billion in 2023 and is projected to grow at a compound annual growth rate of 5.3% from 2024 to 2030 [1]. This market revolution reflects a “return to nature” trend, a term increasingly used in the cosmetic industry’s research and development arena [2,3]. One of the factors behind the growing desire to venture into healthier cosmetics is the concern about potentially harmful synthetic chemicals and their effects on the skin. Natural products are considered safer, have a lower likelihood of causing allergies and irritations, and are more sustainable alternatives for the environment [4,5].
In this regard, food-derived molecules have been explored as ingredients for this emerging skin care market trend. We are now witnessing a process of converging industries—in this case, food and pharmaceuticals—that consists of merging knowledge from different domains to produce hybrid products, technologies, and novel inter-industry segments, and it constitutes a fertile field for entrepreneurs [6,7]. “Food and medicine are homologous” is not a new concept, and it expresses the perception that food, besides its nutritional value, has beneficial physiological effects on the human body, including skin health [8,9]. We already know that some phytochemical compounds have the power to induce rejuvenation, hydration, antioxidant power, and regenerative capacity and, consequently, increase the production of collagen, elastin, and hyaluronic acid, improving skin quality [10,11].
Indeed, phytochemicals from botanical sources have long been used as multifaceted molecules with potent bioactivity and relevant applications for human health. Berries are a popular source of natural bioactive compounds with distinctive aspects, sensory attributes, and generally high phenolic loads, including phenolic acids, anthocyanins, and proanthocyanidin [12,13]. Antibacterial activity, antioxidant and anti-inflammatory effects, and other underlying mechanisms for activating biological responses to skin-related disorders have been consistently reported for berry extracts [14,15]. In addition, possible synergistic interactions showcased in chemically complex extracts, such as berry-derived ones, make them promising ingredients for advancing skin health formulations for cosmetic and skin care products.
Our research group has been actively investigating berries as unique sources of active agents for food and pharmaceutical products with enhanced properties and improved stability [16,17]. However, despite the ever-increasing interest in the field, to the best of our knowledge, there has not been any systematic review addressing the effects of berry extracts on skin health. Therefore, the objective of this study was to conduct a systematic literature survey to provide a realistic overview of the impact of berry fruit extracts on topical skin care interventions. Our work aims to summarize published evidence and elucidate this therapeutic strategy’s main results and limitations to understand better the role of berry extracts as human health and well-being promoters and their potential for the cosmeceutical market.

2. Materials and Methods

2.1. Focus Question and Registration on the Prospero Platform

This systematic review was based on the following focal question: what are the topical effects of berry fruit extracts on skin inflammation in animal models?
The PICO (population, intervention, comparison, and outcomes) strategy was defined as the criteria for including studies in the systematic review. The registration number on the Prospero platform is CRD 42024549567.

2.2. Eligibility Criteria

Studies that assessed the effect of berry fruit extracts on skin inflammation in murine models were included in this systematic review. Studies that approached extracts obtained from edible berry fruit parts (seeds, skin, and pulp) were included. The exclusion criteria were defined as follows: (i) studies ex vivo, (ii) studies with humans, (iii) studies that did not involve murine models, (iv) studies that did not involve berries, (v) studies that involved plant parts other than the berry fruits, and (vi) studies that did not deal with skin applications.

2.3. Literature Search Strategy

This study was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [18], which were used as a guide for the selection, screening, and eligibility of studies (Figure 1), following the PRISMA checklist (Table S1). The literature search included studies available on the databases PubMed/Medline (www.ncbi.nlm.nih.gov/pubmed, accessed on 20 November 2024), Scopus (www.scopus.com, accessed on 20 November 2024), Web of Science (www.webofknowledge.com, accessed on 20 November 2024), and Embase (https://www.embase.com, accessed on 20 November 2024). Filters based on the following criteria were applied in all databases: (i) animal models, (ii) berries, and (iii) skin (please see Table S2).
In this review, the term “berry” refers to the generally round, small, colorful juicy fruits with English common names ending in berry [19]. After a preliminary evaluation of the literature, berries belonging to the families Vitaceae, Rosaceae, Fabaceae, Adoxaceae, Punicaceae, Ericaceae, Schisandraceae, and Caprifoliaceae were included in this study [19].
A search filter was initially developed for PubMed/Medline according to standardized descriptors (Medical Subject Headings, MeSH terms) organized in the hierarchical tree of the MeSH database (https://www.ncbi.nlm.nih.gov/mesh, accessed on 20 November 2024). The commands (MeSH terms) and title and abstract (TIAB) were combined to optimize the retrieval of relevant indexed studies. The search matrix used in the PubMed/Medline database was adapted for Scopus and Web of Science by using the search algorithms TITLE-ABS-KEY or TS=, respectively. For the Embase database, the filters were applied using the “limit to” tool. Table S1 contains a detailed description of the search strategy for this review.
Duplicate records and review articles were removed. Two independent reviewers (FSA and ARP) analyzed the titles and abstracts to ensure that eligibility criteria were met. Other independent researchers (MMS, MAL, GV, RTH, RDN, and RVG) were used to arbitrate and decide whether a given study met the eligibility criteria.

