Human Follicle Dermal Papilla Cells Research Articles

Comparison of In Vitro Hair Growth Promotion and Anti-Hair Loss Potential of Thai Rice By-Product from Oryza sativa L. cv. Buebang 3 CMU and Sanpatong

The bioactive compounds in herbal extracts may provide effective hair loss treatments with fewer side effects compared to synthetic medicines. This study evaluated the effects of Buebang 3 CMU and Sanpatong rice bran extracts, macerated with dichloromethane or 95% ethanol, on hair growth promotion and hair loss prevention. Overall, Buebang 3 CMU extracts contained significantly higher levels of bioactive compounds, including γ-oryzanol, tocopherols, and various polyphenols such as phytic acid, ferulic acid, and chlorogenic acid, compared to Sanpatong extracts. Additionally, ethanolic extracts demonstrated greater bioactive content and antioxidant activities than those extracted with dichloromethane. These compounds enhanced the proliferation of human hair follicle dermal papilla cells (HFDPCs) by 124.28 ± 1.08% (p < 0.05) and modulated anti-inflammatory pathways by reducing nitrite production to 3.20 ± 0.36 µM (p < 0.05). Key hair growth signaling pathways, including Wnt/β-catenin (CTNNB1), Sonic Hedgehog (SHH, SMO, GLI1), and vascular endothelial growth factor (VEGF), were activated by approximately 1.5-fold to 2.5-fold compared to minoxidil. Also, in both human prostate cancer (DU-145) and HFDPC cells, the ethanolic Buebang 3 CMU extract (Et-BB3-CMU) suppressed SRD5A1, SRD5A2, and SRD5A3 expression—key pathways in hair loss—by 2-fold and 1.5-fold more than minoxidil and finasteride, respectively. These findings suggest that Et-BB3-CMU holds promise for promoting hair growth and preventing hair loss.

Anti-Hair Loss Effects of the DP2 Antagonist in Human Follicle Dermal Papilla Cells

Prostaglandin D2 (PGD2) levels are high in the balding areas of human scalps, and PGD2 has been found to inhibit hair growth. It is known that the inhibition of the PGD2 receptor can promote hair growth by preventing hair follicles from entering the catagen phase. Thus, we identified an antagonist of DP2, the receptor for PGD2, as a potential treatment for hair loss using an AI-based DeepZema® drug development program. In this study, we identified that the DP2 antagonist (DP2A) could ameliorate alopecia in human follicle dermal papilla cells (HFDPCs) that were stimulated by dihydrotestosterone (DHT), a known molecule related to hair loss. We observed that the DP2A promoted wound healing efficiency and increased alkaline phosphatase levels in the HFDPCs that were damaged with DHT. In addition, we found that the DP2A diminished the reactive oxygen species (ROS) levels generated in the DHT-damaged HFDPCs. We confirmed that the DP2A effectively recovered the membrane potential of mitochondria in these cells. We also demonstrated that the DP2A enhanced the phosphorylation levels of both Akt and ERK in the HFDPCs that were damaged with DHT. Notably, we revealed that the DP2A slightly enlarged the three-dimensional spheroid size in these cells and confirmed that the DP2A improved hair growth in the organ culture of human hair follicles. Taken together, we suggest that DP2A has therapeutic effects on HFDPCs that are damaged by DHT and holds promise as a potential treatment for treating hair loss.

Synergistic Phytochemical and Pharmacological Actions of Hair RiseTM Microemulsion: A Novel Herbal Formulation for Androgenetic Alopecia and Hair Growth Stimulation.

Androgenetic alopecia (AGA) is a genetic condition characterized by an excessive response to androgens, leading to hairline regression in men and hair thinning at the vertex in women, which can negatively impact self-esteem. Conventional synthetic treatments for AGA are often limited by their side effects. In contrast, Thai medicinal plants offer a promising alternative with fewer adverse effects. This study investigates the synergistic phytochemical and pharmacological effects of a novel Hair RiseTM microemulsion, formulated with bioactive extracts from rice bran (Oryza sativa), shallot bulb (Allium ascalonicum), licorice root (Glycyrrhiza glabra), and corn kernels (Zea mays), for the treatment of hair loss. The microemulsion, in concentrations of 50%, 75%, and 100% (v/v), significantly enhanced the proliferation of human hair follicle dermal papilla cells (HFDPCs) compared to minoxidil. Additionally, it upregulated critical hair growth signaling pathways, including Wnt/β-catenin (CTNNB1), Sonic Hedgehog (SHH, SMO, GLI1), and vascular endothelial growth factor (VEGF), surpassing standard controls such as minoxidil and purmorphamine. The microemulsion also demonstrated potent anti-inflammatory and antioxidant properties by reducing nitric oxide production and oxidative stress, factors that contribute to inflammation and follicular damage in AGA. Furthermore, Hair RiseTM inhibited 5α-reductase (types 1-3), a key enzyme involved in androgen metabolism, in both human prostate cancer cells (DU-145) and HFDPCs. These findings suggest that Hair RiseTM microemulsion presents a promising natural therapy for promoting hair growth and reducing hair loss via multiple synergistic mechanisms, offering a potent, plant-based alternative to synthetic treatments.

