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Promotion effect of norgalanthamine, a component of Crinum asiaticum, on hair growth
Abstract
This study was conducted to evaluate the effect of Crinum asiaticum, a plant native to Jeju Island, Korea, on the promotion of hair growth. When rat vibrissa follicles were treated with a 95% ethanol (EtOH) extract of C. asiaticum, the hair-fiber lengths of the vibrissa follicles increased significantly. In addition, after daily topical application of the EtOH extract of C. asiaticum onto the back of C57BL/6 mice, anagen progression of the hair shaft was induced. Moreover, the extract increased the proliferation of immortalized vibrissa dermal papilla cells. When the vibrissa follicles in the anagen phase were treated with the extract, immunohistochemical analysis revealed that the extract was found to increase the expression of proliferating cell nuclear antigen (PCNA) in the bulb region of the 7-day cultured follicles. In particular, norgalanthamine, a principal of the extract, showed activity that increased the hair-fiber lengths of vibrissa follicles and the proliferation of dermal papilla cells. These results suggest that norgalanthamine, a principal of C. asiaticum, has the potential to promote hair growth via the proliferation of dermal papilla.
... Aconiti ciliare C57BL/6 mice Aqueous Extract Activation of Wnt/β-catenin signaling pathway [62] Allium tuberosum Rottler ex Spreng extract Telogenic C57BL6/N mice Ethanol extract Increase the number of hair Follicles IGF-1 Upregulation [56] Asiasari radix C57BL/6C3Hmice Ethanol extract Regulation of cell growth and growth factor gene expression VEGF upregulation [53] Boehmeria nipononivea Mice Acetone extract Inhibition of 5α-reductase [76] bergamot and boxthorn Mice Aqueous extract NA* [77] Cercidiphyllum japonicum Mice Methanol extract NA* [78] Chamaecyparis obtusa C57BL/6mice Essential Oils Positive regulator of VEGF [54] Crinum asiaticum C57BL/6 mice Ethanol extract Proliferation of dermal papilla [79] Cuscuta reflexa Swiss albino rats ...
... Polyporus umbellatus Fries 3,4-dihydroxybenzaldehyde Acetosyringone and Polyporusterone Terpenoids [93] Polyporus umbellatus Fries A&B Steroids [94] Capsicum annum Capsaicin Alkaloid [95] Apple ProcyanidinB-2 Flavonoids [96] Panax ginseng Ginsenoside Ro Saponin [64] Legume plants Isoflavone Flavones [97] Stephania cepharantha Hayata Bisbenzylisoquinoline Alkaloid [98] Puerariae Flos Soya saponin I, Kaikasaponin III Saponin [90] Crinum asiaticum Norgalanthamine Nardin Alkaloid Sesqueterpene [79] Nardostachys jatamansi DC Jatamansic acid Acid [36] Zingiber officinale 6-Gingerol Flavonoid [43] Panax ginseng GinsenosideF2 Saponin [99] apple reduced TGF-β1 levels and helped in conversion of telogen follicles to anagen hair follicles [72] . PGD2 inhibition or PGE2 and PGF2 enhancement may be considered as a pharmacological mechanism for treating AGA [73] . ...
... Alkaloids are the largest group of phytochemicals present in plant that represent a diverse group of chemical entities with nitrogen atoms at any position of the molecule, excluding the nitrogen in an amide or peptide bond [150]. Piperine from Piper nigrum fruit [141], capsaicin from Capsicum annum [95], and norgalanthamine from Crinum asiaticum [151] are the three significant alkaloids that are reported to have antialopecia activity. ...
Alopecia or hair loss is a worldwide unisex dermatological problem which affects aesthetic lifestyle qualities in humans. In recent years, drug discovery for hair loss has gained significant pharmaceutical research attention. Synthetic drugs such as minoxidil, oral finasteride, anthralin cream and ketoconazole based antifungal shampoos are some of the commercially available product formulations for hair loss treatment. As these products are mostly chemically derived, their long-term exposure to the skin could result in various side effects and skin disorders. Since traditional medicine relies on herbs to treat alopecia, in recent times, different species of herbs are being extracted to generate functional bioactive chemicals as active ingredients to treat hair loss. These biologically derived phytochemicals may offer improved long-term biocompatibility with the skin. This chapter presents an overview of various phytochemicals with anti-alopecia properties and discusses their modes of action. Additionally, the efficiency of flavonoids, which is a major phytochemical constituent of several herbs and a potential 5α reductase enzyme inhibitor, as a potential drug for alopecia treatment is also discussed.
... Daily treatment was applied for 9 days. [15] ...
OBJECTIVES
The roots of Carthamus caeruleus have been used by the population of Northern Algeria to treat several pathological conditions, including wound healing and hair growth. The present study was conducted to evaluate the anti-inflammatory activity, wound-healing potential, and hair growth-promoting activity attributed to C. caeruleus root.
MATERIALS AND METHODS
In this study, we have investigated the anti-inflammatory effect using carrageenan-induced paw edema test, evaluated the wound-healing potential by linear incision wound model, and evaluated hair growth activity using in vivo hair growth-promoting test attributed to C. caeruleus root. Preliminary phytochemical screening and gas chromatography coupled to mass spectrometry (GC/MS) characterization were also performed.
RESULTS
It was found that the methanolic extract of C. caeruleus was characterized by the presence of tannins, flavonoids, anthocyanins, leucoanthocyanins, sennosides, free quinones, saponins, glycosides, mucilage, and coumarins. The GC/MS analysis could identify 22 compounds and showed that the major chemical constituents were palmitic acid (12.88%), mono(2-ethylhexyl) phthalate (12.75%), and 5-(hydroxymethyl)-2-furancarboxaldehyde, (9.19%). The phytoextract strongly inhibited (P < 0.001) paw edema formation in mice. The roots of C. caeruleus also showed a significant (P < 0.05) wound-healing and hair growth-promoting effects.
CONCLUSION
The results indicate the richness of the roots of the Algerian C. caeruleus in biomolecules. These molecules exhibit an excellent reducing inflammation activity, a wound-healing property, and an interesting hair-promoting growth activity. All in all, the findings promote the usage of the Algerian C. caeruleus as an effective and a safe potential skincare alternative remedy.
... Acetylcholinesterase inhibitors can induce hair growth. Norgalanthamine, a principal extract of the plant Crinum asiaticum, has been shown to promote hair growth activity via the proliferation of dermal papilla [12]. We attribute the cause of hypertrichosis to rivastigmine by the temporal relationship, without finding another possible cause. ...
Hypertrichosis is the excessive hair growth in any area of the skin surface. Acquired localized hypertrichosis may be secondary to multiple causes and there is a secondary form due to several drugs, which is usually reversible with discontinuation of the causative agent. Rivastigmine is a reversible and competitive inhibitor of acetylcholinesterase and butyrylcholinesterase used for symptomatic treatment of Alzheimer dementia and Parkinson’s disease. It has an adequate safety profile and cutaneous side effects are unusual. Irritant contact dermatitis, allergic dermatitis, baboon syndrome, and cutaneous rash due to rivastigmine have been reported. We report on a Caucasian 80-year-old male with personal history of Alzheimer’s disease. The patient started therapy with oral rivastigmine one month prior to clinical presentation of localized hypertrichosis on both forearms. Norgalanthamine has been shown to promote hair growth activity via the proliferation of dermal papilla. Acetylcholinesterase inhibitors can induce hair growth.
... 5-reductase inhibitory activity-guided fractionation led to six active fatty acids:) Maesen [98] Kaikasaponin III Saponin Pueraria thomsonii (Benth.) Maesen [98] Norgalanthamine Alkaloid Crinum asiaticum Linn. [83] Senegose A, Senegin II, Senegin III, Senegasaponin b Polysaccharide Saponin Polygara senega Torr. [96] Nardin Jatamansic acid Sesqueterpene Acid Nardostachys jatamansi DC [116] 6-Gingerol Flavonoid Zingiber officinale [125] Ginsenoside F2 Saponin Panax ginseng L. [128] alpha-linolenic, linoleic, palmitic, elaidic, oleic and stearic acids [34]. ...
... 5-reductase inhibitory activity-guided fractionation led to six active fatty acids:) Maesen [98] Kaikasaponin III Saponin Pueraria thomsonii (Benth.) Maesen [98] Norgalanthamine Alkaloid Crinum asiaticum Linn. [83] Senegose A, Senegin II, Senegin III, Senegasaponin b Polysaccharide Saponin Polygara senega Torr. [96] Nardin Jatamansic acid Sesqueterpene Acid Nardostachys jatamansi DC [116] 6-Gingerol Flavonoid Zingiber officinale [125] Ginsenoside F2 Saponin Panax ginseng L. [128] alpha-linolenic, linoleic, palmitic, elaidic, oleic and stearic acids [34]. ...
This review presents an overview on plants identified to possess hair growth activity in various ethno-botanical studies and surveys of tradition medicinal plants. It also highlights the developments in hair rejuvenation strategies from 1926 till-date and reviews the potential of herbal drugs as safer and effective alternatives. There are various causes for hair loss and the phenomenon is still not fully understood. The treatments offered include both natural or synthetic products to treat the condition of hair loss (alopecia), nonetheless natural products are continuously gaining popularity mainly due to their fewer side effects and better formulation strategies for natural product extracts. Plants have been widely used for hair growth promotion since ancient times as reported in Ayurveda, Chinese and Unani systems of medicine. This review covers information about different herbs and herbal formulation that are believed to be able to reduce the rate of hair loss and at the same time stimulate new hair growth. A focus is placed on their mechanism of action and the review also covers various isolated phytoconstituents possessing hair growth promoting effect.
... Effect of ACT extract on anagen induction in C57BL/6 mice C57BL/6 mice were used to investigate the effect of ACT extract on anagen phase induction. The shaved skin of telogen phase mice is pink and darkens with the initiation of anagen (Müller et al., 2001;Kim et al., 2010). The day after the C57BL/6 mice were shaved using a clipper, the dorsal skin of these mice was treated with 10 mg/mL of ACT extract or 20 mg/mL of minoxidil as a positive control 2 times daily for 5 weeks. ...
