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Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG)
Abstract
Green tea is a popular worldwide beverage, and its potential beneficial effects such as anti-cancer and anti-oxidant properties are believed to be mediated by epigallocatechin-3-gallate (EGCG), a major constituent of polyphenols. Recently, it was reported that EGCG might be useful in the prevention or treatment of androgenetic alopecia by selectively inhibiting 5alpha-reductase activity. However, no report has been issued to date on the effect of EGCG on human hair growth. This study was undertaken to measure the effect of EGCG on hair growth in vitro and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. EGCG promoted hair growth in hair follicles ex vivo culture and the proliferation of cultured DPCs. The growth stimulation of DPCs by EGCG in vitro may be mediated through the upregulations of phosphorylated Erk and Akt and by an increase in the ratio of Bcl-2/Bax ratio. Similar results were also obtained in in vivo dermal papillae of human scalps. Thus, we suggest that EGCG stimulates human hair growth through these dual proliferative and anti-apoptotic effects on DPCs.
... Among them are grape skin and grape seeds (Vitis vinifera L.), a rich resource of polyphenols with numerous documented biological benefits for skin and hair (Obreque-Slier et al., 2010;Yarovaya, Waranuch, Wisuitiprot, & Khunkitti, 2022). Regarding the latter, the antioxidant and anti-inflammatory properties of the grape extract are believed to help protect hair follicles from damage and stimulate hair growth (Ferri et al., 2017;Kwon et al., 2007;Takahashi, Kamiya, & Yokoo, 1998). Increases in the number of hair follicles and in hair growth length have been reported in a study on rats topically treated with grape sap (Esmaeilzadeh et al., 2021). ...
... In an earlier study, grape seeds' proanthocyanidins increased the proliferation of mouse hair follicle cells and converted the hair cycle in mice from the telogen phase to the anagen phase, potentially through effects on signal transduction pathways (Takahashi et al., 1998). Moreover, epigallocatechin-gallate (EGCG), commonly found in flavan-3-ol, in green tea and grape seeds improved hair growth in hair follicles ex vivo and increased the proliferation of HDPCs in vitro (Kwon et al., 2007). ...
... To the best of our knowledge, this is the first study to show the inhibitory activity of grape extracts on 5α-reductase tested in HFDPC. However, there were several studies reporting the potent inhibiting capacity of EGCG and other flavonoids containing catechol moieties against 5α-reductase (Hiipakka, Zhang, Dai, Dai, & Liao, 2002;Kwon et al., 2007). The proposed mechanism of competitive 5α-reductase inhibition might be explained by the interaction of catechol groups in flavonoids with amino acid residues in the carboxyl-terminal portion of the protein important for binding of nicotinamide adenine dinucleotide phosphate (NADPH) by 5α-reductase. ...
... DHT suppresses the anagen phase and initiates the catagen phase ( Figure 2) [15] . Testosterone is transformed into a more active androgen by 5α-reductase [16] Dermal papilla cells (DPCs) DPCs are particular fibroblasts in the hair follicle that play a fundamental role in controlling hair growth not only during the normal hair cycle but also in the pathogenesis of specific diseases, such as androgenetic alopecia (Figure3) [18] . [19] Hair FDA-approved treatments The various solutions have been proposed to treat hair loss, however, there are many reports of side effects and ineffectiveness of herbal and synthetic remedies. ...
... Numerous in vitro and in vivo studies on active herbal ingredients suggest that these compounds may help control hair loss when used alone, together, and in combination with synthetic anti-hair loss medicines [30,31,32,42] . [18,33,34] Human Topical Anti-apoptosis Increase DPC proliferation Decrease oxidative cell damage Camellia sinensis [35,36,37] Human Oral& Topical 5-ARI Pumpkin seed oil [31,38] Human Topical 5-ARI Saw palmetto extract [39,40] Animal Topical 5-ARI Transformation of hair follicles from telogen to anagen phase Citrullus colocynthis [41] DPC Cell culture Transform telogen to anagen Morus alba [42] Animal Topical Unknown Zizyphus jujuba [43] Animal Topical Transform anagen in the resting phase Eclipta alba [44,45,46] Human/ Hair follicles Topical/cell culture 5-ARI Phlantus embelica [47,48] Animal/DPC In vitro & In vivo 5-ARI The proliferation of DPC & HaCaT Carthamus Tinctorius [49] Human/Animal/ Hair follicles Topical 5-ARI Panax ginseng ...
... Phytochemical structures of green tea phenolic acids [51] Hair Growth and regrowth enhancement function of Camellia sinensis extract Various dietary ingredients, including polyunsaturated fatty acids, flavonoids, and tea catechin gallate inhibit 5α-Reductase in vitro and in vivo (Figure7) [53] . Kwon et al. [18] investigated hair growth in vitro, and in vivo by EGCG. In the in vivo study, scalp tissue samples obtained from the occipital scalp areas of 5 healthy male volunteers (20-31 years). ...
Alopecia is a condition that impacts over 50% of the global population. The Food and Drug Administration (FDA) only approved topical minoxidil and oral finasteride for prevention of hair loss, and hair regrowth. Numerous in vitro and in vivo studies on active herbal ingredients suggest the herbal active ingredients may help control hair loss when used alone, together, and in combination with synthetic anti-hair loss medicines. For over 100 years, thyme, lavender, rosemary, and cedar wood essential oils have traditionally used to treat hair loss. According to current researches about topical green tea in the prevention and hair re-growth, this plant may be a suitable and relatively reliable alternative to chemical drugs such as minoxidil and finasteride. Green tea contains polyphenol compounds called catechins. Catechins have a significant anti-hair loss due to their effect on the dermal papillae cells (DPCs); DPCs are specialized fibroblasts that control the hair growth cycles. This article reviews the potential impact of green tea (Camellia sinensis) in reducing hair loss, hair re-growth, and its particular effect on DPC.
How to cite this article:
Akbarnejad, F.The Role of Green Tea (Camellia sinensis) in the Management of Androgenetic Alopecia (AGA): A Review.2023; 4(5): 308-316
... This experiment notably explained the efficacy of using polyphenols of green tea aids to cure androgenic alopecia that has relevance mainly with the increased activity of enzymes, 5α-reductase and aromatase. Kwon et al. (2007) proved this mechanism by evaluating the efficacy of EGCG on the growth of human hairs. It was deduced that EGCG stimulates the growth of hairs by dual proliferative and anti-apoptotic effects (Kwon et al. 2007). ...
... Kwon et al. (2007) proved this mechanism by evaluating the efficacy of EGCG on the growth of human hairs. It was deduced that EGCG stimulates the growth of hairs by dual proliferative and anti-apoptotic effects (Kwon et al. 2007). ...
... These cells in small intestine absorb glucose and galactose by coupling with Na+-K+ATPase and are inhibited by EGCG thus improving glycaemic index (Johnston et al. 2005). The effect of it on Glucose transporter 2 (GLUT2) was the same as the absorption gets inhibited by intake of catechins (Kwon et al. 2007). ...
Due to its wide range of properties, green tea has extensively been
turned out as an important substance to be examined experimentally by the analysts. Out of its various properties, the antineoplastic activity of green tea is exclusively acknowledged. Green tea shows therapeutic potential in case of cancers of cervical, lung, colon, liver, stomach, leukemia, prostate, breast, and many other organs. Green tea
extract possesses some carcinoma preventive bioactive components such as polyphenols, proline, lysine, catechin, ascorbic acid, and
epigallocatechin-3-gallate. Earlier investigations have favoured the
relationship between the reasonable intake of green tea polyphenols and the decreased cancer possibility. Various mechanisms have been
proposed to determine the application of green tea components as an
anticancer agent. These mechanisms incorporate modulation of the
immune system and cell signalling pathways, regulation of cell cycle,
anti-oxidant activity, and inhibition of receptor tyrosine kinase pathway. Further, drug tolerance and several harmful side effects have long been a crucial complication in the treatment of tumor. The treatment by chemotherapy has also been transformed from single-drug remedy to multiple-drug remedy. Earlier research results indicated that the amalgam of green tea and chemo-remedial drugs could synergistically intensify the effectiveness of therapy and lessen the worse after-effects of antitumor agents in tumor sufferer. Therefore, we have focused on the use of green tea constituents either alone or in combination with other agents for the treatment of different types of cancers with upgraded life expectancy.
... Ginseng (Panax ginseng): Contains ginsenosides, which have been shown to stimulate hair growth by enhancing dermal papilla cell proliferation(Murata et al., 2015).3. Green Tea (Camellia sinensis):Rich in catechins like epigallocatechin gallate (EGCG), known for their antioxidant properties and potential to inhibit 5-alpha-reductase(Kwon et al., 2007). ...
... Ginseng: Promotes hair growth by enhancing cellular proliferation in hair follicles and may also exert antiapoptotic effects(Murata et al., 2015).• Green Tea: The polyphenols, particularly EGCG, are believed to extend the anagen phase of the hair cycle and may have anti-inflammatory properties beneficial for scalp health(Kwon et al., 2007). ...
Alopecia, a condition characterized by hair loss, affects a significant portion of the population and has various psychological and physical impacts. This review article explores the efficacy and safety of herbal treatments for alopecia, integrating traditional knowledge with contemporary scientific research. The article examines various herbal remedies used across cultures, such as Saw Palmetto, Ginseng, Green Tea, and Phyllanthus Emblica, delving into their bioactive compounds and mechanisms of action. Studies and case reports, adhering to APA citation style, highlight the potential of these natural remedies in promoting hair growth and managing different types of alopecia. The review also addresses the safety profile and toxicological considerations of these herbal treatments, underscoring the importance of comprehensive evaluations and standardized dosages. The integration of herbal treatments with conventional therapies is discussed as a promising avenue for enhancing treatment outcomes. The article concludes by emphasizing the need for more rigorous clinical trials, exploration of new herbal compounds, and the development of standardized, safe herbal formulations for alopecia treatment.
... The cells were cultured for 24 hours for viability (acute cytotoxicity) evaluation and 5 days to detect proliferation. (6) The tests were performed in triplicates. Cell viability was measured at 24 hours using PrestoBlue® reagent (Life Technologies) in RPMI medium. ...
... (7) OSE was added to culture media at 125, 250 and 500 μg/mL and EGCG at 2.3 μg/mL (5 μM) was used as a positive control. (6) Thus 5 treatments were compared in this study (3 concentrations of OSE plus EGCG and a non-treated control). The culture media and treatments were changed every other day. ...
... Cellular studies have shown that EGCG increases cell proliferation and decreases cell death by altering the miRNA profiles in HDP cells and sequentially affects paclitaxel-mediated hair loss [112]. In vitro experiments indicated that EGCG promotes hair growth by upregulating phosphorylated Erk and Akt and by increasing the Bcl-2/Bax ratio [108]. Animal experiments show that topical EGCG administration can also prevent hair loss by reducing the T-induced apoptosis of follicular epithelial cells and provoking hair regrowth after epilation [109]. ...