Novel Synergistic Approach for Bioactive Macromolecules: Evaluating the Efficacy of Goat Placenta Extract in PEGylated Liposomes and Microspicules for Chemotherapy-Induced Hair Loss.

Chemotherapy-induced hair loss is a distressing side effect of cancer treatment, and medical interventions are often needed to address this problem. The objectives of this study were to evaluate the bioactivity of goat placenta (GP) extract on both normal and chemotherapy-induced hair cells and to develop PEGylated liposomes (PL) and microspicule (MS) formulations for promoting hair growth in patients with chemotherapy-induced hair loss. The bioactivities of GP extract on human follicle dermal papilla (HFDP) cells and cells damaged by chemotherapy were assessed. GP extract was incorporated into PLs and MS gel (PL-MS) and then investigated in vitro skin permeation and in vivo studies on the scalps of patients with chemotherapy-induced hair loss. GP extract stimulated HFDP cell proliferation in both normal and cisplatin-damaged cells. PL nanovesicles and MS gel worked synergistically to deliver macromolecular proteins into the skin and hair follicles. The application of GP extract-loaded PL-MS to the scalps of chemotherapy-treated patients for 12 weeks significantly enhanced the hair growth rate, without causing skin irritation. In conclusion, GP extract promoted the proliferation of hair cells damaged by chemotherapy, when this extract, combined with PL-MS, effectively delivered bioactive macromolecules across the skin and hair follicles, resulting in successful regrowth of hair post-chemotherapy.

Ionic Liquid-Based Extraction of Fulvic-like Substances from Wood Sawdust: Reproducing Unique Biological Activities of Fulvic Acids Using Renewable Natural Sources.

Fulvic acids (FAs) have been commercially used in cosmetics and agronomy due to their unique biological activities, such as plant stimulation and anti-inflammatory effects. However, the extraction sources of FAs, such as peat, are currently limited. Consequently, new extraction methods using renewable resources need to be developed, while reproducing the biological functions. Here, ionic liquids (ILs) effectively extracted fulvic-like substances (FLSs) from wood sawdust. The overall molecular weight distributions of FLSs were similar to those of commercial FAs, and key organic groups (e.g., aromatic, phenolic, and methoxy groups) were also found to be shared between commercial FAs and FLSs. Detailed compositional analysis revealed by high-resolution mass spectrometry showed that the extracts contain both lignin-like and lipid-like molecules, while commercial FAs are biased toward lignin-like and carbohydrate-like molecules. FLSs generally showed better and similar performance in radical scavenging activity against ABTS+· and H2O2. Fibroblast proliferation and lettuce growth enhancements were also observed with the extract containing 1-ethyl-3-methylimidazolium acetate and triethylammonium hydrogen sulfate, respectively, which performed better than commercial FAs. Immunofluorescence staining of in vitro human follicle dermal papilla cells supports that coexpression of hair growth-related proteins can be accelerated with FLSs, and this effect was further evidenced by in vivo mouse model experiments. Finally, the reusability of ILs in the extraction process was confirmed by analyzing the structural features of FLSs from each recycling. Our findings indicate that ILs are useful for obtaining biologically functional fulvic analogs from renewable plant sources.

Therapeutic effect of Nepenthes kampotiana Lecomte ethanol extract (Nk-EE) on androgenic alopecia through the inhibition of apoptosis and 5α-reductase activity

There is increasing interest in hair loss treatment because a growing number of people affected. Nepenthes kampotiana Lecomte is known for its anticancer effects, but its potential for preventing hair loss has not been researched. Therefore, this study focused on the hair loss prevention effects of N. kampotiana Lecomte ethanol extract (Nk-EE). The results showed that Nk-EE had a proliferative effect on human follicle dermal papilla cells and inhibited cell death. In vivo experiments using androgenic areata models showed that Nk-EE had a positive effect on a variety of biomarkers such as hair-to-skin ratio, hair type frequency, and hair thickness. The results of this study suggest that Nk-EE has potential as an effective treatment for androgenic alopecia.

