Apple Procyanidin B2 (Annurca Apple Polyphenols)

Patterned hair loss (PHL) or androgenetic alopecia is a condition affecting about 50% of people worldwide. Several pharmacological medications have been developed over the years, but few studies have investigated their effectiveness. Therefore, new, safer and more effective strategies are required. Recent investigations showed that Annurca apple extract application could induce keratin production and promote hair growth thanks to the high amount of procyanidin B2 contained in. Hence, this study aimed to investigate the role of an Annurca apple extract in preventing PHL by testing it on human follicle dermal papilla cells (HFDPCs) for the first time. Treatment of HFDPCs with Annurca apple extract counteracted intracellular reactive oxygen species accumulation by increasing the activity of antioxidant enzymes such as superoxide dismutase 2 and catalase. Furthermore, treatment with Annurca apple extract increased β-catenin and fibroblast growth factor 2, which are involved in hair growth stimulation. These data suggest that Annurca apple extract may be a potential therapeutically useful nutraceutical product for preventing or treating hair loss by reducing oxidative stress and inducing the expression of hair growth-related factors. © 2024 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Hair loss is an important problem affecting the quality of life in modern society. Recent studies show that Annurca apple extract (AAE), enriched in procyanidin B2 and nutraceuticals, promotes hair growth and induces keratin production. In this study, we investigated the effects of AAE by orally administering AAE in six-week-old C57BL/6 mice once a day for 21 d. We observed improvement in hair length, thickness, weight, and density. The gene expression of two growth factors related to hair growth, vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 7 (FGF-7), were measured using the quantitative reverse transcription polymerase chain reaction (qRT-PCR). The gene expression of both VEGFA and FGF-7 increased significantly in the AAE-treated group. Additionally, treatment with AAE suppressed the gene expression of type 1 5α-reductase. Histological analysis showed that protein levels of cytokeratin 5 and 10 were increased in the skin tissues of the AAE-treated group. These results suggest that AAE might be a potential therapeutic natural product that prevents hair loss by promoting the expression of hair growth-related factors.

Hair loss is a disorder in which the hair falls out from skin areas such as the scalp and the body. Several studies suggest the use of herbal medicine to treat related disorders, including alopecia. Dermal microcirculation is essential for hair maintenance, and an insufficient blood supply can lead to hair follicles (HF) diseases. This work aims to provide an insight into the ethnohistorical records of some nutritional compounds containing flavonoids for their potential beneficial features in repairing or recovering from hair follicle disruption. We started from a query for "alopecia" OR "hair loss" AND "Panax ginseng C.A. Mey." (or other six botanicals) terms included in Pubmed and Web of Sciences articles. The activities of seven common botanicals introduced with diet (Panax ginseng C.A. Mey., Malus pumila Mill cultivar Annurca, Coffea arabica, Allium sativum L., Camellia sinensis (L.) Kuntze, Rosmarinum officinalis L., Capsicum annum L.) are discussed, which are believed to reduce the rate of hair loss or stimulate new hair growth. In this review, we pay our attention on the molecular mechanisms underlying the bioactivity of the aforementioned nutritional compounds in vivo, ex vivo and in vitro studies. There is a need for systematic evaluation of the most commonly used plants to confirm their anti-hair loss power, identify possible mechanisms of action, and recommend their best adoption.

Hair disorders may considerably impact the social and psychological well-being of an individual. Recent advances in the understanding the biology of hair have encouraged the research and development of novel and safer natural hair growth agents. In this context, we have previously demonstrated-at both preclinical and clinical level-that an Annurca apple-based dietary supplement (AMS), acting as a nutraceutical, is endowed with an intense hair-inductive activity (trichogenicity), at once increasing hair tropism and keratin content. Herein, in the framework of preclinical investigations, new experiments in primary human models of follicular keratinocytes and dermal papilla cells have been performed to give an insight around AMS biological effects on specific hair keratins expression. As well as confirming the biocompatibility and the antioxidant proprieties of our nutraceutical formulation, we have proven an engagement of trichokeratins production underlying its biological effects on human follicular cells. Annurca apples are particularly rich in oligomeric procyanidins, natural polyphenols belonging to the broader class of bioflavonoids believed to exert many beneficial health effects. To our knowledge, none of the current available remedies for hair loss has hitherto shown to stimulate the production of hair keratins so clearly.