... In comparison to the high number of in vitro and in vivo preclinical studies, there are few clinical trials describing the influence of herbs and their active constituents, as well as that of polyherbal formulations on hair growth. A small clinical study conducted with three volunteers demonstrated that 10% EGCG can promote hair growth by prolonging the anagen phase [108]. In one case series of 14 patients with AA, Morita et al. reported that the topical administration of the immunotherapy agent squaric acid dibutylester (SADBE) for a mean of 6.9 months led to no or poor hair regrowth. ...
Today, about 50% of men and 15–30% of women are estimated to face hair-related problems, which create a significant psychological burden. Conventional treatments, including drug therapy and transplantation, remain the main strategies for the clinical management of these problems. However, these treatments are hindered by challenges such as drug-induced adverse effects and poor drug penetration due to the skin’s barrier. Therefore, various efforts have been undertaken to enhance drug permeation based on the mechanisms of hair regrowth. Notably, understanding the delivery and diffusion of topically administered drugs is essential in hair loss research. This review focuses on the advancement of transdermal strategies for hair regrowth, particularly those involving external stimulation and regeneration (topical administration) as well as microneedles (transdermal delivery). Furthermore, it also describes the natural products that have become alternative agents to prevent hair loss. In addition, given that skin visualization is necessary for hair regrowth as it provides information on drug localization within the skin’s structure, this review also discusses skin visualization strategies. Finally, it details the relevant patents and clinical trials in these areas. Together, this review highlights the innovative strategies for skin visualization and hair regrowth, aiming to provide novel ideas to researchers studying hair regrowth in the future.
... In particular, many polyphenol compounds, including flavonoid and chalcone, contributed to countering hair loss by stimulating the Wnt/β-catenin signaling pathway [76][77][78][79][80][81][82][83][84][85][86][87][88][89][90]. Alpinetin is a natural flavonoid compound isolated from Fabaceae and Zingiberaceae herbs [76]. ...
... EGCG significantly increased the phosphorylation levels of ERK and Akt and the Bcl-2/Bax ratio. Similarly, EGCG has exhibited similar effects in the dermal papillae of human scalps in vivo [83]. ...
Hair loss, or alopecia, is a dermatological disorder that causes psychological stress and poor quality of life. Drug-based therapeutics such as finasteride and minoxidil have been clinically used to treat hair loss, but they have limitations due to their several side effects in patients. To solve this problem, there has been meaningful progress in elucidating the molecular mechanisms of hair growth and finding novel targets to develop therapeutics to treat it. Among various signaling pathways, Wnt/β-catenin plays an essential role in hair follicle development, the hair cycle, and regeneration. Thus, much research has demonstrated that various natural products worldwide promote hair growth by stimulating Wnt/β-catenin signaling. This review discusses the functional role of the Wnt/β-catenin pathway and its related signaling molecules. We also review the molecular mechanism of the natural products or compounds that activate Wnt/β-catenin signaling and provide insights into developing therapeutics or cosmeceuticals that treat hair loss.
... EGCG promoted hair growth in hair follicles in ex vivo culture and the proliferation of cultured dermal papilla cells (DPCs). The growth stimulation of DPCs by EGCG in vitro may be mediated through the upregulation of phosphorylated Erk and Akt and by an increase in the ratio of Bcl-2/Bax [90]. Resveratrol and fisetin regulated the genetic expression of cytokines, such as insulin-like growth factor-1 (IGF-1) and keratinocyte growth factor-2 (KGF), which activate the β-catenin pathway, and TGF-β1, which plays an important role in maintaining the niche of hair follicle stem cells, and were thus thought to play roles in promoting hair growth. ...
... licles in ex vivo culture and the proliferation of cultured dermal papilla cells (DPCs). The growth stimulation of DPCs by EGCG in vitro may be mediated through the upregulation of phosphorylated Erk and Akt and by an increase in the ratio of Bcl-2/Bax [90]. Resveratrol and fisetin regulated the genetic expression of cytokines, such as insulin-like growth factor-1 (IGF-1) and keratinocyte growth factor-2 (KGF), which activate the β-catenin pathway, and TGF-β1, which plays an important role in maintaining the niche of hair follicle stem cells, and were thus thought to play roles in promoting hair growth. ...
The skin is the largest organ of the body and plays multiple essential roles, ranging from regulating temperature, preventing infections, to ultimately affecting human health. A hair follicle is a complex cutaneous appendage. Skin diseases and hair loss have a significant effect on the quality of life and psychosocial adjustment of individuals. However, the available traditional drugs for treating skin and hair diseases may have some insufficiencies; therefore, a growing number of researchers are interested in natural materials that could achieve satisfactory results and minimize adverse effects. Natural polyphenols, named for the multiple phenolic hydroxyl groups in their structures, are promising candidates and continue to be of scientific interest due to their multifunctional biological properties and safety. Polyphenols have a wide range of pharmacological effects. In addition to the most common effect, antioxidation, polyphenols have anti-inflammatory, bacteriostatic, antitumor, and other biological effects associated with reduced risk of a number of chronic diseases. Various polyphenols have also shown efficacy against different types of skin and hair diseases, both in vitro and in vivo, via different mechanisms. Thus, this paper reviews the research progress in natural polyphenols for the protection of skin and hair health, especially focusing on their potential therapeutic mechanisms against skin and hair disorders. A deep understanding of natural polyphenols provides a new perspective for the safe treatment of skin diseases and hair loss.
... EGCG is scientifically proven to have activity against alpha reductase enzyme and thus offer great relief to alopecia. Further EGCG is water soluble and would get absorbed well through scalp epidermis [9,10]. ...
... EGCG has been proven to inhibit alpha reductase enzyme [10]. The hair growth promoting property what we have seen for Phyllanthus emblica, Hibiscus rosa sinensis and Eclipta prostrata along with the active constituent (s) identical to that of EGCG at the absorbance level suggests that the above plants either may possess some bio-similar molecules or some other bio-active constituent (s) other than EGCG also may have strong hair growth promoting property. ...
... 20 Polyphenols (Dihydroquercetin-glycoside [DHQG] and Epigallocatechingallate-glucoside [EGCG2]) induced a stimulation of the metabolism of human fibroblast dermal papilla cells, proliferation and anti-apoptotic effect of the outer root sheath cells, and activation of the Wnt/β-catenin pathway. [21][22][23] Combined with glycine as a constituent of the hair's keratin-associated protein composition 24 and zinc, which is crucial for the incorporation of cysteine into the keratin, 25 DHQG and EGCG2 stimulated the hair growth both in vitro and in vivo, where a 3 months treatment with a hair lotion containing 3% of polyphenols, zinc salt and glycine-complex increased the anagen rate, reduced the telogen, and lead to improved hair density as compared to placebo lotion in an open comparison. 23 The efficacy and safety of a combination of a shampoo and a lotion with the nano-encapsulated combination of the aforementioned ingredients was evaluated in a prospective, single-arm, open-label study with 35 women and 10 men with androgenic alopecia and telogenic effluvium, demonstrating, besides good tolerance, an increase in anagen rate, numbers of total follicular units, a total of hairs, and median hair number per follicle unit with corresponding decrease in hair shedding after 90 days. ...
... For the other ingredients present in verum, but not in vehicle(Table 1) no irritation potential is to be expected at their respective concentration in the formulations. For polyphenols and caffeine anti-inflammatory effects have been described.21,22,26 Besides topical minoxidil and oral finasteride drug therapy ofAGA 6 autologous biotechnologies represented by PRP and Human Follicle Stem Cells (HFSCs) as well as Low-Level Light therapy (LLLT) and microneedling have recently been in the focus of investigation for their potential to maintain improved hair growth instead of requiring permanent therapy. ...
Background:
Considerable parts of the global population are affected by androgenetic alopecia (AGA).
Aims:
The efficacy of a foam containing nicotinic acid hexyl ester, polyphenols, zinc, glycine, and caffeine in comparison with a vehicle control foam was assessed in a double-blind vehicle-controlled study in men with AGA over 6 months.
Patients/methods:
Sixty-two men with AGA were assigned either to the active ingredients (verum) or the vehicle group. They applied the products twice daily on affected scalp areas over 6 months. Automated phototrichograms were obtained at baseline, after 3 and 6 months. In addition, a clinical rating by a dermatologist and by the subjects themselves was documented using standardized questionnaires.
Results:
The reduction of the telogen rate from T0 to T6 was significantly stronger in the verum group compared to the vehicle group. The reduction was significant from T0 to T3 and T6 in the verum group, but in the vehicle group only from T0 to T3, not to T6. Significantly increased hair density was noticed in both groups at all time points, but the change from T0 to T6 did not differ significantly between the groups. Cosmetic acceptance of the foam and its application regimen was generally good in both groups. Slight reddening and burning after application of verum in six cases was probably due to the presence of hexyl nicotinate.
Conclusion:
The study demonstrated a reduction of the telogen rate by a cosmetic foam in men affected by AGA, indicating a benefit for cosmetic intervention against male pattern hair loss.
... On the contrary, phenolic extracts have emerged as a safer and more economical alternative to treat HL. Significant effects of epigallocatechin [56], quercetin [57], and baicalein [57], among others, have been documented in diverse experimental models. ...
Although not frequently lethal, dermatological diseases represent a common cause of consultation worldwide. Due to the natural and non-invasive approach of phytotherapy, research for novel alternatives, such as polyphenols, to treat skin disorders is a subject of interest in modern medicine. Polyphenols, in particular, have been considered because of their anti-inflammatory, antitumoral, antimicrobial, and antioxidant properties, low molecular weight, and lipophilic nature that enables the passage of these compounds through the skin barrier. This review discusses the treatment of common dermatological diseases such as acne vulgaris, fungal infections, dermatitis, alopecia, and skin cancer, using polyphenols as therapeutic and prophylactic options. The specific molecules considered for each disorder, mechanisms of action, current clinical trials, and proposed applications are also reviewed.
... It has been proven to stimulate hair growth by a dual mechanism of proliferating human follicle dermal cells and its antiapoptotic action by increasing Bcl-2/Bax ratio via upregulation of phosphorylated extracellular signalregulated kinase (Erk) and Akt often referred as protein-B kinase. 12 The mitogen activated protein kinases (MAPK) and phosphatidylinositol 3-kinase PI3K/AKT are signalling cascades and are crucial in proliferation and hair-inducing ability of DP cells. 13 This mechanism was also highlighted in the past for epidermal growth factor. ...
