Article

5α-Reductase inhibition and melanogenesis activity of sesamin from sesame seeds for hair cosmetics

Authors:
  • Faculty of Medicine, Chiang Mai University
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Sesamin is the primary compound in sesame seed oil which has been used in ayurvedic treatment for hair loss and canities. Sesamin was isolated, identified and investigated for antioxidative activities (including DPPH radical scavenging, lipid peroxidation inhibition and metal ion chelating activities), 5α-reductase inhibition in DU-145 and melanogenesis activities on B16F10 melanoma. Sesamin at the concentration of 0.001-10 mg/ml showed weak DPPH scavenging activity (the SC50 value of 109.90 ± 6.16 mg/ml), but quite high lipid peroxidation inhibition and metal ion chelating activities (the IPC50 value of 0.83 ± 0.54 and the CC50 value of 1.83 ± 0.90 mg/ml, respectively). At 0.1 mg/ml of sesamin demonstrated high 5α-reductase inhibition activity at 37.38±4.26% of the control, which was higher than the standard finasteride of 1.54 times, but lower than the standard dutasteride of 1.27 times. It gave high melanin and tyrosinase contents of 26.63±3.21 and 39.42±8.30%, respectively, but lower than theophylline of about 1.04 and 1.05 times, respectively. Although sesamin exhibited all investigated activities lower than the standards, the traditional use of sesame seeds containing sesamin for hair cosmetics has been confirmed, which will be beneficial for the further development as anti-hair loss and anti-canities products.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Liang et al. (2015) indicated its lowering the cholesterol level by displaying its effect on the cholesterol absorption pathway. It has been also a cure for hair loss and canities as an alternative medicine, and has been suggested as an active ingredient in hair cosmetic formulations (Manosroi et al. 2015). The findings of Takada et al. (2015) demonstrated that sesamin inhibited the decrease in exercise capacity of high fat diet-induced diabetic mice. ...
Article
Full-text available
The risk of exhaustion of natural resources and raw materials have given rise to emerging trends such as recycling of food waste. From the economical and ecological points of view, conversion of biowaste to high added value compounds has been getting great attention among the science and commercial entities. Due to their high-added value phytochemicals, agricultural and food residues have been a great significant to the researchers around the world. This study focuses on the valorisation of cake derived from sesame oil processing. If the very valuable non-nutrient phytochemicals in sesame cake are not evaluated properly, they would be consumed as just animal feed or fertilizers. They might be employed as antiaging (in pharmaceutical products), or free radical scavenger (in dietary supplements), or preservative additive against lipid oxidation (in fat containing food products). This review article aims to present pharmacological and therapeutic effects of sesame cake extract by pointing out its application in pharmaceutical, cosmetic and food industries.
... Sesamin is commonly present in Piper species, [16] and sesame seeds (Sesamum indicum) have been found with anti-hair loss and anti-canitie uses. [31] Sesamin also helps promote fat oxidation, prevents fat storage, increases insulin sensitivity, prevents free radical damage, promotes anti-inflammatory effects, reduces cholesterol, and acts as a potent antioxidant. [32] β-sitosterol is useful in treating heart disease, high cholesterol, colon cancer, gallstones, the common cold and flu (influenza), HIV/AIDS, rheumatoid arthritis, TB, allergies, fibromyalgia, asthma, hair loss, bronchitis, chronic fatigue syndrome, and for symptoms of menopause. ...
Article
Full-text available
Background: Cholesterol degradation pathway is one of the important pathways in survival of Mycobacterium tuberculosis (Mtb) bacilli, and steroid C26-monooxygenase (CYP125) enzyme of Mtb associated with this pathway is reported to be novel drug target. This study aims to find out novel, safe, and effective inhibitors against CYP125 from natural phytochemicals with reported anti-tubercular activity. Methods: Bioinformatics approach such as homology modeling, virtual screening, and molecular dynamics (MD) simulation was applied to identify best hits among all the shortlisted 148 compounds. The Mtb H37Ra bacilli growth was measured at optical density at 600 nm in minimal media supplemented with cholesterol and monitored for 10 days. Two promising compounds, namely, sesamin and β-sitosterol, were studied to determine their effective minimum inhibitory concentrations (MICs) in Mtb H37Ra bacilli culture. Results: In virtual screening, 15 compounds showed comparatively better binding affinity than natural substrate (choletst-4-en-3-one). In MD simulation study, the protein structure was observed to be stable in alls the interaction complexes, i.e., with choletst-4-en-3-one, sesamin, and β-sitosterol. The MICs of sesamin and β-sitosterol were observed to be 2 μg/ml, inhibiting the growth of the Mtb bacilli by 51% and 53%, respectively. Conclusions: From the above experimental findings, sesamin and β-sitosterol may be proposed as safe and potential inhibitors of CYP125 resulting in diminished growth of Mtb bacilli.