Hair Growth Promoting Effects of 15-Hydroxyprostaglandin Dehydrogenase Inhibitor in Human Follicle Dermal Papilla Cells.

Prostaglandin E2 (PGE2) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF2α, has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, to enhance PGE2 levels while improving hair loss, we found dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using DeepZema®, an AI-based drug development program. Here, we investigated whether DPP improved hair loss in human follicle dermal papilla cells (HFDPCs) damaged by dihydrotestosterone (DHT), which causes hair loss. We found that DPP enhanced wound healing and the expression level of alkaline phosphatase in DHT-damaged HFDPCs. We observed that DPP significantly down-regulated the generation of reactive oxygen species caused by DHT. DPP recovered the mitochondrial membrane potential in DHT-damaged HFDPCs. We demonstrated that DPP significantly increased the phosphorylation levels of the AKT/ERK and activated Wnt signaling pathways in DHT-damaged HFDPCs. We also revealed that DPP significantly enhanced the size of the three-dimensional spheroid in DHT-damaged HFDPCs and increased hair growth in ex vivo human hair follicle organ culture. These data suggest that DPP exhibits beneficial effects on DHT-damaged HFDPCs and can be utilized as a promising agent for improving hair loss.

Hair growth-promoting effects of Enz_MoriL on human dermal papilla cells through modulation of the Wnt/β-Catenin and JAK-STAT signaling pathways.

Enz_MoriL is a naturally occurring substance extracted from the leaves of Morus alba L. through enzymatic conversion. Historically, M. alba L. has been recognized for its potential to promote hair regrowth. However, the precise mechanism by which Enz_MoriL affects human hair follicle dermal papilla cells (hDPCs) remains unclear. The aim of this study was to investigate the molecular basis of Enz_MoriL's effect on hair growth in hDPCs. Interferon-gamma (IFN-γ) was used to examine the effects of Enz_MoriL on hDPCs during the anagen and catagen phases, as well as under conditions mimicking alopecia areata (AA). Enz_MoriL demonstrated the ability to promote cell proliferation in both anagen and catagen stages. It increased the levels of active β-catenin in the catagen stage induced by IFN-γ, leading to its nuclear translocation. This effect was achieved by increasing the phosphorylation of GSK3β and decreasing the expression of DKK-1. This stimulation induced proliferation in hDPCs and upregulated the expression of the Wnt family members 3a, 5a, and 7a at the transcript level. Additionally, Enz_MoriL suppressed JAK1 and STAT3 phosphorylation, contrasting with IFN-γ, which induced them in the catagen stage. In conclusion, Enz_MoriL directly induced signals for anagen re-entry into hDPCs by affecting the Wnt/β-catenin pathway and enhancing the production of growth factors. Furthermore, Enz_MoriL attenuated and reversed the interferon-induced AA-like environment by blocking the JAK-STAT pathway in hDPCs.

Malus pumila Mill. cv Annurca apple extract might be therapeutically useful against oxidative stress and patterned hair loss.

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.

In Vitro and In Vivo Models for the Development of Hair Growth Materials By Regulating the β-Catenin Signaling Pathways.

Although hair loss contributes to various social and economic, research methods for material development are currently limited. In this study, we established a research model for developing materials for hair growth through the regulation of β-catenin. We confirmed that 100 nM tegatrabetan (TG), a β-catenin inhibitor, decreased the proliferation of human hair follicle dermal papilla cells (HFDPCs) at 72 h. In addition, TG-induced apoptosis suppressed the phosphorylation of GSK-3β and Akt, translocation of β-catenin from the cytosol to the nucleus, and the expression of cyclin D1. Interestingly, TG significantly increased the G2/M arrest in HFDPCs. Subcutaneous injection of TG suppressed hair growth and the number of hair follicles in C57BL/6 mice. Moreover, TG inhibited the expression of cyclin D1, β-catenin, keratin 14, and Ki67. These results suggest that TG-induced inhibition of hair growth can be a promising model for developing new materials for enhancing β-catenin-mediated hair growth.

Keratin Microspheres as Promising Tool for Targeting Follicular Growth.

