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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).  

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).  

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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....

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... 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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... 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. ...
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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. ...
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... 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]. ...
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... 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. ...
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... 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 ...
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... 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. ...
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... 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]. ...
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... 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. ...
Chapter
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. ...
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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. ...
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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.