Addressing Aging Changes in the Periorbital Eye Area with Clinically Tested Herbal Extracts

James V Gruber, Nicole Terpak, Sebastien Massard, Elva Chen and Saselah Heywood • Vantage

In a recent survey conducted by Vantage, 2,600 female participants were asked to name the top claims they expect from a skincare product. Ninety-one percent of respondents shared they wanted a product that “makes my skin look and feel healthy.” Breaking these findings down further, 84% of the participants felt that deep lines and wrinkles were their primary concerns not properly addressed by existing products. This was followed by 83% for undereye bags and 83% for dark areas under eyes, suggesting that the undereye skin appearance (dark circles, bags, fine lines and crow’s feet wrinkles) is top of mind for consumers. Given that in 2023, Americans paid nearly $422 million for dermatological treatments to address problems around the eyes, it seems particularly important that new topical treatments that address the eye concerns are still critically important.¹ 

Natural ingredients that topically influence the skin is strategically important as well for consumers. While synthetic molecules, like retinol, are known to be effective for improving the skin, the use of these aggressive topical ingredients does not come without some downsides.² While it is not universally true that botanicals are inherently safe (think about applying an extract of Poison Ivy!), it is commonly felt that botanical ingredients with a long history of safe consumption by humans can lend themselves to extracts that are more gentle, but effective, as topical treatments.  Two sources where these kinds of herbal treatments are well-established are traditional medicine (TM) and Ayurvedic botanicals. Of particular interest for the work being discussed here are the TM mushroom Phellinus linteus (more traditionally referred to as Sang Hwang mushroom) and the root extract from Angelica polymorpha sinensis (more traditionally referred to as Dang Gui).^3,4 A unique blend of these two extracts,  Angel-Eye EFX, was developed by Vantage (referred to hereafter as the “botanical extract blend” or “active blend”).

Development of the extract and its initial testing using in vitro genomic and protein testing methods has been described in greater detail in a previous publication.⁵ From this earlier work, six strategically important protein targets were investigated and shown to be influenced by one or both botanical extracts. A summary of the in vitro targets is shown below in Figure 1.

As can be seen in Figure 1, the extract addressed several important aspects for improving skin health around the eye area including repair of the skin’s barrier function, protection from oxidative stress, reinforcement of the extracellular matrix and, most critically, improving the strength and blood flow capacity in the tiny capillaries that surround the undereye area. A key factor contributing to dark circles is the presence of hemoglobin breakdown products, which are darker in color than the original hemoglobin and arise from leaking blood vessels.^6-8 Vascular Endothelial Growth Factor-A (VEGFA) has been observed to enhance the permeability of these tiny blood vessels, and components in the botanical extract blend have been demonstrated to reduce expression of this important protein, improving capillary strength and angiogenesis.

Clinical Study

To demonstrate the benefits of the botanical extract blend in actual clinical use, Vantage examined the blend in a clinical study on 42 male and female subjects, ranging in age from 36 to 71 years with visible eye aging phenotypes. The study was conducted by an outside cGMP-certified lab following all necessary legal and regulatory guidance for non-invasive clinical studies.  The test participants were divided into two groups, a placebo group comprising 20 individuals and a group of 22 individuals using a cream containing 1.0% of the botanical extract blend as the active ingredient. The participants were instructed to apply the cream around the whole eye area above and below the eyes twice a day for 28 days. They were examined at the beginning of the study and then on day 14 and day 28 using a corneometer to measure hydration and a laser Doppler to measure blood flow.  The individuals were also photographed at the same three timepoints using the BTBP Clarity 3D camera system [BrighTex Bio-Photonics, LLC, San Jose, California] and the images were used to analyze the appearance of fine lines and wrinkles around the crow’s feet area. At the end of the study, participants were asked a series of subjective questions related to the use of the products.

Summary of Hydration Data  

The data from the skin hydration studies conducted on day 14 and day 28 are shown in Figure 2.

The data in Figure 2 demonstrates that the application of the cream containing the botanical extract blend demonstrated a statistically significant improvement in skin hydration compared to both the baseline (p<0.05) and the day 14 application (p<0.05). The placebo cream did not show a similar improvement on day 28 against day 14 data, demonstrating the hydrating benefits of the botanical extract blend.

Summary of Laser Doppler Flowmetry

Because of the profound importance of blood flow as a primary target for improvement in aging eye area, the clinical study examined changes in blood flow measurements on day 14 and day 28 of the treatment schedule. Figure 3 demonstrates a marked improvement in blood flow by day 14, with statistical significance achieved against the placebo cream at the day 28 measurement. This is likely related to the ability of the individual botanicals used in the blend to stimulate important skin proteins that control vascular health and growth as noted above.