2.4. Data Extraction and Synthesis

The essential data from each study were extracted through structured tables according to the following descriptive levels: (i) study characteristics (authors, year, country, scientific journal, and title), (ii) characteristics of the experimental model (sex, age, strain, weight, transgenic, sample number, type of anesthesia, and ethical regulations), (iii) characteristics of the berry intervention (type of berry, scientific name, source, part of the fruit, type of extract, main compounds, dosage, and intervention duration), (iv) inflammation (induction of the inflammation, region, time to treatment application, inflammation measurements), (v) primary outcomes (oxidative stress, antioxidant enzymes, pro-inflammatory markers, and anti-inflammatory markers), and (vi) secondary outcomes (extracellular matrix, inflammatory cells, and associated pathologies).

2.5. Risk of Bias

The risk of bias was analyzed using the program “Systematic Review Centre for Laboratory Animal Experimentation” (SYRCLE) [20]. To help guide the judgment of researchers and increase the transparency and applicability of these studies, some standards and specific questions were applied based on the following domains: (i) random sequence generation (if the animals in the experimental groups were randomly selected), (ii) allocation concealment (whether the allocation of the animals was blinded), (iii) blinding of participants and personnel (whether the animals were blinded during the treatments), (iv) blinding of outcomes assessment (whether the scientists were blinded during the analysis of the material), (v) incomplete outcome data (whether the results corresponded to everything conducted during the methodology), (vi) selective reporting (whether the studies reported all of the data that were extracted), (vii) ethics committee (whether the experiments were approved by an ethics committee), (viii) inflammation measure (whether analyses related to inflammatory processes were conducted), (ix) animals’ information (strain, sex, age, weight, animals per group), (x) phytochemical characterization (whether any analysis regarding the chemical or structural composition of the berry was conducted), (xi) intervention (the methodology used for the treatments conducted), (xii) conflicts of interest, and (xiii) other biases (images, graphs, tables). These items were scored as “low risk of bias”, “high risk of bias”, or “unclear” (indicating that the item was not reported, and, therefore, the risk of bias was unknown). The individual quality criteria obtained using the SYRCLE system were expressed through graphics using the Review Manager 5.4 program (The Nordic Cochrane Centre, Copenhagen, Denmark, The Cochrane Collaboration).

3. Results

3.1. Characteristics of the Publications

From the four databases used in this study, 932 articles were recovered from PubMed, 652 from Scopus, 375 from the Web of Science, and 1149 from Embase, totaling 3108 articles for this study. A total of 397 studies were removed for duplicity, and 2711 were excluded after reading the abstract and title due to lack of adherence to eligibility criteria. The remaining 80 articles were submitted to a full-text review, and 51 were excluded because they did not meet the eligibility criteria: 38 were excluded for not investigating berry extracts, and 13 studies were excluded for not involving skin studies. Therefore, 29 articles were included in this systematic review [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44]. The reference lists of the included articles were examined to determine if additional studies should be included, but no new relevant studies were identified through this method. Of the 29 articles, 6 included both in vivo and in vitro experiments, while the remaining included only in vivo experiments. Figure 1 shows the step by step selection process.
Regarding the location of the studies, Romania and Korea had the highest number of studies (13.79% of the total), followed by Egypt and the United States of America (10.34% of the total each). Iran represented 6.89% of the total, while Canada, Brazil, India, Georgia, Peru, Taiwan, Trinidad and Tobago, Tunisia, Turkey, and China comprised 3.45% of the studies each. All studies were published in the 2000s (Figure 2).

3.2. Characteristics of Animal Models

The most commonly used animal models were mice (68.97%, n = 20), followed by rats (31%, n = 9). Among the studies involving mice and rats, the most frequently used strain was SKH-1 and Wistar, representing 17.24% of the studies, followed by the Balb/C strain (13.79%), the Swiss strain (10.34%), and Sencar and Sprague Dawley strains (6.89%). Lastly, C57BL/6, C57/Black, ICR-Foxn/nu, ICR, Lewis, CD-1, and NC/Nga strains represented 3.45% (n = 1) of the studies each.
Regarding the sex of the animals, most studies used males (58.62%, n = 17), followed by females with 37.93%, n = 11, while only one study used both genders. Predominantly, the age of the animals ranged from 5 to 9 weeks (55.17%; n = 16), while two studies used older animals (3 to 4 months) (6.89%, n = 2). A significant fraction of the studies did not report on the age of the animals (37.93%, n = 11). The weight of the animals varied from 20 g to 25 g (27.58%, n = 8) and from 100 g to 300 g (31%, n = 9). The remaining studies did not provide this information (41.37%; n = 12). Five studies did not provide any information regarding the approval of the study by the ethics committee (Table S3).