Background: Hair loss, a multifactorial condition influenced by factors such as aging, hormonal imbalances, and genetics, has traditionally been treated with synthetic products like minoxidil and finasteride. However, these treatments often come with significant side effects, highlighting the need for safer and more effective alternatives. This study investigates the efficacy and safety of OZiva+ advanced hair growth serum, a formulation containing 3% Redensyl® and 1% Lindera root extract, as a potential treatment for hair loss. Methods: The serum's hair growth-promoting effects were evaluated using the ex vivo Philpott test, involving hair plucks from androgenetic alopecia patients, and its safety was assessed through a clinical patch test on human volunteers. Results: The results demonstrated a significant increase in hair follicle length with the OZiva+ advanced hair growth serum, comparable to 1% minoxidil. Additionally, the serum showed no irritation during the patch study, indicating its safety for use. Conclusions: The findings suggest that OZiva+ advanced hair growth serum is a promising alternative to traditional hair loss treatments, offering comparable efficacy with fewer side effects. This natural formulation, supported by the synergistic action of Redensyl® and Lindera root extract, holds potential for further development as a safer, more effective solution for hair regrowth and overall hair health.
... Serenoa repens extract prevents TGF-β induction, caused by DHT, and interacts with mithocondrial signaling pathway contributing to its protective action [92]. Other are antioxidants which can act against microinflammation (grape seed) or actively inhibits 5α-reductase (green tea [95], ginkgo biloba [94], gingenoside ro [93] or curcumin [96]). Other tea extracts such as Chinese black tea has shown a higher affinity to estrogen receptors promoting also a hair growth enhancer effect [97]. ...
Androgenetic alopecia (AGA) is the most prevalent type of hair loss. Its morbility is mainly psychological although an increased incidence in melanoma has also been observed in affected subjects. Current drug based therapies and physical treatments are either unsuccessful in the long term or have relevant side effects that limit their application. Therefore, a new therapeutic approach is needed to promote regenerative enhancement alternatives. These treatment options, focused on the cellular niche restoration, could be the solution to the impact of dihydrotestosterone in the hair follicle microenvironment. In this context emerging regenerative therapies such as Platelet-rich plasma or Platelet-rich fibrine as well as hair follicle stem cells and mesenchymal stem cell based therapies and their derivatives (conditioned medium CM or exoxomes) are highlighting in the evolving landscape of hair restoration. Nanotechnology is also leading the way in AGA treatment through the design of bioinks and nanobiomaterials whose structures are being configuring in a huge range of cases by means of 3D bioprinting. Due to the increasing number and the rapid creation of new advanced therapies alternatives in the AGA field, an extended review of the current state of art is needed. In addition this review provides a general insight in current and emerging AGA therapies which is intented to be a guidance for researchers highlighting the cutting edge treatments which are recently gaining ground.
... Data from several studies have reported the effect of tea in improving hair regrowth (Esfandiari & Kelly, 2005). Epigallocatechin gallate (EGCG) within tea can increase the Bcl-2/Bax ratio by upregulating Erk and Akt expression, which in turn affects the proliferation of human dermal papilla cells (Kwon et al., 2007). EGCG also inhibits 5α-reductase activity to reduce the occurrence of androgenic alopecia (Hiipakka et al., 2002). ...
Circadian rhythm disorder (CRD) is closely associated with hair regression and shedding, but whether this risk can be transmitted to the offspring is unknown. Whether Pu‐erh tea, with alleviating effects of CRD‐mediated syndrome, can act on the transmission of alopecia risk to offspring is also unproven. Here, we obtained CRD parental mice offspring and found that CRD‐mediated alopecia risk can be transmitted to offspring, especially male offspring. Parental consumption of Pu‐erh tea, especially in females or both parents, reduced the risk of CRD‐mediated alopecia transmitted to offspring by inhibiting subcutaneous fat accumulation (downregulation of Rab18, fat‐specific protein 27 (Fsp27), and perilipin 1 (Plin1)), reducing oxidative stress and inflammation in skin tissue (NADPH oxidase 4 (NOX4)/ nuclear factor kappa‐B (NF‐κB)), balancing androgen and hair growth factor release (hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insulin‐like growth factor 1 (IGF‐1)), and restoring hair follicle DNA repair function (upregulation of Ku70, 8‐Oxoguanine DNA glycosylase 1 (OGG1), and Rad51). Transcriptomic analysis further clarified that the mechanism stemmed from the upregulation of gene expression in pathways such as the Wnt, Hippo, and other signaling pathways.
... In light of such investigations, we conducted this study to examine if the chosen extracts can be used as hair loss prevention agents based on their cosmetological properties [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. To achieve our goals, we evaluated the growth-proliferation abilities of these extracts using changes in the viability of human follicle dermal papilla cells. ...
Although hair loss plays a vital physiological function in present society, their impact on shaping self-esteem is undeniable. Even though there are numerous synthetic drugs available, these days, there are issues with safety, efficiency, and unclear time settings for required outcomes with the current synthetic drug remedies available; therefore, there is growing attention to discovering alternative methods to fight hair loss, primarily through plant-derived formulations. While earlier reports mostly focused on screening compounds or plant extracts affecting 5α-reductase, our research takes a unique direction. We employed a biochemical and molecular biological approach by delving into the complicated biosynthetic pathways involving 17β-hydroxysteroid dehydrogenase (17β-HSD) and 3β-hydroxysteroid dehydrogenase (3β-HSD) in producing testosterone derived from cholesterol. This process conceded requiring experimental results, posing insights into the control of the testosterone/dihydrotestosterone (DHT) production pathway. Our study confirms a discovery platform for finding potential candidates as hair loss inhibitors, highlighting exploring various biochemical mechanisms involving 17β-HSD and 3β-HSD in combination with medicinal plant extracts.
... Some of these compounds have also been shown to have anti-aging properties [142] and the ability to absorb ultraviolet radiation through the presence of chromophores in their composition, causing the entry of radiation into the skin to be blocked by these compounds, protecting it [143]. Hair growth promoting [144] and nail damage prevention [145] properties have also been reported. These characteristics make them extremely interesting compounds for applications in the pharmaceutical industry [135,137] (Figure 4) ...
The pharmaceutical industry is one of the largest pollutants and generator of toxic solvent resi-dues for the environment and human beings. In the last decade, there has been a huge evolution in the design and development of new environmentally friendly products and processes, in re-sponse to the global environmental concern and the growing demand for products with quality ingredients and manufacturing processes aimed at achieving sustainability. Consumers are looking for products with the benefits of natural products, with sustainable and environmentally friendly formulations with few synthetic molecules as possible. Thus, based on the origins of the pharmaceutical industry, it is important to return to Nature and enjoy the benefits that natural products bring to us. Deep eutectic solvents appear as an alternative to toxic solvents commonly used to extract bioactive compounds. These solvents are considered green solvents because they are made up of natural compounds such as sugars, amino acids, and carboxylic acids. In addition, they are simple to prepare, with an atomic economy of 100%, with attractive physicochemical properties. This paper is a comprehensive review in which is described the main properties, characteristics, and production methods of deep eutectic solvents as well as its application to extract from natural sources bioactive compounds with pharmaceutical interest.
... Antioxidant Quercetin, xanthohumol, baicalein, catechin, procyanidin [28,37,78] Antibacterial Procyanidin, quercetin, baicalein, genistein [35,[79][80][81] Antiinflammatory Xanthohumol, dihydroretrochalcones, quercetin [82][83][84] Anticancer Quercetin, procyanidin [85,86] Anti-depression Epigallocatechin-3-gallate, puerarin, genistein [87,88] Anti-obesity Quercetin, cyanidin, myricetin [54,73,76,89] Analgesic Loureirin, cochinchinemin, hesperidin [90,91] Antiviral Apigenin, luteolin, kaempferol [92] Wound healing Apigenin, baicalein, quercetin [93][94][95] Hair repair Luteolin, formononetin, epigallocatechin-3-gallate [96][97][98] Anti-type 2 diabetes ...
Flavonoids are widely distributed in nature and have a variety of beneficial biological effects, including antioxidant, anti‐inflammatory, and anti‐obesity effects. All of these are related to gut microbiota, and flavonoids also serve as a bridge between the host and gut microbiota. Flavonoids are commonly used to modify the composition of the gut microbiota by promoting or inhibiting specific microbial species within the gut, as well as modifying their metabolites. In turn, the gut microbiota extensively metabolizes flavonoids. Hence, this reciprocal relationship between flavonoids and the gut microbiota may play a crucial role in maintaining the balance and functionality of the metabolism system. In this review, we mainly highlighted the biological effects of antioxidant, anti‐inflammatory and antiobesity, and discussed the interaction between flavonoids, gut microbiota and lipid metabolism, and elaborated the potential mechanisms on host lipid metabolism.
... In addition to safflower extract, other plant extracts can also promote hair regeneration, such as Dicerocaryum senecioides, Camellia sinensis (L.) Kuntze, or Coffea arabica L., among others (Kwon et al., 2007;Rambwawasvika et al., FIGURE 9. Schematic diagram of the mechanism by which flavonoids found in safflower extract inhibits cisplatin-induced G2/M cell cycle arrest in primary human follicle dermal papilla cells (HFDPCs). Cisplatin damages the DNA of HFDPCs in the dermal papilla, thereby increasing the phosphorylation of Rad, Chk1, and Cdc25C proteins and reducing the expression of Cdc2, thus arresting the cell cycle at the G2/M phase. ...
Background
Cisplatin is a chemotherapeutic agent commonly used clinically for the treatment of various human cancers. Patients often reduce the use of cisplatin due to its side effects, which in turn affects its treatment. This study explored the mechanism of action of safflower extract as an adjuvant traditional Chinese medicine for chemotherapy.
Methods
Primary human follicle dermal papilla cells (HFDPCs) were used as target cells for cisplatin-induced damage to hair cells. Western blotting was used to investigate the molecular targets of cisplatin and safflower extract in causing HFDPCs damage. Cell survival and cell cycle were analyzed by mitochondrial staining reagent WST-1 and propidium iodide.
Results
Cisplatin could reduce the viability of HFDPCs without causing cell death. Cisplatin increased the level of phospho-Rad17 in HFDPCs and activated the Chk1/Cdc25C signaling to reduce the expression of Cdc2 protein, thereby arresting the cells in the G2/M phase. The combination of safflower extract and the flavonoids could effectively inhibit the signal transduction of Rad17/Chk1/Cdc25 in cisplatin-treated cells and reduce the cell population in the G2/M phase. Finally, we also confirmed that safflower extract could effectively inhibit the damage to HFDPCs caused by cisplatin, mainly at the level of reducing the DNA damage caused by cisplatin.
Conclusions
Safflower extract can be used as an adjuvant Chinese medicine for chemotherapy to reduce the damage caused by chemotherapy to normal hair follicle cells.
... HFDPCs. 11 Meanwhile, Sophora fruit (Sophora japonica) possesses estrogenic, anti-oxidant, anti-inflammation, and immunomodulatory ...
