Article

“Miliacin encapsulated by polar lipids stimulates cell proliferation in hair bulb and improves telogen effluvium in women”

Wiley
Journal of Cosmetic Dermatology
Authors:
  • Independent Researcher
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Abstract

Background Miliacin, the main triterpenoid from millet, is known to stimulate keratinocyte metabolism and proliferation. Polar lipids are able to form vesicles with active compounds and to improve their bioavailability. Objectives We aimed to demonstrate potential benefits of a solution of miliacin encapsulated within polar lipids (MePL) on telogen effluvium prevention and hair condition in women. METHODS After preliminary cell proliferation studies, a placebo‐controlled, multicentric, randomized, double‐blind trial was performed on sixty‐five nonmenopausal women affected by telogen effluvium, to assess the efficacy of a 12‐week oral supplementation with MePL. Telogen and anagen densities were determined by phototrichogram analysis. Scalp dryness and hair brightness were clinically evaluated using a Likert scale. Results MePL further enhanced cell proliferation in hair bulb from human scalp than miliacin alone. Compared to the placebo treatment, MePL supplementation significantly reduced telogen density after 12 weeks of treatment. An increase of anagen density was observed in both groups, although there was no significant difference between the two treatments. Scalp dryness was more decreased in the MePL group than in the placebo group. A better improvement of hair brightness was also observed after 12 weeks of supplementation with MePL. Conclusion Twelve weeks of MePL supplementation significantly reduced the hair density in the telogen phase and, in parallel, improved scalp dryness and hair condition. These effects could be linked to MePL activity on cell proliferation in hair bulb. MePL is an original association of plant extract that could help to prevent and/or limit hair loss in women.

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... Not only do vitamins and minerals have a potential effect on hair growth, but also miliacin, the main triterpenoid from millet, has been shown to have an influence. A combination of miliacin encapsulated in polar lipids was found to enhance cell proliferation in hair bulbs from the human scalp [11]. This is possibly through the stimulation of keratinocyte metabolism and proliferation [11,12]. ...
... A combination of miliacin encapsulated in polar lipids was found to enhance cell proliferation in hair bulbs from the human scalp [11]. This is possibly through the stimulation of keratinocyte metabolism and proliferation [11,12]. The amino acid L-cysteine has also been focused on as a cell growth-stimulating agent [12]. ...
... Their use also decreases the occurrence of gastro-intestinal side effects such as epigastric pain, nausea, vomiting and diarrhoea [22]. The zinc Selenium 55 µg 100 [20] Pantothenic acid (Vitamin B5) 6 mg 100 [21] L-cysteine 4 mg -- [12] Millet extract 17% of the total product -- [11,12] dietary supplement The TrichoScale ® method allows diffuse hair loss to be digitally documented and quantified. From these data, for example, an improvement of the hair status (increase in the anagen phase, i.e. the growth phase of the hair) can be determined. ...
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... Miliacin, a representative phytosterol of MSO, has been reported to promote keratinocyte proliferation (Obrigkeit et al., 2006). In clinical trials, miliacin supplementation significantly reduced the telogen phase and improved scalp dryness and hair conditions (Keophiphath et al., 2020). These properties of miliacin suggest that MSO might have potential benefits for maintaining healthy hair by contributing to hair growth. ...
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The slow-cycling cells in the bulge of the outer root sheath may represent stem cells for the hair follicle. With each new anagen (growing) phase bulge cells would give rise to a population of transient-amplifying cells which differentiate into outer root sheath and matrix keratinocytes. The lowermost part of the telogen (resting) follicle is composed of bulge cells lying in close proximity to the dermal papilla. In the mouse the first hair follicle growth is characterized by rapid follicular neogenesis, but the second and third growth cycles follow the normal follicular growth pattern. We have examined activity of cells in the bulge at the onset of anagen (growing phase) in the third hair cycle in Sencar mice, by treating animals at the end of the second telogen with colchicine to localize mitotic activity in the hair follicle. Mitoses were only seen in bulge cells during early anagen. This confirms that they proliferate transiently, solely at the onset of anagen and strongly supports the suggestion that bulge cells are the origin of the whole lower follicle in anagen.
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We have examined the growth capacity of keratinocytes isolated from human scalp hair follicles. Like the keratinocytes of glabrous epidermis, most of the colony-forming cells are classified as holoclones or meroclones when analyzed in a clonal assay. Some of them have extensive growth potential, as they are able to undergo at least 130 doublings. Therefore, the hair follicle, like the epidermis, contains keratinocytes with the expected property of stem cells: an extensive proliferative capacity permitting the generation of a large amount of epithelium. We have also examined the distribution of clonogenic keratinocytes within the hair follicle. Several hundred colony-forming cells are concentrated at a region below the midpoint of the follicle and outside the hair bulb. This region lies deeper than the site of insertion of the arrector pili muscle, which corresponds with the position of the bulge when the latter can be identified. In contrast, few colony-forming cells are present in the hair bulb, where most of the mitotic activity is observed during the active growth phase of the follicle. Paraclones, which are present both in the midregion and in the bulb of hair follicles, are unlikely to be the transient amplifying cells expected from kinetic studies.
