The timeless human desire for youthful skin spurs the relentless pursuit of skincare innovations. In the anti-aging realm, the search has intensified for effective and safe alternatives to retinol and other industry gold standards and derm-recommended actives. The market is flooded with promises of miraculous transformations, but few ingredients can rival the allure and efficacy of nature’s own elixir: Propolis extract.

Raw propolis is a natural, glue-like resinous mixture meticulously collected by honeybees from the leaf buds of poplar trees. This marvel acts as a natural sealant and defense mechanism within the beehive, protecting it from pathogens and environmental threats. There are over 500 bioactive molecules identified in propolis and most of them are secondary plant metabolites.¹ However, several key bioactive components contribute to its diverse health benefits:

• Phenolic acids: These powerful antioxidants combat free radical damage, a major contributor to skin aging.²
• Flavonoids: This class of compounds possesses anti-inflammatory, antioxidant and antibacterial properties, promoting healthy skin function.³
• Terpenoids: These diverse molecules offer various biological activities, including wound healing and immune modulation.⁴
• Other constituents: Propolis also contains vitamins, minerals and amino acids, which can contribute to its overall skin benefits.

This natural, miraculous material ignited the curiosity of scientists seeking novel ways to utilize it in skin health and beauty. However, the scientific community had faced technical challenges utilizing propolis.

The biggest challenges limiting use of propolis extract is related to its inconsistent composition from batch to batch, instability and use of aggressive solvents. The propolis chemical profile depends on the extraction solvent type, solvent ratio and extraction procedures.

Alcoholic solvents are frequently employed in the extraction process of propolis. However, this extraction method has drawbacks. For instance, ethanol (EtOH) is a relatively aggressive solvent. Furthermore, products derived from this alcohol-based extraction process are unsuitable for certain demographics, including children, pregnant and breastfeeding women, as well as specific patient population groups. Another issue is the high beeswax content in these extracts leads to separation when mixed with water during manufacturing. These challenges underscore the need for alternative extraction methods that are both safe and effective.⁵

Moreover, the exact composition of propolis can vary depending on the geographical location, plant sources available to the bees and harvesting methods.⁶ To date, there has been no validated extraction method that guarantees reproducibility, stability and standardization of propolis extract. This has caused a major hurdle in utilization of propolis extract and therefore, greatly impacted the promise of this compound in delivering consistent health and skin benefits.⁷

A Novel Extraction Process

Researchers at Apiotix Technologies, Split, Croatia, patented an innovative biotechnology method⁸ to overcome the challenge of harnessing the full potential of propolis while ensuring consistency and quality. The method extracts, standardizes and stabilizes phenolic compounds in the propolis extract, guaranteeing a defined concentration and ratio of bioactive compounds. This has been shown to ensure optimal and consistent results from batch to batch in extract production.⁵

This “Next Generation Propolis Extract,” originally introduced as standardized phenolic acids polymer extract (PAPE) in a previous publication,⁹ has been commercialized under “Apinol360.” Apiotix’s invention is a unique, non-alcoholic biotech extraction (NABE) method using a novel carrier solvent system of polyethylene glycol (PEG) and lecithin. This first-of-its-kind approach addresses the traditional challenges associated with propolis extraction techniques, by ensuring a high concentration of bioactive phenolic compounds, specifically para-coumaric acid, trans-ferulic acid, caffeic acid and 2-phenylethyl ester of caffeic acid, with defined concentrations and reproducibility. In addition, the absence of alcoholic solvent makes it suitable for sensitive skin, setting a new benchmark in propolis extraction technology and forming the basis for its patent.⁹

This invention includes creation of a standardized and reproducible propolis extract with the highest chemo-selectivity achieved to date, enhancing its bioactivity, safety and efficacy for skincare. This has been scientifically and clinically validated through in vitro and in vivo. 

The Rise of Propolis Extract

The study performed by Radic et al,⁹ published in the Journal of Cosmetic Dermatology, enhanced our understanding of the role of propolis’ and further highlighted its anti-aging potential. This unique study, employing a dual approach of in vitro experimentation and a randomized clinical trial, unveiled the remarkable potential of PAPE in mitigating wrinkles and improving overall skin health. The study demonstrated PAPE’s ability to modulate key biomarkers associated with skin health while showcasing a favorable safety profile, positioning it as a promising alternative to traditional anti-aging compounds.   