Background
Recent research suggests that persimmon leaf extract (PLE) has an effect on inflammatory skin diseases. Previously, PLE is revealed to inhibit not only nitric oxide production but also inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) expression levels in mouse macrophages in vitro. Moreover, it significantly reduced IL‐6 production and 5α‐reductase expression in human follicle dermal papilla cells (HFDPCs). This study aimed to determine whether the PLE‐containing BLH308 complex improves hair growth in clinical trials.
Materials and Methods
A total of 88 participants were recruited, and were instructed to orally take BLH308 or the placebo twice a day for 24 weeks. The mean age of the test group was 38.52 ± 7.98 years and that of placebo group was 38.98 ± 8.80 years. The study was conducted for 24 weeks, and hair density, thickness, and gloss were evaluated. All participants completed a satisfaction survey questionnaire.
Results
The test group showed significantly increased hair density and hair diameter at week 24 compared with the placebo group (p = 0.0015 and p = 0.0001, respectively). Although not statistically significant, the degree of gloss also showed higher improvement in the test group compared to the placebo group.
Conclusions
Our data demonstrated that oral consumption of the BLH308 complex containing PLE significantly increased hair density and thickness compared to the placebo group, showing its possible role in promoting hair growth.
... The primary constituents of SBM include epigallocatechin gallate (EGCG), epicatechin gallate (ECG), stilbene glycoside (TSG), and various ginsenoside (ginsenoside Rg1, ginsenoside Rf, ginsenoside Rc and ginsenoside Rb2, ginsenoside Rd and ginsenoside Rb1). Previous researches reveal that EGCG ameliorates androgenic alopecia by selectively inhibiting 5α-reductase activity, and up-regulating phosphorylated Erk and Akt and increasing the Bcl-2/Bax ratio on DPCs [35]. Various ginsenosides in ginseng have been reported to regulate key targets in hair growth, including DKK1, SHH, VEGF, TGF-β, MMPs, etc. [36]. ...
Background
As a supplement for promoting hair health, Shi-Bi-Man (SBM) is a prescription comprising various traditional Chinese medicines. Though SBM has been reported to promote hair regeneration, its molecular mechanism remains unclear. Cynomolgus monkeys ( Macaca fascicularis ) are non-human primates with a gene expression profile similar to that of humans. The purpose of this research is to evaluate the effect of SBM on promoting hair regeneration in cynomolgus monkeys and to reveal the underlying mechanism.
Methods
The effect of SBM on hair regeneration was observed by skin administration on 6 cynomolgus monkeys with artificial back shaving. The molecular mechanism of SBM was studied using single-cell RNA sequencing (scRNA-seq) in combination with quantitative polymerase chain reaction (qPCR) detection for gene transcription level, and immunofluorescence staining verification for protein level.
Results
SBM significantly induced hair regeneration in cynomolgus monkeys, increased hair follicle number and facilitated hair follicle development. ScRNA-seq revealed an increase in the number of hair follicle stem cells (HFSCs) with a higher activation state, as evidenced by the higher expression of activation marker LDHA related to metabolism and the proliferation marker MKI67 . Immunofluorescence analysis at the protein level and qPCR at the mRNA level confirmed the sequencing data. Cellchat analysis revealed an enrichment of ligand-receptor pairs involved in intercellular communication in Laminin-related pathways.
Conclusion
SBM significantly promotes hair regeneration in cynomolgus monkeys. Mechanically, SBM can up-regulate LDHA-mediated lactic acid metabolism and drive HFSC activation, which in turn promotes the proliferation and differentiation of HFSCs.
... Dermal papillae cells (DPCs), a subset of specialized fibroblasts found in the hair follicle bulb, are crucial for controlling the hair growth cycle when these phases switch [7] . In order to design a therapeutic for the treatment and/or prevention of hair loss, factors impacting the actions of DPCs are crucial [8] . The anagen initiation of multipotent epithelial stem cells is influenced by a number of signaling molecules, such as Wnts, Sonic hedgehog (Shh), and transforming growth factor-beta (TGF-), among others [9] . ...
... ERK1/2 is closely related to hair follicle growth and is a representative pathway for hair follicle growth stimulation. The activation of the ERK1/2 signaling pathway induces the proliferation of DPCs and inhibits apoptosis [36,37]. In addition, the ERK1/2 signaling pathway mediates VEGF-induced endothelial cell proliferation [38,39] and influences VEGF/VEGFR-2-mediated trichome growth [40]. ...
Dermal papilla cells (DPCs) cultured in vitro induce hair follicle formation. Using a hypoxic microenvironment to culture adipose mesenchymal stem cells (ADSCs) can promote hair follicle growth. However, the exact molecular mechanisms underlying this process remain unclear. In this study, ADSCs and DPCs from Arbas Cashmere goats were used. A hypoxic microenvironment promoted the proliferation of ADSCs and increased the pluripotency of ADSCs. The growth factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) were upregulated in ADSCs in the hypoxia-conditioned medium (Hypo-cm). Hypo-cm also enhanced the ability of DPCs to induce hair follicle formation. Inhibitors of the ERK1/2 signaling pathway caused the expressions of growth factors that increased in hypoxic microenvironments to decrease; moreover, hypoxia-inducible factor-1α (HIF-1α) increased the expression levels of VEGF, bFGF, and PDGF and inhibited the expression of bone morphogenic protein 7 (BMP7). In conclusion, these findings improve the theoretical basis for the development of gene therapy drugs for the treatment of alopecia areata and hair thinning.
... However, smear administration for Minoxidil may cause adverse reactions, such as irritant dermatitis, erythema, and itching, while oral administration may affect male sexual function [7] . Consequently, the development of a mild, long-lasting hair growth-enhancing drug would significantly improve patients' life quality and generate substantial economic benefits [8,9] . Recently, the rapid development of biotechnology, especially omics, has greatly boosted our comprehension of natural product mechanism [10] . ...
Background : As a supplement for promoting hair health, Shi-Bi-Man (SBM) is a natural product comprising various traditional Chinese medicines. Though SBM has been reported to promote hair regeneration, its molecular mechanisms remains unclear. Cynomolgus monkeys (Macaca fascicularis) are non-human primates with a gene expression profile similar to that of humans. The purpose of this research is to evaluate the effect of SBM on promoting hair regeneration in cynomolgus monkeys and to reveal the underlying mechanism.
Methods : The effect of SBM on hair regeneration was observed by skin administration on 6 cynomolgus monkeys with artificial back shaving. The molecular mechanism of SBM was studied using single-cell RNA sequencing (scRNA-seq) in combination with quantitative polymerase chain reaction (qPCR) detection for gene transcription level, and immunofluorescence staining verification for protein level.
Results : SBM significantly promoted hair regeneration on cynomolgus monkeys, increased hair follicle number and facilitated hair follicle development. Single-cell RNA revealed an increase in the number of hair follicle stem cells (HFSCs) with a higher activation state, as evidenced by the higher expression of activation marker LDHA related to metabolism and the proliferation marker MKI67. Immunofluorescence analysis at the protein level and qPCR at the mRNA level have confirmed the sequencing data. Cellchat analysis revealed an enrichment of ligand-receptor pairs involved in intercellular communication in Laminin-related pathways.
Conclusion : SBM significantly promoted hair regeneration on cynomolgus monkeys. Mechanically, SBM could promote LDHA expression and drive HFSC activation. The cell level analysis suggested that SBM promoted the proliferation and differentiation of HFSCs by affecting interaction between HFSCs and others on Laminin-related pathways. Keywords : Hair follicle stem cell activation, Shi-Bi-Man, cynomolgus monkey, single-cell RNA sequencing, LDHA, Laminin pathway.
... Green tea (Camellia sinensis) and its main active ingredient epigallocatechin-3-gallate were found to be effective in the treatment of androgenetic alopecia by selectively inhibiting 5a-reductase activity. 38,39 Pumpkin seed (Cucurbita spp.) oil was reported for the treatment of hair growth in MEDICINAL PLANTS 871 AGA, acting by inhibition of 5a-reductase; this activity could be attributed to its phytosterol content. 40 Its effect was confirmed in a study reporting the inhibitory effect of pumpkin seed oil on testosterone and reduction in the incidence of prostate hyperplasia. ...
Alopecia or hair loss is a widespread issue that has significant effects on personal well-being for both genders nationally and internationally. In addition, alopecia causes extreme emotional stress and negatively impacts the psychological health and self-esteem of cancer patients suffering from chemotherapy-induced alopecia. Unfortunately, available synthetic medications are costly, invasive, or have extreme adverse effects. On the contrary, natural and herbal hair loss products are widely available in the local and international markets in variable pharmaceutical forms with different mechanisms of action, namely, androgen antagonists, nutritional supplements, vasodilators, and 5α-reductase inhibitors or dihydrotestosterone blockers. Thus, it is of great importance to encourage researchers to investigate these natural alternatives that can act as potent therapeutic agents having diverse mechanisms of action as well as limited side effects. Currently, natural remedies are considered a fast-rising pharmaceutical segment with demand from a wide range of consumers. In this study, we present a review of reported herbal remedies and herb combinations recommended for hair loss and their mode of action, along with an overview of available market products and formulations, their composition, and declared effects. In addition, a general outline of the different forms of alopecia, its causes, and recommended treatments are mentioned as well. This was all done with the aim of assisting further studies with developing standardized natural formulations for alopecia as many were found to lack standardization of their bioactive ingredients and efficiency confirmation.
... For its part, cyclin D1 expresses during phase G1 and is involved in the initiation of DPC cell cycle progression [41]. Regarding the MAPK / ERK pathway, its activation is crucial in the proliferation of different cell types, including dermal papilla cells and it has been described that several hair growth activators, such as the Endothelial Growth Factor (EGF), the Placental Growth Factor (PGF) or adenosine, exert their effects through the MAPK / ERK pathway [42,43]. ...
Objective: Capacitive-Resistive Electrothermal Therapies (CRET) have proven effective in
tissue regeneration. This study analyzesthe response to 448-kHz CRET treatment in 20 patients
with Female Pattern Hair Loss (FPHL) and in woman’s Dermal Papilla Cells (DPC).
Methods: Patients received ten 20-minute CRET sessions over an 8-week interval. Three
months after the last session, the effects of the treatment were trichoscopically analysed. DPC
were CRET stimulated intermittently for 12, 24 or 48 h and the effects on cell proliferation and
expression of several proteins involved in cell proliferation were analysed.
Results: Trichoscopic data revealed generalized, statistically significant hair redensification
(10 - 15 % over pre-treatment values) in all the treated scalp areas. In-vitro electrostimulation
significantly increased DPC proliferation and expression of the proteins involved in cell
proliferation. Since dysregulation of DPC proliferation is the main factor underlying abnormal
hair loss, it is likely that electrically-induced DPC proliferation is involved in the redensifying
effects obtained in the trichological study.