... At this temperature L. aestivum 80 shoot culture produced 388 μg/RITA norgalanthamine. This is a very important result because recent studies of Kim and co-authors [31] showed that norgalanthamine possess strong promotion effect on hair growth, as well as it is not difficult to transform the norgalanthamine to galanthamine using simple chemical methylation [30]. One of the most powerful tools for the optimization of secondary metabolite production by plant in vitro systems is statistical optimization of both content of nutrient media [32] and environmental conditions in the cultivation systems [33]. ...
The process of galanthamine and related alkaloids production by Leucojum aestivum shoot culture in a temporary immersion system was studied. It was established that temporary immersion approach is prospective for development of a biosynthetic process for obtaining valuable Amaryllidaceae alkaloids. Both immersion frequency and temperature had significant effect on biomass accumulation and the yields of galanthamine and related alkaloids. The maximal yield of galanthamine was achieved at the cultivation of L. aestivum shoot culture in temporary immersion RITA(®) system at immersion frequency 15 min flooding and 8 h stand-by periods, at 26 °C. Data on the relationships in the biological system "Nutrient medium-L. aestivum shoot culture-galanthamine" are presented as well.
Alopecia can be recognized as a life-threatening disorder. It is a medical disorder wherein hair loss occurs from the scalp, usually in part or all portions of the body. On the other hand, it seriously impairs one's mental health, sense of self-worth, and general quality of life. Numerous factors, such as genetic predispositions, environmental triggers, chemical or medication exposure, dietary deficiencies, severe stress, prolonged sickness, etc., can result in balding. This article has discussed alopecia, including its causes, kinds, and numerous medicinal plants and their parts that are used for alopecia therapy or prevention.
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.
The most unbiased of present study is to treat Alopecia. Alopecia areatatis hit or
miss hair loss - condition. Herbal drug used internally also as externally used hair growth to prevent
premature grayish or hair loss. The claim of higher growth of hair and diminution in loss of hair.
Herbs are starting material for any medicine
research. Approximately about 80% residents recommended herbal drugs for his or her beneficial
effects along with fewer side effects as compared synthetic drugs.
Stress plays a critical role in hair loss, although the underlying mechanisms are largely unknown. γ-aminobutyric acid (GABA) has been reported to be associated with stress; however, whether it affects stress-induced hair growth inhibition is unclear. This study aimed to investigate the potential roles and mechanisms of action of GABA in chronic restraint stress (CRS)-induced hair growth inhibition. We performed RNA-seq analysis and found that differentially expressed genes (DEGs) associated with neuroactive ligand-receptor interaction, including genes related to GABA receptors, significantly changed after mice were treated with CRS. Targeted metabolomics analysis and enzyme-linked immunosorbent assay (ELISA) also showed that GABA levels in back skin tissues and serum significantly elevated in the CRS group. Notably, CRS-induced hair growth inhibition got aggravated by GABA and alleviated through GABAA antagonists, such as picrotoxin and ginkgolide A. RNA sequencing analysis revealed that DEGs related to the cell cycle, DNA replication, purine metabolism, and pyrimidine metabolism pathways were significantly downregulated in dermal papilla (DP) cells after GABA treatment. Moreover, ginkgolide A, a GABAA antagonist extracted from the leaves of Ginkgo biloba, promoted the cell cycle of DP cells. Therefore, the present study demonstrated that the increase in GABA could promote CRS-induced hair growth inhibition by downregulating the cell cycle of DP cells and suggested that ginkgolide A may be a promising therapeutic drug for hair loss.
Androgenic alopecia (AA) is a condition that most commonly affects adult men and is caused by an increase in the hormone dihydrotestosterone (DHT) in the hair follicles. Anti-alopecia drugs should be discovered for hair follicles to enter the anagen growth phase. Therefore, this study evaluated the hair growth-promoting activity of Noni fruit’s water, ethyl acetate, n-hexane fractions, and sub-fractions from the active fraction in the alopecia male white rabbit model. The Matias method was modified by inducing rabbits using DHT for 17 days, followed by topical application of Noni fruit solution for 21 days. Meanwhile, hair growth was evaluated by histological observation of the follicular density and the anagen/telogen (A/T) ratio in skin tissue. In the first stage, five groups of male white rabbits were studied to obtain the active fraction; DHT+Minoxidil as standard, DHT+vehicle (NaCMC 1%), DHT+FW, DHT+FEA, and DHT+FH. The FEA as the active fraction was followed by open-column chromatography separation (DCM:Methanol) with a gradient of 10% to produce sub-fractions. In the second stage, the six main sub-fraction groups of male rabbits studied were DHT+FEA-1 to DHT+FEA-6. The follicular density of groups FEA-3 was 78.00 ± 1.52 compared with 31.55 ± 1.64 and 80.12 ± 1.02 in the Vehicle and Minoxidil groups. Additionally, group FEA-3 showed large numbers of anagen follicles with an A/T ratio of 1.64/1 compared to the vehicle group of 1/1.50 and 1.39/1 for Minoxidil control. Group FEA-3 was identified by LC-MS/MS-QTOF, followed by molecular docking to the androgen receptor (PDB: 4K7A), causing alopecia. The results showed that three alkaloid compounds with skeleton piperazine and piperidine, namely (compounds 2 (−4.99 Kcal/mol), 3 (−4.60 Kcal/mol), and 4 (−4.57 Kcal/mol)) had a binding affinity similar to Minoxidil, with also has alkaloid skeleton piperidine–pyrimidine (−4.83 Kcal/mol). The dynamic behavior showed the stability of all androgen receptor compounds with good RMSD, SMSF, and SASA values after being studied with 100 ns molecular dynamics (MD) simulations. This study produced a common thread in discovering a class of alkaloid compounds as inhibitors of androgen receptors that cause alopecia.
Amaryllidaceae is a significant source of bioactive phytochemicals with a strong propensity to develop new drugs. The genera Allium, Tulbaghia, Cyrtanthus and Crinum biosynthesize novel alkaloids and other phytochemicals with traditional and pharmacological uses. Amaryllidaceae biomolecules exhibit multiple pharmacological activities such as antioxidant, antimicrobial, and immunomodulatory effects. Traditionally, natural products from Amaryllidaceae are utilized to treat non-communicable and infectious human diseases. Galanthamine, a drug from this family, is clinically relevant in treating the neurocognitive disorder, Alzheimer’s disease, which underscores the importance of the Amaryllidaceae alkaloids. Although Amaryllidaceae provide a plethora of biologically active compounds, there is tardiness in their development into clinically pliable medicines. Other genera, including Cyrtanthus and Tulbaghia, have received little attention as potential sources of promising drug candidates. Given the reciprocal relationship of the increasing burden of human diseases and limited availability of medicinal therapies, more rapid drug discovery and development are desirable. To expedite clinically relevant drug development, we present here evidence on bioactive compounds from the genera Allium, Tulgbaghia, Cyrtanthus and Crinum and describe their traditional and pharmacological applications.
Numerous agents (approximately 90) are shown to stimulate hair growth in cellular and animal models in a hormetic-like biphasic dose response manner. These hormetic dose responses occur within the framework of direct stimulatory responses as well as in preconditioning experimental protocols. These findings have important implications for experimental and clinical investigations with respect to study design strategies, dose selection and dose spacing along with sample size and statistical power issues. These findings further reflect the general occurrence of hormetic dose responses within the biological and biomedical literature that consistently appear to be independent of biological model, level of biological organization (i.e., cell, organ, and organism), endpoint, inducing agent, potency of the inducing agent, and mechanism.
Background
Herbs are used since ancient times for the treatment of various ailments. Once such herbs is Sudershan is widely used (Crinum asiaticum, family Amaryllidaceae), in traditional and Ayurvedic system of medicines in India, Honkong, Srilanka, China, Thailand and other countries due to its efficacy in curing and preventing of various diseases. Hence the compilation of the botanical, ethnomedical uses and phytoconstituents data will be of great benefits for mankind.
Method
The literature on the plant was collected from various databases viz. Web of Science, PubMed and Science Direct from 1935 to till present.
Results
The compiled data on the therapeutic efficacy and phytoconstituents nature of the plant gives an overview to the future researcher at a glance.
Conclusion
The data revealed the therapeutic effects viz. antimicrobial, anticancer, antioxidant, antinociceptive and anti-inflammatory, antidiabetic, anti-thrombotic, anti-HIV and hair growth promotion activities of the crude drug, fractions, isolated secondary metabolites by various analytical methods that can be useful in utilization for development and formulation of herbal preparation by future researcher.
Norgalanthamine has been shown to possess hair-growth promoting effects, including increase in hair-fiber length in cultured rat vibrissa follicles and increase in dermal papilla cell (DPC) proliferation. However, the intracellular mechanisms that underlie the action of norgalanthamine in DPCs have not been investigated. In this study, we addressed the ability of norgalanthamine to trigger anagen-activating signaling pathways in DPCs. Norgalanthamine significantly increased extracellular signal-regulated kinase (ERK) 1/2 phosphorylation at 0.1 µM, a concentration at which DPC proliferation was also induced. Furthermore, the increases in norgalanthamine-induced ERK 1/2 activation and subsequent DPC proliferation were suppressed by the mitogen-activated protein kinase/ERK kinase (MEK) 1/2 inhibitor, U0126. A 0.1 µM dose of norgalanthamine also increased phosphorylation of AKT, which was followed by an increase in glycogen synthase kinase 3β phosphorylation and nuclear translocation of β-catenin. In addition, LY294002, a phosphatidylinositol 3 kinase (PI3K) inhibitor, blocked the effect of norgalanthamine on DPC proliferation. These results suggest that norgalanthamine can stimulate the anagen phase of the hair cycle in DPCs via activation of the ERK 1/2, PI3K/AKT, and Wnt/β-catenin pathways.
