The study, conducted at Ichimaru Pharcos Co Ltd in Motosu, Japan, found that peony root extract (PRE) not only blocked biochemical pathways linked to dull, uneven skin tone, but also delivered visible improvements in a human clinical trial after just two weeks of topical application.
The study’s authors noted that this was the first report to show that PRE could control AGE–RAGE signalling and reduce glycation-related dullness.
Targeting glycation as a driver of skin dullness
Skin dullness is a common cosmetic concern, often described as a lack of radiance or uneven tone that contributes to a tired, aged appearance.
While factors such as UV exposure and oxidative stress are well-known contributors, researchers have increasingly turned their attention to glycation.
AGEs are formed when sugars bind to proteins or lipids, a process accelerated by high sugar intake, heat, and oxidative stress. These compounds accumulate in collagen and elastin, leading to loss of elasticity, wrinkles, and sagging.
Importantly, AGEs themselves have a yellow hue, which contributes to what is known as “yellow dullness”.
Beyond colour changes, AGEs activate RAGE, a receptor expressed on keratinocytes, melanocytes and fibroblasts. This interaction stimulates melanin production, drives inflammation and disrupts keratinocyte differentiation, further contributing to uneven tone and skin fatigue.
With both AGE accumulation and RAGE activation now recognised as central drivers of dullness, a solution that targets both mechanisms could have strong cosmetic value.
Screening process
The research team screened 380 natural ingredients to identify potential inhibitors of the AGE–RAGE interaction. PRE, derived from Paeonia albiflora roots, emerged as a strong candidate.
At a concentration of 1%, PRE reduced AGE–RAGE binding by up to 90% in vitro.
While peony root has long been valued in traditional medicine for its anti-inflammatory and antioxidant properties, its antiglycation effects had not been documented prior to this study.
Interestingly, known peony compounds, such as paeoniflorin and albiflorin, showed no inhibitory effect, suggesting that the antiglycation activity arose from other bioactive components or synergistic interactions within the extract.
Effects on melanin production, keratinocyte differentiation and AGE formation
Further experiments revealed that PRE suppressed AGE-induced melanin production in human melanocytes. While AGEs increased melanin by 37% compared with untreated cells, PRE reduced melanin synthesis by up to 12% at non-toxic concentrations.
In keratinocytes, PRE restored differentiation disrupted by glycated basement membrane proteins. Markers of differentiation, including keratin 10 and transglutaminase 1, recovered in a dose-dependent manner when cells were treated with PRE.
This suggested that PRE could not only reduce pigmentation but also help normalise skin turnover, leading to a more even complexion.
In addition to blocking AGE–RAGE binding, PRE directly inhibited the formation of AGEs in vitro. After four weeks of incubation in a protein-sugar system, AGE levels in the PRE-treated group were less than half those of the control.
This dual action — suppressing new AGE formation and reducing AGE–RAGE binding — positioned PRE as a comprehensive antiglycation ingredient.
Human clinical study
To evaluate cosmetic benefits in vivo, the researchers conducted a two-week, single-blinded, split-face trial with 17 participants aged 40 to 62 years.
A lotion containing 1% PRE was applied twice daily to one side of the face, with a placebo lotion applied to the other.
Subsequently, the researchers reported that AGE accumulation in the cheeks, measured by autofluorescence scanning, showed a decreasing trend in the PRE group but not in the placebo group.
At the same time, PRE significantly reduced melanin levels after two weeks, while the placebo showed no change.
Furthermore, imaging analysis found that dark spots tended to increase in the placebo group, but decreased in the PRE-treated group. The researchers also noted that no irritation or adverse reactions were reported during the study.
Industry implications
The discovery may open new opportunities for cosmetic companies targeting the brightening and anti-aging markets.
Unlike conventional whitening agents that act mainly on tyrosinase inhibition, PRE addresses skin dullness through glycation control and modulation of the AGE–RAGE pathway.
This multifunctional activity positions PRE as a high-value cosmetic ingredient for formulations addressing dullness, uneven tone, and pigmentation.
Given rising consumer awareness of lifestyle-related skin ageing, particularly sugar-driven glycation, PRE could appeal to brands seeking to differentiate products in both Asian and global markets.
Limitations and future directions
While the study’s results were promising, the researchers acknowledged that the active compounds responsible for PRE’s antiglycation effects remained unidentified. Attempts to fractionate PRE showed no individual compounds with significant AGE–RAGE inhibition, suggesting synergistic effects or complex phytochemical interactions.
Further work using HPLC fractionation and LC-MS/MS is planned to pinpoint the bioactive molecules.
Additionally, the exact downstream pathways by which PRE influences RAGE signalling, inflammation, and macrophage activity require more investigation.
Nevertheless, the clinical findings support the use of PRE in topical formulations. The researchers concluded: “Given that AGEs are waste products associated with lifestyle factors and ageing, PRE can potentially improve AGE-induced skin dullness across various ethnicities.
“Therefore, PRE is a comprehensive cosmetic ingredient that mitigates skin dullness, offering a promising novel approach that addresses the unmet needs of dullness care.”
Source: International Journal of Cosmetic Science
“Peony Root Extract Controls AGE–RAGE Interaction, Suppresses AGE Formation, and Reduces Skin Dullness”
https://doi.org/10.3390/cosmetics12040163
Authors: Kyoko Kanai, et al.