... The nanoparticles were formed by polylactic-glycolic acid copolymer (PLGA) with encapsulation of rapamycin (RAPA-PLGA NPs), which helps to improve the sustained-release effect and prolong the incubation period of rapamycin [26]. In addition, EGCG has antioxidation and anagen activation effects [27]. Keratin (KE) is the main component of hair [28]. ...
Interest in transdermal delivery methods for stimulating hair regrowth has been increasing recently. The microneedle approach can break the barrier of the stratum corneum through puncture ability and improve drug delivery efficiency. Herein, we report a dissolvable microneedle device for the co-delivery of rapamycin and epigallocatechin gallate nanoparticles that can significantly promote hair regeneration. Compared with the mice without any treatment, our strategy can facilitate hair growth within 7 days. Higher hair shaft growth rate and hair follicle density with inconspicuous inflammation were exhibited in C57BL/6 mice, elucidating its potential for clinical application.
... Studies evaluated that Lawsonia inermis compounds can slow hair loss and help nourish the scalp (25). Epicatechin gallate (ECG) and Epigallactocatechin gallate (EGCG) are extracted from Camellia sinensis leaves (26)(27)(28). Other compounds are β-sitosterol and stigmasterol isolated from Serenoa repens. ...
Background: Dihydrotestosterone (DHT), the most critical pathogenic androgen in hair loss, is identified as an etiologic factor of androgenetic alopecia (AGA). The AGA is a genetically common disorder among men and is characterized by the progressive conversion of hair follicles into small vellus hair. Steroid 5 alpha-reductase type 1 (5AR1) is a crucial target responsible for this gradual replacement. The 5AR1 function is determined by converting testosterone to DHT. The inhibitors of 5AR1 play their role by blocking the DHT production pathway. Objectives: This study focused on the potent inhibitors of the 5AR1 enzyme to suggest effective synthetic drugs for restoring hair loss with fewer side effects. Methods: The three-dimensional structure of 5AR1 was created using homology modeling methods. Then, the inhibitory effects of some significant compounds from natural sources were examined on the 5AR1 protein using molecular docking approaches. Results: The obtained results suggest that two natural compounds isolated from Serenoa repens, including beta-sitosterol and stigmasterol, could inhibit the regular activity of 5AR1 and can be recommended as safe and novel AGA medicines for hair restoration.
... Several clinical findings recommend that the treatment is done through EGCG blocks cancer incidence and diversity in differentiated organ sites, including liver, skin, stomach, lungs, colon, and mammary glands present in the body (Kwon et al., 2007). The objectives of the clinical studies are to study the efficiency of EGCG in treating tumor patients. ...
Epigallocatechin 3-gallate (EGCG) possesses various biological functions, including anti-cancer and anti-inflammatory properties. EGCG is an abundant polyphenolic component originating from green tea extract that has exhibited versatile bioactivities in combating several cancers. This review highlights the pharmacological features of EGCG and its therapeutic implications in cancer and other metabolic diseases. It modulates numerous signalling pathways, regulating cells' undesired survival and proliferation, thus imparting strong tumor chemopreventive and therapeutic effects. EGCG initiates cell death through the intrinsic pathway and causes inhibition of EGFR, STAT3, and ERK pathways in several cancers. EGCG alters and inhibits ERK1/2, NF-κB, and Akt-mediated signaling, altering the Bcl-2 family proteins ratio and activating caspases in tumor cells. This review focuses on anti-cancer, anti-oxidant, anti-inflammatory, anti-angiogenesis, and apoptotic effects of EGCG. We further highlighted the potential of EGCG in various types of cancer, emphasizing clinical trials formulations that further improve our understanding of the therapeutic management of cancer and inflammatory diseases.
... The results of increasing in thickness and the darker color of eyebrows obtained in this work may confirm the in vitro pharmacological activities of C. ternatea and E. caryophyllus previously reported [10][11][12]16 . ...
Clitoria ternatea (butterfly pea) flower and Eugenia caryophyllus (clove) oil have been traditionally used as hair growth stimulating herbal and exhibited hair growth effects in vitro. This work prepared liposome loading with butterfly pea flower extract and clove oil and studied the hair growth promoting effects on eyebrows in volunteers. The liposome of butterfly pea flower extract and clove oil was prepared by loading the extract and oil into a pro-liposome. The formation of liposome was examined using the microscopy and its physical stability was studied at 4°C, 45°C and ambient temperature (30-35°C) for 1 month. The liposome of butterfly pea flower extract and clove oil was macroscopically stable but microscopic examination showed that the liposome vesicles were larger overtime. The loaded liposome was used for eyebrow growth efficacy test in 15 volunteers. The product was applied on both sides of eyebrows twice daily for 60 days. The evaluation was based on the taken photos and the satisfaction assessment scoring from 1 to 5 (very poor-excellent). The eyebrows appeared darker and thicker after 30 day and progressively more obvious at 2 month use. Participants felt that the enhancement of eyebrow thickness and darkness was good (33.3%) to excellent (66.7%). In addition, there was no irritation present which ensure the product safety. Conclusively, this work reported a stable liposome loaded with butterfly pea flower extract and clove oil. The product was subjectively proven to intensify the thickness and darkness of eyebrows.
... The hair im-duction with great potential for use in skincare to improve skin health and protection and with beneficial effects on skin aging [20]. Since studies of polyphenols from green tea and Annurca Apples showed a beneficial effect on hair growth, the influence of OMWW extract on human follicle dermal papilla cells (HFDPC) and their secretion of growth factors (IGF-1 and VEGF) was investigated in this work [21] [22]. In addition, the protective function of the extract regarding the formation of reactive oxygen species (ROS) in the cells was examined. ...
... Treatment of HHDPCs with cisplatin induces production of reactive oxygen species and decreases of Bcl-2/Bax ratios, leading to HHDPC apoptosis and massive hair loss (Luanpitpong et al., 2011). Tea polyphenol epigallocatechin-3-gallate (Kwon et al., 2007) and MNX (Han et al., 2004) enhanced proliferation and inhibited apoptosis (by increasing Bcl-2/Bax ratios) of dermal papilla cells, thereby stimulating hair growth. In mice, 6-gingerol in ginger suppresses cultured human hair elongation and delays telogen-to-anagen transition of hair follicles by inhibitory and pro-apoptotic activities on dermal hair cells (Miao et al., 2013). ...
This study aimed to investigate the underlying mechanisms of red ginseng extract (RGE) on regulating hair growth and hair follicle development. Results from in vitro studies showed that RGE treatment simultaneously enhanced viability and inhibited apoptosis in human hair dermal papilla cells. Moreover, RGE administration promoted telogen-to-anagen transition, prolonged anagen in hair follicular cycling, and increased the size of hair follicles and skin thickness in a C57BL/6 mouse model. Furthermore, RGE treatment significantly upregulated the expression of β-catenin, phospho-glycogen synthase kinase 3β, cyclin D1, cyclin E, and Bcl-2, phospho-extracellular signal-regulated protein kinase, and phospho-Akt, which are associated with promoting hair growth. In addition, RGE enhanced skin health by activation of antiox-idant defense systems. Our data demonstrates that hair regenerative mechanisms of RGE may be mediated by stimulating dermal papilla cell proliferation and enhancing skin functions.
... Formulations with 6% G.T. have a prolonged moisturizing effect, improve microrelief, and reduce skin roughness [151]. Topical application of G.T. prevents UV-oxidative injury, reduces the matrix metalloproteinases, collagenase, and hyaluronidase production [152,153], and decreases UV-induced erythema [154]. Tea used orally and topically decreases sebum production, and prevents and treats acne vulgaris [155]. ...
Nowadays, much attention is paid to issues such as ecology and sustainability. Many consumers choose "green cosmetics", which are environmentally friendly creams, makeup, and beauty products, hoping that they are not harmful to health and reduce pollution. Moreover, the repeated mini-lock downs during the COVID-19 pandemic have fueled the awareness that body beauty is linked to well-being, both external and internal. As a result, consumer preferences for makeup have declined, while those for skincare products have increased. Nutricosmetics, which combines the benefits derived from food supplementation with the advantages of cosmetic treatments to improve the beauty of our body, respond to the new market demands. Food chemistry and cosmetic chemistry come together to promote both inside and outside well-being. A nutricosmetic optimizes the intake of nutritional microelements to meet the needs of the skin and skin appendages, improving their conditions and delaying aging, thus helping to protect the skin from the aging action of environmental factors. Numerous studies in the literature show a significant correlation between the adequate intake of these supplements, improved skin quality (both aesthetic and histological), and the acceleration of wound-healing. This review revised the main foods and bioactive molecules used in nutricosmetic formulations, their cosmetic effects, and the analytical techniques that allow the dosage of the active ingredients in the food.
... Date seed oil contained a significant phenolic compound and showed diverse pharmacological effects, such as antimutagenic, anticarcinogenic, and anti-inflammatory activities [89,90]. Several phenolic and flavonoid compounds were found in date fruits [91][92][93][94][95][96][97][98][99][100]. Phenolic compounds act as natural antioxidants. ...
Abstract: Many recent studies in the field of cosmetics have focused on organically sourced substances. Products made from organic materials are safe, high quality, cruelty-free, and more effective than those made from synthetic materials. Many organic compounds are known to be physiologically active in humans and have an extended storage capacity and long-lasting environmental effects. Agro-industrial waste has recently increased substantially, and the disposal of date palm waste, often performed in primitive ways such as burning, is harmful to the environment. Fruit processing industries generate over 10% of the total date seed waste daily, which could be converted into useful food products. Date fruit and seed are rich in sugar, vitamins, fiber, minerals, and phenolic compounds with antioxidant and anti-inflammatory properties that significantly promote human and animal health. This waste is rich in bioactive compounds and essential oils used in many kinds of food, medicine, and cosmetics. Most active cosmetic ingredients come from natural sources such as fruit, fish, and dairy, and recent research shows that date extract and seed oil help to reduce melanin, eczema, acne, and dry patches, while increasing skin moisture and elasticity. This review details the bioactive compounds and nutraceutical properties of date fruit and seed, and their use as cosmetic ingredients.