Article
Full-text available
Background Lead (Pb) is one of the most hazardous pollutants that induce a wide spectrum of neurological changes such as learning and memory deficits. Sesamin, a phytonutrient of the lignan class, exhibits anti-inflammatory, anti-apoptotic, and neuroprotective properties. The present study was designed to investigate the effects of sesamin against Pb-induced learning and memory deficits, disruption of hippocampal theta and gamma rhythms, inflammatory response, inhibition of blood δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, Pb accumulation, and neuronal loss in rats. Methods Sesamin treatment (30 mg/kg/day; P.O.) was started simultaneously with Pb acetate exposure (500 ppm in standard drinking water) in rats, and they continued for eight consecutive weeks. Results The results showed that chronic exposure to Pb disrupted the learning and memory functions in both passive-avoidance and water-maze tests, which was accompanied by increase in spectral theta power and theta/gamma ratio, and a decrease in spectral gamma power in the hippocampus. Additionally, Pb exposure resulted in an enhanced tumor necrosis factor-alpha (TNF-α) content, decreased interleukin-10 (IL-10) production, inhibited blood δ-ALA-D activity, increased Pb accumulation, and neuronal loss of rats. In contrast, sesamin treatment improved all the above-mentioned Pb-induced pathological changes. Conclusion These data suggest that sesamin could improve Pb-induced learning and memory deficits, possibly through amelioration of hippocampal theta and gamma rhythms, modulation of inflammatory status, restoration of the blood δ-ALA-D activity, reduction of Pb accumulation in the blood and the brain tissues, and prevention of neuronal loss.
Article
Supercritical CO2 extraction was selected to extract oil from pressed sesame seed cake. The effect of extraction parameters on the quantity and quality of extracted oil, namely temperature (40–60°C), pressure (175–225 bar) and time (1–5 hr), was studied. By using response surface methodology with Box‐Behnken design, the optimal extraction condition was achieved at 50°C, 220 bar and 5 hr and provided 29.80%db of the oil yield. The extracted oil contained sesamin (225.79 mg/100 g cake), sesamolin (75.57 mg/100 g cake), tocopherols (7.03 mg/100 g cake) and Folin–Ciocalteu reducing capacity (29.11 mg GAE/100 g cake). Main fatty acids observed in the extracted oil were linoleic acid (36.18–45.38%) and oleic acid (31.84–39.40%). The experimental results indicated that supercritical CO2 extraction could be a viable technique to extract the residual oil from pressed sesame seed cake.
Article
Full-text available
Many enzymes and secondary compounds of higher plants have been demonstrated in in vitro experiments to protect against oxidative damage by inhibiting or quenching free radicals and reactive oxygen species. The roles of many other compounds as potential antioxidants can be inferred by their similarity to synthetic antioxidants of related structure. The evidence supports at least a partial antioxidant role in vivo for many classes of plant metabolite.
Article
Full-text available
In this study, we confirmed that sesamin, an active lignan isolated from sesame seed and oil, is a novel skin-tanning compound. The melanin content and tyrosinase activity were increased by sesamin in a dose-dependent manner in B16 melanoma cells. The mRNA and protein levels of tyrosinase were also enhanced after the treatment with sesamin. Western blot analysis revealed that sesamin induced and sustained up-regulation of microphthalmia-associated transcription factor (MITF). Sesamin could activate cAMP response element (CRE) binding protein (CREB), but it had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK) or Akt. Moreover, sesamin activated protein kinase A (PKA) via a cAMP-dependent pathway. Consistent with these results, sesamin-mediated increase of melanin synthesis was reduced significantly by H-89, a PKA inhibitor, but not by SB203580, a p38 MAPK inhibitor or by LY294002, a phosphatidylinositol-3-kinase (PI3K) inhibitor. Sesamin-mediated phosphorylation of CREB and induction of MITF and tyrosinase expression were also inhibited by H-89. These findings indicated that sesamin could stimulate melanogenesis in B16 cells via the up-regulation of MITF and tyrosinase, which was, in turn, due to the activation of cAMP signaling.
Article
Full-text available
Sulforhodamine B (SRB) protein staining has been widely used for cell proliferation and chemosensitivity testing, substituting for tetrazolium-based assays. However, the cell fixation step in the original assay is subject to error. We tested whether aspiration of medium with an automatic microplate multiwash device prior to fixation improves the method for adherent cells. A panel of adherent cell lines was used. Signal-to-noise ratios were significantly increased in the new assay. Coefficients of variation (CV) between replicate wells were significantly lower especially at lower cell densities. The linearity of the method improved, with absolute linearity over the whole range of cell densities. The aspiration procedure dislodged only negligible numbers of cells. Cytotoxicity testing using the cytotoxic agent paclitaxel showed no IC50 (50% inhibitory concentration) differences between the new and original methods but a better CV was associated with the optimized protocol. We conclude that aspiration of the growth medium prior to fixing comprises a safe and reliable practice which improves CV, linearity and the signal-to-noise ratio of the SRB assay.
Article
Full-text available
The first mouse microphthalmia transcription factor (Mitf ) mutation was discovered over 60 years ago, and since then over 24 spontaneous and induced mutations have been identified at the locus. Mitf encodes a member of the Myc supergene family of basic helix-loop-helix zipper (bHLH-Zip) transcription factors. Like Myc, Mitf regulates gene expression by binding to DNA as a homodimer or as a heterodimer with another related family member, in the case of Mitf the Tfe3, Tfeb, and Tfec proteins. The study of Mitf has provided many insights into the biology of melanocytes and helped to explain how melanocyte-specific gene expression and signaling is regulated. The human homologue of MITF is mutated in patients with the pigmentary and deafness disorder Waardenburg Syndrome Type 2A (WS2A). The mouse Mitf mutations therefore serve as a model for the study of this human disease. Mutations and/or aberrant expression of several MITF family member genes have also been reported in human cancer, including melanoma (MITF), papillary renal cell carcinoma (TFE3, TFEB), and alveolar soft part sarcoma (TFE3). Genes in the MITF/TFE pathway may therefore also represent valuable therapeutic targets for the treatment of human cancer. Here we review recent developments in the analysis of Mitf function in vivo and in vitro and show how traditional genetics, modern forward genetics and in vitro biochemical analyses have combined to produce an intriguing story on the role and actions of a gene family in a living organism.