The study combines in vitro and clinical trial components to provide a comprehensive evaluation of PAPE’s efficacy. The in vitro studies assessed PAPE’s impact on key skin health biomarkers in keratinocytes and dermal fibroblasts, demonstrating its potential to modulate inflammation and tissue remodeling. These findings provide a preliminary basis for understanding the mechanistic basis for PAPE’s observed anti-wrinkle effects.

The randomized double-blind clinical trial, involving 40 female participants aged 30-70, evaluated the wrinkle-reducing efficacy of face creams formulated with two concentrations of PAPE (1.5% and 3%), applied twice daily, over a 28-day period. The study employed both objective device measurements (wrinkle depth) and subjective assessments (participant ratings) to assess PAPE’s wrinkle reduction impact.

The results (shown above) were compelling, with both PAPE concentrations demonstrating significant wrinkle reduction compared to the baseline. Notably, the 3% PAPE formulation exhibited a more pronounced effect, suggesting a dose-dependent relationship. Moreover, the study reported high participant satisfaction with the PAPE-containing creams, highlighting their potential acceptability for consumers.

A head-to-head comparison of PAPE’s efficacy to other established anti-wrinkle actives, such as retinol and bakuchiol revealed its comparable effectiveness and performance in reducing wrinkles while offering the added benefit of a favorable safety profile with a gentler effect on the skin. This positions PAPE as a compelling natural alternative for individuals and skincare brands seeking effective anti-aging solutions with comparable efficacy to dermatologically recommended actives like retinol but without the associated adverse effects, such as irritation and dryness.

The underlying mechanism of PAPE’s anti-wrinkle action involves its potent antioxidant and anti-inflammatory properties, which help combat oxidative stress and reduce inflammation, key contributors to skin aging. Additionally, PAPE’s ability to modulate collagen synthesis and extracellular matrix components further supports its role in improving skin texture and reducing the appearance of wrinkles.

While the study highlights the promising potential of PAPE, further research is warranted to elucidate its long-term effects and safety profile. Expanding the sample size and duration of clinical trials, as well as conducting comparative studies with other anti-aging ingredients, will provide a more comprehensive understanding of PAPE’s efficacy and its place in the evolving landscape of anti-aging skincare.

The incorporation of PAPE into cosmetic formulations represents a significant advancement in the field of natural effective anti-aging solutions. Its ability to address multiple facets of skin aging, coupled with its excellent safety profile, positions PAPE as a valuable asset in the development of innovative skincare products that cater to the growing demand for safe, efficacious and sustainable beauty solutions.

As the cosmetics industry continues to evolve, the integration of phenolic acids, particularly those derived from propolis, holds immense promise.² The potential of these natural phenolic compounds to address a wide range of skin concerns, from wrinkles and inflammation to wound healing and photoprotection,^10-11 underscores their versatility and value. PAPE’s patented technology introduced a novel optimized NABE technology for extraction of phenolic acids from propolis. This will undoubtedly lead to the development of even more effective and targeted skincare products that harness the power of nature to enhance skin health and beauty.

Promising Comparisons

PAPE’s efficacy was found to be comparable to other established anti-wrinkle compounds like retinol and bakuchiol, which successfully positions PAPE as a compelling alternative with a favorable safety profile for individuals seeking effective anti-aging solutions without the associated irritation often caused by retinol.

While the study provides strong evidence for PAPE’s anti-wrinkle reduction efficacy, it is essential to consider its limitations. The relatively small sample size and short duration of the clinical trial necessitate further research to establish PAPE’s long-term effects and safety in a broader population. Additionally, the absence of a head-to-head comparison with established anti-aging ingredients limits our ability to directly assess PAPE’s relative efficacy.

Despite these limitations, the study provides compelling evidence for PAPE’s potential as an anti-aging ingredient. Its ability to modulate key biomarkers associated with skin health and reduce wrinkle depth is promising. Moreover, the favorable safety profile observed in the study positions PAPE as a potential alternative to more irritating anti-aging treatments.