Alopecia is a common dermatological disorder of patchy hair loss with substantial patient burden. Phytotherapeutic compounds are increasingly used as a source of new therapeutic options. This review aimed to synthesize the evidence on plant species in hair growth and the methodological aspects of in vivo experimental models. The systematic scoping review was conducted following the PRISMA checklist, Joanna Briggs Institute and in accordance with Cochrane. A systematic search was carried out in the Pubmed, Scopus, Web of Science, and SciELO databases. In vivo experiments that evaluated hair growth activity using natural substances of plant origin were included. Data collection and analysis: A total of 1,250 studies were identified, of which 175 were included for qualitative synthesis. Of these, 128 used mice, 37 rats, 10 rabbits, 1 guinea pig, and 1 sheep as animal models. The methodologies mapped were: hair growth analysis, histological analysis, immunohistochemistry, gene expression analysis, Western blot, enzyme-linked immunosorbent assay, and biochemical analysis. Minoxidil and finasteride were the most commonly used positive controls. The studies evaluated plant species (166), algae (11) or isolated substances (31). Overall 152 plant species and 37 isolated substances were identified. This is the first systematic scoping review on methodological aspects of in vivo hair growth activity. We created a checklist to be completed by authors to allow data comparison and reproducibility, facilitate data interpretation by readers and ensure better quality of evidence. This work may become a valuable tool for future research and contribute to significant advances in hair growth studies.
Nutraceuticals combine health-promoting bioactive ingredients with various foods or supplements. Many such products are commercially available for ingestion or application, and are touted for improved hair appearance, thickness, density, and growth. The overwhelming number of products can make it difficult for consumers to understand which products have the best data available. This chapter will examine the medical literature to identify the most evidence-based ingredients for hair growth, discuss their underlying mechanisms of action, and raise further questions about how best to formulate and incorporate them into our lifestyle.
Phytochemicals, which are predominantly found in plants, hold substantial medicinal value. Despite their potential, challenges such as poor oral bioavailability and instability in the gastrointestinal tract have limited their therapeutic use. Traditional intra/transdermal drug delivery systems offer some advantages over oral administration but still suffer from issues such as limited penetration depth, slow drug release rates, and inconsistent drug absorption. In contrast, microneedles (MNs) represent a significant advancement in intra/transdermal drug delivery by providing precise control over phytochemical delivery and enhanced penetration capabilities. By circumventing skin barriers, MNs directly access dermal layers rich in blood vessels and lymphatics, thus facilitating efficient phytochemical delivery. This review extensively discusses the obstacles of traditional oral delivery and the benefits of intra/transdermal delivery routes with a particular focus on the transformative potential of MNs for phytochemical delivery. This review explores the complexities of delivering phytochemicals through intra/transdermal routes, the development and types of MNs as innovative delivery tools, and the optimal design and properties of MNs for effective phytochemical delivery. Additionally, this review examines the versatile applications of MN-mediated phytochemical delivery, including its role in administering phytophotosensitizers for photodynamic therapy, and concludes with insights into relevant patents and future perspectives.
Strawberry (Fragaria × ananassa) is a fruit that is rich in bioactive components and nutrients. A previous study revealed that strawberries offer beauty benefits, including anti-inflammatory effects. In this study, we investigated the potential hair growth-promoting properties of strawberries by measuring dehydrogenase activity as an indicator of cellular metabolism, and assessed the expression of hair growth-related genes in human follicle dermal papilla cells (HFDPC). Additionally, we performed chemical analyses to characterize the active compounds contributing to the observed effects. The results indicated that strawberry water-extract promotes the metabolism of HFDPC, and that this effect was reduced with heat treatment. The expression levels of hair growth-related genes (FGF7, VCAN, and TGFB2) were examined, but no significant differences were detected. Although further investigation into the components and mechanisms underlying this bioactivity is required, these results lay a foundation for the development of hair-care cosmetics.
Background
Androgenetic alopecia (AGA) affects both men and women. Standard treatments include topical minoxidil and oral finasteride, which can cause undesirable side effects. Therefore, a natural herbal extract is required for an alternative treatment.
Objectives
This study aims to assess both the efficacy and safety profiles of an herbal extract comprising a combination of dihydroquercetin glucoside, epigallocatechin gallate glucoside, zinc, and glycine, compared to the minoxidil solution for the treatment of AGA.
Methods
About 30 males and 30 females were recruited. The males and females were divided equally into two groups (n=30), randomly receiving either a minoxidil solution or herbal extraction twice a day for 24 weeks. Clinical efficacy, total hair count, and hair mass index (HMI) were evaluated.
Results
A total of 30 males and 30 females completed the study. The total hair counts (hairs/cm ² ) at baseline in the herbal group and minoxidil group were 334.8±108.8 and 368.3±178.4, respectively, and the total hair counts at 24 weeks in the herbal group and minoxidil group were 345.0±119.2 and 391.5±183.1 (p<0.001, p<0.001), respectively. The HMI in the herbal and minoxidil groups significantly increased by 25.83±17.18 and 33.70±15.17 (p=0.001, p<0.001) at 24 weeks. However, there was no significant difference in total hair count and HMI between the two groups at 24 weeks (p= 0.250, p=0.065). No local adverse effects were observed in both groups.
Conclusions
The non-significant difference in efficacy and safety to minoxidil solution suggests that the herbal extraction could be an alternative treatment for AGA.
Clinical Trial Registration Number
TCTR20220927001.
The extraction of bioactive compounds of pharmaceutical interest from natural sources has been significantly explored in recent decades. However, the extraction techniques used were not very efficient in terms of time and energy consumption; additionally, the solvents used for the extraction were harmful for the environment. To improve the environmental impact of the extractions and at the same time increase the extraction yields, several new extraction techniques were developed. Among the most used ones are ultrasound-assisted extraction and microwave-assisted extraction. These extraction techniques increased the yield and selectivity of the extraction in a smaller amount of time with a decrease in energy consumption. Nevertheless, a high volume of organic solvents was still used for the extraction, causing a subsequent environmental problem. Neoteric solvents appeared as green alternatives to organic solvents. Among the neoteric solvents, deep eutectic solvents were evidenced to be one of the best alternatives to organic solvents due to their intrinsic characteristics. These solvents are considered green solvents because they are made up of natural compounds such as sugars, amino acids, and carboxylic acids having low toxicity and high degradability. In addition, they are simple to prepare, with an atomic economy of 100%, with attractive physicochemical properties. Furthermore, the huge number of compounds that can be used to synthesize these solvents make them very useful in the extraction of bioactive compounds since they can be tailored to be selective towards a specific component or class of components. The main aim of this paper is to give a comprehensive review which describes the main properties, characteristics, and production methods of deep eutectic solvents as well as its application to extract from natural sources bioactive compounds with pharmaceutical interest. Additionally, an overview of the more recent and sustainable extraction techniques is also given.
Healthy hair is an important part of a beautiful body. Thus, new developments in hair science and hair care have been reported in the literature, and innovations and ideas in hair care and cosmetics are required. Hair care products are used to keep the scalp clean and moisturize the hair. Hair care products also help control hair structure and behavior, keeping hair in a controlled environment if necessary. Natural cosmetics are safer to use when compared with other synthetic products. They are hypoallergenic, dermatologist-tested and proven to be safe to use anytime, anywhere. Hair cosmetics consist of different agents such as hair oil, hair tonic, anti-dandruff, hair dye, etc. This review focuses on different types of herbs that can be used cosmetically for hair care.
Hair is a complex system that exhibits distinct chemical and physical characteristics depending on the individual. It's multifunctional structure made up of various morphological components that work together as unit to protect skins and communicate sexually and socially. Hair has been subject of several studies in literature, with topics ranging from biology to dermatology to aesthetics to forensics to medicine. Despite fact that contemporary humans' hair has no physiological purpose, it is critical to our sense of self-worth. Alopecia areata, or circular/spot baldness, a very frequent kind of baldness caused by androgenic alopecia (male pattern baldness). Many synthetically derived active substances are accessible for therapy, but they come with variety of drawbacks. They're uncertain considering effectiveness as well as reliability, and length of time it takes to see results is both long and ambiguous. Because of this, there is growing demand for hair loss remedies including botanicals and/or isolated active elements.
Background
Hair serum is recommended therapy for the management of hair fall problems. People of all ages suffer from hair fall.
Aim
To evaluate safety and efficacy of hair growth promoting product in healthy adult subjects with hair fall complaints (Alopecia).
Methods
In this safety and efficacy clinical study, 32 healthy individuals (aged 18–45 years) experiencing hair loss were enrolled. Participants applied 0.5 mL of the product to the affected scalp area daily for 60 days. The study evaluated various factors, including hair growth rate, thickness, density, scalp condition using CASLite‐Nova, anagen‐to‐telogen ratio, hair fall reduction, overall hair and scalp appearance, hair strength, and participants' subjective perceptions of the product.
Results
Highly statistically significant improvement was observed in hair growth rate, thickness, and density at Day 30 and Day 60. Hair growth rate increased ( p ‐value <0.01) by 10.52% in 30 days and 31.62% in 60 days after test product application. Average hair growth increased by 424.21 μm/day and 487.31 μm/day at Day 30 and 60 respectively. The hair growth improved by up to 1.5 times after 60 days of usage in healthy subjects with hair fall complaints. No adverse events or product‐related adverse events were reported.
Conclusion
Hair serum containing Redensyl, AnaGain, Procapil, Capilia longa, and 5 kDa hyaluronic acid was efficacious and well tolerable in reducing hair fall (Alopecia). Hair serum significantly improved hair growth, hair density, hair thickness, and hair strength within 60 days of usage, thereby demonstrating it worth as a beneficial inclusion as a daily haircare product.
Herbata chińska charakteryzuje się wysoką zawartością składników farmakologicznie i kosmetycznie czynnych (kofeina i szereg związków polifenoliwych). Stanowi składnik wielu nawilżających preparatów kosmetycznych. Celem badania była ocena wpływu maski do rąk z wodno-glicerynowym ekstraktem z Camelia sinesis (L.) O. Kuntze na wybrane cechy skóry. Z grupy 24 wolontariuszek (20,2 ±0,53 lat) wyłoniono grupę badaną (kosmetyk z ekstraktem roślinnym, n = 8), porównawczą (kosmetyk placebo, n = 8) i kontrolną (brak stosowania kosmetyku, n = 8). Łącznie badanie ukończyły 22 osoby. Badanie ankietowe dotyczące
subiektywnej oceny jakości skóry dłoni oraz pomiary cech skóry z zastosowaniem specjalistycznych sond (korneometr, pHmetr, tewametr, identometr) wykonano przed oraz po 3 dniach stosowania kosmetyku. Jedynie dla grupy placebo wykazano znamienne różnice poziomu nawilżenia (p = 0,005). Pokazuje to znaczenie bazy kosmetyku jako składnika wpływającego na nawilżenie. Dodatek ekstraktu niwelował ten efekt. Inne badane cechy skóry nie uległy zmianie. Oceniając wyniki oceny subiektywnej i obiektywnej poziomu nawilżenia skóry, uwidoczniono dodatnią korelację pomiędzy jej wynikami. Pozostałe cechy (pH, TEWL, elastyczność skóry) nie uwidoczniły znamiennych korelacji. Ekstrakt z zielonej herbaty wykorzystany w prostej formie kosmetycznej nie jest składnikiem poprawiającym nawilżenie. Jego dodatek do kosmetyku zamaskował wręcz działanie nawilżające składników bazy kosmetycznej, za co odpowiadają
najprawdopodobniej związki garbnikowe obecne w surowcu roślinnym. W krótkotrwałej obserwacji nie wpływa także na jej odczyn kwasowo-zasadowy, funkcje barierowe skóry i jej sztywność. W trakcie naboru ani w trakcie przeprowadzania badań żadna z uczestniczek nie miała żadnych działań niepożądanych wynikających ze stosowania badanego preparatu kosmetycznego.