Graphical Abstract Fullsize Image
Galantamine is widely used in medicine as a strong reversible inhibitor of acetylcholineserase for the treatment of Alzheimer’s disease and other neurological diseases. The main aim of this PhD thesis is to analyze the potential of shoot type in vitro systems from Leucojum astivum L. as producers of galanthamine. The optimized conditions of cultivation by shoot type lines L. aestivum in temporary immersion systems type RITA were established. The bubble column bioreactor with internal sections was the most suitable cultivation system for galanthamine production, when the maximum productivity 48 μg/(L.day) and the maximum volumetric yield (1.7 mg/L) were achieved at 22°C and flow rate of inlate air 18 L/(L.h). For the first time acetylcholinesterase inhibitory activity of complex alkaloids mixture obtained from plant in vitro systems of L. aestivum was investigated. Multymetabolite analyzes showed that temperature of cultivation influence on phenol-oxidative coupling of 4-O-methylnorbelladine and formation of alkaloids with different structure type. Jasmonic acid was an appropriate elisitor for inducing biosynthesis of galanthamine. New protocol for shoots obtaining was developed. Shoot type line biosynthesing 3.3 mg/L galanthamine cultivated in the bubble column bioreactor with internal section was selected. When Amberlite XAD-4 was used, as a second phase in the cultivation process the maximum production of galanthamine (5.9 mg/L) was obtained and 3-O-methylgalanthamine was identified, which is a new alkaloid for L. aestivum.
Abstract
Ethnopharmacological relevance
Research in the past half a century has gradually sketched the biological mechanism leading to androgenetic alopecia (AGA). Until recently the aetiological paradigm has been too limited to enable intelligent commentary on the use of folk remedies to treat or reduce the expression of this condition. However, our understanding is now at a point where we can describe how some folk remedies work, predict how effective they will be or why they fail.
Results
The new paradigm of AGA is that inheritance and androgens (dihydrotestosterone) are the primary contributors and a secondary pathology, microinflammation, reinforces the process at more advanced stages of follicular miniaturisation. The main protagonist to microinflammation is believed to be microbial or Demodex over-colonization of the infundibulum of the pilosebaceous unit, which can be ameliorated by antimicrobial/acaricidal or anti-inflammatory therapies that are used as adjuvants to androgen dependent treatments (either synthetic or natural). Furthermore, studies reveal that suboptimal androgen metabolism occurs in both AGA and insulin resistance (low SHBG or high DHT), suggesting comorbidity. Both can be ameliorated by dietary phytochemicals, such as specific classes of phenols (isoflavones, phenolic methoxy abietanes, hydroxylated anthraquinones) or polycyclic triterpenes (sterols, lupanes), by dual inhibition of key enzymes in AGA (5α-reductase) and insulin resistance (ie., DPP-4 or PTP1B) or agonism of nuclear receptors (PPARγ). Evidence strongly indicates that some plant-based folk remedies can ameliorate both primary and secondary aetiological factors in AGA and improve insulin resistance, or act merely as successful adjuvants to mainstream androgen dependent therapies.
Conclusion
Thus, if AGA is viewed as an outcome of primary and secondary factors, then it is better that a ‘multimodal’ or ‘umbrella’ approach, to achieve cessation and/or reversal, is put into practice, using complementation of chemical species (isoflavones, anthraquinones, procyanidins, triterpenes, saponins and hydrogen sulphide prodrugs), thereby targeting multiple ‘factors’.
Hair disorders such as hair loss (alopecia) and androgen dependent, excessive hair growth (hirsutism, hypertrichosis) may impact the social and psychological well‐being of an individual. Recent advances in understanding the biology of hair have accelerated the research and development of novel therapeutic and cosmetic hair growth agents. Preclinical models aid in dermocosmetic efficacy testing and claim substantiation of hair growth modulators. The in vitro models to investigate hair growth utilize the hair follicle Dermal Papilla cells (DPCs), specialized mesenchymal cells located at the base of hair follicle that play essential roles in hair follicular morphogenesis and postnatal hair growth cycles. In this review, we have compiled and discussed the extensively reported literature citing DPCs as in vitro model to study hair growth promoting and inhibitory effects. A variety of agents such as herbal and natural extracts, growth factors and cytokines, platelet‐rich plasma, placental extract, stem cells and conditioned medium, peptides, hormones, lipid‐nanocarrier, light, electrical and electromagnetic field stimulation, androgens and their analogs, stress‐serum and chemotherapeutic agents etc. have been examined for their hair growth modulating effects in DPCs. Effects on DPCs’ activity were determined from untreated (basal) or stress induced levels. Cell proliferation, apoptosis and secretion of growth factors were included as primary end‐point markers. Effects on a wide range of biomolecules and mechanistic pathways that play key role in the biology of hair growth were also investigated. This consolidated and comprehensive review summarizes the up‐to‐date information and understanding regarding DPCs based screening models for hair growth and may be helpful for researchers to select the appropriate assay system and biomarkers. This review highlights the pivotal role of DPCs in the forefront of hair research as screening platforms by providing insights into mechanistic action at cellular level, which may further direct the development of novel hair growth modulators. This article is protected by copyright. All rights reserved.
Effects of hot water extracts of oriental melon leaves (OML) on promotion of hair growth were investigated. Topical OML extract administration for hair regeneration was investigated using an in vivo model with C57BL/6 mice. Effects of OML extracts on the human hair growth were investigated using a hair follicle organ culture. OML extracts induced a shortened telogen to anagen conversion and promoted hair growth in the C57BL/6 mouse model. Culture of human hair follicles in the presence of OML extracts for 8 days promoted hair growth and prolonged the anagen duration due to induction of hair follicle cell proliferation in the bulb region. OML extracts exert a hair growth promotion effect and, therefore, can be used as a therapeutic agent for prevention of hair loss.
Plants of the Amaryllidaceae family, including ca. 75 genera and about 1,100 species, are among the top 20 in the most widely considered medicinal plant families. A number of pharmacologically active compounds, such as phenols, alkaloids, lectins, peptides, etc., have been identified and characterized from this family. As primary constituents, up to 500 structurally diverse Amaryllidaceae alkaloids have been isolated to date. These biogenetically related alkaloids are basically classified into 12 different skeleton types according to their ring systems. Representative structures for each type of Amaryllidaceae alkaloids are shown in this chapter. Biosynthetic pathways for each type of Amaryllidaceae alkaloids including those newly established subgroups are also discussed. In addition, recent reports on the occurrence and biological activity profiles of Amaryllidaceae alkaloids are summarized.
Crinum is a well-known traditional herb belongs to family Amaryllidaceae. Worldwide, different Crinum species are commonly used to treat various conditions due to their excellent medicinal values. Members of this genus are also best known biofactories for the unique Amaryllidaceae alkaloids. Due to the significant phytoconstituents produced by this plant as well as their therapeutic potentials, many Crinum species have been subjected to extensive chemical, cytological and pharmacological investigations. This part of our comprehensive review work on the chemical and biological profiles of Crinums describes the results of biological and toxicological studies conducted on different species. In addition, general analytical conclusions as well as some suggestions for future phytochemical and biological work on Crinums are discussed.
Abstract The alkaloid patterns of sea daffodil (Pancratium maritimum L.) shoot culture, cultivated in a temporary immersion cultivation system were investigated. The shoots accumulated maximal amounts of biomass (0.8 g dry biomass/L and Growth Index=1.6) at immersion frequency with 15 min flooding and 12 h stand-by periods. At this
regime P. maritimum shoots achieved the highest degree of utilization of carbon source. Twenty-two alkaloids, belonging to narciclasine, galanthamine, haemanthamine, lycorine,
montanine, tazettine, homolycorine and tyramine types were identified in intracellular and extracellular alkaloid extracts. The immersion frequency affected strongly the capacity of
alkaloid biosynthesis in P. maritimum shoots and at the optimum conditions of cultivation, the total intracellular alkaloid content reached up to 3,469 μg/g dry biomass. The main biosynthesized alkaloids were haemanthamine (900.1 μg/g) and lycorine (799.9 μg/g). The obtained results proved that temporary immersion technology, as a
cultivation approach, and P. maritimum shoots, as a biological system, are prospective for producing wide range bioactive alkaloids.
Ginger (Zingiber officinale) has been traditionally used to check hair loss and stimulate hair growth in East Asia. Several companies produce shampoo containing an extract of ginger claimed to have anti-hair loss and hair growth promotion properties. However, there is no scientific evidence to back up these claims. This study was undertaken to measure 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo, and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. 6-Gingerol suppressed hair growth in hair follicles in culture and the proliferation of cultured DPCs. The growth inhibition of DPCs by 6-gingerol in vitro may reflect a decrease in the Bcl-2/Bax ratio. Similar results were obtained in vivo. The results of this study showed that 6-gingerol does not have the ability to promote hair growth, on the contrary, can suppress human hair growth via its inhibitory and pro-apoptotic effects on DPCs in vitro, and can cause prolongation of telogen phase in vivo. Thus, 6-gingerol rather than being a hair growth stimulating drug, it is a potential hair growth suppressive drug; i.e. for hair removal.
Among the lipids in bovine milk, minor components such as conjugated linoleic acids and phospholipids are more attractive than triacylglycerols from the standpoint of biological activity. To explore novel functions of bovine milk polar lipids (MPL), topical application to murine dorsal skin was introduced as an assay system. The acetone-insoluble lipid fraction derived from bovine milk was dispersed in ethanol and applied to 9-wk-old C57BL/6N female mice for 3 wk. In combination with visual assessment of the dorsal pigmentation, the progression of the hair cycle was estimated by calculating the ratio of subcutis to dermis thickness. The administration of MPL led to earlier progression of the hair cycle compared with administration of the vehicle. In some cases, the extent of MPL-induced hair cycle progression was comparable to that in animals treated with minoxidil, the most well-known reagent that initiates anagen. These results indicate that the MPL preparation contains a dermal penetrative component that can regulate the hair cycle and, thus, this preparation possesses potential for cosmetic use.
