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An early indicator of aging may appear around the eyes and the surrounding eye infrastructure. With aging, there come diminishing changes in vascular microcirculation and the accumulation of hemoglobin by-products that gather in the fatty pads beneath the eyes as dark circles, akin to skin bruising. In addition, the extracellular matrix that surrounds the eye is exposed to external threats like UV radiation, weather and pollution, as well as lifestyle choices that create fatigue. This causes the eyes to express wrinkles well before they begin to appear on the rest of the face, particularly in the corners of the eyes called the crow’s feet region. Consumers spend considerable amounts of resources combatting these effects. If consumers could treat some of the sources of these problems, in advance of the inevitable influences of aging, a kind of prejuvenation of the eye infrastructure, then perhaps the inevitable outcomes of aging apparent around the eyes could be slowed. This paper examines the development and in vitro testing of two unique botanical extracts, one based on a traditional medicine mushroom called Phellinus linteus (Huang Sang) and the other based on a traditional medicine root from the plant Angelica polymorpha sinensis (Dong Quai). When combined, these two extracts create a blend called ANGEL-EYE EFX® [INCI: Water (and) Glycerin (and) Phellinus Linteus Extract (and) Angelica polymorpha sinensis Root Extract]. There are several key biomolecules of interest present in this blend, including hispolon, dihydrozingerone, and arginine, as demonstrated using advanced liquid chromatography/mass spectral analyses. The individual extracts were also broadly examined using human genomic microarray assays and then more specifically for their ability to influence several important skin proteins associated with undereye skin aging, including CYGB (Human Cytoglobin), OXSR1 (Oxidative Stress Response Kinase-1), LCE3B (Late Cornified Envelope-3B), EGFR (Epidermal Growth Factor Receptor), VEGFA (Vascular Endothelial Growth Factor-1), and NINJ1 (Ninjurin-1). It was found that the treatment of Normal Human Epidermal Keratinocytes (NHEKs) with increasing concentrations of the active blend between 0.05 and 2.0% showed statistically significant increases in all the proteins noted except VEGFA, which showed a statistically significant decrease in protein expression with the treatment of the Angelica polymorpha sinensis extract at 1.0%.