Beyond its anti-aging properties, PAPE exhibits a range of beneficial activities, including antimicrobial and anti-inflammatory effects. These properties have expanded potential application of PAPE in various health domains, such as wound care, oral health, supplement and immune function. 

However, the broader context of propolis utilization must be considered. The potential for allergic reactions,^12-13 particularly in individuals with bee venom allergies, underscores the importance of appropriate labeling and consumer education. Not inherently vegan due to its bee-derived nature, propolis may not align with everyone’s lifestyle preferences. 

Beyond Wrinkles

Propolis extract offers a multitude of benefits beyond anti-aging. Here’s a glimpse into the broader therapeutic potential of propolis:

Anti-inflammatory effects: Propolis extract can help soothe and calm irritated skin, making it potentially beneficial for conditions like acne, eczema and rosacea.¹⁴ 

Wound healing: Studies suggest that propolis extract can accelerate wound healing due to its antimicrobial and tissue regeneration properties.¹⁵ 

Antioxidant protection: The potent antioxidant activity of propolis extract helps shield the skin from damaging free radicals, potentially aiding in preventing premature aging and sun damage.¹⁶ 

Antimicrobial properties: Propolis has broad-spectrum antimicrobial activity against various bacteria, fungi and viruses, making it potentially useful in preventing and treating skin infections.¹⁷ 

The applications of propolis extend beyond anti-aging and topical use. Its antimicrobial and anti-inflammatory properties have shown promise in wound healing and oral care. Studies investigated propolis’ potential to accelerate wound closure, reduce inflammation and prevent infection. In oral health, propolis has been explored for its ability to combat oral bacteria and gingivitis.¹⁸   

Moreover, emerging research suggests propolis may possess immunomodulatory properties. Some studies indicate that propolis can stimulate the immune system, potentially benefiting conditions like the common cold and influenza.¹⁹ However, the evidence supporting these applications is still emerging, and further research is needed to establish clear guidelines for propolis supplementation in these areas.

Consumer Perception and Market Trends

The growing consumer interest in natural and sustainable beauty has propelled propolis into the mainstream. Its association with beekeeping, often perceived as environmentally friendly, aligns with the values of many consumers. However, ensuring ethical sourcing and sustainable beekeeping practices is crucial to maintain consumer trust. It’s important to note that the composition of propolis, and therefore PAPE, can vary depending on its geographical origin and the plant sources available to bees.²⁰ 

Nevertheless, propolis extract market is experiencing steady growth fueled by rising consumer demand for natural and sustainable skincare solutions. Consumers increasingly seek products that are safe, effective and derived from natural sources, making propolis extract a highly attractive ingredient. The availability of propolis extract in various product formats, including serums, creams and masks, caters to diverse consumer preferences. 

A  Bright Future

The journey of propolis from beehive to skincare solution is a testament to the power of nature and human ingenuity. While the potential benefits of propolis extract are undeniable, continued research is essential to unlock its full potential. 

By addressing the limitations of current research, such as expanding sample sizes and exploring long-term effects, scientists can provide a more comprehensive understanding of propolis extract’s efficacy and safety. Additionally, investigating propolis extract’s interactions with other skincare ingredients and its potential synergistic effects can lead to innovative product formulations.   

As consumer demand for natural and effective skincare solutions grows, propolis is poised to play a significant role in the beauty industry. By prioritizing scientific rigor, ethical sourcing and consumer education, the propolis industry can harness the full potential of this remarkable natural resource.

Conclusions

The quest for youthful skin is a timeless pursuit, and the market overflows with anti-aging products promising dramatic results. However, the desire for efficacy is often accompanied by concerns about harsh chemicals and potential side effects. This is where natural ingredients like propolis extract emerge as compelling alternatives. Apiotix’s patented NABE technology has produced a standardized propolis extract, Apinol360, with enhanced bioactivity and a defined concentration of phenolic compounds. There is emerging evidence for the anti-wrinkle efficacy of propolis extract, marking a significant step forward in the quest for natural and effective anti-aging solutions. This research, coupled with previous studies highlighting propolis extract’s broader bioactivities, underscores its potential as a valuable ingredient in skincare and beyond. 

