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Naturally Occurring Hair Growth Peptide: Water-Soluble Chicken Egg Yolk Peptides Stimulate Hair Growth Through Induction of Vascular Endothelial Growth Factor Production
Abstract
Alopecia is divided into two categories: androgenic alopecia and nonandrogenic alopecia. An androgen-dependent abnormality of biological functions causes alopecia in males, but the role of androgens is not yet elucidated in female pattern hair loss (FPHL). Modulation of androgenic activity is not effective in certain kinds of androgenic alopecia in females, as well as in cases of nonandrogenic alopecia in males and females. The hair growth drug, minoxidil, stimulates vascular endothelial growth factor (VEGF) production as well as vascularization and hair growth in females. Yet, because minoxidil has side effects with long-term use, a safe alternative hair growth agent is needed. Whereas hair develops after birth in mammalian species, hair mostly grows in a precocial bird, in the chicken, between hatching day 14 and 15. Therefore, we hypothesized that the chicken egg contains a key hair growth factor. In this study, we demonstrated that water-soluble peptides derived from the egg yolk stimulate VEGF production and human hair follicle dermal papilla cell growth. We also found that these peptides enhance murine hair growth and improve hair growth in FPHL. Finally, we characterized that water-soluble egg yolk peptides induce VEGF expression through insulin growth factor-1 receptor activation-induced hypoxia-inducible factor-1α transcription pathway. We have given the name 'hair growth peptide (HGP)' to this water-soluble egg yolk peptide.
... Reversed-phase HPLC The peptide QSLVSVPGMS showed strong antioxidative (DPPH free radical scavenging) and ACE-inhibitory activities. (Eckert et al., 2019) Water-soluble peptides appeared in the hatching period Peptide purification; Cell culture; Cell signaling analysis Induce expression of vascular endothelial growth factor (through the IGF-1/HIF-1 pathway); Stimulate human hair follicle dermal papilla cell proliferation; Stimulate hair growth (Nakamura et al., 2018) Proteolysis by chymotrypsin-like and pepsin-like enzymes Peptidomic study; Functional screening assays; MALDI-TOF-TOF-MS; nanoLC-ESI-Q-Orbitrap-MS/MS Bioactive peptides were found in proteolytic fractions of yolk plasma; 198 peptides were characterized to have potential antihypertensive, antimicrobial, anticancer, and anti-inflammatory effects (Arena and Scaloni, 2018) Treated by peptide-N4-asparagineamidase; N-glycans were released SDS-PAGE; Normal phase liquid chromatography; MALDI-TOF/TOF MS; nanoLC-ESI MS IgY is a new therapeutic glycoprotein in yolk; N-glycan sites and structures of IgY were revealed; Two N-glycosylation sites linked to ASN308 and ASN409 were identified, with high-mannose, hybrid and complex oligosaccharides (Sheng et al., 2018) Polypeptide Y complex (Yolkin) from egg yolk Rat learning tasks and behavioural tests Pro-cognitive effect; Immunoregulatory effect; Benefit behavioural and cognitive functions; Prevent dementia (Lemieszewska et al., 2016) Precipitation and purification using ethanol and acetone Cellular studies; Cytokine measurement Yolkin, an active polypeptide complex isolated from egg yolk; Stimulate human blood cells to release anti-inflammatory cytokines and neurotrophins; Neuroprotective effect: may be a natural food supplement or therapeutic agent for cognitive disorders (Zambrowicz et al., 2017) human diseases. ...
... The long-term disadvantages of hair-growth drugs need to be reduced in the treatment of adult alopecia (Nakamura et al., 2018). Considering that chicken hairs grow fast at day 14 of hatching, Nakamura et al identified a key hair-growth peptide (HGP) in HEY, and HGP stimulated the IGF-1 receptor/HIF-1/VEGF signaling pathway and promoted human hair-follicle-cell growth and murine hair growth, putting forward to a natural alternative agent for preventing hair loss (Nakamura et al., 2018). ...
... The long-term disadvantages of hair-growth drugs need to be reduced in the treatment of adult alopecia (Nakamura et al., 2018). Considering that chicken hairs grow fast at day 14 of hatching, Nakamura et al identified a key hair-growth peptide (HGP) in HEY, and HGP stimulated the IGF-1 receptor/HIF-1/VEGF signaling pathway and promoted human hair-follicle-cell growth and murine hair growth, putting forward to a natural alternative agent for preventing hair loss (Nakamura et al., 2018). Kobayashi et al determined the role of HEY hydrolysates in the bone metabolism of dogs, and the EDPs up-regulated the bone growth biomarker BAP in dog serum and promoted bone formation in dogs (Kobayashi et al., 2015a,b). ...