3.3. Characteristics of the Berries

Most (93%) of the studies reported which type of berry was used in the study. Among them, 44.83% (n = 13) were conducted with the Vitis genus and 13.79% (n = 4) with Prunus, Schisandra, and Rubus, while 6.89% (n = 2) of the studies approached the Vaccinium genus. Additionally, 3.45% (n = 1) involved Dipteryx, Punica, Lonicera, and Sambucus. Most studies (82.75%, n = 24) indicated berries’ sourcing (Table S4).
The seeds were the most commonly studied berry part, with 44.83% (n = 13) of the studies. The whole berry, juice, and skins accounted for 34.48% (n = 10), 10.34% (n = 3), and 6.89% (n = 2) of the studies, respectively. Additionally, 3.45% (n = 1) investigated seed oil, and 3.45% (n = 1) of the studies used two different parts of the berry (fruit and seed) (Figure 2).
Concerning the type of extract, the most predominant (31% of the studies) was water-based extracts, followed by the ethanolic, acetone, and methanolic extracts, which were used in 24.14% (n = 7) and 10.34% (n = 3) of the studies, respectively. Powdered extracts were investigated in 6.89% (n = 2) of the studies, and 4.16% (n = 1) used the juice extracted from the berry and ethyl acetate extract. Three studies did not mention the type of extract used. Regarding the main compound present in the extract, 24.14% (n = 7) included types of phenolic compounds, like polyphenols, phenolic acids, anthocyanidins, and cyanidins, followed by 3.45% of the studies characterizing the main compound as glycosides and schisandrin B. Furthermore, 62.07% of the studies did not mention the main compound found in the extract (Table S4).

3.4. Characteristics of the Intervention

The time length of the intervention varied between 1 and 30 days in 79.31% of the studies (n = 23). In 13.69% (n = 4) of the studies, the intervention lasted from 40 to 140 days. One study consisted of just a single treatment, while another did not mention the length of the intervention.
All of the studies considered in this review treated the wounds topically. Skin wounds were treated once a day in 34.48% (n = 10) of the studies, 13.79% (n = 4) treated the wound only once during the length of the experiment, and 10.34% (n = 3) treated the wounds twice a day. One study (3.45%) included a treatment conducted twice weekly, while 31% (n = 9) of the studies did not mention the frequency of treatment application. Regarding the wound inflicted on the animals, 34.48% (n = 10) of the studies did it through UVB light radiation, 31% (n = 9) induced the wound using surgery clippers, a biopsy tool, and excision, 13.79% (n = 4) inflicted the wound through 12-O-tetradecanoylphorbol 13-acetate (TPA) application, and 6.89% (n = 2) used 1-Fluoro-2,4-dinitrofluorobenzene to inflict the wound. The rest of the studies used different methods to induce the wound and inflammation, like 7,12-dimethylbenz[a]anthracene (DMBA) plus TPA together and calcipotriol and a hot rod (3.45%, n = 1 each). Only one study did not mention the induction of the wound. Concerning the region of the wound, 82.75% (n = 24) of the studies inducted wounds in the dorsal region of the animal, 3.45% (n = 1) inducted wounds in the ear and the thorax each, and one study did not mention it (Table S4).