Comment in J Med Food. 2019 Dec;22(12):1303-1304. doi: 10.1089/jmf.2019.29003.gct. Comment on J Med Food. 2018 Jan;21(1):90-103. doi: 10.1089/jmf.2017.0016.

Comment on J Med Food. 2019 Dec;22(12):1301-1302. doi: 10.1089/jmf.2019.0220.

Androgenetic alopecia (AGA) is characterized by non-scarring follicle miniaturization. Despite the success of approved therapies, commonly reported side effects and the need for continual use has led to the investigation of alternative therapies. The aim of this paper is to critically review the success of off-label, topical monotherapies for treatment of AGA in men. A literature search was conducted to obtain randomized, controlled and blinded studies that investigated off-label, topical, monotherapies in male patients. Hair density, hair diameter and hair growth were used to evaluate treatment success. Fourteen off-label topical therapies were investigated among the 16 studies that met inclusion criteria. Nine off-label therapies were reported to produce a significantly greater improvement in hair restoration parameters (e.g. mean change from hair count and hair diameter) as compared to placebo (p < 0.05 for all treatments). In two studies, procyanidin oligomers exhibited greater efficacy over vehicle with response to mean change in hair density (hairs/cm2)

Chemotherapy-induced alopecia (CIA) is a common side effect of conventional chemotherapy and represents a major problem in clinical oncology. Even months after the end of chemotherapy, many cancer patients complain of hair loss, a condition that is psychologically difficult to manage. CIA disturbs social and sexual i

9. Nutrients. 2018 Oct 2;10(10):1406. doi: 10.3390/nu10101406. Annurca Apple Polyphenols Ignite Keratin Production in Hair Follicles by Inhibiting the Pentose Phosphate Pathway and Amino Acid Oxidation. Badolati N(1), Sommella E(2), Riccio G(3), Salviati E(4)(5), Heintz D(6), Bottone S(7), Di Cicco E(8), Dentice M(9), Tenore G(10), Campiglia P(11), Stornaiuolo M(12), Novellino E(13). Author information: (1)Department of Pharmacy, University of Naples Federico II. Via Montesano 49, 80149 Naples, Italy. [email protected]. (2)Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, Italy. [email protected]. (3)Department of Pharmacy, University of Naples Federico II. Via Montesano 49, 80149 Naples, Italy. [email protected]. (4)Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, Italy. [email protected]. (5)PhD Program in Drug Discovery and Development, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, Italy. [email protected]. (6)Plant Imaging and Mass Spectrometry, Institut de Biologie Moleculaire des Plantes, CNRS, Universite de Strasbourg, 67000 Strasbourg, France. [email protected]. (7)Department of Pharmacy, University of Naples Federico II. Via Montesano 49, 80149 Naples, Italy. [email protected]. (8)Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80149 Naples, Italy. [email protected]. (9)Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80149 Naples, Italy. [email protected]. (10)Department of Pharmacy, University of Naples Federico II. Via Montesano 49, 80149 Naples, Italy. [email protected]. (11)Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, Italy. [email protected]. (12)Department of Pharmacy, University of Naples Federico II. Via Montesano 49, 80149 Naples, Italy. [email protected]. (13)Department of Pharmacy, University of Naples Federico II. Via Montesano 49, 80149 Naples, Italy. ettore.novel

Comment in J Med Food. 2019 Dec;22(12):1301-1302. doi: 10.1089/jmf.2019.0220. 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 th