The alkaloid patterns in Leucojum aestivum L. shoot culture cultivated at temporary immersion conditions were investigated using gas chromatography-mass spectrometry. 18 alkaloids were identified, and galanthamine, hamayne and lycorine were dominant. The L. aestivum 80 shoot culture, cultivated at temporary immersion conditions, is a prospective biological matrix for obtaining wide range Amaryllidaceae alkaloids, showing valuable biological and pharmacological activities. The temperature of cultivation influenced enzyme activities, catalyzing phenol oxidative coupling of 4'-O-methylnorbelladine and formation of the different groups Amaryllidaceae alkaloids. Decreasing the temperature of cultivation of L. aestivum 80 shoot culture led to activation of para-ortho' phenol oxidative coupling (formation of galanthamine type alkaloids) and inhibited ortho-para' and para-para' phenol oxidative coupling (formation of lycorine and haemanthamine types alkaloids).
Dermal papilla (DP) cells play a regulatory role in hair growth, and also play a role in alopecia (hair loss). However, effects of taxol, which is a widely used chemotherapy drug, on DP cells remain unclear, despite that theoretically taxol can impact on DP cells to contribute to taxol-induced alopecia. To better understand pathophysiology of taxol-induced damage in DP cells, morphological and biochemical analyses were performed to check whether taxol can cause apoptosis in cultured DP cells or not. If it can, proteomics and bioinformatics analyses were then performed to investigate the protein networks which are impacted by the taxol treatment. Our data showed that taxol can cause apoptotic damage in DP cells in a concentration-dependant manner, as demonstrated by various apoptotic markers. Proteomic analysis on DP cells treated with the lowest apoptosis-inducible concentration of taxol revealed that taxol can affect expression of proteins involved in Ca2+-regulated biological processes, vesicles transport, protein folding, reductive detoxification, and biomolecules metabolism. Furthermore, bioinformatics analysis indicated that taxol can impact on multiple biological networks. Taken together, this biochemical, proteomics, and bioinformatics data may give an insight into pathophysiology of taxol-induced damage in DP cells and shed light on mechanisms underlying taxol-induced alopecia.
Radix panax ginseng (Panax ginseng C.A. Meyer, Araliaceae, RPG) has been documented to possess hair growth activity and widely used to treat alopecia, while no report has been issued to date on the effect of Fructus panax ginseng (FPG) on hair regeneration.
To investigate the effects of FPG extract on the proliferation of human hair dermal papilla cells (DPCs) and on the promotion of hair regeneration in C57BL6 mice, cell proliferation was evaluated in cultured DPC by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and measured the expressions of Bcl-2 and Bax by immunoblot assay. We also compared the effects of topical FPG extract (1 and 10 mg/ml, 100 μl/d) with the effects of minoxidil as a positive control (5%, 100 μl/d) or vehicle control (30% ethanol) on the depilation-induced hair cycling in 7 week-old-C57BL/6 mice.
FPG extract significantly increased the proliferation of DPCs in dose and time dependent manners (P<0.05, P<0.01 and P<0.001). FPG extract also enhanced Bcl-2 expression and decreased Bax expression compared with control (P<0.01). Moreover, significant elongations of anagen phase during hair cycle after application of FPG were evaluated by photographical and histological observations.
FPG extract improves the cell proliferation of human DPCs through anti apoptotic activation. Topical administration of FPG extract might have hair regeneration activity for the treatment of hair loss.
Alkaloids from the plants of Amaryllidaceae family consist of an unique class of nitrogen-containing compounds showing diverse and significant biological activities, including anticancer and acetylcholinesterase (AChE) inhibitory activities. This review summarizes the research into the isolation, structure elucidation, biological activity, and chemical synthetic aspects of the Amaryllidaceae alkaloids over the last two years. In addition, structurally closely related Sceletium alkaloids are also discussed.
In a search for natural product inhibitors of hypoxia inducible factor-1 (HIF-1) function, crinamine (1), a crinane type alkaloid, showed potent dose dependent inhibition (IC50 = 2.7 mu m) of HIF-1 alpha in a cell-based reporter gene assay. Crinamine (1) was isolated from the aerial parts of Crinum asiaticum var.japonicum together with ly-corine (2), norgalanthamine (3) and epinorgalanthamine (4). The other components (2-4) showed no significant inhibition of HIF-1 alpha induced transcriptional activity.
Crinum asiaticum Linne var. japonicum has long been used as a rheumatic remedy, as an anti-pyretic and as an anti-ulcer treatment, and for the alleviation of local pain and fever in Korea and Malaysia. In order to investigate the possibility of Crinum asiaticum Linne var. japonicum extract as a cosmetic ingredient, we measured its anti-inflammatory effect by its inhibition of iNOS (inducible nitric oxide synthase) and the release of PGE2, IL-6, and IL-8. We also measured its anti-allergic effect by its inhibition of beta-hexosamidase release. An HPLC experiment after extraction with 95% EtOH at pH 3.5 showed that Crinum asiaticum Linne var. japonicum was mainly composed of lycorine (up to 1%), a well-known immunosuppressor. The content of lycorine varied, depending on the type of plant tissue analyzed and the extraction method. In an anti-inflammatory assay for inhibition of nitric oxide formation on lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells, the ethanol extract of Crinum asiaticum showed an inhibitory activity of NO production in a dose-dependent manner (IC50 = 58.5 microg/ml). Additional study by RT-PCR demonstrated that the extract of Crinum asiaticum significantly suppressed the expression of the iNOS gene. Moreover, the extract of Crinum asiaticum did not show any cytotoxicity, but did show a cell proliferation effect against LPS (a 10 approximately 60% increase in cell viability). In an assay to determine inhibition of the H2O2-activated release of PGE2, IL-6, and IL-8 in human normal fibroblast cell lines, the release of PGE2 and IL-6 was almost completely inhibited above concentrations of 0.05% and 1%, respectively. Moreover, the release of IL-8 was completely inhibited over the entire range of concentration (>0.0025%). In order to investigate the skin-sensitizing potentials of the extract of Crinum asiaticum, a human clinical test was performed after repeated epicutaneous 48-h applications under an occlusive patch (RIPT). The repeated and single cutaneous applications of Crinum asiaticum Linne var. japonicum extract under the occlusive patch did not provoke any cumulative irritation and sensitization reactions. The result showed that the extract of Crinum asiaticum Linne var. japonicum has a sufficient anti-inflammatory effect. Therefore, Crinum asiaticum Linne var. japonicum extract may be useful for development as an ingredient in cosmetic products.
The dermal papilla is a discrete group of cells at the base of the hair follicle and is implicated in controlling the hair growth cycle. Early passage dermal papilla cells can induce hair growth in vivo, but, upon further culturing, this property is lost. In order to study the events occurring in hair induction, a representative dermal papilla cell line was required. We have transfected passage 1 rat vibrissa dermal papilla cells with a polyomavirus large T gene encoding a temperature-sensitive T antigen, and generated permanent cell lines in which the immortalizing function can be switched off by temperature shift. The cells established without crisis, resembled cells in the starting population, and retained the aggregative properties of early passage dermal papilla cells. Growth studies were performed on the immortalized cell lines, which showed that transferring the cells to the restrictive temperature for the large T gene product resulted in cell senescence or quiescence, and changes in morphology. Implantation of cell pellets into the ears of immunologically compatible rats showed that the immortal cells retained hair-inductive ability.
Cytokines are believed to have an important role in the control of hair growth. The pattern of cytokine gene expression in the immortal cell lines was compared with early passage dermal papilla cells and a non-hair-inducing dermal papilla cell line, using reverse transcriptase-polymerase chain reaction. Epidermal growth factor, tumour necrosis factor, and interleukin-1a were detected in the immortalized and non-hair-inducing dermal papilla cell lines, but were absent in passage 2 dermal papilla cells. All other cytokines examined were detected in all the cell types under study.
These results demonstrate that the polyomavirus large Ttsa-immortalized dermal papilla cell lines are very similar to passage 2 dermal papilla cells and thus provide a good model for hair growth studies. Cytokine expression profiles indicate that the expression of several cytokines may be implicated in hair induction. Further studies are under way to investigate the relationship between cytokine expression and the hair growth cycle.
The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.
The bulbs of Crinum asiaticum L. var. japonicum BAKER (Amaryllidaceae) were found to contain N-demethylgalanthamine (II) as well as lycorine (III) and crinamine (IV). This is the first time that II has been isolated directly, as an single base, from a member of the Amaryllidaceae.
Background: Androgenetic alopecia (male pattern hair loss) is caused by androgen-dependent miniaturization of scalp hair follicles, with scalp dihydrotestosterone (DHT) implicated as a contributing cause. Finasteride, an inhibitor of type II 5α-reductase, decreases serum and scalp DHT by inhibiting conversion of testosterone to DHT. Objective: Our purpose was to determine whether finasteride treatment leads to clinical improvement in men with male pattern hair loss. Methods: In two 1-year trials, 1553 men (18 to 41 years of age) with male pattern hair loss received oral finasteride 1 mg/d or placebo, and 1215 men continued in blinded extension studies for a second year. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, and review of photographs by an expert panel. Results: Finasteride treatment improved scalp hair by all evaluation techniques at 1 and 2 years (P < .001 vs placebo, all comparisons). Clinically significant increases in hair count (baseline = 876 hairs), measured in a 1-inch diameter circular area (5.1 cm2 ) of balding vertex scalp, were observed with finasteride treatment (107 and 138 hairs vs placebo at 1 and 2 years, respectively; P < .001). Treatment with placebo resulted in progressive hair loss. Patients’ self-assessment demonstrated that finasteride treatment slowed hair loss, increased hair growth, and improved appearance of hair. These improvements were corroborated by investigator assessments and assessments of photographs. Adverse effects were minimal. Conclusion: In men with male pattern hair loss, finasteride 1 mg/d slowed the progression of hair loss and increased hair growth in clinical trials over 2 years. (J Am Acad Dermatol 1998;39:578-89.)