Article
As a search for natural antioxidants from plant materials, strong antioxidative activity was observed in leaf waxes extracted from Eucalyptus species. A novel type of antioxidant was isolated from the leaf wax of Eucalyptus globulus and identified as n-tritriacontan-16, 18-dione. Antioxidative activities were determined by different methods; a thiocyanate method, a thiobarbituric acid method, a total carbonyl value method and a weighing test. The antioxidant showed remarkable antioxidative activity in a water/alcohol system and was more effective than α-tocopherol and BHA; however, it has no antioxidative activity in an oil system.
Article
The presence of 5α-reductase (5α-R) in skin may indicate that the androgen regulation of sebaceous glands and sebum production requires the local conversion of testosterone to dihydrotestosterone. The goals of this study were to identify which isozyme of 5α-R (type 1 or type 2) is expressed in sebaceous glands from facial areas, scalp, and non-acne-prone areas; to determine if 5α-R activity is concentrated in sebaceous glands; to assess whether there are regional differences in this enzyme's activity; and to test the effects of azasteroid inhibitors and 13-cis retinoic acid on 5α-R in these tissues. Sebaceous glands were microdissected from facial skin, scalp, and non-acne-prone skin (arm, breast, abdomen, leg), and the activity of 5α-R was determined. A total of 49 samples from 23 male and 21 female subjects without acne (age range, 16 to 81 years, 56 ± 20 years [mean ± SD]) was analyzed. The biochemical properties of the enzyme in each of the samples tested are consistent with those of the type 1 5α-R. Minimal to no type 2 5α-R was detected. The level of 5α-R activity was significantly higher in the sebaceous glands compared to whole skin in facial skin (p = 0.047), scalp (p = 0.039), and non-acne-prone skin (p = 0.04). Enzyme activity in sebaceous glands from facial skin and scalp was significantly higher than in a comparable amount of sebaceous gland material obtained from non-acne-prone areas (32 ± 6 [mean ± SEM]), 35 ± 7 (mean ± SEM) versus 6.0 ± 3.0 (mean ± SEM) pmol/min/mg protein, p = 0.014 and 0.007, respectively). Finasteride and 13-cis retinoic acid were poor inhibitors of the enzyme with 50% inhibitory concentration values greater than 500 nM. These data demonstrate that in the skin from older patients without acne the type 1 isozyme of 5α-R predominates, its activity is concentrated in sebaceous glands and is significantly higher in sebaceous glands from the face and scalp compared to non-acne-prone areas, and the action of 13-cis retinoic acid in the control of acne is not at the level of 5α-R. Furthermore, we suggest that specific inhibition of the type 1 5α-R may offer a viable approach to the management of sebum production and, hence, acne.
Article
Iron was released from ferritin by both cysteine and ascorbate at the pH found in muscle foods (5.5-6.9). The rate of iron release from ferritin was influenced by temperature and ferritin and reducing agent concentrations. Storing beef muscle at 4°C for 11 days resulted in a decrease in the concentration of ferritin antibody precipitatable iron, suggesting that iron is released from ferritin in situ. Physiological concentrations of ferritin catalyzed lipid oxidation in vitro, and heating ferritin increased the rate of lipid oxidation. These data suggest that ferritin could be involved in the development of off-flavors in both cooked and uncooked muscle foods.
Article
Osteoarthritis (OA) is a major disability of elderly people. Sesamin is the main compound in Sesamun indicum Linn., and it has an anti-inflammatory effect by specifically inhibiting Δ5-desaturase in polyunsaturated fatty acid biosynthesis. The chondroprotective effects of sesamin were thus studied in a porcine cartilage explant induced with interleukin-1beta (IL-1β) and in a papain-induced osteoarthritis rat model. With the porcine cartilage explant, IL-1β induced release of sulfated-glycosaminoglycan (s-GAG) and hydroxyproline release, and this induction was significantly inhibited by sesamin. This ability to inhibit these processes might be due to its ability to decrease expression of MMP-1, -3 and -13, which can degrade both PGs and type II collagen, both at the mRNA and protein levels. Interestingly, activation of MMP-3 might also be inhibited by sesamin. Moreover, in human articular chondrocytes (HACs), some pathways of IL-1β signal transduction were inhibited by sesamin: p38 and JNK. In the papain-induced OA rat model, sesamin treatment reversed the following pathological changes in OA cartilage: reduced disorganization of chondrocytes in cartilage, increased cartilage thickness, and decreased type II collagen and PGs loss. Sesamin alone might increase formation of type II collagen and PGs in the cartilage tissue of control rats. These results demonstrate that sesamin efficiently suppressed the pathological processes in an OA model. Thus, sesamin could be a potential therapeutic strategy for treatment of OA.
Article
Ethnopharmacological relevance: Eclipta alba is traditionally known to potentiate hair growth promotion. Aim of the study: The study was aimed to investigate the efficacy of methanol extract of Eclipta alba as hair growth promoter. Materials and methods: Pigmented C57/BL6 mice, preselected for their telogen phase of hair growth were used. In these species, the truncal epidermis lacks melanin-producing melanocytes and melanin production is strictly coupled to anagen phase of hair growth. The extract was applied topically to assess telogen to anagen transition. Immunohistochemical investigation was performed to analyze antigen specificity. Animals in anagen phase of hair growth were positive for FGF-7 and Shh and negative for BMP4, whereas the animals in telogen phase were positive only for BMP4 antigen. Results: The methanol extract of whole plant when tested for hair growth promoting potential, exhibited dose dependent activity in C57BL6 mice. The activity was assessed by studying the melanogenesis in resected skin, follicle count in the subcutis, skin thickness and surrogate markers in vehicle control and extract treated animals. Conclusion: These findings suggest that methanol extract of Eclipta alba may have potential as a hair growth promoter.