Crataegus pinnatifida has a long history of use in traditional oriental herbal medicine to stimulating digestion and improving blood circulation. Based on nutrition of hair, the present study was conducted to assess the effect of C. pinnatifida extract on hair growth using mouse model and its mechanisms of action. The C. pinnatifida extract containing the contents of total polyphenol of 5.88□0.82 g gallic acid/100 g extract and proanthocyanidin of 9.15□1.58 mg cyaniding chloride/100 g extract was orally administered daily at a dosage of 50 mg/kg weight to the 7-week-old C57BL/6 mice in telogen. The C. pinnatifida extract promoted hair growth by inducing anagen phase in mice in telogen, reflected by color of skin, thickness of hair shaft, and density of hair. The ratio of anagento telogen was determined by shape of hair follicles in vertically sectioned slide and increased by oral administration of C. pinnatifida extract. The number and the size of hair follicles were also enlarged, indicating anagen phase induction. The proliferation of human dermal papilla cells (hDPC) was accelerated by addition of C. pinnatifida extract, which activated the signaling of mitogen-activated protein kinases (Erk, p-38, and JNK) and Akt. Moreover, the ratio of Bcl-2/Bax as the determinant of cell fate was also raised in skin. These results suggest that the C. pinnatifida extract promotes hair growth by inducing anagen phase, which might be mediated by the activation of cellular signalings that enhance the survival of cultured hDPC and the increase of the ratio of Bcl-2 to Bax that protects cells against cell death.

The WD40 repeat protein TRANSPARENT TESTA GLABRA1 (TTG1) is involved in a multitude of developmental and biochemical reactions in Arabidopsis thaliana such as the production of seed coat colour and mucilage, pigmentation by anthocyanins as well as the formation of trichomes and root hairs. In this study, a putative TTG1 homologue was isolated from apple (Malus x domestica Borkh.) showing 80.2% identity to A. thaliana TTG1 on nucleotide and 90.7% similarity on amino acid level. The MdTTG1 candidate was able to activate the AtBAN promoter in cooperation with the A. thaliana transcription factors TT2 and TT8 in A. thaliana protoplasts. This indicates that the encoded protein can be integrated into the complex that activates BAN in A. thaliana, and that a similar complex might also be present in apple. When transformed into ttg1 mutants of A. thaliana, the apple sequence was able to restore trichome growth, anthocyanin production in young seedlings as well as proanthocyanidin production in seeds. Additionally, roots of complemented mutant plants showed root hair formation resembling wild type. These results show that the studied apple WD40 gene is a functional homologue of AtTTG1 and we refer to this gene as MdTTG1.

WD40 repeat proteins regulate biosynthesis of anthocyanins, proanthocyanidins (PAs), and mucilage in the seed and the development of trichomes and root hairs. We have cloned and characterized a WD40 repeat protein gene from Medicago truncatula (MtWD40-1) via a retrotransposon-tagging approach. Deficiency of MtWD40-1 expression blocks accumulation of mucilage and a range of phenolic compounds, including PAs, epicatechin, other flavonoids, and benzoic acids, in the seed, reduces epicatechin levels without corresponding effects on other flavonoids in flowers, reduces isoflavone levels in roots, but does not impair trichome or root hair development. MtWD40-1 is expressed constitutively, with highest expression in the seed coat, where its transcript profile temporally parallels those of PA biosynthetic genes. Transcript profile analysis revealed that many genes of flavonoid biosynthesis were down-regulated in a tissue-specific manner in M. truncatula lines harboring retrotransposon insertions in the MtWD40-1 gene. MtWD40-1 complemented the anthocyanin, PA, and trichome phenotypes of the Arabidopsis (Arabidopsis thaliana) transparent testa glabrous1 mutant. We discuss the function of MtWD40-1 in natural product formation in M. truncatula and the potential use of the gene for engineering PAs in the forage legume alfalfa (Medicago sativa).

Procyanidins is the generic term of a large class of polyphenol compounds widespread in the plant kingdom. Because of its potential ability to eliminate free radicals, and also the characteristics of high efficiency and low toxicity, it is the latest craze all over the word, widely used in medicines, cosmetics, health products, etc. This paper reviews the newest research progress of pharmacological effects of procyanidins and its possible action mechanism, such as antioxidation, cardiovascular protection, prevention and treatment of cancer, anti-inflammatory action, anti-diabetic effect, liver protection, and the role of anti-gastrelcosis, anti-radiation, improving learning and memory, promoting hair growth and so on at home and abroad in recent few years.

