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Effect of topical application of 20 drops of a 5% mixture of acetyl tetrapeptide-3 and red clover extract (TP) on hair cycle: (A) average anagen hair density at 4 months (T = 4) of treatment, compared to baseline (T = 0); (B) average telogen hair density at 4 months of treatment (T = 4), compared to baseline (T = 0); and (C) average ratio of hair in the anagen versus telogen phase of the hair cycle, at 4 months of treatment (T = 4), compared to baseline (T = 0).
Source publication
Male pattern hair loss is a major cosmetic concern affecting both genders with a preference for men. Major causes of hair loss in genetically predisposed individuals include hormonal dysfunction, loss of extracellular matrix (ECM) proteins in the follicular bed, and localized microinflammation. Few options are yet available to correct the problem....
Contexts in source publication
Context 1
... tolerability of the topical formulations was excellent and no adverse events were reported. Results, which are expressed graphically in Figure 7, show that treatment with a mixture of red clover extract and acetyl tetrapeptide-3 statistically increased anagen hair density after 4 months of treatment (p < 0.1), whereas there is no statistic difference in the anagen hair density after treatment with the placebo lotion. Within 4 months, the number of hair in the anagen phase increased by an average of +13% in the treated group, whereas the number decreased by −2% in the placebo group. ...
Context 2
... 4 months, the number of hair in the anagen phase increased by an average of +13% in the treated group, whereas the number decreased by −2% in the placebo group. Treatment with the test product also induced a strong reduction in telogen hair density compared to the placebo group ( Figure 7B). Average telogen hair density decreased by −29% over baseline in the treated group but increased by +23% in the pla- cebo group, over the 4-month study. ...
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Currently, biomimetic peptides have been developed to treat alopecia, which consists of amino acid residues and are able to selectively interact with cell receptors. This article studies the expression of growth factors (VEGF, KGF, EGF, TGF-β1) in the hair follicle of patients with telogen effluvium and healthy individuals and evaluating the effica...
Citations
... On the other hand, their potential clinical use in alopecia has gained interest in the last few years. In a randomized controlled placebo study, Trifolium pratense flower extract and a biomimetic peptide were applied to thirty patients with mild-to-moderate active HL for four months [96]. A significant increase (46%) in the treated group was found between the anagen/telogen (A/T) relationship. ...
... A significant increase (46%) in the treated group was found between the anagen/telogen (A/T) relationship. The anagen hair increased by +13%, and telogen hair density decreased by −29% [96]. Similarly, in a randomized controlled placebo study, Loing et al. [96] analyzed the hair-growing activity of procyanidin oligomers in 43 subjects. ...
... The anagen hair increased by +13%, and telogen hair density decreased by −29% [96]. Similarly, in a randomized controlled placebo study, Loing et al. [96] analyzed the hair-growing activity of procyanidin oligomers in 43 subjects. The treated subjects showed a significantly improved hair density and number of total scalp hair. ...
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.
... Topical formulations containing natural extracts have been evaluated for their effectiveness and safety in human subjects such as saw palmetto (Serenoa repens (W.Bartram) Small), 23 rosemary oil, 24 procyanidin from apple juice, 25 Curcuma aeruginosa, 16 and Trifolium pratense. 26 The results have demonstrated promising outcomes for their influence on hair growth. Among these, S. repens, C. aeruginosa, and T. pratense exhibited the mechanism to stimulate hair growth through the inhibition of the S5AR enzyme. ...
... Among these, S. repens, C. aeruginosa, and T. pratense exhibited the mechanism to stimulate hair growth through the inhibition of the S5AR enzyme. 16,23,26 Additionally, teak leaf extract has emerged as a prospective active ingredient for promoting hair growth, primarily due to its ability to inhibit the S5AR enzyme and it also exhibits other activities relevant to AGA risk. 14,15 Our assessment of HT-teak's effectiveness in promoting hair regrowth yielded promising results comparable to the performance of minoxidil. ...
... The observed phenomenon must reasonably be attributed to the natural progression of AGA, which aligns with previous research findings and the trend of a decrease in the A/T ratio within the placebo group. 26,28 This finding is supported by the fact that there was no statistically significant difference in hair loss in the placebo group. ...