3.5. Main Outcomes

Oxidative Stress and Inflammation Markers

Animals treated topically with berry extracts showed reduced oxidative stress markers in skin cells. There was a decrease in the malondialdehyde (MDA) marker by 10.34% (n = 3), carbonylated proteins (PC) by 3.45% (n = 1), nitric oxide by 6.89% (n = 2), and DNA damage markers, such as 8-OHdG and pyrimidine dimers (CPD), by 13.79% (n = 4), indicating that treatment with berries was efficient in controlling the free radicals and reactive oxygen species (ROS) generation inside of the cells due to its capacity as a free radical scavenger. Regarding antioxidant enzymes, berries were shown to act as catalysts in activating the cells’ natural defense mechanisms in two studies, which showed an increase in superoxide dismutase, catalase, and glutathione S-transferase (GST) activity (6.89%, n = 2). One study reported that the decrease in GST was due to radiation’s potential inhibition of enzyme activity. However, another study observed a 3.45% increase in GST levels. Notably, the second study had a longer treatment duration, suggesting a potential long-term activation effect of GST. Only one study did not show differences in the activity of CAT and GST (3.45%).
Regarding inflammatory markers, the topical treatment with berries directly influenced nuclear inflammation pathways, reducing NF-κB expression (13.79%, n = 4). Consequently, there was a decrease in the expression of iNOS (inducible nitric oxide synthase) by 10.34% (n = 3), which contains two binding sites in NF-κB promoter genes responsible for increasing its expression. In four studies, berries’ treatment also reduced the expression of COX-2 (cyclooxygenase-2) (13.79%) and, in one of them, the MAPK pathway also decreased (3.45% each). Additionally, a decrease in certain pro-inflammatory cytokines was observed, including IL-6 and TNF-α in five studies (17.2%), IL-1β in two studies (6.89% each), and IFN-γ, IL-4, IL-8, and MCP-1 in one study each (3.45%). However, two studies reported an increase in IL-1β and TGF-β levels (3.45% each). Regarding anti-inflammatory markers, there was a decrease in Nrf2 and IκBα pathway expression (3.45% each), which act as antagonists to NF-κB. Furthermore, there was an increase in IL-10 (10.34%), a cytokine known for inhibiting the inflammatory action of other cytokines.

3.6. Secondary Outcomes

Histological Markers and Associated Disorders

Collagen was the extracellular matrix component that exhibited the greatest enhancement caused by the berry extract treatments, showing an increase in its deposition (17.24%; n = 5), followed by elastin, fibronectin, and hydroxyproline (3.45%, n = 1, each), indicating the effect of topical berry treatment on wound closure and healing. In two studies, there was a decrease in metalloproteinases MMP-1 and MMP-2 (3.45%, n = 1, each), which are directly related to collagen degradation. Regarding the cells involved in the inflammatory processes, there was a reduction in nonspecific inflammatory infiltrates in animals treated with berry extracts (13.8%, n = 4) and a decrease in mast cells (6.89% n = 2), along with a decreased number of mononuclear cells and neutrophils (3.45%, n = 1 for each).
The topical treatment with berries affected the pathological conditions associated with animal wound models. Regarding skin health, six studies showed increased wound closure (20.69%, n = 6). Concerning disturbances in cell proliferation, there was an increase in epidermal thickness in four studies (13.8%, n = 4). Additionally, a decrease in tumors and improved skin wrinkling were observed (3.45%, n = 1 each).
When it comes to circulation disorders, two studies demonstrated a decrease in erythema (10.34%, n = 3), and one study showed a reduction in edema (3.45%, n = 1), followed by a study indicating an increase in tissue nutrition due to the increase of angiogenesis (3.45%, n = 1). Additionally, berry topical treatments reduced cellular apoptosis (10.34%, n = 3) by reducing the activation of apoptosis pathways like caspase 3 and BAX proteins. Figure 3 provides a summary of the results.

3.7. Reporting the Bias of Studies

The bias analysis results are shown in Figure 4 and Figure S1. Only three items (incomplete outcome data, animal information, and intervention) were reported in 100% of the studies, which was considered a low risk of bias (100%; n = 29). Among the items evaluated for risk of bias, nine were predominantly assessed as low risk of bias: blinding of participants and personnel (96.55%; n = 28), included ethics committee information (93%; n = 27), inflammation measure (89.6%; n = 26), random sequence generation (44.8%; n = 13), conflicts of interest (75.86%; n = 22), statistical analysis (93.1%; n = 27), and other biases (more information about the inflammation or berries or presentation of images, tables, or graphs) (79.3%; n = 23). The items with a predominantly high risk of bias were allocation concealment (48.3%; n = 14), blinding outcome assessment (96.5%; n = 28), selective reporting (58.6%; n = 17), and phytochemical characterization (55.17%; n = 16). Three items were assessed in some studies as unclear risk, indicating that the information provided was insufficient to understand the risk of bias: random sequence generation, allocation concealment, and other biases (17.24%; n = 5) (20.7%; n = 6) (10.34%; n = 3).