References:

1. Huang, S., Zhang, C.-P.; Wang, K., Li, G.Q., Hu, F.L. (2014). Recent Advances in the Chemical Composition of Propolis. Molecules 19, 19610–19632. doi: 10.3390/molecules191219610. PMID: 25432012; PMCID: PMC6271758.
2. Dudonné S, Poupard P, Coutière P, Woillez M, Richard T, Mérillon JM, Vitrac X. (2011). Phenolic composition and antioxidant properties of poplar bud (Populus nigra) extract: individual antioxidant contribution of phenolics and transcriptional effect on skin aging. J Agric Food Chem. 11;59(9):4527-36. doi: 10.1021/jf104791t. Epub 2011 Mar 22. PMID: 21425781.
3. Cushnie, T. P., & Lamb, A. J. (2005). Antimicrobial activity of flavonoids. International Journal of Antimicrobial Agents, 26(5), 343-356. doi:10.1016/j.ijantimicag.2005.09.002   
4. Stavropoulou MI, Stathopoulou K, Cheilari A, Benaki D, Gardikis K, Chinou I, Aligiannis N. (2021). NMR metabolic profiling of Greek propolis samples: Comparative evaluation of their phytochemical compositions and investigation of their anti-ageing and antioxidant properties. J Pharm Biomed Anal. 194:113814. doi: 10.1016/j.jpba.2020.113814. Epub 2020 Dec 2. PMID: 33308921.
5. Šuran, J., Cepanec, I., Mašek, T., Radić, B., Radić, S., Tlak Gajger, I., & Vlainić, J. (2021). Propolis Extract and Its Bioactive Compounds—From Traditional to Modern Extraction Technologies. Molecules, 26(10), 2930. doi: 10.3390/molecules26102930. PMCID: PMC8156449. PMID: 34069165.)
6. Kurek-Górecka A, Keskin Ş, Bobis O, Felitti R, Górecki M, Otręba M, Stojko J, Olczyk P, Kolayli S, Rzepecka-Stojko A. (2022). Comparison of the Antioxidant Activity of Propolis Samples from Different Geographical Regions. Plants (Basel). 29;11(9):1203. doi: 10.3390/plants11091203. PMID: 35567206; PMCID: PMC9104821.
7. de Lima GG, de Souza RO, Bozzi AD, Poplawska MA, Devine DM, Nugent MJ. (2016).  Extraction Method Plays Critical Role in Antibacterial Activity of Propolis-Loaded Hydrogels. J Pharm Sci.105(3):1248-57. doi: 10.1016/j.xphs.2015.12.027. Epub 2016 Feb 9. PMID: 26886307.
8. Radić, S., Radić, B., & Šuran, J. (2020). Liquid propolis extract, its formulation and use thereof. World Intellectual Property Organization. WO2020169425A1.).https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2020169425
9. Radić B, Radić S, Mašek T, Šuran J. (2024). Anti-wrinkle efficacy of standardized phenolic acids polymer extract (PAPE) from propolis: Implications for antiaging and skin health. J Cosmet Dermatol. 23(10):3372-3381. doi: 10.1111/jocd.16405. Epub 2024 Jun 28. PMID: 38943252.
10. Permana AD, Utami RN, Courtenay AJ, Manggau MA, Donnelly RF, Rahman L. (2020).  Phytosomal nanocarriers as platforms for improved delivery of natural antioxidant and photoprotective compounds in propolis: An approach for enhanced both dissolution behaviour in biorelevant media and skin retention profiles. J Photochem Photobiol B. 205:111846. doi: 10.1016/j.jphotobiol.2020.111846. Epub 2020 Mar 2. PMID: 32151785.
11. El-Sakhawy M, Salama A, Tohamy HS. (2023). Applications of propolis-based materials in wound healing. Arch Dermatol Res. 27;316(1):61. doi: 10.1007/s00403-023-02789-x. PMID: 38151671; PMCID: PMC10752841.
12. Ndreu L, Hurben AK, Nyman GSA, Tretyakova NY, Karlsson I, Hagvall L. (2023).  Investigation into Propolis Components Responsible for Inducing Skin Allergy: Air Oxidation of Caffeic Acid and Its Esters Contribute to Hapten Formation. Chem Res Toxicol. 19;36(6):859-869. doi: 10.1021/acs.chemrestox.2c00386. Epub 2023 May 15. PMID: 37184291; PMCID: PMC10283018.
13. Burdock, G. A. (1998). Review of the biological properties and toxicity of bee propolis (propolis). Food and Chemical Toxicology, 36(4), 347-363. doi:10.1016/S0278-6915(97)00145-2.
14. Mazzarello V, Donadu MG, Ferrari M, Piga G, Usai D, Zanetti S, Sotgiu MA. (2018). Treatment of acne with a combination of propolis, tea tree oil, and Aloe vera compared to erythromycin cream: two double-blind investigations. Clin Pharmacol.;10:175-181. doi: 10.2147/CPAA.S180474. PMID: 30588129; PMCID: PMC6298394.
15. Machado Velho JC, França TA, Malagutti-Ferreira MJ, Albuquerque ER, Lívero FADR, Soares MR, Soares AEE, Ribeiro-Paes JT. (2023). Use of propolis for skin wound healing: systematic review and meta-analysis. Arch Dermatol Res.315(4):943-955. doi: 10.1007/s00403-022-02455-8. Epub 2022 Nov 23. PMID: 36418601.
16. Lotfy Khalil, M. (2007). Biological activity of bee propolis in health and disease. Asian Pacific Journal of Cancer Prevention, 7(1):22-31. PMID: 16629510.
17. Przybyłek I, Karpiński TM. (2019). Antibacterial Properties of Propolis. Molecules. 29;24(11):2047. doi: 10.3390/molecules24112047. PMID: 31146392; PMCID: PMC6600457.
18. Saeed MA, Khabeer A, Faridi MA, Makhdoom G. (2021) Effectiveness of propolis in maintaining oral health: a scoping review. Can J Dent Hyg.55(3):167-176. PMID: 34925517; PMCID: PMC8641552.
19. Shimizu T, Hino A, Tsutsumi A, Park YK, Watanabe W, Kurokawa M. (2008). Anti-influenza virus activity of propolis in vitro and its efficacy against influenza infection in mice. Antivir Chem Chemother.19(1):7-13. doi: 10.1177/095632020801900102. PMID: 18610553.
20. Kurek-Górecka A, Keskin Ş, Bobis O, Felitti R, Górecki M, Otręba M, Stojko J, Olczyk P, Kolayli S, Rzepecka-Stojko A (2022). Comparison of the Antioxidant Activity of Propolis Samples from Different Geographical Regions. Plants (Basel). 29;11(9):1203. doi: 10.3390/plants11091203. PMID: 35567206; PMCID: PMC9104821.