Tea is the most popular beverage globally, with areas of Asia reporting the highest consumption per capita. In 2013, the global production of green tea was approx. 1.7 million tons, with a forecast to double in volume by 2023 [1]. Green tea, just like all types of tea, is made from the processed leaves of evergreen shrub Camellia sinensis. The leaves of Camellia sinensis undergo different withering and oxidation processes to attain varying levels of oxidation, resulting in different tea colors, namely green tea, white tea, yellow tea, oolong, pu-erh tea, and black tea [2]. Drinking tea has been considered a health-promoting habit since antiquity, and more than two-thirds of the world’s population consumes this beloved beverage, making it the second-most popular beverage next to water. However, most of the tea consumed in the world is black tea (78%), whereas green tea consumption comprises only 20% [3].
Introduction: Hair follicle regeneration and control of growth cycling is a small but growing field of study. Here we considered some of the more common in vitro and ex vivo hair follicle models that are available for examining follicle growth and cycling, epithelial-mesenchymal signaling, stem cell activity, and follicular neogenesis. Methods: Cited literature was selected using the Pubmed database and the associated MESH terms, or conference proceedings. Results: A variety of in vitro and ex vivo assay models have been developed over the last 35 years. In vitro research started with simple 2D culture of dermal papilla or dermal sheath cells, but this has now progressed to 3D single cell type aggregate cultures that more accurately reflect the gene and protein expression profiles of dermal papilla and dermal sheath cells in vivo. Combining hair follicle mesenchyme and epithelial cells together in 3D “organoid” cultures enables formation of rudimentary proto-hair follicles. More recently, 3D cultured skin equivalents incorporating hair follicle-like structures have been produced from adult cells as well as induced pluripotent stem cells (iPSCs). Ex vivo models are focused on amputated or full-length hair follicles microdissected from scalp skin, follicular units, or whole scalp skin explant culture. Conclusions: Each of the culture systems described holds potential for modelling different aspects of hair follicle growth and regeneration. Potentially, several methods may also be used to provide cells or tissue constructs for treating hair loss. The advantages and limitations of each approach are explored in this review.
Objectives:
Camellia seed cake is a byproduct of Camellia oleifera Abel seed after oil extraction. Washing hair with Camellia seed cake extract is a traditional Chinese custom that has lasted for over one thousand years. However, the hair growth-promoting effects of Camellia seed cake extract were not investigated so far. This work examined the effects of de-saponinated Camellia seed cake extracts (DS-CSE) on hair growth, using in vitro and in vivo models.
Methods:
The studies on cell proliferation, cell cycle regulation and K+ channels activation effects of DS-CSE were performed on human dermal papilla cells (DPCs). Relative expression of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and transforming growth factor-β (TGF-β1) in DPCs was determined by RT-PCR. Relative expression of ERK and AKT was determined by western blot analysis. Hair growth promoting effects was also measured in C57BL/6J mice model.
Results:
DS-CSE treatment significantly proliferated DPCs, relating to the increased proportion of DPCs in S and G2 /M phases, the activation of potassium channels as well as the promoted phosphorylation of ERK and AKT in DPCs. DS-CSE treatment also significantly upregulated the mRNA levels of HGF, VEGF and IGF-1, and downregulated the mRNA level of TGF-β1. Topical application of DS-CSE promoted hair growth on shaven back mice and also upregulated the expression of VEGF in mice.
Conclusion:
Our results demonstrated that DS-CSE exerts a hair growth promoting effect in vitro and in vivo by proliferating DPCs through the ERK and AKT signaling pathways and regulating the expression of growth factors.
Hair is a deeply rooted component of identity and culture. Recent articles in this series have focused on scientific evidence relating to hair growth and new insights into the pathogenesis and mechanism of hair loss. This article reviews emerging evidence that has advanced our understanding of hair growth in both of these areas to provide a context for outlining current and emerging therapies. These include finasteride, minoxidil, topical prostaglandins, natural supplements, microneedling, low-level laser light, platelet-rich plasma, fractional lasers, cellular therapy, Wnt activators and SFRP1 antagonism.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the synovial joints. RA has well-known clinical manifestations and can cause progressive disability and premature death along with socioeconomic burdens. Interleukin-6 (IL-6) has been implicated in the pathology of RA where it can stimulate pannus formation, osteoclastogenesis, and oxidative stress. Flavonoids are plant metabolites with beneficial pharmacological effects, including anti-inflammatory, antioxidant, antidiabetic, anticancer, and others. Flavonoids are polyphenolic compounds found in a variety of plants, vegetables, and fruits. Many flavonoids have demonstrated anti-arthritic activity mediated mainly through the suppression of pro-inflammatory cytokines. This review thoroughly discusses the accumulate data on the role of flavonoids on IL-6 in RA.
The primary aim of this study is to access the salient herbal plants with the active constituent of potentially anti-hair fall activities. It also presents the various reasons behind hair loss ailments. As part of this study, a focus is placed on active phytochemicals within these medicinal plants or natural products in terms of various hair fall disease treatments. As natural products have a beneficial effect to minimize hair loss and have promoted the potential for new hair growth, it presents the medicinal values of natural plants in reference to safety and effectiveness for health.
The Ras oncogene regulates cellular proliferation, differentiation, transformation, and survival through multiple downstream
signals. Ras signals through its effector phosphoinositide 3 (PI3) kinase to the Pak protein kinase (p65pak), but the steps from Ras to Pak remain to be elucidated. PI3 kinase can stimulate the small G protein, Rac, a direct activator
of Pak, as well as the Akt proto-oncogene, a serine-threonine protein kinase. We found that activated Akt stimulated Pak,
whereas a dominant negative Akt inhibited Ras activation of Pak in transfection assays. Akt stimulation of Pak was not inhibited
by dominant negative mutants of either Rac or Cdc42 suggesting that Akt activated Pak through a GTPase-independent mechanism.
We also developed a novel cell-free system to study Ras activation of Pak. In this system Ras activated Pak only in the presence
of a crude cell extract but failed to activate Pak when Akt was immunodepleted from the extract. Akt protects cells from apoptosis
through phosphorylation of downstream targets such as the Bcl-2 family member, Bad. We found that activated Pak decreased
apoptosis and increased phosphorylation of Bad, whereas dominant negative Pak increased apoptosis and decreased phosphorylation
of Bad. These studies define a new oncogene-mediated cell survival signal.
We report for the first time the successful maintenance and growth of human hair follicles in vitro. Human anagen hair follicles were isolated by microdissection from human scalp skin. Isolation of the hair follicles was achieved by cutting the follicle at the dermo-subcutaneous fat interface using a scalpel blade. Intact hair follicles were then removed from the fat using watchmakers’ forceps.
Isolated hair follicles maintained free-floating in supplemented Williams E medium in individual wells of 24-well multiwell plates showed a significant increase in length over 4 days. The increase in length was seen to be attributed to the production of a keratinised hair shaft, and was not associated with the loss of hair follicle morphology. [methyl-3H]thymidine autoradiography confirmed that in vitro the in vivo pattern of DNA synthesis was maintained; furthermore, [35S]methionine labelling of keratins showed that their patterns of synthesis did not change with maintenance.
The importance of this model to hair follicle biology is further demonstrated by the observations that TGF-βl has a negative growth-regulatory effect on hair follicles in vitro and that EGF mimics the in vivo depilatory effects that have been reported in sheep and mice.
The Ras oncogene regulates cellular proliferation, differentiation, transformation, and survival through multiple downstream signals. Ras signals through its effector phosphoinositide 3 (PI3) kinase to the Pak protein kinase (p65(pak)), but the steps from Ras to Pak remain to be elucidated. PI3 kinase can stimulate the small G protein, Rac, a direct activator of Pak, as well as the Akt proto-oncogene, a serine-threonine protein kinase. We found that activated Akt stimulated Pak, whereas a dominant negative Akt inhibited Ras activation of Pak in transfection assays. Akt stimulation of Pak was not inhibited by dominant negative mutants of either Rac or Cdc42 suggesting that Akt activated Pak through a GTPase-independent mechanism. We also developed a novel cell-free system to study Ras activation of Pak. In this system Ras activated Pak only in the presence of a crude cell extract but failed to activate Pak when Akt was immunodepleted from the extract. Akt protects cells from apoptosis through phosphorylation of downstream targets such as the Bcl-2 family member, Bad. We found that activated Pak decreased apoptosis and increased phosphorylation of Bad, whereas dominant negative Pak increased apoptosis and decreased phosphorylation of Bad. These studies define a new oncogene-mediated cell survival signal.
Nearly 50 years ago, Chase published a review of hair cycling in which he detailed hair growth in the mouse and integrated hair biology with the biology of his day. In this review we have used Chase as our model and tried to put the adult hair follicle growth cycle in perspective. We have tried to sketch the adult hair follicle cycle, as we know it today and what needs to be known. Above all, we hope that this work will serve as an introduction to basic biologists who are looking for a defined biological system that illustrates many of the challenges of modern biology: cell differentiation, epithelial-mesenchymal interactions, stem cell biology, pattern formation, apoptosis, cell and organ growth cycles, and pigmentation. The most important theme in studying the cycling hair follicle is that the follicle is a regenerating system. By traversing the phases of the cycle (growth, regression, resting, shedding, then growth again), the follicle demonstrates the unusual ability to completely regenerate itself. The basis for this regeneration rests in the unique follicular epithelial and mesenchymal components and their interactions. Recently, some of the molecular signals making up these interactions have been defined. They involve gene families also found in other regenerating systems such as fibroblast growth factor, transforming growth factor-beta, Wnt pathway, Sonic hedgehog, neurotrophins, and homeobox. For the immediate future, our challenge is to define the molecular basis for hair follicle growth control, to regenerate a mature hair follicle in vitro from defined populations, and to offer real solutions to our patients' problems.