Background
Androgenic alopecia (AGA) is commonly known as male patterned baldness. A high level of dihydrotestosterone (DHT) plays a significant role in AGA development. Inhibition of the enzyme steroid 5-alpha reductase (S5AR), responsible for converting testosterone into DHT, has been shown to delay the progression of AGA. Teak (Tectona grandis L.f) leaf extract exhibited a potent S5AR inhibitory activity. To prove the effectiveness and safety of teak leaf extract as a hair growth promotor, a double-blind, randomized placebo-controlled trial was conducted.
Methods
Eighty-one AGA subjects were randomly assigned to receive either a hair tonic containing 1% teak leaf extract (HT-teak), 5%minoxidil (positive control), or a placebo administered twice daily, for 24 weeks. Efficacy was assessed through target area hair count (TAHC), anagen-to-telogen ratio (A/T), hair shedding every 4 weeks, and patients’ subjective assessments of hair regrowth were assessed at the end of the experiment. Data was analyzed using repeated measure ANOVA.
Results
Both the HT-teak and minoxidil groups exhibited a significant increase in TAHC and A/T, along with a decrease in hair shedding compared to baseline values. Conversely, the placebo group showed no observable signs of hair regrowth. Furthermore, the HT-teak group reported the highest satisfaction scores, and there were no indications of skin irritation or systemic effects on sexual dysfunction and palpitation after 24 weeks of HT-teak application.
Conclusion
Teak leaf extract, as incorporated in HT-teak, demonstrates potential as an alternative mild hair growth promoter for individuals with AGA, offering both efficacy and safety.
Trial registration
This study was retrospectively registered on International Standard Randomised Controlled Trial Number (ISRCTN.com); ISRCTN24541842 (registered on January 8, 2024).
... Resveratrol and fisetin induced a shift from telogen to anagen in the hair follicle by inducing proliferation of hair follicle bulge stem cells, thus promoting hair growth [91]. Procyanidin has been found to decrease the expression of protein kinase C (PKC) in hair epithelial cells and stimulate anagen induction [92]. Additionally, it is also posited that procyanidin and flavonoids may counteract TGF-β-induced cell death by inhibiting 5-α-reductase, antioxidant-related mechanisms, and upregulating the expression of anti-apoptotic factors, such as Bcl-xL [92]. ...
... Procyanidin has been found to decrease the expression of protein kinase C (PKC) in hair epithelial cells and stimulate anagen induction [92]. Additionally, it is also posited that procyanidin and flavonoids may counteract TGF-β-induced cell death by inhibiting 5-α-reductase, antioxidant-related mechanisms, and upregulating the expression of anti-apoptotic factors, such as Bcl-xL [92]. Oligomeric procyanidins have also shown remarkable hair growth stimulant effects in vitro and in vivo, being able to promote hair epithelial cell growth and anagen induction of the hair cycle [93]. ...
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.
... The etiology of AGA is multifactorial and polygenic. Hormonal imbalance, genetic susceptibility, inadequate scalp blood flow and loss of extracellular matrix (ECM) proteins in the follicle bed are regarded as the main triggers of hair loss [3,6]. The hair follicle (HF), as an essential unit for hair proliferation and differentiation, is a dynamic mini-organ made up of distinct cell populations associated with ectodermal, mesodermal and neural crest origins [7]. ...
... CAM-NLPs (4 g) and equal concentrations of CAM suspension (4 g) were loaded into dialysis bags (14 kDa, Biosharp, USA) and immersed in 80 ml of PBS (pH 7.4) as the receptor medium. The medium was shaken at 120 rpm on a shaker with the temperature maintained at 37 • C. One milliliter of the sample was withdrawn at predetermined time intervals (1,2,4,6,8,10,12,24,36 and 48 h) and immediately replaced with fresh release medium [26]. The concentration of bioactive peptides released from the samples was measured with HPLC. ...
... Collagen III, one of the ECM proteins, is also a key component of the connective tissue in HFs and is produced by the DP throughout the entire hair cycle, playing a critical role in maintaining the development and regulating the volume of HFs [6]. The effects of CAM-NLPs on the secretion of collagen III by HDPCs are shown in Fig. 7A. ...