Footnote

NextGen Actives, a premier platform for the development and distribution of advanced pharmaceutical bio-actives, is introducing Apinol360 as an alternative brand name for PAPE, offered exclusively in the US. Apinol360 embodies the same properties as PAPE, providing consumers with a safe and effective anti-aging ingredient backed by scientific research. This rebranding aligns with NextGen Actives’ mission to transfer cutting-edge pharmaceutical innovation to the skincare industry, enabling skincare brands to succeed in delivering efficacious yet safe topical products.

Apinol360, akin to PAPE, stands as a testament to the potential of natural bioactive compounds in skincare Retinol alternatives and anti-aging innovation. It offers a new approach to visibly reducing skin roughness and wrinkles, understanding skin aging as a process intricately tied to chronic inflammatory mechanisms. As the industry evolves, Apinol360 is poised to become a central component in the development of derm-like cosmetic products that meet modern consumer demands for effectiveness and sustainability www.nextgenactives.com.

About the Author

Professor Ardeshir Bayat, MD, PhD, has over 20 years of experience spanning clinical practice, academic research, and the beauty industry. An internationally recognized figure in skin health, anti-aging and skin healing innovation, he has delivered more than 600 presentations and authored over 520 publications. His robust H-index of 80 highlights his significant influence and thought leadership in dermatological science as well as contribution to cosmetic advancements. 

ardeshir.bayat@uct.ac.za