Wrinkle Analysis and 3D Mapping 

The BrighTex Bio-Photonics Clarity 3D camera system [San Jose, California] is a state-of-the art, high resolution skin imaging system that allows for images of the face to be analyzed for various important markers. For the purposes of these studies, the camera was used to analyze participants for their wrinkles in the crow’s feet area. Data from these studies are provided in Figure 4.

The camera software allows for the images to be mapped, and the wrinkle profilometry can be analyzed for various parameters including % Surface Area and % Wrinkle Length allowing for comparisons to be made for various treatments. From the data is can be seen that the treatment containing the botanical extract blend demonstrated an ability to improve the surface area and average length of the crow’s feet compared to the placebo cream at the end of the 28-day study. 

Figures 5A & B show images of a 3D map of a volunteer’s crow’s feet in which the Clarity 3D software has mapped the changes in wrinkles from baseline (Figure 5A) compared to day-28 (Figure 5B).

The same profilometric analysis of wrinkles over the eye in a different volunteer who used the formulation containing the botanical extract blend at baseline and day-28 showed similar benefits (data not shown). It was found that the treatment helped to reduce the sagging seen in the upper eyelids of this volunteer after 28 days of use of the same active formulation.

Summary of Responses    

At the completion of the study, the volunteers who used the formulation containing the active botanical extract ingredient were asked a series of six questions shown below:

1. My skin feels hydrated

2. The eyes look less tired

3. Firmness in the eye area has increased

4. The eye area appears more even toned

5. The product improves the overall appearance of the eye area

6. Would you buy this product

The participants were asked to rate questions 1-5 on a four-point scale: Strongly Agree, Agree, Disagree, Strongly Disagree.  Question 6 required only a yes or no answer. The percentage of participants who responded favorably, the top 2 boxes for question 1-5 and yes for question 6, is shown in Figure 6 below.

It is suggested that the eyes are the mirror to the soul and most certainly, for consumers increasingly focused on wellness, the eye area reflects their dedication to more balanced lifestyles. In this paper a summary of studies conducted on a new botanical blend of a TM mushroom extract, Phellinus linteus, and a TM root extract, Angelica polymorpha sinensis, which have been combined strategically to enhance the benefits of both extracts has been shown to improve the overall eye conditions within a short, 28-day time frame.  

The blend was designed principally to help improve the blood flow problems that lead to dark circles and bagging under the eyes and to help rebuild the extracellular matrix proteins that lead to sagging around the upper and lower eyelids. The blend is a natural way to help improve the appearance of the eyes and to help consumers delay or avoid the use of more aggressive techniques such as injections and surgery to help keep the eyes looking their best.

More info: Vince Gruber PhD, Vincent.Gruber@vantagegrp.com

References

1. American Society of Plastic Surgeons 2023 Procedural Statistics Release. https://www.plasticsurgery.org/documents/news/statistics/2023/plastic-surgery-statistics-report-2023.pdf.  Last Accessed 03/10/25
2. Gruber JV, Stojkoskov V, Riemer J. (2020) Retinol has a skin dehydrating effect that can be improved by a mixture of water-soluble polysaccharides. Cosmetics 7:80. Doi:10.3390/cosmetics7040080.  
3. Chen W, Tan H, Liu Q, Zheng X, Zhang H, Liu Y. Xu L. (2019) A review: the bioactives and pharmacological applications of Phellinus linteus. Molecules  24:1888. Doi:10.3390/molecules24101888.
4. Tang W, Chen Y, Guo F. (2023) Comparative analysis of roots from Vicatia thibetica de Boiss and Angelica sinensis based on chemical composition, antioxidant, nitrite-scavenging and enzyme inhibition activities. Molecules 28:1942. Doi.org/10.3390/molecules28041942. 
5. Gruber, J.V.; Terpak, N.; Massard, S.; Chen, X.; Craffey, J.; Holtz, R. In Vitro Examination of Fungal and Root Extracts Inspired by Traditional Medicine for Potential Periorbital Eye Infrastructure Treatments. Cosmetics 2025, 12, 95. https://doi.org/10.3390/cosmetics12030095.
6. Grishchenko SV, Borkhunova EN, Filatova A, Vissarionova V. (2011) Ageing eyelid: clinical, morphological manifestations and peculiarities of microcirculation. Adv Gerontol. 24: 331-339.
7. Sarkar R, Ranjan R, Garg S, Garg YK, Sonthalia S, Bansal S. (2016) Periorbital hyperpigmentation: A comprehensive review. J Clin Aesthet Dermatol 9:49-55.
8. Ryan T. (2004) The ageing of the blood supply and the lymphatic drainage of the skin. Micron. 35:161-171.