Mangiferin and Hesperidin Transdermal Distribution and Permeability through the Skin from Solutions and Honeybush Extracts (Cyclopia sp.)—A Comparison Ex Vivo Study

Abstract

Polyphenolic compounds—mangiferin and hesperidin—are, among others, the most important secondary metabolites of African shrub Cyclopia sp. (honeybush). The aim of this study was to compare the percutaneous absorption of mangiferin and hesperidin from solutions (water, ethanol 50%, (v/v)) and extracts obtained from green and fermented honeybush (water, ethanol 50%, (v/v)). Research was performed with the Bronaugh cells, on human dorsal skin. The mangiferin and hesperidin distributions in skin layers (stratum corneum, epidermis, and dermis) and in acceptor fluid (in every 2, 4, 6, and 24 h) were evaluated by HPLC–Photodiode Array Coulometric and Coulometric Electrochemical Array Detection. The transdermal distribution of hesperidin was also demonstrated by fluorescence microscopy. Results indicated that mangiferin and hesperidin were able to cross the stratum corneum and penetrate into the epidermis and dermis. An advantage of hesperidin penetration into the skin from the water over ethanol solution was observed (451.02 ± 14.50 vs. 357.39 ± 4.51 ng/cm2), as well as in the mangiferin study (127.56 ± 9.49 vs. 97.23 ± 2.92 ng/cm2). Furthermore, mangiferin penetration was more evident from nonfermented honeybush ethanol extract (189.85 ± 4.11 ng/cm2) than from solutions. The permeation of mangiferin and hesperidin through the skin to the acceptor fluid was observed regardless of whether the solution or the honeybush extract was applied. The highest ability to permeate the skin was demonstrated for the water solution of hesperidin (250.92 ± 16.01 ng/cm2), while the hesperidin occurring in the extracts permeated in a very low capacity. Mangiferin from nonfermented honeybush ethanol extract had the highest ability to permeate to the acceptor fluid within 24 h (152.36 ± 8.57 ng/cm2).

Hesperidin, Hesperetin, Rutinose, and Rhamnose Act as Skin Anti-Aging Agents

“…In our study, the anti-aging potential of the flavonoids hesperidin and hesperetin and their carbohydrate components rutinose, and rhamnose were investigated. The transdermal distribution of hesperidin has already been demonstrated, so we focused on its biological activity during skin aging [ 11 ]. First, their ability to inhibit the activities of enzymes associated with skin aging, specifically hyaluronidase, collagenase, and elastase, which degrade the components of the ECM, was determined in the tube test.…”

“…Transdermal distribution of hesperidin has also been demonstrated. The results of the study by Hering et al (2021) showed that hesperidin was able to cross the stratum corneum , the upper layer of the epidermis, and penetrate the deeper layers of the epidermis and dermis [ 11 ]. Although the bioavailability of hesperidin and hesperetin is relatively low, it can be increased by modifying a number of substances for topical application.…”

In vitro diffusion of plant phenolics through the skin: A review update

“…An infinite dose protocol in a flow‐through cell was applied, and it was observed that hesperidin permeated poorly from the extract, while a moderate to high ability to cross the membrane was seen in solutions of the isolated compound. The capacity of mangiferin to reach the acceptor fluid from the fermented honeybush extract was higher than from the green aerial parts extract after 24 h, showing that the extract composition modulates the behaviour of its various components [70].…”

Photoprotection and Antiaging Activity of Extracts from Honeybush (Cyclopia sp.)—In Vitro Wound Healing and Inhibition of the Skin Extracellular Matrix Enzymes: Tyrosinase, Collagenase, Elastase and Hyaluronidase

“…The ex vivo experiments indicated that hesperidin penetrates the skin from water and ethanol solutions with higher efficiency than from honeybush extracts. In addition, hesperidin indicates a lack of ability to interact with skin macromolecules, but, being unbound, may be capable of protecting cells against UV radiation and oxidative stress [ 24 , 25 ]. Mangiferin, in contrast to hesperidin, from honeybush extracts has shown a greater ability to penetrate the skin [ 21 , 24 ] and exhibited an ability to interact with skin extracellular matrix (ECM) molecules, incompetently inhibiting elastase and collagenase activity [ 21 ].…”

“…In addition, hesperidin indicates a lack of ability to interact with skin macromolecules, but, being unbound, may be capable of protecting cells against UV radiation and oxidative stress [ 24 , 25 ]. Mangiferin, in contrast to hesperidin, from honeybush extracts has shown a greater ability to penetrate the skin [ 21 , 24 ] and exhibited an ability to interact with skin extracellular matrix (ECM) molecules, incompetently inhibiting elastase and collagenase activity [ 21 ]. ECM compounds, such as collagen and elastin, are the structural and elasticity fibres of many organs and tissues [ 26 , 27 ], and they are also presented in abundant amounts among skin layers, where, with hyaluronic acid, they determine the skin functions [ 28 , 29 , 30 ].…”