Article
It is well-known that some trace element imbalances play a significant role in the pathomechanism of many forms of alopecia. Androgenetic alopecia, however, is a specific local sensitivity of hair follicle receptors to androgens. In a clinical and laboratory study, 153 women with androgenetic alopecia (AGA) and 32 control women were examined. In AGA patients telogen hair and vellus hair (miniaturization, D < 30 μm) significantly differed in frontal and parietal hair comparison with occipital area (20±0.9% vs. 12±0.5% and 33±0.9% vs. 12±0.6% respectively). In the AGA group levels of androstenedione and dihydrotestosterone were higher than in the control group. Hair elemental content, analyzed by ICP-MS, demonstrated a lowered Cu and Zn content in the frontal area in comparison to the occipital area. It is important to note, that the AGA patients with elevated levels of androstenedione and dihydrotestosterone presented an increased Cu content and decreased Mn, Se, Zn contents in the occipital area of scalp. The occipital level of Cu positively correlated with the concentration of free testosterone in the serum. A negative correlation between the Zn content in the occipital area and the dehydroepiandrosterone level in the blood was found. Unfortunately, a routine treatment course of AGA patients, including topical inhibitor of 5-alpha-reductase and minoxidil, had no effect on the Cu hair content in occipital and frontal areas. However, there were positive changes in the morphological structure and other trace element contents. These data led us to hypothesize a key role of Cu metabolism disturbances in the AGA onset, development of AGA, and potential pharmaceutical targets for the treatment of AGA.
Article
This study was undertaken to examine the efficacy of essential oil from seeds of Zizyphus jujuba for its potential role on hair growth by in vivo method. Essential oil was applied at different concentrations (0.1%, 1% and 10%) over the shaved skin onto the backs of BALB/c mice and monitored for 21 days. After 21 days, mice treated with 1% and 10% of oil produced a greater effect on the length of hair which were measured to be 9.96 and 10.02 mm, respectively, as compared to the control (8.94 mm). We measured the weight of hair/cm(2) area of dorsal skin and also evaluated hair thickness and hair follicles microscopically after plucking the hair immediately from the shaved area of mice and found the best results for 1% of essential oil-treated mice. From this study, it is concluded that Z. jujuba essential oil possesses hair growth promoting activity.
Article
Sesamin, a major lignan in sesame seeds, exhibits various health benefits. Here, we investigated effects of sesamin, its stereoisomer episesamin, and their metabolites on neuronal differentiation in rat pheochromocytoma PC12 cells. Among all compounds tested, primary metabolites of sesamin and episesamin, SC-1 and EC-1 {S- and R-epimer of 2-(3,4-methylenedioxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo [3.3.0]octane}, were the most potent to induce neuronal differentiation. SC-1 alone induced neuronal differentiation through extracellular signal-regulated kinase (ERK) 1/2 activation that is essential for nerve growth factor (NGF)-induced neuronal differentiation, as shown by the suppression with MEK1/2 inhibitors, PD98059 and U0126. However, SC-1 did not increase phosphorylation of TrkA, a high-affinity NGF receptor, and a TrkA inhibitor, K252a, did not affect SC-1-induced neuronal differentiation. Furthermore, SC-1 potentiated neuronal differentiation in cells co-treated with NGF, which was associated with enhanced ERK1/2 activation and increased expression of neuronal differentiation markers. Interestingly, when treated with SC-1 and a high dose of NGF, formation of synaptic connections and synaptophysin accumulation at the neurite terminals were markedly enhanced. These results indicate that (1) SC-1 alone induces neuronal differentiation, (2) SC-1 potentiates neuronal differentiation in NGF-treated cells, (3) SC-1 enhances formation of synaptic connections in cells treated with a high dose of NGF, all of which are associated with ERK1/2 activation. It is therefore concluded that SC-1 may promote neuronal differentiation by tapping into the ERK1/2-MAPK (mitogen-activated protein kinase) signaling pathway downstream from the TrkA receptor in PC12 cells.
Article
Cis-unsaturated fatty acids (c-UFAs) such as gamma-linolenic acid (GLA), arachidonic acid (AA) and eicosapentaenoic acid (EPA) can kill tumor cells selectively in vitro. As c-UFAs have the ability to augment free radical generation, the effect of antioxidants, free radical quenchers and augmentors of free radical generation such as iron and copper salts on fatty acid-induced tumor cell death was studied. In addition, the role of lipid peroxidation in the tumoricidal action of c-UFAs was also examined. Results indicate that vitamin E, uric acid, glutathione peroxidase, superoxide dismutase and ATP can block, whereas iron, copper and catalase enhance the tumoricidal action of GLA. The ability of GLA, AA and EPA to kill tumor cells correlated with the amount of lipid peroxidation these fatty acids can induce as measured by thiobarbituric acid test. It was also observed that 14C-labelled linoleic acid uptake was almost the same whereas that of 14C-labelled arachidonic acid and eicosapentaenoic acid were substantially less in tumor cells compared to normal cells. Tumor cells incorporated major portions of the fatty acids in the ether lipid and phospholipid fractions, whereas normal cells incorporated the fatty acids primarily in the phospholipid fraction. These results suggest that c-UFA-induced tumoricidal action is a free radical dependent process and that there are significant differences between normal and tumor cells in fatty acid uptake and distribution.