4. Discussion

4.1. General Information

Berries are popular fruits worldwide and have gained prominence due to their anti-inflammatory and antioxidant properties [45,46]. While commonly consumed as part of the diet, berries have recently gained attention in research for their potential for developing topical treatments for inflammatory skin conditions. However, little is known about the relationship between inflammatory and oxidative stress markers in the skin after berry exposure. A comprehensive analysis of signaling pathways and the relationship of mechanisms involved in oxidative damage with its physiological response has not been systematically evaluated. Understanding the therapeutic potential of berries in treating inflammatory skin diseases may not only advance the field of dermatology—by promoting wound healing, enhancing cell regeneration, and improving collagen and elastin synthesis—but also contribute to the cosmetics industry by supporting the development of products that increase skin hydration and radiance. Furthermore, this knowledge may pave the way for the formulation of new natural drugs within the pharmaceutical field (Figure 5). With that in mind, this systematic review aims to provide a comprehensive overview of the current state of knowledge on the development of this area of study.
The inflammatory process is activated in response to external or internal stressors and threats requiring an immune defense. Stressors activate a cascade of pro-inflammatory mediators that recruit immune cells to the target tissue, including macrophages, neutrophils, and leukocytes [47,48,49]. The enzymes and substances like hydrogen peroxide and pro-inflammatory cytokines released into the tissues are responsible for pathogen elimination and the resolution of inflammation [50,51,52]. However, in chronic cases, these molecules are detrimental to the tissue, leading to increased production of free radicals and reactive oxygen species (ROS) and subsequent oxidative stress [53,54,55]. This process, known as oxinflammation, forms a vicious cycle that continuously damages cells, prompting them to activate apoptotic pathways [56]. Our findings showed that berries, grapes, and their varieties have been the most prevalent in the scientific literature, probably because they are rich in polyphenols, catechins, and anthocyanins. It is already known that these compounds present high scavenger potential and, consequently, anti-inflammatory capacity [57,58]. In addition, berries can control the oxinflammation process by controlling the activated inflammatory cells releasing free radicals and controlling enzymes, oxidative signaling, and inflammatory mediators responsible for producing molecular damage (DNA, proteins, and lipids). These characteristics can justify the significant interest of the studies included in this review in testing the seeds of berries. Also, it can perhaps explain the tremendous commercial interest of a considerable number of different countries in studying berries to improve the health of the skin.
Another point that is important to highlight is the animal models that were predominantly chosen (rats and mice), with different strains to be discussed in our systematic review due to their genetic similarity to humans, as well as being the most manageable animal models during experiments [59,60]. Additionally, the skin structure and response to injury vary significantly among species, so using an animal model closely related to human skin physiology is ideal for studies involving the treatment of skin diseases. Among the commonly used wound models, UVB radiation and excision (using scissors, biopsy punches, and other apparatuses) were predominant. UVB radiation is commonly used in experiments targeting the development of topical treatments, as it is one of the major causes of skin carcinogenesis in humans. Indeed, UVB rays can penetrate the dermis layer, reaching and damaging the DNA of cells, which induces cellular responses to inflammation [61]. From excision wounds, it is possible to determine and differentiate the stages of wound healing and inflammation in the tissue, making it easier to macroscopically quantify the results of the compounds used as treatments [62,63]. The wound created on the dorsum of the animal is commonly used in experiments related to skin inflammation [64,65,66], likely due to its large surface area, which facilitates wound creation, and its location, which makes it difficult for the animal to access, preventing interference during treatments. Skin wound repair is a dynamic and complex process with multiple phases of an intrinsic mechanism. Therefore, any disruption to this process can lead to poor healing or chronic inflammation. For this reason, most studies included in this review span a treatment period of 30 days or more to ensure that the healing process is thoroughly observed from start to finish and that the results obtained are reliable.