Hair loss is a benign, treatable and chronic disorder which will cause the worse life quality of patients over time. Bioactive peptides can be used for hair growth promotion with many advantages such as low toxicity, high selectivity and targeted specificity. However, the bioactive peptides have limited efficacy alone and difficulty in transdermal absorption into the hair growth targeted cells - dermal papilla cells (DPCs). We developed nanoliposomes loaded with copper peptide, acetyl tetrapeptide-3 and myristoyl pentapeptide-4 (CAM-NLPs) simultaneously to achieve a synergistic effect of multiple bioactive peptides combination, improve their delivery efficiency for promoting hair growth. The CAM-NLPs exhibited uniform particle sizes, high encapsulation efficiency and loading capacity for the bioactive peptides. In vitro experiments revealed that the CAM-NLPs remarkably promoted the proliferation of immortalized human keratinocytes (HaCaT) and human dermal papilla cells (HDPCs), boosted the migration ability of HDPCs and increased the secretion of collagen III, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) from HDPCs. Furthermore, it was revealed that CAM-NLPs promoted hair growth by up-regulating the expression of VEGF and β-catenin and down-regulating the expression of transforming growth factor-β1 in the skin of C57BL/6 mice in vivo via western blotting assay. In summary, CAM-NLPs are effective transdermal co-delivery nanocarrier for alleviating hair loss in androgenetic alopecia with hair growth promotion, high safety and great potential.
... 22 Capixyl, a biomimetic peptide (mixed with red clover extract), demonstrated increase in hair width and density by rebalancing anagen/telogen ratio and promoting healthy hair growth. 23 ...
p class="abstract">The diagnosis and management of hair loss needs an organized and systematic approach for recognizing pattern of hair loss and identification of hair loss etiology. Early and specific diagnosis is essential to initiate appropriate treatment in the early phases of hair loss. Topical minoxidil and oral finasteride are the only approved drugs for androgenetic alopecia (AGA). Various other treatment options are widely used but have limited clinical evidence. Similarly, there are no specific treatments recommended for telogen effluvium (TE). However, the treatment may become challenging with increasing availability of new formulations and drugs with no substantial evidence to support them. Multiple focused group discussions were conducted among Indian dermatologists to gain expert opinion on appropriate management of AGA and TE in the current scenario. This article summarizes the consensus clinical viewpoints for topical and oral medications, role of nutritional supplements, and other adjunctive therapies in managing AGA and TE. The panel highlighted that the choice of treatment for AGA and TE depends on the individual hair loss pattern and response to medications. A brief discussion on the use of shampoos and procedures has also been highlighted. </p
... However, there is limited evidence of this in men. Red clover flower extract, often used to improve hair and skin texture [33,34], has also been reported to inhibit 5-α-reductase activity [35]. Interestingly, Almstrup and colleagues [35] reported that red clover flowers inhibit aromatase activity at low concentrations, but become estrogenic at higher concentrations, resulting in a U-shaped dose-response curve. ...
Elevations in the circulating concentration of androgens are thought to have a positive effect on the anabolic processes leading to improved athletic performance. Anabolic-androgenic steroids have often been used by competitive athletes to augment this effect. Although there has been concerted effort on examining how manipulating training variables (e.g., intensity and volume of training) can influence the androgen response to exercise, there has been much less effort directed at understanding how changes in both macronutrient and micronutrient intake can impact the androgen response. Thus, the focus of this review is to examine the effect that manipulating energy and nutrient intake has on circulating concentrations of testosterone and what the potential mechanism is governing these changes.
... The literature about the antimicrobial activity of clover species contains the evaluation of the efficiency of plant extracts from Trifolium species [69][70][71]. Testing of the antimicrobial and antifungal activity of the extracts of these species was performed on grampositive bacteria (Streptococcus pyogenes and Staphylococcus aureus), gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and fungi (Candida albicans). According to the literature, the extraction solvent of the active principles has a major importance on the antibacterial and antifungal activity of the Trifolium species [72]. ...
... According to the literature, the extraction solvent of the active principles has a major importance on the antibacterial and antifungal activity of the Trifolium species [72]. Studies on the antimicrobial properties of Trifolium pratense included a comparison of the actions of different extracts (using solvents such as ethanol, methanol, water, ether), all pathogens examined were inhibited by the extract made in methanol, which was declared to have the highest antibacterial and antifungal activity [46,69]. ...