Article
The free radical theory proposes that photoaging, which is both qualitatively and quantitatively different from chronological aging, may result from imperfect protection against cumulative stress of free radicals produced by chronic and repeated ultraviolet irradiation. Since the skin is always in contact with oxygen and is occasionally exposed to ultraviolet light, skin is one of the best target organs of environmental photo-oxidative stress. A growing body of evidence suggests that reactive oxygen species are generated by ultraviolet irradiation resulting in the structural and functional alteration of cutaneous components which should affect the photoaging process over a long period. The age-related alteration of cutaneous antioxidant defense capacity against cumulative effects of continual photo-oxidative stress to the skin may also affect the photoaging. Thus the possible use of antioxidants that attenuate photo-oxidative toxicity is believed to be an important strategy modulating photoaging. Several antioxidants have readily been proved to work in the experimental conditions. This paper reviews photoaging from a photo-oxidative standpoint and discusses the possible regulation of photoaging by antioxidants that is an important issue in the photodermatological field.
Article
The purpose of this study was 2-fold: (1) to identify the 5 alpha-reductase (5 alpha-R) isozyme(s) present in DU 145 cells, a human cell-line of low androgen sensitivity derived from a cerebral metastasis of an epithelial prostate cancer; and (2) to compare the inhibitory potencies of three compounds on the 'basic' 5 alpha-R isozyme expressed in a baculovirus-directed insect cell system. Conversion of testosterone (T) into 5 alpha-dihydrotestosterone (DHT) in DU 145 cells was measured by HPLC coupled to a Flo-one HP radioactivity detector. DU 145 cells exhibited 5 alpha-R activity (21 pmol DHT/min/mg protein) at pH 7.4 which disappeared at pH 5.5 suggesting that, of the two genomically distinct human isozymes identified so far, type 1 5 alpha-R is expressed in DU 145 cells. This was confirmed by at least two observations: first, 5 alpha-R activity in DU 145 cells was inhibited with much higher potency by 4-MA than by finasteride which is known to be a very poor competitor of the 'basic' enzyme (IC50s = 2.8 +/- 0.2 and 264 +/- 55 nM, respectively). Second, only the type 1 5 alpha-R cDNA and not type 2 5 alpha-R cDNA hybridized with DU 145 RNA. A high potency differential was also recorded for the inhibition of 'basic' type 1 5 alpha-R expressed in a baculovirus-directed-insect cell system by these two compounds, 4-MA being considerably more active than finasteride (Ki = 8.4 +/- 2.3 and 330 +/- 9 nM, respectively). This inhibition was competitive. On the other hand, inhibition by an n-hexane lipid/sterol extract of Serenoa repens (LSESr) was non-competitive and, when expressed in terms of recommended therapeutic doses, was 3-fold greater for LSESr than for finasteride. These studies suggest that LSESr might exert a regulatory inhibitory activity due to its specific lipid/sterol composition.
Article
In this study, 12 women and 12 men, ages 18-33 y, with androgenetic alopecia were selected for biopsies from frontal and occipital scalp sites. The androgen receptor, type I and II 5alpha-reductase, cytochrome P-450-aromatase enzyme were measured and analyzed in hair follicles from these scalp biopsies. Findings revealed that both women and men have higher levels of receptors and 5alpha-reductase type I and II in frontal hair follices than in occipital follicles, whereas higher levels of aromatase were found in their occipital follicles. There are marked quantitative differences in levels of androgen receptors and the three enzymes, which we find to be primarily in the outer root sheath of the hair follicles in the two genders. Androgen receptor content in female frontal hair follicles was approximately 40% lower than in male frontal hair follicle. Cytochrome P-450-aromatase content in women's frontal hair follicles was six times greater than in frontal hair follicles in men. Frontal hair follicles in women had 3 and 3.5 times less 5alpha-reductase type I and II, respectively, than frontal hair follicles in men. These differences in levels of androgen receptor and steroid-converting enzymes may account for the different clinical presentations of androgenetic alopecia in women and men.
Article
Compelling evidence has been gathered indicating that pro-opiomelanocortin peptides, alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH), through the cyclic AMP pathway, play a pivotal role in melanocyte differentiation and in the regulation of melanogenesis. Recently, the molecular events linking cAMP to melanogenesis up-regulation have been elucidated. This cascade involves the activation of protein kinase A and CREB transcription factor, leading to the up-regulation of the expression of Microphthalmia associated transcription factor (MITF). MITF has been found mutated in patients with Waardenburg syndrome 2A, and plays a crucial role in melanocyte development. MITF binds and activates melanogenic gene promoters, thereby increasing their expression which results in an increased melanin synthesis. Beyond this simplified scheme, It appears that melanogenic gene expression is controlled by a complex network of regulation involving other transcription factors such as Brn2, TBX2, PAX3 and SOX10. Further studies are required to better understand the respective roles of these factors in the regulation of melanin synthesis. In addition, other intracellular signaling pathways, like the phosphatidyl inositol 3-kinase pathway, as well as the molecular cascade of events governed by the small GTP-binding protein Rho, seem to be involved in the regulation of melanogenesis and melanocyte dendricity. Finally, it should be mentioned that cAMP activates a melanocyte-specific pathway leading to MAP kinase activation. MAP kinase, ERK2, phosphorylates MITF, thereby targeting the transcription factor to proteasomes for degradation. Thus, in addition to the complex transcriptional regulation, melanogenesis is also subjected to a post-translational regulation that controls MITF or tyrosinase function. Taken together, these complex molecular processes would finally allow a fine tuning of melanocyte differentiation leading to melanin synthesis.