Article
Growth factors are polypeptides that regulate growth and differentiation of many cell types. Different growth factor families including the epidermal growth factor (EGF)-related ligands, fibroblast growth factors (FGF), transforming growth factor-beta (TGF-beta), insulin-like growth factor (IGF), hepatocyte growth factor/scatter factor (HGF/SF), and platelet-derived growth factor (PDGF) have been shown to be crucial for the regulation of the hair cycle and hair growth. Growth factors and their receptors have been localized to the skin and hair follicles. Their biological activities on cells comprising the hair follicle have been tested in vitro and increasingly in transgenic mice. Herein we review selected important aspects of growth factors with regard to the hair organ, its development, and the hair growth cycle.
Article
The hair follicle (HF) undergoes life-long cyclic transformations between "resting" (telogen), growth (anagen), and apoptosis-driven regression (catagen). Contrary to conventional wisdom, cyclic remodelling affects even the distal HF epithelium; telogen is not a mere resting period, since it shows substantial metabolic and proliferative activity and may encompass a phase of controlled hair shaft-extrusion ("exogen"). Even under physiological circumstances, very few (malfunctioning?) HF may leave this cycle over time to be removed by inflammatory cells ("programmed organ deletion"). Although numerous systemic, metabolic, immunological, and nerve-derived factors (e.g. hormones, cytokines, neuropeptides, neurotransmitters, mast cells) can profoundly alter hair growth in vivo, neither vascular nor neural stimuli nor extrafollicular cells are essential for HF development or cycling. Rather, an intrafollicular "hair cycle clock" of as yet unknown nature drives the HF cycle. This elusive chronobiological timing device likely exploits secondary changes in the intra- and perifollicular signalling milieu for guiding the HF through its transformations. However, the supreme generator of cycling activity ("oscillator") that dictates any of these signalling switches is still as unknown as is its exact location. Since, clinically, the control of catagen is of paramount importance (too early anagen termination: alopecia, effluvium; catagen too late: hirsutism, hypertrichosis), the controls of catagen-associated keratinocyte apoptosis and of dermal papilla secretory activities are discussed as crucial targets for future therapeutic manipulations.
Article
With advancing age insulin-like growth factor (IGF)1 blood levels decrease continuously, but with great interindividual differences. There is a relationship between the IGF1 serum concentration and biomarker behaviour, indicating that growth hormone (GH) secretion is a determinant of organismic well being and surviving in advanced age. In contrast, the secretion of insulin rises with age, which is related to both increasing body fat mass and ageing itself. In vitro insulin stimulates the proliferation, migration and collagen secretion of human vascular smooth muscle cells (SMCs). The mechanism underlying these processes mainly involves occupancy of ICF1 receptors by insulin, with the exception of migration. With advancing age of the donor, the in vitro proliferation rate and migration capacity of SMCs decreases. When insulin or IGF1 is added, there is no reversibility, so that there is no recovery to the values of SMCs from young donors. The blockade of Ca2+ channels by diltiazem inhibits the in vitro stimulation by IGF1 and insulin on SMC proliferation and migration. We conclude that the acceleration of ageing is related to the decline of IGF1 in such a manner that ageing rates progress as GH secretion diminishes. Biomarkers are affected correspondingly. The role of insulin in atherogenesis is related to hyperinsulinaemia, but the increase in insulin secretion belongs to the process of ageing regulation. Nevertheless, the effect of insulin in changing the phenotype of SMCs is atherogenic. Diltiazem may thcrefore act as an antiatherogenic agent. In advanced age the risk of atherogenesis decreases because of lowered propensity of SMCs to proliferate and migrate, which is probably due to a greater proportion of senescent cells.
Article
We studied the effect of plant triterpenoid miliacin on dexamethasone-induced apoptosis in thymocytes and splenocytes. Miliacin produced a protective effect on splenocytes by decreasing the degree of DNA fragmentation due to blockade of the cascade cell death distally to the intramembrane phosphatidylserine translocation.
