A systematic review of natural products for skin applications: Targeting inflammation, wound healing, and photo-aging
Open accessAbstract
BACKGROUND: Every day the skin is constantly exposed to several harmful factors that induce oxidative stress. When the cells are incapable to maintain the balance between antioxidant defenses and reactive oxygen species, the skin no longer can keep its integrity and homeostasis. Chronic inflammation, premature skin aging, tissue damage, and immunosuppression are possible consequences induced by sustained exposure to environmental and endogenous reactive oxygen species. Skin immune and non-immune cells together with the microbiome are essential to efficiently trigger skin immune responses to stress. For this reason, an ever-increasing demand for novel molecules capable of modulating immune functions in the skin has risen the level of their development, particularly in the field of natural product-derived molecules. PURPOSE: In this review, we explore different classes of molecules that showed evidence in modulate skin immune responses, as well as their target receptors and signaling pathways. Moreover, we describe the role of polyphenols, polysaccharides, fatty acids, peptides, and probiotics as possible treatments for skin conditions, including wound healing, infection, inflammation, allergies, and premature skin aging. METHODS: Literature was searched, analyzed, and collected using databases, including PubMed, Science Direct, and Google Scholar. The search terms used included "Skin", "wound healing", "natural products", "skin microbiome", "immunomodulation", "anti-inflammatory", "antioxidant", "infection", "UV radiation", "polyphenols", "polysaccharides", "fatty acids", "plant oils", "peptides", "antimicrobial peptides", "probiotics", "atopic dermatitis", "psoriasis", "auto-immunity", "dry skin", "aging", etc., and several combinations of these keywords. RESULTS: Natural products offer different solutions as possible treatments for several skin conditions. Significant antioxidant and anti-inflammatory activities were reported, followed by the ability to modulate immune functions in the skin. Several membrane-bound immune receptors in the skin recognize diverse types of natural-derived molecules, promoting different immune responses that can improve skin conditions. CONCLUSION: Despite the increasing progress in drug discovery, several limiting factors need future clarification. Understanding the safety, biological activities, and precise mechanisms of action is a priority as well as the characterization of the active compounds responsible for that. This review provides directions for future studies in the development of new molecules with important pharmaceutical and cosmeceutical value.
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Chronic stress-induced immune alterations target the skin, and cytokine imbalance (mostly IL-6 and TNF-α) can delay wound healing and accelerate cutaneous aging.
“The skin is another major target of stress-induced immune alterations; cytokine imbalance in this context—mostly IL6 and TNFa—can delay wound healing and accelerate cutaneous aging [47].”
From Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation (2025) · cites this paper as [47]
The wound-healing section (page not provided) links altered cytokine patterns, including IL-6 and TNF-α, to nonhealing wounds. The abiotic-factors section links oxidative stress to premature skin aging, but the cited passages do not establish that chronic stress-induced changes in IL-6 and TNF-α cause both delayed healing and accelerated aging. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe majority of studies included in Fernandes et al.'s review were preclinical or small-scale clinical trials.
“The majority of studies included in the review were preclinical or small‐scale clinical trials, warranting further research to establish the efficacy and safety of these interventions.”
From Cosmeceuticals in photoaging: A review. (2024) · cites this paper as [50]
The review discusses animal and cell studies alongside clinical trials, and its Conclusions and future directions section calls for further research on safety and biological activity. Our copy does not establish that a majority of the studies were preclinical or small-scale clinical trials; the cited evidence supports the need for further research, but not that characterization of the study mix. (LLM, conf=0.78)
Experimental — accuracy not yet measuredHeterogeneity of studies in Fernandes et al.'s review makes it challenging to draw definitive conclusions on overall effectiveness of natural products for skin health.
“Additionally, the heterogeneity of the included studies makes it challenging to draw definitive conclusions on the overall effectiveness of natural products for skin health.”