A major challenge to the study of hair follicle growth is an appropriate assay system. Because equine mane follicles are large and noncurved, enabling easy dissection; are readily accessible from a single defined source; and possess a long anagen growth phase, we initiated a study of them in culture. As in our previous studies of human and sheep follicles (Dev Biol 165:469, 1994), we found in this system that transection level dictates the pattern of (follicle growth in vitro: follicles transected below the sebaceous gland show a type I growth pattern (the shaft grows out with an adherent sheath), while nontransected follides show a type 2 growth pattern (a naked shaft grows out lacking a sheath). In the present study, we searched for compounds that might influence type 1 or type 2 patterns of growth. We found that 13-tisrethaoic acid induced, in a concentration-dependent fashion, a type l-like pattern of growth under conditions for which a type 2 pattern was expected, gS1trans-retinoic acid, SR11237 (a synthetic retinoid X receptor-specific ligand), and meta-carboxy-TTNPB (an inactive synthetic retinold) did not have these properties. We hypothesize that sheath growth/processing is mediated by the follicle at the level of the sebaceous gland, or by the sebaceous gland itself, and that persistence of the follicle sheath about the outgrowing shaft in vitro (i) in the physical absence of the sebaceous portion of the follicle, or (ii) in the presence of 13-cis-retinoic acid, is due to the reduced expression of a factor that regulates important shaft-sheath interactions.Keywords: follicle sheath, sebaceous gland
This study was conducted to evaluate the effect of Schisandra nigra, a plant native to Jeju Island, South Korea, on the promotion of hair growth. When rat vibrissa follicles were treated with 85% ethanol (EtOH) extract of S. nigra, the hair-fiber lengths of the vibrissa follicles increased significantly. In addition, after topical application of the EtOH extract of S. nigra onto the back of C57BL/6 mice every other day, anagen progression of the hair shaft was induced. Moreover, the extract increased both the expression of proliferating cell nuclear antigen (PCNA) in the bulb matrix region and the proliferation of immortalized vibrissa dermal papilla cells. In order to determine the mechanism by which S. nigra promotes hair growth, we examined its relationship with the transforming growth factor-beta2 (TGF-beta2) signal pathway, which is known to be a regulator of catagen induction. When the vibrissa follicles in the anagen phase were treated with S. nigra extract for 7 days, the expression of TGF-beta2 in the bulb matrix region was found to be lower than that of the control follicles that were expected to be in the anagen-catagen transition phase. These results suggest that S. nigra extract has the potential to promote hair growth via down regulation of TGF-beta2 and the proliferation of dermal papilla.
A case of hypertrichosis due to the hypotensive drug minoxidil is described. A review of the literature suggests that this complication appears in nearly all patients treated with this drug. The mechanism is unknown, but the similarity to the cases of hypertrichosis due to diazoxide, another potent vasodilator, suggests that increased cutaneous blood flow may be a factor.
Examinations were made on the neutral components of Crinum asiaticum var. japonicum BAK.. Methyl linoleate, stigmasterol, 4, 5-etheno-8, 9-methylenedioxy-6-phenanthridone, and three triterpene alcohols (cycloartenol, cyclolaudenol, and N-F) were isolated. N-F was assumed to be 31-norcyclolaudenol (IV) from its physical data. These triterpene alcohols were isolated for the first time from Amaryllidaceae.
The growth of hair from the mystacial vibrissal follicles of C3H mice and Wistar rats has been measured for up to seven cycles. Normally growth in length and thickness was regular and little affected by age or sex. Plucking vibrissae at any stage during the growing period was followed by the appearance of a new vibrissa 8-11 days later. Plucking when growth had ceased had no effect on the time of appearance of the subsequent cycle. New whiskers emerging after plucking grew at the normal rate. Withholding food slowed the growth of vibrissae within 1 day. Normal growth was re-established 3 days after return to full diet.
A series of 23 Amaryllidaceae isoquinoline alkaloids and related synthetic analogues were isolated or synthesized and subsequently evaluated in cell culture against the RNA-containing flaviviruses (Japanese encephalitis, yellow fever, and dengue viruses), bunyaviruses (Punta Toro, sandfly fever, and Rift Valley fever viruses), alphavirus (Venezuelan equine encephalomyelitis virus), lentivirus (human immunodeficiency virus-type 1) and the DNA-containing vaccinia virus. Narciclasine [1], lycoricidine [2], pancratistatin [4], 7-deoxypancratistatin [5], and acetates 6-8, isonarciclasine [13a], cis-dihydronarciclasine [14a], trans-dihydronarciclasine [15a], their 7-deoxy analogues 13b-15b, lycorines 16 and 17, and pretazettine [18] exhibited consistent in vitro activity against all three flaviviruses and against the bunyaviruses, Punta Toro and Rift Valley fever virus. Activity against sandfly fever virus was only observed with 7-deoxy analogues. In most cases, however, selectivity of the active compounds was low, with toxicity in uninfected cells (TC50) occurring at concentrations within 10-fold that of the viral inhibitory concentrations (IC50). No activity was observed against human immunodeficiency virus-type 1, Venezuelan equine encephalomyelitis virus, or vaccinia viruses. Pancratistatin [4] and its 7-deoxy analogue 5 were evaluated in two murine Japanese encephalitis mouse models (differing in viral dose challenge, among other factors). In two experiments (low LD50 viral challenge, variant I), prophylactic administration of 4 at 4 and 6 mg/kg/day (2% EtOH/saline, sc, once daily for 7 days, day -1 to +5) increased survival of Japanese-encephalitis-virus-infected mice to 100% and 90%, respectively. In the same model, prophylactic administration of 5 at 40 mg/kg/day in hydroxypropylcellulose (sc, once daily for 7 days, day -1 to +5) increased survival of Japanese-encephalitis-virus-infected mice to 80%. In a second variant (high LD50 viral challenge), administration of 4 at 6 mg/kg/day (ip, twice daily for 9 days, day -1 to +7) resulted in a 50% survival rate. In all cases, there was no survival in the diluent-treated control mice. Thus, 4 and 5 demonstrated activity in mice infected with Japanese encephalitis virus but only at near toxic concentrations. To our knowledge, however, this represents a rare demonstration of chemotherapeutic efficacy (by a substance other than an interferon inducer) in a Japanese-encephalitis-virus-infected mouse model.
The effects of cepharanthine and minoxidil on proliferation, differentiation and keratinization of cultured cells from the murine hair apparatus were examined electron microscopically. Both cepharanthine and minoxidil stimulated cell proliferation and delayed initiation of differentiation and keratinization of the cultured cells. On day 6, most control cells (87%) cultured in a 0.03 mM calcium medium without cepharanthine and minoxidil were differentiated into several subpopulations corresponding to those of in vivo cell layers of the hair apparatus, while most of the cells cultured with cepharanthine (71%) or minoxidil (70%) were still immature. On day 13, the number of degenerated cells increased (63%) in the control culture, whereas in the culture treated with cepharanthine or minoxidil, cell degeneration scarcely occurred (5% and 8%, respectively). Differentiated cells having tonofilaments were often observed in the cepharanthine- and minoxidil-treated cultures (76% and 72%, respectively). Elevation of extracellular calcium up to 1.0 mM induced keratinization (34%) in the control culture on day 6, while no keratinized cells were observed in the cepharanthine- or minoxidil-treated culture. On day 13 keratinization similarly occurred in the cultures with cepharanthine (30%) or minoxidil (48%). These results show that both cepharanthine and minoxidil may directly influence proliferation, differentiation and keratinization of cultured cells from the hair apparatus.
Pelage hair follicles were isolated by gentle microdissection from 8-12-day-old rats, and maintained in supplemented Williams E medium. Length measurements made on freshly isolated hair follicles, and at 24-h intervals, showed a significant increase in hair follicle length over 48 h, after which time no further significant increase in length was observed. Photomicrographs of maintained follicles showed that this increase in hair follicle length could be attributed to the production of a keratinized hair shaft. Histology and [methyl-3H] thymidine autoradiography of freshly isolated hair follicles showed the dermal papilla to be elongated, with thymidine uptake located predominantly in the matrix cells of the hair follicle bulb adjacent to the dermal papilla. This pattern remained unaltered for the first 48 h of maintenance, but after 72 h the dermal papilla had rounded into a tight ball of cells, with very little thymidine uptake occurring in the adjacent matrix cells. On maintenance, fetal calf serum (FCS), epidermal growth factor (EGF) and 12-o-tetradecanoyl phorbol 13-acetate (TPA) all significantly stimulated [methyl-3H] thymidine and [U-14C] leucine uptake, but inhibited hair follicle elongation. Insulin-like growth factor-1 (IGF-1) had no significant effect on rates of hair follicle elongation and [methyl-3H] thymidine uptake, but significantly stimulated rates of [U-14C] leucine uptake. Transforming growth factor-beta 1 (TGF-beta 1) significantly inhibited both the rate of [methyl-3H] thymidine uptake and hair follicle elongation.
The opening of intracellular potassium channels has been suggested as a mechanism regulating hair growth. Enhancing the flux of potassium ions is a mechanism shared by several structurally diverse antihypertensive agents including minoxidil sulfate (the active metabolite of minoxidil), pinacidil, P-1075 (a potent pinacidil analog), RP-49,356, diazoxide, cromakalim, and nicorandil. Of these drugs, minoxidil, pinacidil, and diazoxide have been reported to elicit hypertrichosis in humans. This potassium channel hypothesis was examined by testing these drugs for effects on hair growth both in vitro and in vivo. For the in vitro studies, mouse vibrissae follicles were cultured for 3 d with drug and the effects on hair growth were measured by metabolic labeling. All drugs, except diazoxide, enhanced cysteine incorporation into the hair shafts of the cultured vibrissae. Diazoxide was poorly soluble and thus was tested only at low doses. Minoxidil, P-1075, cromakalim, and RP-49,356 were also evaluated in vivo by measuring hair growth effects in balding stumptail macaque monkeys. The drugs were administered topically to defined sites on balding scalps once per day for 4-5 months and the amount of hair grown was determined by monthly measurements of shaved hair weight. Three of the drugs produced significant increases in hair weight whereas, the RP-49,356 had no effect. These studies provide correlative evidence that the opening of potassium channels is an important regulatory mechanism for hair growth. This provides the impetus for further studies on this potentially important mechanism affecting hair biology.