Article
Knowledge of the hair follicle anatomy and the dynamics of hair cycling is substantial. Recognizing the anagen, catagen and telogen phases as well as teloptosis and the hair eclipse phenomenon clearly characterizes the typical hair chronobiology. Physiological modulators include hormones, neuromediators, miscellaneous biomolecules, seasons, micro-inflammation and ageing. For individuals who present with the complaint of increased hair shedding or alopecia, a host of evaluation techniques are available in addition to history, physical examination and laboratory assessment. Various clinical hair techniques can help in assessing the efficacy of drugs and cosmetics on hair growth. The methods are quite similar to those used to establish a definite diagnosis in dermatological practice. Great strides have been made during the recent decades in the methodology of hair growth trials in dermatology and cosmetology. Clinical evaluations benefit from a few additional specific techniques that enhance the perception of hair (re-) growth, shedding and alopecia. These assessments include the determination of hair patterning and density that may be helped by the 'black-and-white felt' examination. Daily hair counts, the 'hair pull test' and the 'hair feathering test' are also available. Instrumental methods provide reliable quantitative information that is useful if there are adequate controls. Some photographic methods, the trichogram, hair weighing and variants of the hair growth window technique including the phototrichogram, videotrichogram and tractio-phototrichogram provide insight into the complexities of hair cycling and shedding. Skin biopsy is indicated for diagnostic purposes, especially when the hair loss is accompanied by scarring.
Article
To investigate the effect of cell growth-stimulating agents on human epidermal keratinocytes, we exposed monolayers of normal human keratinocytes derived from foreskin to different concentrations of the amino acid L-cystine, the member of the vitamin B family D-pantothenat, the phytosterol miliacin, and a combination thereof in keratinocyte growth medium. As a test system for the metabolic capacity, we used the activity of mitochondrial deyhdrogenases as measured by XTT, and for the cell proliferation, we determined the BrdU-uptake. The additives, active ingredients of the hair growth drug PRIORIN, were added in the presence of fully supplemented keratinocyte growth medium or a deficient medium without L-cystine, L-methionine, L-histidin, D-pantothenat, epidermal growth factor, and bovine pituary gland extract. Deficient medium itself reduced the metabolic capacity of keratinocytes to 35% compared with keratinocytes in fully supplemented growth medium. In deficient medium cell, proliferation was not measurable. Increasing doses of L-cystine restored the reduced metabolic capacity from 46% (0.009 mg/L) to 54% (0.09 mg/L) and 92% (0.45 mg/L) in deficient medium. Addition of D-pantothenat (0.43 mg/L) enhanced the metabolic capacity to 150% only in fully supplemented growth medium, compared with untreated controls with growth medium. Miliacin (6 mg/mL) increased not only the metabolic capacity (162%) but also stimulated cell proliferation (215%) as measured by BrdU-uptake in growth medium. The combination of all three additives increased the metabolic capacity (245%) synergistically in growth medium. We were able to show effects of D-panthenol, L-lysine, and miliacin on proliferation and metabolic capacity of keratinocyte monocell culture, which was further increased by combination of the three substances. These basic results suggest a beneficial effect on keratinocyte growth and stimulation by products combining these substances (e.g., Priorin). Furthermore, this work emphasizes the suitability of keratinocyte monolayers for pharmacological testings.
Article
Naringenin is a naturally occurring flavanone, possessing a variety of biological activity. Due to its rapid elimination, naringenin needs frequent administration to maintain an effective plasma concentration. We have evaluated the therapeutic potential of naringenin-phospholipid complex under oxidative stress conditions compared with free naringenin. Naringenin-phospholipid complex was prepared and assessed for antioxidant activity in carbon tetrachloride intoxicated rats at a dose level of 100 mg kg-1 (p.o.). Liver function tests were studied by assessing serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum alkaline phosphatase and total bilirubin. Marker enzymes of liver, namely glutathione peroxidase, superoxide dismutase, catalase and thiobarbituric acid reactive substances, were measured to evaluate the antioxidant potential at the same dose level. The plasma concentration of naringenin was also measured. It was observed that the naringenin-phospholipid complex enhanced the antioxidant activity of the biomolecule and protected the liver significantly for a longer time as compared with free naringenin at the same dose level. Phospholipid complex of naringenin produced better antioxidant activity than the free compound with a prolonged duration of action, which may be helpful in reducing the fast elimination of the molecule from body.
Article
Insulin-like growth factor-I (IGF-I) plays an important role in hair growth. Capsaicin activates vanilloid receptor-1, thereby increasing the release of calcitonin gene-related peptide (CGRP) from sensory neurons, and CGRP has been shown to increase IGF-I production. We recently reported that isoflavone, a phytoestrogen, increases production of CGRP by increasing its transcription in sensory neurons. These observations raise the possibility that administration of capsaicin and isoflavone might promote hair growth by increasing IGF-I production. In the present study, we examined this possibility in mice and humans with alopecia.
EEMCO group (European Expert Group on Efficacy Measurement of Cosmetics and other Topical Products). EEMCO guidance for the assessment of hair shedding and alopecia
  • Piérard GE