Article
The visual appearance of humans derives predominantly from their skin and hair color. The phylogenetical pathway underling this phenomenon is called melanogenesis and results in the production of melanin pigments in neural crest-derived melanocytes, followed by its transfer to epithelial cells. While melanin from epidermal melanocytes clearly protects human skin by screening harmful ultraviolet radiation, the biologic value of hair pigmentation is less clear. In addition to important roles in social/sexual communication, one potential benefit of pigmented scalp hair in humans may be the rapid excretion of heavy metals, chemicals, toxins from the body by their selective binding to melanin.
Article
The antioxidative properties of the leaves extracts of Murraya koenigii using different solvents were evaluated based on the oil stability index (OSI) together with their radical scavenging ability against 1-1-diphenyl-2-picrylhydrazyl (DPPH). The methylene chloride (CH(2)Cl(2)) extract and the ethyl acetate (EtOAc) soluble fraction of the 70% acetone extract significantly prolonged the OSI values comparable to those of alpha-tocopherol and BHT. Five carbazole alkaloids were isolated from the CH(2)Cl(2) extract and their structures were identified to be euchrestine B (1), bismurrayafoline E (2), mahanine (3), mahanimbicine (4), and mahanimbine (5) based on (1)H and (13)C NMR and mass (MS) spectral data. The OSI value of carbazoles at 110 degrees C decreased in the order 1 and 3 > alpha-tocopherol > BHT > 2 > 4, 5 and control. It is assumed that compounds 1 and 3 contributed to the high OSI value of the CH(2)Cl(2) extract of M. koenigii. The DPPH radical scavenging activity for these carbazoles was in the order ascorbic acid > 2 > 1, 3 and alpha-tocopherol > BHT > 4 and 5.
Article
Sesamin, a major lignan in sesame oil, is known to have many biological activities, especially protective effects against oxidative damage in the liver. As sesamin itself has no antioxidative properties in vitro, to elucidate the mechanism of its antioxidative effects, the reaction products of sesamin in rat liver homogenate were analyzed. The methylenedioxyphenyl moiety in the structure of sesamin was shown to be changed into a dihydrophenyl (catechol) moiety. The enzymatic reaction products in vitro were identified as (1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo[3,3,0]octane and (1R,2S,5R,6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane, which showed strong radical scavenging activities; the latter was a novel compound. The same metabolites were found as glucuronic acid and/or sulfic acid conjugates in substantial amounts in rat bile after oral administration of sesamin. It is suggested that sesamin is a prodrug and the metabolites containing the catechol moieties in their structures are responsible for the protective effects of sesamin against oxidative damage in the liver.
Article
Reactive oxygen species (ROS) are important mediators of a variety of pathological processes, including inflammation and ischemic injury. The neuroprotective effects of sesame antioxidants, sesamin and sesamolin, against hypoxia or H2O2-induced cell injury were evaluated by cell viability or lactate dehydrogenase (LDH) activity. Sesamin and sesamolin reduced LDH release of PC12 cells under hypoxia or H2O2-stress in a dose-dependent manner. Dichlorofluorescein (DCF)-sensitive ROS production was induced in PC12 cells by hypoxia or H2O2-stress but was diminished in the presence of sesamin and sesamolin. We evaluated further the role of mitogen-activated protein kinases (MAPKs) and caspase-3 in hypoxia-induced PC12 cell death. Extracellular signal-regulated protein kinase (ERK) 1, c-jun N-terminal kinase (JNK), and p38 MAPKs of signaling pathways were activated during hypoxia. We found that the inhibition of MAPKs and caspase-3 by sesamin and sesamolin correlated well with the reduction in LDH release under hypoxia. Furthermore, the hypoxia-induced apoptotic-like cell death in cultured cortical cells as detected by a fluorescent DNA binding dye was reduced significantly by sesamin and sesamolin. Taken together, these results suggest that the protective effect of sesamin and sesamolin on hypoxic neuronal and PC12 cells might be related to suppression of ROS generation and MAPK activation.
Article
A novel, accurate, rapid and modestly labor-intensive method has been developed to quantitate specific mRNA species by reverse transcription-polymerase chain reaction (RT-PCR). This strategy combines the high degree of specificity of competitive PCR with the sensitivity of laser-induced fluorescence capillary electrophoresis (LIF-CE). The specific target mRNA and a mimic DNA fragment, used as an internal standard (IS), were co-amplified in a single reaction in which the same primers are used. The amount of mRNA was then quantitated by extrapolation from the standard curve generated with the internal standard. PCR primers were designed to amplify both a 185 bp fragment of the target cDNA for steroid 5alpha-reductase 1 (5alpha-R1) and a 192 bp fragment of the target cDNA for steroid 5alpha-reductase type 2 (5alpha-R2). The 5' forward primers were end-labeled with 6-carboxy-fluorescein (6-FAM). Two synthetic internal standard DNAs of 300 bp were synthesized from the sequence of plasmid pEGFP-C1. The ratio of fluorescence intensity between amplified products of the target cDNA (185 or 192 bp fragments) and the competitive DNA (300 bp fragment) was determined quantitatively after separation by capillary electrophoresis and fluorescence analysis. The accurate quantitation of low-abundance mRNAs by the present method allows low-level gene expression to be characterized.