Plant extracts have been widely used as topical applications for wound-healing, anti-aging, and disease treatments. Examples of these include ginkgo biloba, echinacea, ginseng, grape seed, green tea, lemon, lavender, rosemary, thuja, sarsaparilla, soy, prickly pear, sagebrush, jojoba, aloe vera, allantoin, feverwort, bloodroot, apache plume, and papaya. These plants share a common character: they all produce flavonoid compounds with phenolic structures. These phytochemicals are highly reactive with other compounds, such as reactive oxygen species and biologic macromolecules, to neutralize free radicals or initiate biological effects. A short list of phenolic phytochemicals with promising properties to benefit human health includes a group of polyphenol compounds, called catechins, found in green tea. This article summarizes the findings of studies using green tea polyphenols as chemopreventive, natural healing, and anti-aging agents for human skin, and discusses possible mechanisms of action.
Apoptosis plays an important role during neuronal development, and defects in apoptosis may underlie various neurodegenerative
disorders. To characterize molecular mechanisms that regulate neuronal apoptosis, the contributions to cell death of mitogen-activated
protein (MAP) kinase family members, including ERK (extracellular signal-regulated kinase), JNK (c-JUN NH2-terminal protein kinase), and p38, were examined after withdrawal of nerve growth factor (NGF) from rat PC-12 pheochromocytoma
cells. NGF withdrawal led to sustained activation of the JNK and p38 enzymes and inhibition of ERKs. The effects of dominant-interfering
or constitutively activated forms of various components of the JNK-p38 and ERK signaling pathways demonstrated that activation
of JNK and p38 and concurrent inhibition of ERK are critical for induction of apoptosis in these cells. Therefore, the dynamic
balance between growth factor-activated ERK and stress-activated JNK-p38 pathways may be important in determining whether
a cell survives or undergoes apoptosis.
AKT1 (c-AKT, PKBα) is the cellular homolog of the protein-serine/threonine kinase oncogene, v-akt. AKT1 is activated through the insulin and platelet-derived growth factor signaling pathways in transfected fibroblasts, but little is known about the regulation of endogenous AKT1 in tumor cells. AKT1 levels were higher in a panel of human breast carcinoma cell lines than in breast epithelial cells, particularly those with higher HER2 expression. AKT1 activity was increased by either estradiol or IGF-I in estrogen-dependent MCF-7 cells, and both factors acted synergistically to increase AKT1 activity and promote cell proliferation. Stimulation of AKT1 activity by estradiol and IGF-I was blocked by the antiestrogen ICI 182780 and by the phosphatidylinositol-3-kinase inhibitor wortmannin. MCF-7 cells transfected with AKT1 exhibited partial estrogen- and IGF-I-independent growth and were more responsive to the combination of IGF-I and estradiol. AKT1-overexpressing MCF-7 cells were less sensitive to apoptosis induced by wortmannin. These findings suggest that AKT1 is a downstream effector of estrogen- and IGF-I-dependent proliferation and survival in hormone-responsive MCF-7 breast carcinoma cells.
Dermal papillae were isolated from human hair follicles and primary cell cultures were established from the papilla explants. The cultured papilla cells spread slowly, initially as a monolayer, and eventually formed multi-layered parallel arrays of fibroblast-like cells. At the edges of expanding colonies the cells were large and flattened and showed a tendency to form clumps. The behaviour of human dermal papilla cells in culture is very similar to that reported in cultures of papilla cells from rat vibrissa follicles.
A tetrazolium salt has been used to develop a quantitative colorimetric assay for mammalian cell survival and proliferation. The assay detects living, but not dead cells and the signal generated is dependent on the degree of activation of the cells. This method can therefore be used to measure cytotoxicity, proliferation or activation. The results can be read on a multiwell scanning spectrophotometer (ELISA reader) and show a high degree of precision. No washing steps are used in the assay. The main advantages of the colorimetric assay are its rapidity and precision, and the lack of any radioisotope. We have used the assay to measure proliferative lymphokines, mitogen stimulations and complement-mediated lysis.
Nearly all cell surface receptors utilize one or more of the mitogen-activated protein kinase cascades in their repertoire of signal transduction mechanisms. Recent advances in the study of such cascades include the cloning of genes encoding novel members of the cascades, further definition of the roles of the cascades in responses to extracellular signals, and examination of cross-talk between different cascades.
REVIEW
Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development,
tissue homeostasis, and protection against pathogens. Those most similar to Bcl-2 promote cell survival by inhibiting adapters
needed for activation of the proteases (caspases) that dismantle the cell. More distant relatives instead promote apoptosis,
apparently through mechanisms that include displacing the adapters from the pro-survival proteins. Thus, for many but not
all apoptotic signals, the balance between these competing activities determines cell fate. Bcl-2 family members are essential
for maintenance of major organ systems, and mutations affecting them are implicated in cancer.
The enzyme steroid 5 alpha-reductase (EC 1.3.99.5) catalyzes the NADPH-dependent reduction of the double bond of a variety of 3-oxo-Delta(4) steroids including the conversion of testosterone to 5 alpha-dihydrotestosterone. In humans, 5 alpha-reductase activity is critical for certain aspects of male sexual differentiation, and may be involved in the development of benign prostatic hyperplasia, alopecia, hirsutism, and prostate cancer. Certain natural products contain components that are inhibitors of 5 alpha-reductase, such as the green tea catechin (-)-epigallocatechin gallate (EGCG). EGCG shows potent inhibition in cell-free but not in whole-cell assays of 5 alpha-reductase. Replacement of the gallate ester in EGCG with long-chain fatty acids produced potent 5 alpha-reductase inhibitors that were active in both cell-free and whole-cell assay systems. Other flavonoids that were potent inhibitors of the type 1 5alpha-reductase include myricetin, quercitin, baicalein, and fisetin. Biochanin A, daidzein, genistein, and kaempferol were much better inhibitors of the type 2 than the type 1 isozyme. Several other natural and synthetic polyphenolic compounds were more effective inhibitors of the type 1 than the type 2 isozyme, including alizarin, anthrarobin, gossypol, nordihydroguaiaretic acid, caffeic acid phenethyl ester, and octyl and dodecyl gallates. The presence of a catechol group was characteristic of almost all inhibitors that showed selectivity for the type 1 isozyme of 5 alpha-reductase. Since some of these compounds are consumed as part of the normal diet or in supplements, they have the potential to inhibit 5 alpha-reductase activity, which may be useful for the prevention or treatment of androgen-dependent disorders. However, these compounds also may adversely affect male sexual differentiation.
The effect of the green tea polyphenol-(-)epigallocatechin-3-gallate (EGCG) was tested in cultures of normal and transformed NIH-pATM ras fibroblasts. In this system transformation can be induced at will by the addition of dexamethasone, which induces the expression of H- ras by activating the mammary tumor virus long terminal repeat (MMTV-LTR) promoter. This facilitates a reliable comparison of the susceptibility of normal and transformed cells to EGCG. It has been shown that EGCG inhibited the growth of transformed but not of the normal fibroblasts. In an attempt to elucidate the mode of the preferential inhibitory activity of EGCG, its effect on growth promoting factors has been examined. The level of ornithine decarboxylase (ODC, EC 4.1.1.17), which is a signal for cellular proliferation, was reduced by EGCG in the transformed but not in the normal cells. EGCG also showed strong inhibition of tyrosine kinase and mitogen-activated protein kinase (MAPK) activities, without affecting the kinases in the normal cells. Similarly, EGCG also preferentially decreased the levels of the oncogenes Ras and Jun in transformed cell. EGCG preferentially induced apoptosis in the transformed fibroblasts. In vitro chemosensitivity tests demonstrated that EGCG inhibited the proliferation of leukemic cells. These findings suggest that EGCG has a therapeutic potential in the combat against cancer.
We attempted to establish a coculture model of human dermal papilla cells (DPCs) from androgenetic alopecia (AGA) and keratinocytes (KCs) to study the pathomechanism of AGA. Since expression of mRNA for the androgen receptor (AR) decreased during subcultivation of DPCs in vitro, we transiently transfected the AR expression vector into the DPCs and cocultured them with KCs. In this coculture, androgen inhibited the growth of KCs by 50%, indicating that the DPCs produce diffusible growth suppressive factors into the medium in an androgen-dependent manner. Since recently increasing evidence has shown the importance of transforming growth factor-beta1 (TGF-beta1) in hair growth, we further examined the concentration of TGF-beta1 in this coculture medium after androgen treatment by ELISA assays. The results showed that androgen treatment increased the secretion of TGF-beta1 into the conditioned medium. Moreover, neutralizing anti-TGF-beta1 antibody reversed the inhibition of KC proliferation. Thus, we suggest that androgen-inducible TGF-beta1 derived from DPCs mediates hair growth suppression in AGA.
Beneficial effects attributed to green tea, such as its anticancer and antioxidant properties, may be mediated by (-)-epigallocatechin-3-gallate (EGCG). In this study, the effects of EGCG on cell proliferation and UV-induced apoptosis were investigated in normal epidermal keratinocytes. When topically applied to aged human skin, EGCG stimulated the proliferation of epidermal keratinocytes, which increased the epidermal thickness. In addition, this topical application also inhibited the UV-induced apoptosis of epidermal keratinocytes. EGCG was found to increase the phosphorylation of Bad protein at the Ser112 and Ser136. Moreover, EGCG-induced Erk phosphorylation was found to be critical for the phosphorylation of Ser112 in Bad protein, and the EGCG-induced activation of the Akt pathway was found to be involved in the phosphorylation of Ser136. Furthermore, EGCG increased Bcl-2 expression but decreased Bax expression, causing an increase in the Bcl-2-to-Bax ratio. In addition, we demonstrate the differential growth inhibitory effects of EGCG on cancer cells. In conclusion, this study demonstrates that EGCG promotes keratinocyte survival and inhibits the UV-induced apoptosis via two mechanisms: by phosphorylating Ser112 and Ser136 of Bad protein through Erk and Akt pathways, respectively, and by increasing the Bcl-2-to-Bax ratio. Moreover, these two proposed mechanisms of EGCG-induced cell proliferation may differ kinetically to promote keratinocyte survival.
The most abundant green tea polyphenol, epigallocatechin-3-gallate (EGCG), was found to induce differential effects between tumor cells and normal cells. Nevertheless, how normal epithelial cells respond to the polyphenol at concentrations for which tumor cells undergo apoptosis is undefined. The current study tested exponentially growing and aged primary human epidermal keratinocytes in response to EGCG or a mixture of the four major green tea polyphenols. EGCG elicited cell differentiation with associated induction of p57/KIP2 within 24 h in growing keratinocytes, measured by the expression of keratin 1, filaggrin, and transglutaminase activity. Aged keratinocytes, which exhibited low basal cellular activities after culturing in growth medium for up to 25 days, renewed DNA synthesis and activated succinate dehydrogenase up to 37-fold upon exposure to either EGCG or the polyphenols. These results suggest that tea polyphenols may be used for treatment of wounds or certain skin conditions characterized by altered cellular activities or metabolism.
Mitogen-activated protein kinase pathways
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