OBJECTIVE: To investigate the regulatory effect of procyanidins (PC) on the expressions of Th1 type cytokines (IFN-gamma and IL-12) and the transcription factor T-bet mRNA in peripheral blood mononuclear cell (PBMC) in patients with alopecia areata (AA). METHODS: Above-mentioned expressions were detected using RT-PCR technique in 20 AA patients (8 of mild and 12 of severe degree) and 10 healthy subjects after phytoaemagglutinin (PHA) or PHA + PC stimulation. RESULTS: After being stimulated by PHA and PHA + PC, in patients with severe AA, the expression of T-bet mRNA was 0.581 +/- 0.148 and 0.419 +/- 0.113 respectively; that of IFN-gamma mRNA, 0.689 +/- 0.219 and 0.430 +/- 0.162; and that of IL-12 mRNA, 0.198 +/- 0.056 and 0.136 +/- 0.035, respectively. As compared with those before stimulation, the respective difference was statistically significant (P < 0.05). CONCLUSIONS: PC can inhibit the expressions of Th1 type cytokines and transcription factor T-bet in PBMC of severe AA patients, and reverse the Th1 responses. The authors offered that it maybe part of the acting mechanism of pine needle for treatment of AA.

Oligonol((R)) is an optimised phenolic product containing catechin-type monomers and lower oligomers of proanthocyanidin that emanate from a technology process which converts polyphenol polymers into oligomers. In a single dose toxicity study administration of Oligonol (2000mg/kg bw) by gavage for 4 weeks was found to be safe with no side effects (such as abnormal behavior and alopecia). Body weight gain and food consumption were within normal range. Oligonol had no observed toxicity at the dose (1/25 of LD(50)) administered for 6 months. This suggests that Oligonol is safe at repeated human intakes of Oligonol in doses lower than 200mg/day. The highest dose used in this study is equal to 12g daily for an adult man with 60kg body weight. The LD(50) was calculated to be 5.0g/kg body weight (95% confidence limit: 3.5-6.4g/kg). Studies conducted on 30 healthy volunteers consuming Oligonol at doses of 100mg/day and 200mg/day for 92 days showed good bioavailability. The biochemical parameters attesting to liver and kidney functions as well as the hematological parameters were within the normal ranges. The potential of Oligonol to induce gene mutation (a reverse mutation test) was tested using Salmonella typhimurium TA98, TA100, TA104, TA1535, TA153 and Escherichia coli WP2uvrA. Oligonol was not mutagenic to the tester strains. The lack of toxicity supports the potential use of Oligonol as a food or dietary supplement and for use as an additive in pharmaceutical and cosmetological applications.

Procyanidin oligomers are polyphenol compounds we have identified in apples and barley which have hair growth stimulant effects, and which are able to promote hair epithelial cell growth and induce anagen induction of the hair cycle in the in vivo murine model. For the purpose of examining the hair-growing mechanisms of procyanidin oligomers, we examined their relationship to the TGF-beta signal pathway, known to be a regulator of catagen induction, and the mitogen-activated protein kinase cascade linked to cell proliferation. Addition of TGF-beta(1) or TGF-beta(2) to hair epithelial cell cultures dose-dependently decreased cell growth and induced apoptosis; however, addition of procyanidin B-2 to the culture neutralized the growth-inhibiting effects of both TGF-beta(1) and TGF-beta(2) and protected the cells from apoptosis. The same effects were observed with procyanidin B-3. We confirmed that procyanidin B-2 upregulates the expression of MEK-1/2 in cultured murine hair epithelial cells. We speculate that the hair-growing activity of procyanidin oligomers is at least linked to their growth-promoting effects on hair epithelial cells that follow MEK activation and their protective action on TGF-beta(1)- or TGF-beta(2)-induced apoptosis that is assumed to trigger catagen induction in the hair cycle.

