Annurca Apple Nutraceutical Formulation Enhances Keratin Expression in a Human Model of Skin and Promotes Hair Growth and Tropism in a Randomized Clinical Trial

Abstract

Several pharmaceutical products have been formulated over the past decades for the treatment of male and female alopecia, and pattern baldness, but relatively few metadata on their efficacy have been published. For these reasons, the pharmaceutical and medical attention has recently focused on the discovery of new and safer remedies. Particularly, great interest has been attracted by oligomeric procyanidin bioactivity, able to promote hair epithelial cell growth as well as to induce the anagen phase. Specifically, the procyanidin B2, a dimeric derivative extracted from apples, has demonstrated to be one of the most effective and safest natural compounds in promoting hair growth, both in vitro and in humans by topical applications. By evaluating the polyphenolic content of different apple varieties, we have recently found in the apple fruits of cv Annurca (AFA), native to Southern Italy, one of the highest contents of oligomeric procyanidins, and, specifically, of procyanidin B2. Thus, in the present work we explored the in vitro bioactivity of AFA polyphenolic extract as a nutraceutical formulation, named AppleMets (AMS), highlighting its effects on the cellular keratin expression in a human experimental model of adult skin. Successively, testing the effects of AMS on hair growth and tropism in healthy subjects, we observed significant results in terms of increased hair growth, density, and keratin content, already after 2 months. This study proves for the first time the impact of apple procyanidin B2 on keratin biosynthesis in vitro, and highlights its effect as a nutraceutical on human hair growth and tropism.

Induction of Hair Keratins Expression by an Annurca Apple-Based Nutraceutical Formulation in Human Follicular Cells

“…In this context, recent preclinical evidence and clinical trials have shown an Annurca apple extract (AMS) as a nutraceutical able to effectively counteract adult baldness and patterned hair loss caused by various factors, including androgenetic and metabolic ones. Indeed, significant results in terms of increased hair growth, hair number, hair weight, and keratin content could be measured after two months of oral treatment [24]. The active ingredient behind this formulation is a dry extract derived from the Annurca apple, a variety particularly rich in oligomeric procyanidins, among natural polyphenols belonging to the broader class of bioflavonoids [39,40].…”

“…Annurca apples have been repeatedly extracted with water, and the obtained solution was filtered, centrifuged, and concentrated. Then, the solution was spry-dried in combination with maltodextrins, obtaining a fine powder named AnnurMetS (AMS) [24], actually branded as AnnurtriComplex ® . The supplement was formulated by the Department of Pharmacy, University of Naples "Federico II" (Naples, Italy), while large-scale production was accomplished by MB-Med Company (Turin, Italy).…”

“…Biochemical investigations were thereby performed to study AMS bioactivity in human hair follicular epidermal keratinocytes (HHFK cells) and in hair dermal papilla cells (HHDPC) in vitro, focusing on the evaluation of cell viability as well as on cell growth and proliferation following exposure up to 96 h to a range of concentrations of the nutraceutical formulation (0.5 ÷ 3 mg/mL). The range of in vitro concentrations used for preclinical evaluations was chosen on the basis of preliminary investigations [24]. In addition, by using high in vitro concentrations (up to 3 mg/mL in the bioscreen), we have tested the nutraceutical for undesirable cellular responses, to validate its safety, and for complete biocompatibility.…”

“…In continuity with preclinical studies performed on HaCaT cells [24], selected bioscreens on human hair follicular keratinocytes (HHFK) and human hair dermal papilla cells (HHDPC) were performed in order to evaluate cell responses to AMS treatment. For this purpose, experimental protocols in vitro reproducing systemic administration of AMS in vivo were accomplished.…”

Complementary and Alternative Treatments for Alopecia: A Comprehensive Review

“…The supplement can be prepared with the addition of biotin, zinc, and selenomethionine (AMSbzs) or without (AMS). Both supplements lead to improvement in all hair clinical parameters, with the AMSbzs cohort demonstrating increased hair density by 125.2%, hair weight by 42.1%, and keratin content by 40.1% at 2 months [60]. Procyanidins also upregulate MAPK/extracellular signal-related kinase kinase (MEK) in hair epithelial cells and counteract hair growth inhibitory effects of TGF-β in vitro, which may account for these clinical results [61,62].…”