Abstract

Patterned hair loss (PHL) affects around 50% of the adult population worldwide. The negative impact that this condition exerts on people’s life quality has boosted the appearance of over-the-counter products endowed with hair-promoting activity. Nutraceuticals enriched in polyphenols have been recently shown to promote hair growth and counteract PHL. Malus pumila Miller cv. Annurca is an apple native to Southern Italy presenting one of the highest contents of Procyanidin B2. We have recently shown that oral consumption of Annurca polyphenolic extracts (AAE) stimulates hair growth, hair number, hair weight and keratin content in healthy human subjects. Despite its activity, the analysis of the molecular mechanism behind its hair promoting effect is still partially unclear. In this work we performed an unprecedented metabolite analysis of hair follicles (HFs) in mice topically treated with AAE. The metabolomic profile, based on a high-resolution mass spectrometry approach, revealed that AAE re-programs murine HF metabolism. AAE acts by inhibiting several NADPH dependent reactions. Glutaminolysis, pentose phosphate pathway, glutathione, citrulline and nucleotide synthesis are all halted in vivo by the treatment of HFs with AAE. On the contrary, mitochondrial respiration, β-oxidation and keratin production are stimulated by the treatment with AAE. The metabolic shift induced by AAE spares amino acids from being oxidized, ultimately keeping them available for keratin biosynthesis.

Highlights

  • IntroductionA human healthy hair follicle (HF) undergoes cyclical rounds of growth, active fiber production (anagen), degeneration (catagen) and rest (telogen) [1]

  • During its life, a human healthy hair follicle (HF) undergoes cyclical rounds of growth, active fiber production, degeneration and rest [1]

  • HFs appeared mainly located in the dermis with only few dermal papillas (DP) touching the subcutis border

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Summary

Introduction

A human healthy hair follicle (HF) undergoes cyclical rounds of growth, active fiber production (anagen), degeneration (catagen) and rest (telogen) [1]. Nutrients 2018, 10, 1406 extension occurs, can last years in humans and is fueled by hair matrix cells (HMs) located in the hair bulb (HB). These highly proliferating cells are stimulated by the dermal papillas (DP) to differentiate into different lineages of cell including the outer (ORS) and inner (IRS) root sheaths, all differently involved in the production, deposition, protection and hardening of keratins [1,2,3,4]. Independent of age and gender, this condition exerts a profound negative impact on some people’s quality of life [4] and, especially when occurring at an early age, it is frequently associated to depression [5,6].

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