Proliferating cell nuclear antigen (PCNA) is a 36 kD nuclear protein associated with the cell cycle. A monoclonal antibody, PC10, that recognizes a fixation and processing resistant epitope has been used to investigate its tissue distribution. Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues. PCNA immunoreactivity is induced in lectin stimulated peripheral blood mononuclear cells in parallel with bromodeoxyuridine incorporation and the number of cells with PCNA immunoreactivity is reduced by induction of differentiation in HL60 cells. In non-Hodgkin's lymphomas a linear relation between Ki67 and PCNA staining was demonstrated. These data suggest that in normal tissues and lymphoid neoplasms, PCNA immunolocalization can be used as an index of cell proliferation. However, in some forms of neoplasia, including breast and gastric cancer and in vitro cell lines, the simple relation between PCNA expression and cell proliferation is lost. In some breast and pancreatic tumours there is apparent deregulation of PCNA with increased expression in tissues adjacent to the tumours. The over-expression in some tumours and in adjacent morphologically normal tissue may represent autocrine or paracrine growth factor influence on PCNA gene expression.
An important step in understanding minoxidil's mechanism of action on hair follicles was to determine the drug's active form. We used organ-cultured vibrissa follicles to test whether it is minoxidil or its sulfated metabolite, minoxidil sulfate, that stimulates hair growth. Follicles from neonatal mice were cultured with or without drugs and effects were assessed by measuring incorporation of radiolabeled cysteine in hair shafts of the treated follicles. Assays of minoxidil sulfotransferase activity indicated that vibrissae follicles metabolize minoxidil to minoxidil sulfate. Dose-response studies showed that minoxidil sulfate is 14 times more potent than minoxidil in stimulating cysteine incorporation in cultured follicles. Three drugs that block production of intrafollicular minoxidil sulfate were tested for their effects on drug-induced hair growth. Diethylcarbamazine proved to be a noncompetitive inhibitor of sulfotransferase and prevented hair growth stimulation by minoxidil but not by minoxidil sulfate. Inhibiting the formation of intracellular PAPS with chlorate also blocked the action of minoxidil but not of minoxidil sulfate. Acetaminophen, a potent sulfate scavenger blocked cysteine incorporation by minoxidil. It also blocked follicular stimulation by minoxidil sulfate apparently by directly removing the sulfate from the drug. Experiments with U-51,607, a potent minoxidil analog that also forms a sulfated metabolite, showed that its activity was inhibited by both chlorate and diethylcarbamazine. These studies show that sulfation is a critical step for hair-growth effects of minoxidil and that it is the sulfated metabolite that directly affects hair follicles.
The Chinese medicinal plant Zephyranthes candida was found to contain a cytostatic constituent. Separation of a n-BuOH extract directed by results of a bioassay employing the P-388 lymphocytic leukemia led to trans-dihydronarciclasine [2] as the principal cytostatic agent with ED50 3.2 X 10(-3) micrograms/ml.
Minoxidil applied topically on the bald scalp of stumptailed macaques seems to have a favorable effect in enlarging some hair follicles that then produce thicker hairs. It also seems to prevent hair follicles from becoming smaller during the peri-adolescence period in these animals. A novel method, the folliculogram, revealed that minoxidil accelerates the cyclic turnover of vellus follicles and simultaneously induces enlargement of regrowing follicles during early anagen phases. Minoxidil appears to enhance a proliferation of follicular cells in the secondary bud, thus producing a larger follicle than that of the previous cycle. The study revealed that 'transformed vellus follicles' in the bald scalp have a potential to recover their ability to produce thick hair. However, recovery from baldness may take as long as the time it takes for baldness to develop. Thus, treatment in early stages of baldness should be more effective than treatment at advanced stages.
Mammalian hairs are formed by differentiation and keratinization of cells produced in the epidermal matrix (Figs 3, 4). Using the rodent vibrissa follicle as a model, transplantation studies have shown that the dermal papilla, a discrete population of specialized fibroblasts, is of prime importance in the growth of hair. Papillae induce hair growth when implanted into follicles and can interact with skin epidermis to form new hair follicles. When grown in culture, papilla cells display singular morphological and behavioural characteristics compared with connective tissue cells from other skin sources. We report here that serially cultured adult papilla cells can induce the growth of hair when implanted into follicles which otherwise would not grow hairs. This finding presents an opportunity to characterize properties distinguishing the papilla cell population from other skin fibroblasts, and, more specifically, those which control hair growth. The eventual application of this work to human hair replacement techniques can also be envisaged.
Androgen significantly stimulates the proliferation of outer root sheath cells that are cocultured with beard dermal papilla cells without cell contact. The expression of insulin-like growth factor I (IGF-I) mRNA in beard dermal papilla cells was stimulated by androgen and antagonized by cyproterone acetate. Outer root sheath cells did not express mRNA for IGF-I either in the presence or absence of androgen. Both of these two types of cells expressed mRNA for IGF-I receptor and the expression was not affected by androgen. Neutralizing antibody against IGF-I antagonized the stimulatory effect of androgen on the growth of outer root sheath cell cocultured with beard dermal papilla cells. These findings suggest that IGF-I is a candidate for androgen induced hair growth factors.
Programmed cell death is central to hair biology, as the hair follicle undergoes cycles of growth (anagen), regression (catagen), and rest (telogen). During catagen, the hair follicle shortens via a pathway of programmed cell death and apoptosis. The molecular mechanisms involved in this process have not been elucidated yet. Using reverse transcriptase-polymerase chain reaction, we examined in this study the expression in total skin, throughout one hair cycle, of a series of regulatory genes associated with apoptosis. We show that gene expression within skin is hair-cycle-dependent. Transforming growth factor-beta was expressed immediately before catagen; therefore, it might be involved in the early signaling of this process. Tumor necrosis factor-beta was expressed during catagen and might be involved in follicular apoptosis. Several proto-oncogenes and transcription factors have been described in the regulation of apoptosis in other systems. Here we show that the transcript levels of c-myc, c-myb, and c-jun changed immediately before or during early catagen and thus could be involved in the signaling or regulation of catagen. Levels of p53 remained constant throughout anagen and catagen, suggesting that p53 is not involved in the developmentally induced apoptosis of the hair follicle. The variable expression throughout the hair cycle of the genes described demonstrates the dynamic changes of the skin and underscores the importance of studying the complete hair cycle when characterizing any molecule in skin.
The function of keratinocyte growth factor (KGF) in normal and wounded skin was assessed by expression of a dominant-negative KGF receptor transgene in basal keratinocytes. The skin of transgenic mice was characterized by epidermal atrophy, abnormalities in the hair follicles, and dermal hyperthickening. Upon skin injury, inhibition of KGF receptor signaling reduced the proliferation rate of epidermal keratinocytes at the wound edge, resulting in substantially delayed reepithelialization of the wound.
In this study we have used a recently developed human hair follicle whole-organ culture system to investigate the effect of IL-1 alpha on hair follicle growth and hair fiber production. In the presence of 10 ng/ml IL-1 alpha, the growth of cultured human hair follicles ceased within 2-4 days, whereas control hair follicles grew for a period of 7-10 days. IL-1 alpha also inhibited hair fiber growth, but with an onset which occurred 3 days later than that of follicle growth inhibition. An IC50 value of approximately 30 pg/ml was obtained for IL-1 alpha inhibition of follicle growth. Incubation of hair follicles with IL-1 alpha resulted in a rapid, transient reduction in the rate of whole-follicle DNA synthesis. 1000-fold molar excess of IL-1 receptor antagonist prevented IL-1-induced follicle growth inhibition, while antagonist alone was without effect. The selective PKC inhibitor, Ro 31-7549, augmented IL-1-induced inhibition of hair follicle growth, but did not itself affect hair follicle growth. These findings indicate that IL-1 alpha exerts a rapid antiproliferative effect on hair follicles, and that inhibition of hair fiber growth is a secondary response. Thus, IL-1 may play a role in the pathophysiology of inflammatory hair loss conditions, such as alopecia areata, through a direct growth-inhibitory effect on hair follicles.
From the bulbs of Crinum amabile (Amaryllidaceae), a new alkaloid (-)-amabiline [1], together with the known alkaloids (-)-lycorine [2], (-)-buphanisine [3], (-)-augustine [4], and (+)-crinamine [5], were isolated. The structural characterization of 1 and the revised 1H- and 13C-nmr assignments of 2 are discussed. Alkaloids 2, 4, and 5 were found to be the principal cytotoxic and antimalarial constituents.
We studied the effect of cyclosporin A on human hair growth using a recently described model in which isolated hair follicles are grown in vitro. Cyclosporin A had no effect on the rate of hair growth, but at 10(-7) M, a dose within the therapeutic blood range, it maintained hair growth for longer than control to give a 42% greater mean follicle elongation after 15 d (p < 0.05). Eighteen of 42 cyclosporin-treated follicles (43%) were still growing after 15 d compared with one of 42 control follicles (2%). These results suggest that the hypertrichotic action of cyclosporin A may be due to prolongation of the anagen phase of the hair-growth cycle.