4.2. Berries and Bioactive Compounds

Bioactive compounds are the molecules in berries that have anti-inflammatory and antioxidant properties [67]. Therefore, unveiling their main mechanisms of action for skin health is relevant. The most studied and well-known compounds for their anti-inflammatory properties (polyphenols) are responsible for the characteristic colors of berries, especially anthocyanins, which are a subclass of polyphenols, such as red, blue, and purple [68], indicating why grapes and blueberries are the most sought-after berries for the development of treatments against inflammatory diseases. Grapes and blueberries are rich in polyphenols, anthocyanins, and cyanidins that are responsible for their biological effects. In our review, we observed that the Vitis genus was the most studied for skin treatment, as it is rich in proanthocyanidins in its seeds, which explains why seeds were the most commonly used parts of berries in the studies analyzed. In addition, this genus is widely cultivated and comprises approximately 79 species, making its acquisition easier and the extracts more cost-effective [19,69].
Polyphenols are bioactive compounds derived from secondary metabolites of berries, and they are mainly divided into four major groups: flavonoids, stilbenes, phenolic acids, and lignans. These compounds have gained interest in nutrition and pharmaceutical research due to their potent antioxidant and anti-inflammatory properties [70]. The antioxidant action of polyphenols consists of their ability to inhibit the activity of the NOX enzyme and, consequently, the production of superoxide anion, as well as directly neutralizing the production of more unstable free radicals derived from hydrogen peroxide [71]. Furthermore, polyphenols can inhibit membrane receptor, such as TLRs, suppressing NF-κB pathway activation and releasing pro-inflammatory cytokines, a characteristic common among berry phytochemicals [72]. This pathway possibly supports the findings of this review, in which a decrease in the NF-κB pathway and NOX enzyme activity was observed, contributing to reduced ROS production.
Knowledge of their chemical properties has made them widely used in projects involving their intake for the treatment of intestinal, renal, and other diseases [73]. Currently, there is great interest in the development of skin therapeutical compounds to improve the health of the skin, mainly due to the antioxidant activity of polyphenols and their potential to neutralize the pro-inflammatory cascade resulting from the presence of reactive oxygen species (ROS), which cause tissue damage and the recruitment of inflammatory cells. Furthermore, long-term treatment with polyphenols has regulated the expression of pro-inflammatory cytokines, such as IL-1 beta and IL-6, indicating their potential as a post-exposure treatment to stressful agents [74]. Corroborating the literature results in our review, we observe that after berry exposure, there was a reduction in important markers related to the oxinflammatory process, especially related to the TLR and NF-κB pathway. The consequences were a decrease in the influx of inflammatory cells, a decrease in the release of free radicals, and a reduction in the triggering transcription factors related to inflammation and ROS biosynthesis.
Other types of polyphenols that were identified in the berries of the studies in this review were anthocyanins and cyanidins, especially in studies that demonstrated a decrease in oxidative stress and inflammation markers, such as 8-OhDG, COX-2, and NF-κB. This is because anthocyanins and cyanidins can scavenge reactive oxygen species, protect the body from oxidative stress, inhibit pathways, such as NF-κB, reduce IL-6 levels, and downregulate matrix metalloproteinase activation. As a result, they improve extracellular matrix quality in tissues and reduce inflammatory processes [75]. It has been observed in other studies that the inhibition of NF-κB pathways in airway inflammation is associated with the microRNA family (miR-138) and, by inhibiting this microRNA, anthocyanins can regulate the activation of the NF-κB pathway [4]. Our systematic review reveals that the regulation of microRNAs from the miR-210, miR-155, and miR-146a families may be related to inflammation in murine skin tissues [76].
Furthermore, it has been observed that anthocyanins downregulate the expression of NF-κB pathways in keratinocytes and melanomas [77]. Also, the anti-inflammatory potential of cyanidins may be related to the inhibition of TLR2 and TLR4 pathways and the inhibition of the NF-κB pathway [78]. In the studies reviewed, cyanidin, as the primary compound of intervention, was responsible for inhibiting the NF-κB pathway, likely by activating its antagonistic pathway, Nrf2 [79]. Furthermore, the reduction of MAPK and COX-2 also observed in studies with cyanidins in this review suggests the anti-inflammatory potential of this bioactive compound [80]. The reduction of inflammatory processes promoted by COX-2 also leads to decreased extracellular matrix degradation, such as collagen [81], which also showed an increase during the treatments.
Another biocompound found in the studies in this review was glycosides, which are a chemical class of secondary metabolites that are characterized by aglycones conjugated to a sugar moiety [82]. This compound was isolated due to its anti-inflammatory action and the potential to inhibit the expression of proteins, such as STAT1, STAT3, and JAK2 in the JAK/STAT inflammatory pathway, which regulates the release of pro-inflammatory cytokines like IL-6. This was observed in keratinocytes from skin treated with glycosides, which demonstrated protection against the action of signaling molecules, such as IL-6, TNF-α, and IFN-γ, in concentrations much lower than those found in this review (80 ng/mL) [83]. This indicates the potential for using glycosides in treating inflammatory diseases, as low concentrations are sufficient to regulate numerous proteins, making their use more cost effective. Regarding their antioxidant properties, glycosides can increase the activity of enzymes, such as superoxide dismutase (SOD), and decrease reactive oxygen species levels. They can prevent membrane depolarization induced by mitochondrial plasma membranes and reduce the expression of BAX proteins, consequently limiting the release of cytochrome C into the nucleus and preventing cellular apoptosis [84], which supports the study found in this review indicating a reduction in a skin tumor in mice treated with isolated glycosides. Glycosides show significant potential to be a target compound in the formulation of topical products for the treatment of skin diseases, including, mainly, conditions that involve cancer, as the condition affects both the aesthetics and health of the individual.
Another important class of polyphenols found in this review was catechins. Catechins have two benzene rings and a dihydropyran heterocycle ring with five hydroxyl groups in their structure [85], which are responsible for their antioxidant properties, allowing them to scavenge free radicals and stabilize biomolecules. These hydroxyl groups can bind to proteins, lipids, and nucleic acids in tissues, stabilizing them during damage caused by reactive oxygen species and their derivatives [85]. The study in this review using catechin as the main compound showed a reduction of inflammatory and oxidative stress markers, such as 8-OhDG and COX2. Their anti-inflammatory activity can explain this, as it has been observed that catechins can reduce the expression of TNF-α and IL-6 factors in central nervous system macrophages (microglia).
Additionally, pre-treatment with green tea before exposure to a stressor also reduced the expression of iNOS and COX-2 proteins [86]. Furthermore, an anti-apoptotic effect of catechins was observed through the modulation of pro-apoptotic proteins, such as BAX, CAPS-3, and CAPS-9 [87]. In addition, catechins have shown potent antioxidant effects on the skin, preventing lipid peroxidation and inhibiting the formation of metalloproteinases and collagenases, thereby supporting skin integrity and health [88]. This finding explains why, in some studies, there was an increase in wound closure and a reduction in skin wrinkling. These effects highlight the broad therapeutic potential of bioactive compounds like catechins. There may be other pathways and proteins involved in the properties of these compounds, as well as other yet-to-be-identified compounds in berries that could regulate cellular inflammatory activity. Understanding these bioactive compounds’ primary mechanisms of action is crucial for identifying which berries could be the most promising candidates for further investigation and application in improving tissue health. This comprehensive approach is essential for harnessing the full potential of these compounds to enhance overall tissue health.