Article
Although hair greying is a very common phenomenon characterized by loss of pigment in the hair shaft, the events that cause and control natural hair whitening with age in humans are still unclear. To decipher the origin of natural hair whitening. Human hair melanocytes were immunohistochemically characterized at different stages of whitening. Loss of hair shaft melanin was found to be associated with a decrease in both bulb melanin content and bulb melanocyte population. Although few melanocytes were present in the bulbs of grey hair, they still expressed tyrosinase and tyrosinase-related protein-1, synthesized and transferred melanins to cortical keratinocytes as seen by the presence of melanin granules. In white hair bulbs, no melanocytes could be detected either with pMel-17 or vimentin labelling. Pigmented hair follicles are known to contain inactive melanocytes in the outer root sheath (ORS), and grey and white hairs were also found to contain some of these quiescent melanocytes. However, their population was decreased compared with pigmented hair follicles, ranging from small to nil. This depletion of melanocytes in the different areas of white hairs was detected throughout the hair cycle, namely at telogen and early anagen stages. In contrast, the infundibulum and sebaceous gland of both pigmented and white hairs showed a similar distribution of melanocytes. Furthermore, other distinct cell populations located in the ORS, namely putative stem cells, Merkel cells and Langerhans cells were equivalently identified in pigmented and white hairs. Thus, hair greying appears to be a consequence of an overall and specific depletion of bulb and ORS melanocytes of human hair.
Article
Sesamin and sesamolin were tested for their ability to protect BV-2 microglia from hypoxia-induced cell death. These antioxidants dose-dependently reduced hypoxia-induced lactate dehydrogenase (LDH) release and dichlorofluorescein (DCF)-sensitive reactive oxygen species (ROS) production. Their effects on signaling pathway mitogen-activated protein kinases (MAPKs) and caspase-3 in hypoxia-induced cell death were further examined. Extracellular signal-regulated protein kinases (ERK1/2), c-jun NH(2)-terminal kinase (JNK), and p38 MAPKs were activated during hypoxia. The sesamin or sesamolin reduced caspase-3 and MAPK activation correlated well with diminished LDH release in BV-2 cells under hypoxia. Furthermore, they preserved superoxide dismutase (SOD) and catalase activities in BV-2 cells under hypoxia. Taken together, these results indicate that the mechanism of sesame antioxidants involves inhibition of MAPK pathways and apoptosis through scavenging of ROS in hypoxia-stressed BV-2 cells.
Article
Sesamin was orally administered to rats, and blood, bile and urine were collected periodically. Over 40% of the dose of sesamin was detected in bile as glucuronides of 2-(3, 4-methylenedioxyphenyl)-6-(3, 4-dihydroxyphenyl)-cis-dioxabicyclo[3.3.0] octane and 2-(3, 4-dihydroxyphenyl)-6-(3, 4-dihydroxyphenyl)-cis-dioxabicyclo[3.3.0] octane by 24∼hr after administration. Antioxidant activities of these metabolites were compared and catechol metabolites showed strong radical scavenging activities against not only superoxide anion radical but also hydroxyl radical. It was suggested that sesamin was absorbed by the route of portal vein and metabolized to mono- or di-catechol metabolite by drug metabolizing enzymes in the liver cells. Both metabolites exhibited antioxidant activity in the liver and were finally conjugated with glucuronic acid and to excrete in bile. Sesamin can be classified as a pro-antioxidant. The profiles of gene expression of the liver in rats given sesamin or vehicle were compared. The gene expression levels of the late stage enzymes of β-oxidation including trifunctional enzyme, acyl-CoA oxidase, bifunctional enzyme and 3-ketoacyl-CoA thiolase were significantly increased by sesamin. On the other hand, the transcription of the genes encoding the enzymes for fatty acid synthesis was decreased. Moreover, in sesamin rats, the gene expression of aldehyde dehydrogenase was increased about 3-fold, whereas alcohol dehydrogenase, liver catalase and CYP2E1 were not changed. These results suggested that sesamin ingestion regulated the transcription levels of hepatic metabolizing enzymes for lipids and alcohol.
Article
New chemical entities, steroidal C-17 benzoazoles (5, 6, 9 and 10) and pyrazines (14 and 15) were rationally designed and synthesized. The key reaction for synthesis of the benzoazoles involved the nucleophilic vinylic "addition-elimination" substitution reaction of 3beta-acetoxy-17-chloro-16-formylandrosta-5,16-diene (2) and benzoazole nucleophiles, while that for synthesis of pyrazines involved palladium-catalyzed cross-coupling reaction of 17-iodoandrosta-5,16-dien-3beta-ol (13) with tributylstannyl diazines. Some of the compounds were shown to be potent inhibitors of human CYP17 enzyme as well as potent antagonist of both wild type and mutant androgen receptors (AR). The most potent CYP17 inhibitors were 3beta-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene (5, code named VN/124-1), 3beta-hydroxy-17-(5(1)-pyrimidyl)androsta-5,16-diene (15) and 17-(1H-benzimidazole-1-yl)androsta-4,16-dien-3-one (6), with IC(50) values of 300, 500 and 915 nM, respectively. Compounds 5, 6, 14 and 15 were effective at preventing binding of (3)H-R1881 (methyltrienolone, a stable synthetic androgen) to both the mutant LNCaP AR and the wild-type AR, but with a 2.2- to 5-fold higher binding efficiency to the latter. Compounds 5 and 6 were also shown to be potent pure AR antagonists. The cell growth studies showed that 5 and 6 inhibit the growth of DHT-stimulated LNCaP and LAPC4 prostate cancer cells with IC(50) values in the low micromolar range (i.e., <10 microM). Their inhibitory potencies were comparable to that of casodex but remarkably superior to that of flutamide. The pharmacokinetics of compounds 5 and 6 in mice were investigated. Following s.c. administration of 50 mg/kg of 5 and 6, peak plasma levels of 16.82 and 5.15 ng/mL, respectively, occurred after 30 to 60 min, both compounds were cleared rapidly from plasma (terminal half-lives of 44.17 and 39.93 min, respectively), and neither was detectable at 8 h. Remarkably, compound 5 was rapidly converted into a metabolite tentatively identified as 17-(1H-benzimidazol-1-yl)androsta-3-one. When tested in vivo, 5 proved to be very effective at inhibiting the growth of androgen-dependent LAPC4 human prostate tumor xenograft, while 6 was ineffective. Compound 5 (50 mg/kg/twice daily) resulted in a 93.8% reduction (P = 0.00065) in the mean final tumor volume compared with controls, and it was also significantly more effective than castration. To our knowledge, this is the first example of an antihormonal agent (an inhibitor of androgen synthesis (CYP17 inhibitor)/antiandrogen) that is significantly more effective than castration in suppression of androgen-dependent prostate tumor growth. In view of these impressive anticancer properties, compound 5 is a strong candidate for development for the treatment of human prostate cancer.