With the aim of identifying natural products, which possess hair-growing activity, we examined more than 1000 plant extracts with respect to their growth-promoting effects on hair epithelial cells. We discovered intensive growth-promoting activity, about 140% relative to controls, in barley extract. Our strategy for identifying active compounds in barley extract involved subjecting it to column chromatography using HP-20 resin columns, an LH-20 resin column, and preparative high-performance liquid chromatography (HPLC) using an ODS column. The 60% (v/v) aqueous methanol eluted fraction from the HP-20 column and the 75% (v/v) aqueous methanol eluted fraction from the subsequent LH-20 column showed high hair-growing activity in vivo. We isolated two major substances from the LH-20 active fraction using preparative HPLC. By means of mass spectrometry, 1H-NMR, and 13C-NMR analyses, one substance was revealed to be procyanidin B-3 and the other substance was identified as (+)-catechin. Purified procyanidin B-3 showed high hair-growing activity in the form of in vitro hair epithelial cell growth-promoting activity and in vivo anagen-inducing activity; however (+)-catechin showed no hair-growing activity. For the purpose of examining the hair-growing mechanisms of procyanidin B-3, we examined its relationship to the TGF-beta signal pathway, which is known to be a regulator of catagen induction. Addition of TGF-beta1 to hair epithelial cell cultures dose-dependently decreased the cell growth, and addition of procyanidin B-3 to the culture neutralized the growth-inhibiting effect of TGF-beta1. From these results, it is concluded that procyanidin B-3 can directly promote hair epithelial cell growth in vitro, has the potential to counteract the growth-inhibiting eff

BACKGROUND: We have previously reported that several selective protein kinase C (PKC) inhibitors, including procyanidin B-2, promote hair epithelial cell growth and stimulate anagen induction. OBJECTIVES: We discuss the hypothesis that the hair-growing activity of procyanidin B-2 is related to its downregulation or inhibition of translocation of PKC isozymes in hair epithelial cells. METHODS: We examined the effect of procyanidin B-2 on the expression of PKC isozymes in cultured murine hair epithelial cells as well as PKC isozyme localization in murine dorsal skin at different stages in the hair cycle. RESULTS: We observed that procyanidin B-2 reduces the expression of PKC-alpha, -betaI, -betaII and -eta in cultured murine hair epithelial cells and also inhibits the translocation of these isozymes to the particulate fraction of hair epithelial cells. Our immunohistochemical analyses demonstrated that PKC-alpha, -betaI, -betaII and -eta are specifically expressed in the outer root sheaths of both anagen and telogen hair follicles. The hair matrix at the anagen stage showed no positive staining for these PKC isozymes. Moderate to intense staining for PKC-betaI and -betaII in the epidermis and hair follicles was observed in a telogen-specific manner; however, expression of PKC-alpha and -eta during the telogen stage was not conspicuous. Gö 6976, an inhibitor of calcium-dependent (conventional) PKC, proved to promote hair epithelial cell growth. CONCLUSIONS: These results suggest that PKC isozymes, especially PKC-betaI and -betaII, play an important role in hair cycle progression and that the hair-growing mechanisms of procyanidin B-2 are at least partially related to its downregulation of PKC isozymes or its inhibition of translocation of PKC isozymes to the particulate fraction of hair epithelial cel

Procyanidin B-2 is a compound we have identified in apple which acts as a growth-promoting factor on murine hair epithelial cells. This report describes our investigation of the hair-growing effects of 1% procyanidin B-2 tonic after sequential use for 4 months. A double-blind clinical trial was performed, involving a total of 29 subjects (procyanidin B-2, 19 men; placebo, 10 men). No adverse side effects were observed in either group. In the procyanidin B-2 group, 78.9% showed an increased mean value of hair diameter, whereas only 30.0% in the placebo group showed any increase (p < 0.02, Fisher's exact probability test). The increased ratio of hairs measuring more than 40 microm in diameter after 4 months of procyanidin B-2 treatment was significantly higher than that of the placebo controls (p < 0.05, two-sample-t-test). The increase in number of total hairs in the designated scalp area (0.25 cm(2)) of procyanidin B-2 subjects after a 4 month trial was significantly greater than that of the placebo controls (procyanidin-B-2, 3.67 +/- 4.09 (mean +/- SD)/0.25 cm(2); placebo, -2.54 +/- 4.00/0.25 cm(2); p < 0.001, two-sample t-test). Procyanidin B-2 therapy shows potential as a promising cure for male pattern baldness. Copyright 2001 John Wiley & Sons, Ltd.