4.3. Influence of Bioactive Compounds on Tissue Regeneration

In this regard, the influence of bioactive compounds on tissue regeneration is critical, as prolonged inflammation disrupts tissue homeostasis, impairs extracellular matrix production, and compromises skin function [89]. Oxidative stress generates unstable molecules that are eager to acquire new electrons, attacking the intact molecules of cells (lipids, proteins, and carbohydrates), leading to the formation of cellular debris and subsequent recruitment of macrophages to the site, along with other inflammatory cells, such as leukocytes and neutrophils [90]. The activity of these cells within the tissue increases ROS production, which are enzymes involved in the defense against stressors, creating a vicious, self-perpetuating cycle of tissue damage [91]. With that in mind, this review shows that by inhibiting inflammatory pathways and increasing enzymes that protect against oxidative stress, berry extracts promote an improvement in the synthesis of collagen, elastin, and fibronectin, which are essential proteins for maintaining skin integrity [92]. In addition, there is an increase in angiogenesis and wound contraction, key indicators of tissue healing. The macroscopic evaluation of the tissue reflects the molecular processes occurring during topical treatments; therefore, these observations are essential for demonstrating these compounds’ potential in treating skin disorders.

4.4. Risk of Bias and Limitations

The studies in this review presented a low risk of bias regarding the experiments with animals and treatment with berries, making it possible for other researchers to reproduce these experiments. However, the studies provided only subtle details on the phytochemical characterization of the extracts, limiting a thorough discussion of how the extract influences intracellular pathways responsible for the observed results. Additionally, the risk of bias analysis revealed limitations in the experiment reports, particularly regarding information related to random sequence generation, allocation concealment, blinding of outcome assessment, and selective reporting. The risk of bias does not imply that researchers failed to evaluate these parameters but suggests that this information was not included in the studies. We hope this systematic review highlights the importance of better reporting methodological details and compound characterization to enhance reproducibility and provide a clearer understanding of the results obtained. The limitations of this review include methodological heterogeneity in treatment types and variations in the phytochemical descriptions of the compounds used. However, we identified a potential explanation within the results that may account for the observed heterogeneity.

5. Conclusions

The potential of berries for treating skin diseases and wounds is recognized for the bioactive compounds already known for their beneficial properties. In general, treatments have shown improvements in wound healing, extracellular matrix protein production essential for healthier skin, and stimulation of cellular regeneration. Additionally, they assist in angiogenesis and modulation of oxinflammation pathways. With this perspective, it is ideal for pharmaceutical industries to focus more on formulating topical products based on berry extracts for dermatological applications, including treating burns, open wounds, psoriasis, dermatitis, and other skin conditions. Additionally, exploring the potential of underutilized berries and identifying new bioactive compounds could further expand therapeutic options.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/cosmetics12030087/s1, Figure S1: Summary of risk of bias. Green: low risk of bias; yellow: unclear risk of bias; and red: high risk of bias; Table S1: Full search strategy in PubMed, Scopus, and Web of Science, including search terms and filters; Table S2: Characteristics of the animals used in all studies included in this systematic review; Table S3: Characteristics of all types of berries and interventions used in the studies included in this systematic review; Table S4: Characteristics of all types of berries and interventions used in the studies included in this systematic review.