Hen eggs (HEs) provide valuable nutrients for humans, including proteins, carbohydrates, lipids and vitamins. Recent studies revealed a number of novel egg-derived proteins/peptides (EDPs), and EDPs may play a crucial role in food industry and medical therapy. First, these EDPs were purified from the enzyme-catalyzed hydrolysates of egg proteins and were characterized by biochemical assays such as gel electrophoresis, HPLC, mass spectrometry, proteomic and peptideomic analysis, etc. Second, some EDPs can be used as nontoxic bio-preservatives and functional nutraceuticals for replacing harmful sodium nitrite, inhibiting foodborne pathogens, promoting metal-ion absorption and improving meat-product quality, and these new features will be widely used in the field of food production. Third, novel medical properties of EDPs comprise anti-oxidative, anti-microbial, anti-inflammatory and anti-nociceptive activities, which will benefit prevention of cardiovascular diseases, cancers, diabetic mellitus, immune disorders, etc. In summary, this review gives a real insight into the novel nutritional, biological and medical functions of EDPs, predictably facilitating the applications of EDPs in production of nutritive supplements, functional nutraceuticals and therapeutic medicines.
... While studies regarding the use of egg yolks in treating hair loss remains limited, one study has suggested that key peptides within egg yolks contain growth factor-stimulating properties that contribute to induction of hair growth (Table 8) [102]. Nakamura et al. found that water-soluble hair growth peptides (HGP) contained within egg yolks were capable of stimulating vascular endothelial growth factor (VEGF) and subsequent proliferation of human dermal papilla cells [102]. ...
... While studies regarding the use of egg yolks in treating hair loss remains limited, one study has suggested that key peptides within egg yolks contain growth factor-stimulating properties that contribute to induction of hair growth (Table 8) [102]. Nakamura et al. found that water-soluble hair growth peptides (HGP) contained within egg yolks were capable of stimulating vascular endothelial growth factor (VEGF) and subsequent proliferation of human dermal papilla cells [102]. Hair growth was also observed in a murine model and in a female pattern hair loss model [102]. ...
... Nakamura et al. found that water-soluble hair growth peptides (HGP) contained within egg yolks were capable of stimulating vascular endothelial growth factor (VEGF) and subsequent proliferation of human dermal papilla cells [102]. Hair growth was also observed in a murine model and in a female pattern hair loss model [102]. Additionally, they found that HGP likely promotes VEGF expression via activation of an insulin-like growth factor-1 receptor and subsequent induction of a hypoxia-inducible factor-1α transcription pathway [102]. ...
Background: The impact that hair loss has on an individual's psychological wellness, and subsequent quality of life, is widespread and long lasting. The current standard treatments for hair loss include surgery and medications, ranging from over-the-counter treatments to corticosteroid injections and immunosuppressants. Unfortunately, these current treatments are either expensive, invasive, or have extremely negative side effects. Recently, the role of vitamins, minerals, and functional foods with their associated bioactive compounds, have gained increasing recognition as a potential means to address this issue. Some of these compounds have been shown to decrease the risk of specific forms of hair loss, particularly alopecia, a form of balding that results due from an autoimmune disorder. These include experimental studies using black raspberry extract and egg yolks as well as epidemiological studies using Mediterranean diets and various micronutrients. Other compounds have been shown to promote hair growth on a more general scale, including in vivo studies using rice bran extract and mouse models using red ginseng oil and annurca apple polyphenols. This review identifies key hair growth promoting vitamins, minerals, and functional foods, as well as summarizes the relevant mechanisms of action of these compounds that have been elucidated. Knowledge regarding the effects of these nutriceuticals on reducing hair loss is rapidly expanding. However, it is imperative that further research be done in order to delineate mechanisms of actions for all compounds related to managing and treating hair loss and subsequently integrate these dietary modifications into clinical treatment recommendations for hair loss.Keywords: Hair loss, alopecia, berry extract, mediterranean diet, rice bran, ginseng, annurca apple, thuja orientalis, marine supplement, honey, egg yolk, functional foods, bioactive compounds
... IGF-1 is a key signalling molecule that stimulates hair follicle growth (Grymowicz et al., 2020). The IGF-1 receptor can activate VEGF, which is mediated by phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K) and hypoxia-inducible factor (HIF-1α) (Nakamura et al., 2018). FGFR is a fibroblast growth factor (FGF) receptor, which is crucial for hair growth (Haenzi A et al., 2014). ...