Article
Melanogenesis is a principal parameter of differentiation in melanocytes and melanoma cells. Our recent study has demonstrated that phospholipase D1 (PLD1) regulates the melanogenic signaling through modulating the expression of tyrosinase, the rate-limiting step enzyme in the melanin biosynthesis. The current study was designed to gain more insight into the involvement of PLD1 in the regulation of melanogenesis. To investigate the role of PLD1, we examined the effect of knockdown of endogenous PLD1 by small interference RNA (siRNA) on melanogenesis in B16 melanoma cells. It was shown that the melanin synthesis was induced in PLD1-knockdowned cells, and also that the level of melanin synthesis was well correlated with increases in expression level of tyrosinase and its related proteins (Tyrp1 and Dct). Furthermore, the reduction of expression levels of PLD1 by siRNA transfection was accompanied by diminution of ribosomal S6 kinase 1 (S6K1) phosphorylation. The activity of mammalian target of rapamycin (mTOR) is essential for phosphorylation of S6K1 and the treatment malanoma cells with rapamycin, a potent inhibitor of mTOR effectively induced melanogenesis. The results obtained here provide possible evidence that PLD1 exerts a negative regulatory role in the melanogenic process through mTOR/S6K1 signaling.
Article
Prostate cancer eventually recurs during androgen deprivation therapy despite castrate levels of serum androgens. Expression of androgen receptor and androgen receptor-regulated proteins suggests androgen receptor activation in recurrent prostate cancer. Many groups have pursued mechanisms of ligand-independent androgen receptor activation but we found high levels of testicular androgens in recurrent prostate cancer tissue using RIA. Prostate specimens from 36 men were procured preserving blood flow to prevent ischemia and cyropreserved immediately. Recurrent prostate cancer specimens from 18 men whose cancer recurred locally during androgen deprivation therapy and androgen-stimulated benign prostate specimens from 18 men receiving no hormonal treatments were studied. Tissue levels of testosterone and dihydrotestosterone were measured in each specimen using liquid chromatography/electrospray tandem mass spectrometry. Testosterone and dihydrotestosterone levels were compared with clinical variables and treatment received. Testosterone levels were similar in recurrent prostate cancer (3.75 pmol/g tissue) and androgen-stimulated benign prostate (2.75 pmol/g tissue, Wilcoxon two-sided, P=0.30). Dihydrotestosterone levels decreased 91% in recurrent prostate cancer (1.25 pmol/g tissue) compared with androgen-stimulated benign prostate (13.7 pmol/g tissue; Wilcoxon two-sided, P < 0.0001) although dihydrotestosterone levels in most specimens of recurrent prostate cancer were sufficient for androgen receptor activation. Testosterone or dihydrotestosterone levels were not related to metastatic status, antiandrogen treatment, or survival (Wilcoxon rank sum, all P > 0.2). Recurrent prostate cancer may develop the capacity to biosynthesize testicular androgens from adrenal androgens or cholesterol. This surprising finding suggests intracrine production of dihydrotestosterone and should be exploited for novel treatment of recurrent prostate cancer.
Article
The results of recent food chemical and nutraceutical studies on the traditionally well-known health value of sesame are described, including some aspects of the utilization of sesame. The highly antioxidative activity of sesame oil was clarified and found to involve newly discovered lignans. The antiaging effect of sesame was elucidated to be due to the strong vitamin E activity caused by a novel synergistic effect of sesame lignans with tocopherols resulting from the inhibition of metabolic decomposition of tocopherols by sesame lignans. The specific inhibitory action of sesame lignans on Delta5 desaturase in polyunsaturated fatty acid synthesis was found in studies on the microbial production of polyunsaturated fatty acids. This effect of sesame lignans was extended to various effects on fatty acid metabolism involving lowering fatty acid concentration in liver and serum due to acceleration of fatty acid oxidation and suppression of fatty acid synthesis, and the controlling influence on the ratio of n-6/n-3 polyunsaturated fatty acids under excess intake of either n-6 or n-3 fatty acids in the diet. Sesame lignans lowered the cholesterol concentration in serum, especially in combination with tocopherol, due to the inhibition of absorption from the intestine and suppression of synthesis in the liver. Sesame lignans also showed other useful functions such as acceleration of alcohol decomposition in the liver, antihypertensive activity, immunoregulatory activities, anticarcinogenic activity, and others.