Author Contributions

Conceptualization, F.S.A. and A.R.P.; methodology, F.S.A. and A.R.P.; validation, M.M.S., R.V.G. and R.T.H.; formal analysis, F.S.A.; investigation, F.S.A. and A.R.P.; resources, M.M.S., R.V.G. and R.T.H.; data curation, G.V., M.A.L. and R.D.N.; writing—original draft preparation, F.S.A.; writing—review and editing, F.S.A., A.R.P., R.T.H., M.M.S. and R.V.G.; visualization, F.S.A.; supervision, G.V., R.V.G., M.M.S. and R.T.H.; project administration, M.M.S. and R.T.H.; funding acquisition, R.V.G. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Fundação de Amparo à Pesquisa do Estado de Minas Gerais [FAPEMIG, process APQ-03519-22 and APQ-04164-22), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES, Finance Code 001), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, processes 310413/2023-0, 306733/2023-4 and 403194/2023-7).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data are contained within the article and the Supplementary Materials.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. The flowchart indicates the research records obtained at all standardized stages of the search process required to develop systematic reviews and meta-analyses. Based on the PRISMA statement (http://www.prisma-statement.org, accessed on 20 November 2024). * Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). ** If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools.
Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. The flowchart indicates the research records obtained at all standardized stages of the search process required to develop systematic reviews and meta-analyses. Based on the PRISMA statement (http://www.prisma-statement.org, accessed on 20 November 2024). * Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). ** If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools.
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Figure 2. The places where the studies were conducted and the types of berries used. The places where the studies were conducted were reported in all studies reviewed, while 4% did not report the types of berries studied.
Figure 2. The places where the studies were conducted and the types of berries used. The places where the studies were conducted were reported in all studies reviewed, while 4% did not report the types of berries studied.
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Figure 3. An overview of the effects of berry topical application on skin inflammation disorders based on the information provided by the individual studies included in this systematic review.
Figure 3. An overview of the effects of berry topical application on skin inflammation disorders based on the information provided by the individual studies included in this systematic review.
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Figure 4. Results for the risk of bias and methodological quality indicators for all studies included in this systematic review that evaluated the effects of topical applications of berry formulations on skin diseases. The items in the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) Risk of Bias assessment were scored with green, indicating low risk of bias, red, indicating high risk of bias, or “unclear”, indicating that the item was not reported, resulting in an unknown risk of bias (yellow).
Figure 4. Results for the risk of bias and methodological quality indicators for all studies included in this systematic review that evaluated the effects of topical applications of berry formulations on skin diseases. The items in the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) Risk of Bias assessment were scored with green, indicating low risk of bias, red, indicating high risk of bias, or “unclear”, indicating that the item was not reported, resulting in an unknown risk of bias (yellow).
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Figure 5. A scheme describing the utility of berry fruit extracts in the scientific field of dermatology, including wound healing, cosmetics, and pharmaceuticals.
Figure 5. A scheme describing the utility of berry fruit extracts in the scientific field of dermatology, including wound healing, cosmetics, and pharmaceuticals.
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MDPI and ACS Style

Azevedo, F.S.; Pires, A.R.; Lila, M.A.; Valacchi, G.; Hoskin, R.T.; Sarandy, M.M.; Novaes, R.D.; Goncalves, R.V. Berry Fruit Extracts as Topical Cosmeceuticals for Skin Health Applications: A Systematic Review. Cosmetics 2025, 12, 87. https://doi.org/10.3390/cosmetics12030087

AMA Style

Azevedo FS, Pires AR, Lila MA, Valacchi G, Hoskin RT, Sarandy MM, Novaes RD, Goncalves RV. Berry Fruit Extracts as Topical Cosmeceuticals for Skin Health Applications: A Systematic Review. Cosmetics. 2025; 12(3):87. https://doi.org/10.3390/cosmetics12030087

Chicago/Turabian Style

Azevedo, Filipe Silveira, Allan Rodrigues Pires, Mary Ann Lila, Giuseppe Valacchi, Roberta Targino Hoskin, Mariaurea Matias Sarandy, Rômulo Dias Novaes, and Reggiani Vilela Goncalves. 2025. "Berry Fruit Extracts as Topical Cosmeceuticals for Skin Health Applications: A Systematic Review" Cosmetics 12, no. 3: 87. https://doi.org/10.3390/cosmetics12030087

APA Style

Azevedo, F. S., Pires, A. R., Lila, M. A., Valacchi, G., Hoskin, R. T., Sarandy, M. M., Novaes, R. D., & Goncalves, R. V. (2025). Berry Fruit Extracts as Topical Cosmeceuticals for Skin Health Applications: A Systematic Review. Cosmetics, 12(3), 87. https://doi.org/10.3390/cosmetics12030087

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