A Unique Acylated Flavonol Glycoside from Prunus persica (L.) var. Florida Prince: A New Solid Lipid Nanoparticle Cosmeceutical Formulation for Skincare

Abstract

Polyphenols are known dietary antioxidants. They have recently attracted considerable interest in uses to prevent skin aging and hyperpigmentation resulting from solar UV-irradiation. Prunus persica (L.) leaves are considered by-products and were reported to have a remarkable antioxidant activity due to their high content of polyphenols. This study aimed at the development of a cosmeceutical anti-aging and skin whitening cream preparation using ethanol leaves extract of Prunus persica (L.) (PPEE) loaded in solid lipid nanoparticles (SLNs) to enhance the skin delivery. Chemical investigation of PPEE showed significantly high total phenolic and flavonoids content with notable antioxidant activities (DPPH, ABTS, and β-carotene assays). A unique acylated kaempferol glycoside with a rare structure, kaempferol 3-O-β-⁴C₁-(6″-O-3,4-dihydroxyphenylacetyl glucopyranoside) (KDPAG) was isolated for the first time and its structure fully elucidated. It represents the first example of acylation with 3,4-dihydroxyphenyl acetic acid in flavonoid chemistry. The in-vitro cytotoxicity studies against a human keratinocytes cell line revealed the non-toxicity of PPEE and PPEE-SLNs. Moreover, PPEE, PPEE-SLNs, and KDPAG showed good anti-elastase activity, comparable to that of N-(Methoxysuccinyl)-Ala-Ala-Pro-Val-chloromethyl ketone. Besides, PPEE-SLNs and KDPAG showed significantly (p < 0.001) higher anti-collagenase and anti-tyrosinase activities in comparison to EDTA and kojic acid, respectively. Different PPEE-SLNs cream formulae (2% and 5%) were evaluated for possible anti-wrinkle activity against UV-induced photoaging in a mouse model using a wrinkle scoring method and were shown to offer a highly significant protective effect against UV, as evidenced by tissue biomarkers (SOD) and histopathological studies. Thus, the current study demonstrates that Prunus persica leaf by-products provide an interesting, valuable resource for natural cosmetic ingredients. This provides related data for further studying the potential safe use of PPEE-SLNs in topical anti-aging cosmetic formulations with enhanced skin permeation properties.

Keywords: antioxidant; in-vitro skin related enzymes; in-vivo anti-wrinkle; kaempferol 3-O-β-4C1-(6″-O-3,4-dihydroxyphenylacetyl glucopyranoside) by-products; solid lipid nanoparticles.

Figure 1

kaempferol 3-O-β-⁴C₁-(6″-O-3,4-dihydroxyphenylacetyl glucopyranoside).

Figure 2

Viability of human keratinocytes treated with PPEE, PPEE-SLNs, Extract-free-SLNs, and KDPAG for 24 h; At the concentration of 1 mg/mL, there was a significant reduction in the viability of the cells treated with PPEE, PPEE-SLNs and KDPAG. The data represents% cell viability at each concentration (mean ± S.D.), n = 3. Statistical significance using One-way ANOVA, followed by Tukey’s test: * p < 0.05.

Figure 3

(a) Particle size (nm), (b) zeta potential (mV), (c) Scanning electron microscopy (SEM) (nm) and (d) Transmission electron microscopy (TEM) (nm) micrographs of PPEE-SLNs.

Figure 4

FT-IR of (a): PPEE, (b) PPEE-SLNs with similar characteristic peaks indicating no significant interaction between PPEE and the lipid.

Figure 5

In-vitro permeation study of PPEE cream 2% and 5% Cumulative amount of PPEE released from PPEE-SLNs cream (2% and 5%) is expressed as mean ± S.D.

Figure 6

Anti-wrinkle score measurement. The commercial product and the PPEE-SLNs formulations showed a statistically significant increase in the anti-wrinkle activity compared to the control group (G2). 5% PPEE-SLNs (G5) showed comparable activity to the commercial product (G3). p < 0.05 / n= 10.

Figure 7

Photographs of hairless mice skins. G1 showed normal skin surface. Thick and deep wrinkles were identified in G2 whereas G3–G5 showed a very smooth skin surface due to the applied treatment.

Figure 8

Histological observation of mice skin stained with hematoxylin-eosin. G2 showed a significant decline in elastic fibers compared to G1. Treated groups had enhanced elasticity compared to G2. All treated groups, G3-G5 showed enhanced elasticity. The arrow represents elastic fibers viewed at ×200 magnification.

Figure 9

Effect of treatment on the thickness of (a) epidermis, (b) dermis. @: significant difference in comparison to normal group #: significant difference in comparison to control group p < 0.05/n = 10.

Figure 10

Effect of treatment on the SOD activity. All treated groups showed higher SOD activity compared to the G2 group with no significant difference among them. Data represented as the mean ± SD. @: significant difference in comparison to normal group #: significant difference in comparison to control group p < 0.05/n = 10.