Finasteride is the first of a new class of 5 alpha-reductase inhibitors which allows selective androgen deprivation affecting dihydrotestosterone (DHT) levels in target organs such as the prostate and scalp hair without effecting circulating levels of testosterone thus preserving the desired androgen mediated effects on muscle strength, bone density and sexual function. Finasteride has been demonstrated to produce significant effects in men with an enlarged prostate gland. The long-term data now emerging suggests that progression of benign prostatic hyperplasia (BPH) may be arrested providing additional long term benefits. Experimental uses in prostate cancer prevention and male pattern baldness offer new and exciting possibilities for this class of compounds.
The effect of hepatocyte growth factor/scatter factor (HGF/SF) on human hair follicle growth was examined using a serum-free organ culture system. The DNA synthesis in human hair follicles and elongation of the hair shaft were measured subsequent to the follicle isolation and culture at 31 degrees C in 95% O2-5% CO2 for 72 h. Results showed that HGF/SF significantly increased 3H-thymidine (P < 0.001) incorporation and hair follicle length (P < 0.05). The effect of HGF/SF was dose-dependent with a maximal stimulation at 10 ng/ml.
Using RNA in situ hybridization analysis, we have characterized the expression domains of the four known members of the FGF receptor-tyrosine kinase gene family in the murine hair follicle at various stages of the hair growth cycle. During anagen, we detected Fgfr1 RNA in the dermal papilla, Fgfr2 RNA in hair matrix cells near the dermal papilla, Fgfr3 RNA in pre-cuticle cells in the periphery of the hair bulb, and Fgfr4 RNA in cells in the periphery of the hair bulb and also in the inner and outer root sheath in the lower half of the follicle neck. No RNA expression of these genes was detected during late catagen or telogen. We have previously shown that Fgf5 is expressed in the outer root sheath in the transient portion of the follicle (Hébert et al. [1994] Cell 78:1017-1025). In the present study we have also assayed for the expression of six other members of the FGF ligand gene family, Fgf3, Fgf4, Fgf6, Fgf7, Fgf8, and Fgf9. Among these FGF genes, only Fgf7 was found to be expressed in the hair follicle. Fgf7 RNA is localized to the dermal papilla during anagen, but expression is down-regulated by the late-anagen VI stage. We have also demonstrated that addition of FGF5 protein to the culture medium changes the behavior of dermal papilla cells in vitro, indicating that they are capable of responding to FGF5. Together with previously published data, these results provide a complete analysis of FGF ligand and FGF receptor-tyrosine kinase gene expression in the hair follicle, and suggest that FGF signalling may have several functions in the hair growth cycle.
The dermal papilla plays an important role in the regulation of hair follicle matrix cell proliferation and hair fiber production, at least in part through mesenchymal-epithelial interactions. In the present study, we have investigated the regulation of interleukin-1 (IL-1) production by protein kinase C in cultured human dermal papilla cells. Treatment of dermal papilla cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) elicited the rapid and transient production of mature (17 kDa) cytosolic IL-1beta protein, but not IL-1alpha, with maximal levels achieved after 12 h. Rapid secretion of IL-1beta into the medium occurred subsequent to increased intracellular cytokine levels, after which medium IL-1beta protein levels were stable for 4 days. Northern blot analysis showed that TPA treatment elicited a transient induction of IL-1beta mRNA expression, maximal after 12 h, indicating that TPA regulates dermal papilla cell IL-1beta production at the transcriptional level. Pretreatment of dermal papilla cells with Ro 31-7549, a selective protein kinase C inhibitor, dose dependently and completely reversed phorbol-induced IL-1beta protein production. In addition, we demonstrated that IL-1beta is a highly potent inhibitor of the growth of human hair follicles in whole-organ culture, with an IC50 value of approximately 5 pg/ml. These findings, taken together with a previous report that follicular matrix cells express type I IL-1 receptors but dermal papilla cells do not, raise the possibility that dermal papilla cell-derived IL-1beta may act as a negative paracrine factor in the regulation of matrix cell proliferation.
Numerous spontaneous and experimentally induced mouse mutations develop a hair phenotype, which is often associated with more or less discrete abnormalities in hair follicle development. In order to recognize these, it is critically important to be able to determine and to classify accurately the major stages of normal murine hair follicle morphogenesis. As an aid, we propose a pragmatic and comprehensive guide, modified after previous suggestions by Hardy, and provide a list of easily recognizable classification criteria, illustrated by representative micrographs. Basic and more advanced criteria are distinguished, the former being applicable to all mouse strains and requiring only simple histologic stains (hematoxylin and eosin, Giemsa, periodic acid Schiff, alkaline phosphatase activity), the latter serving as auxiliary criteria, which require a pigmented mouse strain (like C57BL/6J) or immunohistochemistry (interleukin-1 receptor type I, transforming growth factor-beta receptor type II). In addition, we present simplified, computer-generated schematic drawings for the standardized recording and reporting of gene and antigen expression patterns during hair follicle development. This classification aid serves as a basic introduction into the field of hair follicle morphogenesis, aims at standardizing the presentation of related hair research data, and should become a useful tool when screening new mouse mutants for discrete abnormalities of hair follicle morphogenesis (compared with the respective wild type) in a highly reproducible, easily applicable, and quantifiable manner.
The size of a hair follicle is thought to be determined by the volume of its dermal papilla. The volume of the dermal papilla depends on the number of cells it contains and on the volume of the extracellular matrix. To establish which of these two variables is related to differences in hair follicle size we performed a stereologic study on 235 hair follicles from different sites, including male facial skin (beard), female facial skin, and scalp. In facial follicles there was a strong correlation between the area of the hair cortex and the volume of the dermal papilla. The area of the hair cortex also correlated with the number of cells in the dermal papilla and with the volume of dermal papilla per cell. In scalp hair follicles, where there was a smaller range of sizes, the correlations between these variables were weaker. In large male facial follicles the mean total dermal papilla volume was almost 40-fold higher than in vellus follicles from female facial skin. This difference was associated with a mean 17-fold greater number of cells in the dermal papilla and a 2.4-fold greater volume associated with each cell. Intermediate results were obtained in scalp follicles. In many regions of the skin hair follicles enlarge in response to androgens during adult life hair. Our results imply that the increase in the volume of the dermal papilla in these follicles is due to an increase in the number of cells, either through proliferation or through the migration of cells from the follicular dermal sheath, and to an increase in the amount of extracellular matrix per cell. As androgens are thought to act primarily on the dermal papilla, these changes may have a direct bearing on the mechanism of androgen-mediated alterations in hair follicle size.
In mammals hair growth is cyclical; however, the factors that regulate the hair growth cycle are still poorly understood. The recent development of methods for culturing hair follicles in vitro has proved an important tool to investigate many aspects of the regulation of hair follicle growth. At present, however, these models are based on the culture of anagen hair follicles and have only partially been used to address the cyclical nature of hair growth. In this study we have made use of the fact that in rodents the hair growth cycle is synchronized, well characterized, and relatively short. We have isolated vibrissa follicles from 12 d old rats and confirmed by histology that these follicles are in the anagen stage of their first hair growth cycle. We have then maintained these follicles in vitro, on Gelfoam supports, for up to 23 d (35 d of age) and compared their histology with in vivo follicles from equivalent age littermates. We observed that 12 d old follicles maintained in vitro for up to 23 d show changes in morphology that suggest that cultured rat vibrissa follicles retain cyclical activity in vitro. Cyclical changes in hair follicle morphology were only seen in follicles maintained on gelfoam supports and moreover, hair follicle size appears to be a key feature in determining the ability of the follicle to cycle in vitro. All follicles that showed cyclical changes in vitro, however, appeared to remain blocked in pro-anagen. These data suggest that the vibrissa follicle is a in vitro good model system with which to investigate hair cycle control. J Invest Dermatol 115:1152-1155 2000
Cholinesterase inhibitors are the only approved drug treatment for patients with mild to moderately severe Alzheimer's disease. Interestingly, the clinical potency of these drugs does not correlate well with their activity as cholinesterase inhibitors, nor is their action as short lived as would be expected from purely symptomatic treatment. A few cholinesterase inhibitors, including galantamine, produce beneficial effects even after drug treatment has been terminated. These effects assume modes of action other than mere esterase inhibition and are capable of inducing systemic changes. We have recently discovered a mechanism that could account, at least in part, for the above-mentioned unexpected properties of some cholinesterase inhibitors. We have found that a subgroup of cholinesterase inhibitors, including galantamine but excluding tacrine, directly interacts with nicotinic acetylcholine receptors. These compounds, named allosterically potentiating ligands, sensitize nicotinic receptors by increasing the probability of channel opening induced by acetylcholine and nicotinic agonists and by slowing down receptor desensitization. The allosterically potentiating ligand action, which is not necessarily associated with cholinesterase inhibition, has been demonstrated by whole-cell patch-clamp recordings to occur in natural murine and human neurons and in murine and human cell lines expressing various subtypes of neuronal nicotinic acetylcholine receptors.
Numerous strains of mice with defined mutations display pronounced abnormalities of hair follicle cycling, even in the absence of overt alterations of the skin and hair phenotype; however, in order to recognize even subtle, hair cycle-related abnormalities, it is critically important to be able to determine accurately and classify the major stages of the normal murine hair cycle. In this comprehensive guide, we present pragmatic basic and auxiliary criteria for recognizing key stages of hair follicle growth (anagen), regression (catagen) and quiescence (telogen) in C57BL/6NCrlBR mice, which are largely based on previous work from other authors. For each stage, a schematic drawing and representative micrographs are provided in order to illustrate these criteria. The basic criteria can be employed for all mouse strains and require only routine histochemical techniques. The auxiliary criteria depend on the immunohistochemical analysis of three markers (interleukin-1 receptor type I, transforming growth factor-beta receptor type II, and neural cell-adhesion molecule), which allow a refined analysis of anatomical hair follicle compartments during all hair cycle stages. In contrast to prior staging systems, we suggest dividing anagen III into three distinct substages, based on morphologic differences, onset and progression of melanogenesis, and the position of the dermal papilla in the subcutis. The computer-generated schematic representations of each stage are presented with the aim of standardizing reports on follicular gene and protein expression patterns. This guide should become a useful tool when screening new mouse mutants or mice treated with pharmaceuticals for discrete morphologic abnormalities of hair follicle cycling in a highly reproducible, easily applicable, and quantifiable manner.