Skin is the body barrier that constrains the infiltration of particles and exogenous aggression, in which the hair follicle plays an important role. Recent studies have shown that small particles can penetrate the skin barrier and reach the hair follicle, making them a potential avenue for delivering hair growth-related substances. Interestingly, keratin-based microspheres are widely used as drug delivery carriers in various fields. In this current study, we pursue the effect of newly synthesized 3D spherical keratin particles on inducing hair growth in C57BL/6 male mice and in human hair follicle dermal papilla cells. The microspheres were created from partially sulfonated, water-soluble keratin. The keratin microspheres swelled in water to form spherical gels, which were used for further experiments. Following topical application for a period of 20 days, we observed a regrowth of hair in the previously depleted area on the dorsal part of the mice in the keratin microsphere group. This observation was accompanied by the regulation of hair-growth-related pathways as well as changes in markers associated with epidermal cells, keratin, and collagen. Interestingly, microsphere keratin treatment enhanced the cell proliferation and the expression of hair growth markers in dermal papilla cells. Based on our data, we propose that 3D spherical keratin has the potential to specifically target hair follicle growth and can be employed as a carrier for promoting hair growth-related agents.

Pharmacological activities of extracts from different parts of <i>Cirsium japonicum</i> var <i>spinossimum</i>

Purpose: To evaluate the antioxidant, anti-inflammatory, inhibitory and cell proliferation activities of Cirsium japonicum (C. japonicum) var. spinossimum.
 Methods: Phytochemicals (polyphenols, flavonoids, and silymarin) in leaves, roots, and seeds of C. japonicum var. spinossimum were quantified using high-performance liquid chromatography (HPLC). Antioxidant activity was investigated on 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. Anti-inflammatory activity was investigated on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Immunostimulant and hair loss prevention was confirmed through 3'-{1-((phenylamino)-carbonyl)-3, 4-tetrazolium}bis(4-methoxy-6-nitro)benzenesulfonic acid hydrate (XTT)-based cell proliferation assays using Jurkat cells and human follicle dermal papilla cells (HFDPC).
 Results: Extract from seeds exhibited the highest total polyphenol content (610.08 ± 32.40 mg GAE/g), as well as the highest total flavonoid content, while the total polyphenol content of leaves and root extracts were similar. The RC50 values for seed extract against ABTS and DPPH radicals were 8.20 ± 0.02 µg/mL and 40.13 ± 2.47 µg/mL, respectively. In particular, all six Silymarin derivatives were found to be highest in the seed extract. The C. japonicum var. spinossimum seed extract (CSE) showed significant (p < 0.05) nitric oxide (NO) inhibitory activity in RAW264.7 cells induced by LPS at all concentrations (12.5, 25, 50, 100 and 200 µg/mL) and exhibited significant (p < 0.05) cell proliferation activity in Jurkat and hair follicle dermal papilla cells (HFDPC) at 25 µg/mL.
 Conclusion: Extract of C. japonicum var. spinossimum seeds contain polyphenols and flavonoids and show significant NO inhibitory and cell proliferation activity in Jurkat and HFDPC. Therefore, Cirsium japonicum is a promising source of anti-inflammatory and anticancer agents.

Chemical Constituents of Halophyte Suaeda glauca and Their Therapeutic Potential for Hair Loss.

Suaeda glauca, a halophyte in the Amaranthaceae family, exhibits remarkable resilience to high salt and alkali stresses despite the absence of salt glands or vesicles in its leaves. While there is growing pharmacological interest in S. glauca, research on its secondary metabolites remains limited. In this study, chemical constituents of the aerial parts of S. glauca were identified using 1D- and 2D-NMR experiments, and its biological activity concerning hair loss was newly reported. Eight compounds, including alkaloids (1~3), flavonoids (4~6), and phenolics (7 and 8), were isolated. The compounds, except the flavonoids, were isolated for the first time from S. glauca. In the HPLC chromatogram, quercetin-3-O-β-d-glucoside, kaempferol-3-O-β-d-glucoside, and kaempferol were identified as major constituents in the extract of S. glauca. Additionally, the therapeutic potential of the extract of S. glauca and the isolated compounds 1~8 on the expressions of VEGF and IGF-1, as well as the regulation of Wnt/β-catenin signaling, were evaluated in human follicle dermal papilla cells (HFDPCs) and human umbilical vein endothelial cells (HUVECs). Among the eight compounds, compound 4 was the most potent in terms of increasing the expression of VEGF and IGF-1 and the regulation of Wnt/β-catenin. These findings suggest that S. glauca extract and its compounds are potential new candidates for preventing or treating hair loss.