... Both extracts (Trifolium and Ocimum) are characterized by high content of antioxidants compounds, which are also responsible for the radiance and resistance of the skin and the slowing down of the aging process by maintaining estrogen levels [86]. Additionally, due to the existence of isoflavone-like compounds, the extracts of these plants quickly heal wounds and burns and reduce the chances of skin cancer [69,86]. ...
Nowadays, the tendency in pharmaceutical and food industries is to replace synthetic antioxidants with the natural ones. For this reason, there is a growing interest in analyzing natural, healthy and non-toxic additives as potential antioxidants. Some plants, which contain high levels of phenolic compounds, present an increasing interest for medicine due to their ability to scavenge free radicals, along with other pharmacological activities, such as antibacterial activity, wound healing and anti-inflammatory effect, to mention only a few. The aim of this review is to explore the therapeutic potential of Ocimum basilicum and Trifolium pratense in relation with their phytochemical profile and to highlight the pharmacological activity of aqueous or ethanol extracts. Special attention was devoted to the dermal pathology and wound healing effects, in the context of multiple skin conditions such as acne, eczema boils, psoriasis and rashes. Additionally, both extracts (Trifolium sp. and Ocimum sp.) are characterized by high content of antioxidant compounds, which are responsible for the radiance and resistance of the skin and slowing down of the aging process by maintaining estrogen levels. Moreover, the potential combined effect of the mixed extract is pointed out in terms of future applications for wound healing, based on some preliminary results obtained from a “scratch tests” assay performed with respect to human dermal fibroblasts.
... Trifolium pretense extract was developed and its clinical efficacy was checked in men by daily topical application in a placebo-controlled study. The product significantly increased anagen hairs by reducing inflammatory reactions and stimulating protein synthesis in the hair follicles (Loing et al., 2013). Isoflavones-based phytoestrogen therapy has been known as an alternative option to hormone-replacement therapy. ...
Natural products have emerged as a treasure trove of novel chemical scaffolds for drug discovery against various diseases including inflammation, cardiovascular diseases, osteoporosis, and cancer. Isoflavones, polyphenolic compounds, from plants belonging to the Fabaceae family act as phytoestrogens and possess a pseudo-hormonal effect by binding with estrogen receptors in the human body. Due to this property, isoflavones exhibit multiple health-promoting benefits. In the class of isoflavones, biochanin A and biochanin B (formononetin) are prominent compounds renowned for their wide therapeutic window against numerous pathological conditions. Biochanin A and B possess antidiabetic, antiobesity, hepatoprotective, anticancer, and antiinflammatory activities. Biochanin A and B are rapidly absorbed in the body and possess safe pharmacokinetics as indicated by several in vivo investigations. This chapter aims to elaborate on the natural sources, pharmacological potential as well as bioavailability and pharmacokinetics of biochanin A and B, suggesting these compounds as interesting and safe candidates for drug design and development in the near future.
... 4 The combination of biochanin A, acetyl tetrapeptide-3, and ginseng extracts has been shown to stimulate dermal papilla ECM proteins by increasing hydroxyproline, Collagen Type 3, and laminin, yielding a significant improvement in hair follicle size and hair anchoring. 13 Increased hair growth has been observed after the seven-day culture by biochanin A and acetyl tetrapeptide-3 compared to minoxidil in part of the activation of hair growth. [13][14][15] Observed in in-vitro studies, biochanin A and acetyl tetrapeptide-3 appear to exert an anti-inflammatory effect by decreasing pro-inflammatory cytokines. ...
... 13 Increased hair growth has been observed after the seven-day culture by biochanin A and acetyl tetrapeptide-3 compared to minoxidil in part of the activation of hair growth. [13][14][15] Observed in in-vitro studies, biochanin A and acetyl tetrapeptide-3 appear to exert an anti-inflammatory effect by decreasing pro-inflammatory cytokines. 13,16 A fourmonth, randomized, placebo-controlled study evaluated the efficacy of biochanin A and acetyl tetrapeptide-3 compared to placebo for the treatment of AGA using microscopic evaluation with a phototrichogram revealed that the herbal lotion increased the anagen hair density (13%) with greater ratio from the anagen to telogen (46%) when compared to a reduction of -33 percent for the placebo. ...