... At present, few studies have analysed the effect of OA on alopecia. However, the treatment of alopecia with natural medicines, such as egg yolk peptides that stimulate hair growth and prevent hair loss has been extensively examined (Choi, 2018;Nakamura et al., 2018). AGA was used as the alopecia model. ...
Oleanolic acid (OA) is a pentacyclic triterpenoid with favourable physiological activity. It is widely distributed in more than 200 species of plants. OA has garnered significant interest because of its potential biological activities, such as antioxidant, bacteriostatic, and hair growth-promoting effects. To study the effect of OA on hair growth and related mechanisms, we investigated hair growth in mice with testosterone-induced androgenetic alopecia (AGA) that were treated with three different concentrations of OA. The antioxidant, bacteriostatic, and cytotoxic effects of OA were evaluated. We found that mice with testosterone-induced AGA treated with 1% or 0.5% OA showed significantly enhanced hair growth and increased vascular endothelial growth factor/glyceraldehyde-3-phosphate dehydrogenase ratio and levels of fibroblast growth factor receptor and insulin-like growth factor 1. Using an immunofluorescence staining assay, we demonstrated that β-catenin, a key Wnt signalling transducer, was highly expressed in the OA-treated groups. These results suggest that OA may promote hair growth by stimulating hair matrix cell proliferation via the Wnt/β-catenin pathway and lowering the levels of tumour necrosis factor-alpha, and transforming growth factor-beta 1, dihydrotestosterone, and 5α-reductase.
... Campiche et al. [68] identified the effects of Leontopodium alpinum in regulating hair follicle growth, including inhibition of hair loss in vitro and an increase in hair regrowth in vivo. Nakamura et al. [69] discovered that water-soluble peptides from egg yolk, also known as hair growth peptide (HGP), stimulate the production of vascular endothelial growth factor (VEGF) and human dermal papilla cell growth by inducing hypoxia-induced factor (HIF)-1a-mediated transcriptional pathways and VEGF expression. With the known side effects of long-term minoxidil use, alternative hair growth strategies have been evaluated. ...
Pattern hair loss can occur in both men and women, and the underlying molecular mechanisms have been continuously studied in recent years. Male androgenetic alopecia (M-AGA), also termed male pattern hair loss, is the most common type of hair loss in men. M-AGA is considered an androgen-dependent trait with a background of genetic predisposition. The interplay between genetic and non-genetic factors leads to the phenotype of follicular miniaturization. Although this similar pattern of phenotypic miniaturization can also be found in female pattern hair loss (FPHL), the corresponding genetic factors in M-AGA do not account for the phenotype in FPHL, indicating that there are different genes contributing to FPHL. Therefore, the role of genetic factors in FPHL is still uncertain. Understanding the genetic mechanism that causes FPHL is crucial for the future development of personalized treatment strategies. This review aims to highlight the differences in the ethnic prevalence and genetic background of FPHL, as well as the current genetic research progress in nutrition, Wnt signaling, and sex hormones related to FPHL.
... We prove that soluble peptides extracted from egg yolks stimulate VEGF production and human follicle skin papilla cell growth, and also find that these peptides improve hair growth in mice and improve hair growth in FPHL. 13 The biotin contained in the yolk of an egg is covalently bound to a specific protein that comprises 0.03% (0.8 mg/yolk) of the total yolk protein. This biotin-binding protein cannot be detected by general avidin analysis because it is tightly bound, and the exchange of biotin is the basis for the analysis of this protein. ...
Background:
Our bodies are a collection of nutrients. For healthy body production and activities, good nutrients must be balanced and supplied steadily. However, as modern people eat more irregular meals and fast food, they are running out of nutrients needed by the human body. As a result, research was conducted on the effect of eggs with good cost-effectiveness on the human body and hair.
Purpose:
The purpose of this paper is to review the literature investigated to convey knowledge of the positive nutrients of modern people's nutrition and eggs.
Methods:
These data were reviewed to identify agreement between each section and the unique guiding area. Regarding the survey criteria, it was finally decided that 33 papers were suitable for evaluating the purpose of research as follows. PRISMA flowcharts allow you to determine the number of records identified, included, and excluded.
Results:
Eggs are considered the most cost-effective foods that deliver protein, biotin, choline, and vitamin A to the world, and eggs that can be easily consumed are known as nutritional foods because they contain protein, lipids, minerals, and embryonic development growth factors. It is widely consumed as a food that can be eaten by anyone, including the elderly and children.
Conclusions:
In this study, eggs can be used as important data for modern people by delivering nutrients to the human body and hair of modern people and understanding positive nutrients.