Effect of applying Lactiplantibacillus plantarum subsp. plantarum N793 to the scalps of men and women with thinning hair: a randomized, double-blind, placebo-controlled, parallel-group study.

Lactiplantibacillus plantarum subsp. plantarum N793 (N793) is a lactic acid bacterium (LAB) isolated from corn. We previously showed that N793 increases the level of keratinocyte growth factor, which is required for hair growth, in the culture supernatant of human follicle dermal papilla cells. Additionally, an open-label, single-arm study reported that applying a lotion containing N793 to the scalp for 24 weeks improved hair density in men and women with thinning hair. The present study was a double-blind, placebo-controlled, parallel-group study aimed at verifying the efficacy of N793 for thinning hair. A lotion containing N793, and a control lotion (placebo) were applied once daily for 24 weeks to 104 healthy Japanese men and women. Analysis of all participants revealed no difference in hair density between the N793 and placebo groups. However, an additional analysis limited to participants with relatively mild progression of thinning hair showed a significantly better hair density in the N793 group than in the placebo group. These findings suggest that topical application of N793 improves thinning hair in men and women when the condition's progression is relatively mild.

Strawberry water-extract increases cellular dehydrogenase activity in human follicle dermal papilla cells

Strawberry water-extract increases cellular dehydrogenase activity in human follicle dermal papilla cells

Three-Dimensional Cultured Human Dermal Papilla Cells in HGC-Coated Environments Enhance Hair Regeneration and Artificial Skin Integration

The rapid development of biomimetic materials in the field of regenerative medicine has made it possible to mimic natural cellular environments and allow in vitro systems to replace in vivo systems. In particular, the emergence of hexanoyl glycol chitosan (HGC) is playing an important role the development of 3-dimensional (3D) cell culture and tissue engineering. We employed HGC-coated dishes to cultivate human hair follicle dermal papilla (HDP) cells in 3D spheroids, assessing their ability to form hair-like structures. The study also tested the effect of minoxidil on these spheroids and explored their integration into artificial skin models. HDP cell spheroids successfully formed hair-like structures within the 3D culture. Minoxidil treatment showed enhanced hair growth in spheroids cocultured with keratinocytes. In addition, transplantation of these spheroids into artificial skin led to the formation of functional papilla structures, suggesting a closer mimicry of human skin. Hair-like structure formation and successful integration into artificial skin models pave the way for innovative approaches in hair loss treatment research, cosmetic, and pharmaceutical evaluations and skin restoration therapies.

Wearable and Wavelength-Tunable Near-Infrared Organic Light-Emitting Diodes for Biomedical Applications.

Near-infrared organic light-emitting diodes (NIR OLEDs) have significant potential for wearable phototherapeutic applications because of the unique properties of the OLEDs, including their free-form electronics and the excellent biomedical effects of NIR emission. In spite of their tremendous promise, given that the majority of NIR OLEDs in previous research have relied on the utilization of an intrinsically brittle indium tin oxide (ITO) electrode, their practicality in the field of wearable electronics is inherently constrained. Here, we report wearable and wavelength-tunable NIR OLEDs that employ a high-performance NIR emitter and an innovative architecture by replacing the ITO with a silver (Ag) electrode. The NIR OLEDs permit wavelength tuning of emissions from 700 to 800 nm and afford stable operation even under repeated bending conditions. The NIR OLEDs provide a lowered device temperature of 37.5 °C even during continuous operation under several emission intensities. In vitro experiments were performed with freshly fabricated NIR OLEDs. The outcomes were evaluated against experimental results performed using the same procedure utilizing blue, green, and red OLEDs. When exposed to NIR light irradiation, the promoting effect of cell proliferation surpassed the proliferative responses observed under the influence of visible light irradiation. The proliferation effect of human hair follicle dermal papilla cells is clearly related to the irradiation wavelength and time, thus underscoring the potential of wavelength-tunable NIR OLEDs for efficacious phototherapy. This work will open novel avenues for wearable NIR OLEDs in the field of biomedical application.

Hair Growth Promotion and Anti-Hair Loss Effects of By-Products Arabica Coffee Pulp Extracts Using Supercritical Fluid Extraction.