... [13][14][15] Observed in in-vitro studies, biochanin A and acetyl tetrapeptide-3 appear to exert an anti-inflammatory effect by decreasing pro-inflammatory cytokines. 13,16 A fourmonth, randomized, placebo-controlled study evaluated the efficacy of biochanin A and acetyl tetrapeptide-3 compared to placebo for the treatment of AGA using microscopic evaluation with a phototrichogram revealed that the herbal lotion increased the anagen hair density (13%) with greater ratio from the anagen to telogen (46%) when compared to a reduction of -33 percent for the placebo. 13 Panax ginseng root extract appears to exert an anti-apoptotic effect with dermal papilla cell proliferation 16 in the pathogenesis of both male and female pattern hair loss. ...
OBJECTIVE: We sought to evaluate the efficacy and safety profile of an herbal extract combination comprising biochanin A, acetyl tetrapeptide-3, and ginseng extracts, and compare this to 3% minoxidil solution for the treatment of andogenetic alopecia (AGA). METHODS: A 24-week, triple-blinded, randomized controlled study was conducted in male and female subjects (N=32) with mild to moderate AGA. All were randomized to receive twice-daily, 1mL applications of the herbal extract combination or 3% minoxidil solution. Clinical efficacy from photographic assessment and adverse reactions were evaluated. RESULTS: There were thirty-two subjects (16 male, mean age 41.3±13.8 years), with AGA onset and duration of 35.5±13.6 and 6.5±5.1 years, respectively. The herbal extract combination demonstrated a comparable efficacy to 3% minoxidil solution. Expert panel photographic assessment observed a response to both treatments in most patients at 24 weeks, with no statistically significant difference in an increase of terminal hair counts (8.3% [P=0.009] and 8.7% [P=0.002] at 24 weeks in the herbal extract combinations and the 3% minoxidil solution groups, respectively). No local adverse reactions from the herbal extract combination were observed, but one subject developed scalp eczema after using the 3% minoxidil solution. CONCLUSION: The non-significant difference in clinical efficacy and safety to 3% minoxidil solution suggests that the herbal extract combination evaluated here could potentially be an alternative treatment with for AGA. Further studies with larger groups and longer follow-up periods are recommended to verify our results.
... Inhibition is said to be more potent than that of EGCG from green tea [34]. In addition, research has demonstrated that biohanin A inhibited both the isoforms of the enzyme reductase (type I and II) stronger than EGCG in intact cells [72]. Both isomeric forms are present in the scalp, however, type II is the one that contributes to male baldness [73]. ...
... In a clinical study, the effectiveness of red clover extract in combination with acetyltetrapeptide 3 in reducing hair loss was tested [72]. The TrichoScan method, technology that combines epiluminescence microscopy and digital imaging analysis for in vivo hair growth measurements, was used. ...
... The telogen hair density decreased, and the ratio of anagen to telogen phase follicles increased. A noticeable increase in the ratio indicates the possibility of promoting hair growth [72]. This mixture combines all the positive effects of biohanin A and acetyltetrapeptide 3 to treat alopecia. ...
Though hair does not serve any crucial physiological function in modern humans, it plays an important role in our self-esteem. Androgenic baldness (androgenic alopecia) and circular/spot baldness (alopecia areata) are the most common forms of hair loss. Many active ingredients of synthetic origin are available for treatment; however, they have a number of limitations. Their effectiveness and safety are questionable and the amount of time needed to achieve the effect is both long and unclear. This has increased interest in finding an alternative approach against hair loss using preparations containing plants and/or their isolated active ingredients. A number of studies (mostly randomized, placebo-controlled) of plants and preparations made of plants have been performed to confirm their effectiveness in treating hair loss. The plants with the most evidence-based effect against alopecia are Curcuma aeruginosa (pink and blue ginger), Serenoa repens (palmetto), Cucurbita pepo (pumpkin), Trifolium pratense (red clover), and Panax ginseng (Chinese red ginseng). The assumed mechanism of action is predominately inhibition of 5α-reductase, with enhanced nutritional support and scalp blood circulation playing a role as well.