Background
Cerasus serrulata has an excellent antioxidative, antibacterial, and anti-alopecia effect, but its active ingredients and the underlying mechanism are currently unclear, in addition to the fact that the active products vary with the extraction methods.
Aim
Therefore, this study aims to clarify the active components and antioxidative property of C. serrulata extracted by two different methods (low-temperature vacuum extraction and ethanol extraction) and explore its potential biofunction.
Materials and Methods
First, the compositions in extracts were characterized by gas chromatographic mass spectrometry (GC-MS) and liquid chromatography-mass spectrography (LC-MS). Then, the antioxidative activity of both extracts was evaluated using free radical scavenging assay (ABTS) and ORAC. Next, the antibacterial activity of both extracts was measured via a bacteriostatic circle experiment. The anti-alopecia effects of both extracts were studied using a mouse model of alopecia. The hematoxylin and eosin (H&E) staining was used to evaluate hair follicles; vascular endothelial-derived growth factor (VEGF) and interleukin-6 (IL-6) expression in mouse skin were evaluated by immunohistochemistry, while β-catenin expression in tissues was used by immunofluorescence. The expression of FGFR and insulin-like growth factor 1 (IGF-1) in the skin was determined to evaluate using real-time quantitative polymerase chain reaction (RT-qPCR). The levels of DHT and 5α-reductase in the experimental mice were determined by ELISA.
Results
The GC-MS analysis results showed that the extracts were rich in alkanes and aromatic compounds, specifically benzaldehyde, which was the highest component in the cold vacuum extraction, while pipecolic acid was the main component in the ethanol extract. This indicates that C. serrulata has components that exhibit strong inhibitory ability against the growth of five common bacterial strains, expressing excellent free radical scavenging ability. In addition, the active ingredients in C. serrulata were found to significantly deregulate the protein levels in the skin of androgenetic alopecia (AGA) mice, with the levels of IL-6. They were also able to significantly inhibit VEGF reduction. The β-catenin was being significantly upregulated in skin tissue. In addition, FGFR and IGF-1 gene expression also increased. The 5α-reductase and dihydrotestosterone (DHT) can be reduced in the C. serrulata treatment.
Conclusion
Our data indicate that C. serrulata extract could be beneficial supplements of natural antioxidative, antibacterial, and anti-alopecia agents.
Pathological hair loss (also known as alopecia) and shortage of hair follicle (HF) donors have posed an urgent requirement for HF regeneration. With the revelation of mechanisms in tissue engineering, the proliferation of HFs in vitro has achieved more promising trust for the treatments of alopecia and other skin impairments. Theoretically, HF organoids have great potential to develop into native HFs and attachments such as sweat glands after transplantation. However, since the rich extracellular matrix (ECM) deficiency, the induction characteristics of skin-derived cells gradually fade away along with their trichogenic capacity after continuous cell passaging in vitro. Therefore, ECM-mimicking support is an essential prelude before HF transplantation is implemented. This review summarizes the status of providing various epidermal and dermal cells with a three-dimensional (3D) scaffold to support the cell homeostasis and better mimic in vivo environments for the sake of HF regeneration. HF-relevant cells including dermal papilla cells (DPCs), hair follicle stem cells (HFSCs), and mesenchymal stem cells (MSCs) are able to be induced to form HF organoids in the vitro culture system. The niche microenvironment simulated by different forms of biomaterial scaffold can offer the cells a network of ordered growth environment to alleviate inductivity loss and promote the expression of functional proteins. The scaffolds often play the role of ECM substrates and bring about epithelial-mesenchymal interaction (EMI) through coculture to ensure the functional preservation of HF cells during in vitro passage. Functional HF organoids can be formed either before or after transplantation into the dermis layer. Here, we review and emphasize the importance of 3D culture in HF regeneration in vitro. Finally, the latest progress in treatment trials and critical analysis of the properties and benefits of different emerging biomaterials for HF regeneration along with the main challenges and prospects of HF regenerative approaches are discussed.
Androgenetic alopecia (AGA) is characterized by a non-scarring progressive miniaturization of the hair follicle in predisposed men and women with a pattern distribution. Although AGA is a very prevalent condition, approved therapeutic options are limited. This article discusses the current treatment alternatives including their efficacy, safety profile, and quality of evidence. Finasteride and minoxidil for male androgenetic alopecia and minoxidil for female androgenetic alopecia still are the therapeutic options with the highest level evidence. The role of antiandrogens for female patients, the importance of adjuvant therapies, as well as new drugs and procedures are also addressed.