A new pyrrolophenanthridone alkaloid, criasiaticidine A (1), was isolated from the bulbs of Crinum asiaticum var. japonicum, together with pratorimine (2), lycorine (3) and 4'-hydroxy-7-methoxyflavan (4). The structure of the new alkaloid was determined to be 4,5-etheno-9,10-dihydroxy-6-phenanthridone by spectroscopic means. The cytotoxicity of the isolated compounds 1-4 was evaluated in vitro against Meth-A (mouse sarcoma) and Lewis lung carcinoma (mouse lung carcinoma) tumor cell lines. Furthermore, 3 was examined for in vivo antitumor activity with LLC tumor cells.
Fibroblast growth factor (FGF) 5 inhibits hair growth and induces catagen in mouse hair follicles, in vivo. Given that FGF-5 receptor (FGFR1) is expressed in dermal papilla cells (DPCs), which are known to stimulate outer root sheath cell (ORSC) proliferation, we hypothesized that FGF-5 attenuates DPC-mediated ORSC proliferation. In the present study, DPCs and ORSCs were isolated from rat vibrissae, after which the effects of FGF-5 on proliferation of ORSCs cultured in DPC-conditioned medium were assessed. We first confirmed that FGFR1 was expressed in cultured DPCs and detected FGFR2-4 as well. ORSC proliferation was increased approximately twofold when the cells were cultured in DPC-conditioned medium, and the effect was unaltered by FGF-5. In addition, FGF-5 did not directly inhibit ORSC proliferation; indeed, it actually promoted proliferation of both DPCs and ORSCs. When DPCs were first activated by exposure to FGF-1 and FGF-2, which are expressed in hair follicles during anagen, ORSC proliferation observed in the resultant conditioned medium was substantially greater than in medium conditioned by unstimulated DPCs. The FGF-1-induced enhancement was reversed by FGF-5, diminishing ORSC proliferation to control levels. By contrast, the enhancement of DPC-mediated ORSC proliferation by FGF-2 was not suppressed by FGF-5. Proliferation of ORSCs did not depend on DPC proliferation, nor did FGF-1 directly promote ORSC proliferation. Dermal papillae thus appear to require activation before they will efficiently stimulate hair growth, and FGF-5 appears to inhibit hair growth and induce catagen by blocking that activation.
The objective of this study is to investigate whether or not the controlled release of vascular endothelial growth factor (VEGF) is effective in promoting the hair follicle growth of mice in second anagen of hair cycle. VEGF was incorporated into a biodegradable collagen hydrogel for its controlled release. Following implantation of the collagen hydrogel incorporating 0 or 2 microg of VEGF and injection of 0 or 2 microg of VEGF in the solution form into the back subcutis of mice, the hair follicle growth was evaluated photometrically and histologically in terms of the skin color of reverse side of the implanted or injected site, the skin thickness, and the area occupied by hair follicle tissue. Ten days later, the skin color of mice implanted with the collagen hydrogel incorporating 2 microg of VEGF was significantly darker than that injected with 2 pg of VEGF. The collagen hydrogel incorporating VEGF increased the hair follicle area at the implanted site to a significantly greater extent than other agents while significant angiogenetic effect in the skin tissue was observed. VEGF-free, empty collagen hydrogels did not affect the skin darkness, hair follicle growth, and the angiogenesis. Moreover, the hair shaft length was significantly elongated by the collagen hydrogel incorporating VEGF, in marked contrast to other agents. Immunohistolchemicalstaining with proliferating cell nuclear antigen revealed that the collagen hydrogel incorporating VEGF promoted the proliferation of cells around the hair follicle more frequently than free VEGF. We concluded that the controlled release of VEGF more positively acted on the hair growth cycle of mice for hair growth than the injection of free VEGF.
Amaryllidaceous plants produce pharmacologically active alkaloids, galanthamine being the most interesting for its use in the treatment of Alzheimer's disease as a cholinesterase inhibitor. The aim of this work was to test 23 pure Amaryllidaceae alkaloids and 26 extracts from different species of the genus Narcissus for their acetylcholinesterase inhibitory activity using galanthamine as a reference. Only seven alkaloids, belonging to the galanthamine and lycorine skeleton types, exhibited such an effect, sanguinine being the most active, even more than galanthamine. All the extracts with the highest acetylcholinesterase inhibitory activity contained galanthamine except that of N. assoanus, a lycorine type alkaloid-bearing species.
Minoxidil has been widely used to treat androgenetic alopecia, but little is known about its pharmacological activity or about the identity of its target cells in hair follicles. We hypothesized that minoxidil has direct effects on the proliferation and apoptosis of dermal papilla cells (DPCs) of human hair follicle.
To elucidate the mechanism of topical minoxidil action in terms of stimulating hair growth.
We evaluated cell proliferations in cultured DPCs by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and measured the expressions of extracellular signal-regulated kinase (ERK), Akt, Bcl-2, and Bax by Western blot. We also measured elongation of hair follicles in organ culture.
Minoxidil significantly increased the proliferation of DPCs. The levels of ERK phosphorylation and of phosphorylated Akt increased significantly 1 h post-treatment; percentage increase of ERK phosphorylation was 287% at 0.1 microM and 351% at 1.0 microM of minoxidil, and that of Akt phosphorylation was 168% at 0.1 microM and 257% at 1.0 microM of minoxidil. 1.0 microM of minoxidil increased Bcl-2 expression over 150%, while 1.0 microM of minoxidil decreased Bax expression by more than 50%. Moreover, a significant elongation of individual hair follicles in organ culture was observed after adding minoxidil.
Minoxidil promotes the survival of human DPCs by activating both ERK and Akt and by preventing cell death by increasing the ratio of Bcl-2/Bax. We suggest that minoxidil stimulates the growth of human hairs by prolonging anagen through these proliferative and anti-apoptotic effects on DPCs.
The 80% aqueous methanolic extract from the bulbs of Crinum yemense showed a potent inhibitory effect on nitric oxide production in lipopolysaccharide-activated macrophages. Three new crinine-type alkaloids, yemenines A (1), B (2), and C (3), were isolated from the herbal extract together with six known alkaloids. The absolute configurations of 1-3 were determined on the basis of chemical and physicochemical evidence. The effects of the isolated alkaloids on nitric oxide production in lipopolysaccharide-activated macrophages were examined, and several alkaloids, e.g. 1, (+)-bulbispermine (6), (+)-crinamine (7), (+)-6-hydroxycrinamine (8), and (-)-lycorine (9), showed inhibitory effects on nitric oxide production and induction of inducible nitric oxide synthase.
The bulbs of Crinum jagus and Crinum glaucum are used in traditional medicine in southern Nigeria for memory loss and other mental symptoms associated with ageing. Alkaloidal extracts of bulbs from each species showed inhibition of acetylcholinesterase, an activity exploited therapeutically to raise the depressed levels of acetylcholine in the brain associated with Alzheimer's disease. Using the in situ bioautographic test method for enzyme inhibition, a number of alkaloids were isolated and their activity quantified using the Ellman spectrophotometric test. The most active alkaloids isolated were hamayne (IC50 250 microM) and lycorine (IC50 450 microM) whilst other alkaloids were comparatively inactive with haemanthamane giving 3% inhibition and crinamine giving 4.4% inhibition at 50 mg ml(-1) (174 microM). These contrast with the positive control physostigmine which gave IC50 of 0.25 microM. Cholinesterase activity appears to be associated with the presence of two free hydroxy groups in this structural type of Amaryllidaceae alkaloid.
Relatively little is known about the progression of androgenetic alopecia (AGA; male pattern hair loss) in untreated men. We evaluated the long-term (5-year) progression of AGA in men treated with placebo in a controlled clinical trial setting. We analyzed pooled data over 5 years from two replicate studies with finasteride 1 mg/day in men with predominantly vertex-pattern AGA. Each study consisted of an initial 1-year, randomized, double-blind, placebo-controlled base study and four consecutive, 1-year, double-blind, placebo-controlled extension studies. Change over time in scalp hair growth was evaluated by four predefined endpoints: scalp hair counts; assessment of standardized clinical photographs by an expert panel; investigator clinical assessment; and patient self-assessment. All four predefined endpoints demonstrated progressive scalp hair loss in men receiving placebo over the 5-year study period, with a loss of 239 hairs from baseline (26.3% decline in hair density) measured in the target area at 5 years (p < 0.001 vs. baseline). Similarly, visible progression of scalp hair loss was demonstrated by global photographic assessment, with 75% of placebo patients rated as worsened from baseline at 5 years. We found that scalp hair loss continued in a progressive manner over a 5-year period in placebo-treated men with AGA.
There are no reports on the effects of pharmacologic treatment on the likelihood of developing further visible hair loss in men with androgenetic alopecia (AGA). Our objectives were to examine whether finasteride 1 mg treatment decreases the likelihood of developing further visible hair loss in men with AGA. We conducted an analysis of global photographic assessment data from two Phase III trials in which 1553 men with AGA received finasteride 1 mg/day or placebo for up to 5 years. Finasteride 1 mg treatment led to a 93% decrease relative to placebo in the 5-year likelihood of developing further visible hair loss (95% CI: 89-97%; p < 0.001). We conclude that, in men with AGA, treatment with finasteride 1 mg/day over 5 years led to a marked and sustained decrease in the likelihood of developing further visible hair loss.
Auteur(s) : Dominique Van Neste Skin Study Center, Skinterface sprl, 9 rue du Sondart, B-7500 Tournai, Belgium For those involved in medical practice it may seem trivial to state that a doctor’s daily work consists in the subtle balance between art and science, deep belief and hard evidence. In this editorial I wish to share some thoughts that we in the scientific hair evaluation community might consider as technological shortcomings or uncertainties around “hair measurement”. We think that [...]