From Cosmeceuticals in photoaging: A review. (2024) · cites this paper as [50]
The β-glucans section (page not provided) says that variation in studies using crude versus purified extracts hinders interpretation of the data. The Conclusions and future directions section (page not provided) also says much information is lacking. Neither passage attributes difficulty drawing conclusions about the overall effectiveness of natural products for skin health to heterogeneity across all included studies. (LLM, conf=0.84)
Experimental — accuracy not yet measuredBased on Fernandes et al.'s systematic review, natural products show promise in addressing skin conditions and promoting skin health.
“Based on the evidence presented in the review, it can be concluded that natural products show promise in addressing skin conditions and promoting skin health.”
From Cosmeceuticals in photoaging: A review. (2024) · cites this paper as [50]
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Costa-Pinto, A. R., Lemos, A. L., Tavaria, F. K., et al. (2021) · Materials · doi:10.3390/ma14040804 · Cited by 76 · see citing works
Self-citationAccelerated wound healing mediated by activation of Toll-like receptor 9
Sato, T., Yamamoto, M., Shimosato, T., & Klinman, D. M. (2010) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2010.00632.x · Cited by 75 · see citing works
Wound Repair and Regeneration: Mechanisms, Signaling
Akita, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20246328 · Cited by 75 · see citing works
Wound healing activity of<i>Persea americana</i>(avocado) fruit: a preclinical study on rats
Nayak, B. S., Raju, S. S., & Chalapathi Rao, A. V. (2008) · Journal of Wound Care · doi:10.12968/jowc.2008.17.3.28670 · Cited by 74 · see citing works
The skin barrier and use of moisturizers in atopic dermatitis
Lodén, M. (2003) · Clinics in Dermatology · doi:10.1016/s0738-081x(02)00373-5 · Cited by 74 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Turksen, K., 2017. Wound Healing: Stem Cells Repair and Restorations, Basic and Clinical Aspects, 1st ed. Wiley-Blackwell.
Cited by
Sorted by citations
Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation
Nunez, S. G., Rabelo, S. P., Subotic, N., Caruso, J. W., & Knezevic, N. N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26209994 · Cited by 138 · see citing works
“The skin is another major target of stress-induced immune alterations; cytokine imbalance in this context—mostly IL6 and TNFa—can delay wound healing and accelerate cutaneous aging [47].”
Cosmeceuticals in photoaging: A review.
Chan, L. K. W., Lee, K. W. A., Lee, C. H., Lam, K. W. P., Lee, K. F. V., Wu, R., Wan, J., Shivananjappa, S., Sky, W. T. H., Choi, H., et al. (2024) · Skin Research and Technology · doi:10.1111/srt.13730 · Cited by 23 · see citing works
“Overall, Fernandes et al.’s 50 systematic review offers a comprehensive overview of the current evidence on natural products for skin applications.”
BackgroundInfluential
- Authors
- Fernandes, A., Rodrigues, P. M., Pintado, M., & Tavaria, F. K.
- Affiliations
- Universidade Católica Portuguesa (PT)
- Corresponding author
- Fernandes, A.
- Venue
- Phytomedicine
- Publisher
- Elsevier BV
- Published
- 2023-07
- Volume
- 115
- Pages
- 154824
- ISSN
- 0944-7113 (ISSN-L)
- OpenAlex
- W4366245600
- Cited by
- 264
- References
- 329
- Citations by year
- 2026: 91 · 2025: 95 · 2024: 60 · 2023: 18
- FWCI
- 12.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Phytomedicine (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by)
- Funders
- FCT (UIDB/50016/2020, UI/BD/151390/2021)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- natural products, skin care, skin inflammation, wound healing, photoaging, oxidative stress, skin microbiome, immunomodulation, polyphenols, polysaccharides, fatty acids, antimicrobial peptides, probiotics, atopic dermatitis, psoriasis, autoimmunity, dry skin, ultraviolet radiation, cosmeceuticals
- MeSH terms
- Anti-Inflammatory Agents, Antioxidants, Biological Products, Humans, Inflammation, Peptides, Polysaccharides, Skin Aging, Reactive Oxygen Species, Polyphenols
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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