Coffee has been a common ingredient in many traditional hair loss remedies, but limited scientific evidence supports its use, particularly in coffee pulp. Androgenetic alopecia (AGA) is caused by androgens, inflammation, and oxidative stress. In the present study, supercritical fluid extraction (SFE) was used under various conditions to obtain six coffee pulp extracts. The SFE-4 extract, using 50% (v/v) ethanol as a co-solvent at conditions of 100 °C and 500 bars for 30 min, exhibited the highest phenolic, flavonoid, and caffeine contents. Additionally, the SFE-4 extract increased the migration and cell proliferation of HFDPCs (human hair follicle dermal papilla cells), which control hair cycle regulation, and had scavenging effects on ABTS and DPPH radicals. Additionally, the SFE-4 extract showed potassium ion channel opener activity in HFDPCs, as well as a stimulation effect on the enzyme matrix metalloproteinase-2 (MMP-2) (28.53 ± 1.08% of control), which may be related to the vascular endothelial growth factor (VEGF) gene upregulation. In human prostate cancer cells (DU-145) and HFDPC cells, the SFE-4 extract significantly decreased the expression of SRD5A1, SRD5A2, and SRD5A3, an essential pathway involved in AGA. Hair growth factor genes in the Wnt/-catenin (CTNNB1) and Sonic Hedgehog (SHH, SMO, and GLI1) pathways could be significantly activated by the SFE-4 extract. These results imply that employing SFE in coffee pulp extraction could help AGA treatment by preventing hair loss and promoting hair growth pathways. This would help small coffee producers gain economic empowerment and ensure the long-term sustainability of agricultural waste utilization.

In vitro hair growth-promoting effect of Lgr5-binding octapeptide in human primary hair cells.

Hair loss occurs due to various biological and environmental causes, which can have psychosocial consequences. The Wnt/β-catenin signaling is well-known for its role in hair growth and regeneration, as it induces the proliferation and differentiation of hair cells. When the leucine-rich G protein-coupled receptor 5 (Lgr5) interacts with the R-spondins, the frizzled receptor (FZD), a Wnt receptor, becomes stabilized, resulting in an increased β-catenin activity. We investigated whether the octapeptide that binds to Lgr5 enhances proliferation and differentiation of human primary hair cells through the activation of Wnt/β-catenin signaling. The binding affinity of the octapeptide to Lgr5 was evaluated using surface plasmon resonance (SPR). We confirmed changes in proliferation and related factors like β-catenin activation and growth factors (GFs) expression in human hair follicle dermal papilla cells (HHFDPCs). Additionally, we observed the proliferation and the expression of differentiation markers in human hair follicle outer root sheath cells (HHFORSCs), human hair follicle germinal matrix cells (HHFGMCs), and human hair follicle stem cells (HHFSCs). We used three-dimensional HHFDPC spheroid culture treated with dihydrotestosterone (DHT) to create invitro conditions that mimic androgenetic alopecia, and we studied the effects of octapeptide on Wnt expression and HHFSC differentiation. The binding of the octapeptide to Lgr5 was confirmed using SPR analysis. In HHFDPCs, treatment with octapeptide resulted in a concentration-dependent increase in proliferation. We also observed increased nuclear translocation of β-catenin and increased expression of its downstream targets. HHFDPCs treated with octapeptide exhibited increased expression of growth factors and phosphorylation of Akt and ERK. In addition, we confirmed that octapeptide increased proliferation and induced differentiation in HHFORSCs, HHFGMCs, and HHFSCs. Under the HHFDPC spheroid culture conditions, we found that octapeptide restored the inhibition of Wnt-5a and Wnt-10b expressions by DHT. In HHFSCs treated with HHFDPC spheroid culture media, we observed that octapeptide recovered the inhibition of differentiation by DHT. We found that octapeptides activated the Wnt/β-catenin signaling and induced the proliferation and differentiation of human primary hair cells by acting as an exogenous ligand for Lgr5. In addition, octapeptides recovered inhibited hair regeneration characters by DHT in androgenetic alopecia-mimic invitro model. These findings suggest that octapeptides may be a promising therapeutic option for treating hair loss.

Salmon nasal cartilage proteoglycan stimulates hair growth.

Hair loss is a commonly encountered problem. In this study, hair growth was enhanced by daily oral ingestion of salmon nasal cartilage proteoglycan (PG) in mice. Proteoglycan stimulated vesicular endothelial growth factor production in human follicle dermal papilla cells through insulin growth factor-1 receptor signaling, suggesting the possibility of hair loss improvement by PG ingestion.