Daily ingestion of grains of paradise (Aframomum melegueta) extract increases whole-body energy expenditure and decreases visceral fat in humans.

We reported previously that a single ingestion of an alcohol extract of grains of paradise (GP, Aframomum melegueta), a species of the ginger family, increases energy expenditure (EE) through the activation of brown adipose tissue, a site of sympathetically mediated metabolic theromogenesis. The present study aimed to examine a daily ingestion of GP extract on whole-body EE and body fat in humans. Whole-body EE and body fat content were measured before and after daily oral ingestion of GP extract (30 mg/d) for 4 wk in 19 non-obese female volunteers aged 20-22 y in a single-blind, randomized, placebo-controlled, crossover design. Four-week daily ingestion of GP and a placebo decreased and increased slightly the visceral fat area at the umbilicus level, respectively. The GP-induced change was significantly different from that induced by the placebo (p<0.05), and negatively correlated with the initial visceral fat area (r=-0.64, p<0.01). Neither GP nor placebo ingestion affected subcutaneous or total fat. The daily ingestion of GP, but not the placebo, increased whole-body EE (p<0.05). These results suggest that GP extract may be an effective and safe tool for reducing body fat, mainly by preventing visceral fat accumulation.

Grains of paradise (Aframomum melegueta) extract activates brown adipose tissue and increases whole-body energy expenditure in men.

Brown adipose tissue (BAT) is responsible for cold- and diet-induced thermogenesis, and thereby contributes to the control of whole-body energy expenditure (EE) and body fat content. BAT activity can be assessed by fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) in human subjects. Grains of paradise (GP, Aframomum melegueta), a species of the ginger family, contain pungent, aromatic ketones such as 6-paradol, 6-gingerol and 6-shogaol. An alcohol extract of GP seeds and 6-paradol are known to activate BAT thermogenesis in small rodents. The present study aimed to examine the effects of the GP extract on whole-body EE and to analyse its relation to BAT activity in men. A total of nineteen healthy male volunteers aged 20-32 years underwent FDG-PET after 2 h of exposure to cold at 19°C with light clothing. A total of twelve subjects showed marked FDG uptake into the adipose tissue of the supraclavicular and paraspinal regions (BAT positive). The remaining seven showed no detectable uptake (BAT negative). Within 4 weeks after the FDG-PET examination, whole-body EE was measured at 27°C before and after oral ingestion of GP extract (40 mg) in a single-blind, randomised, placebo-controlled, crossover design. The resting EE of the BAT-positive group did not differ from that of the BAT-negative group. After GP extract ingestion, the EE of the BAT-positive group increased within 2 h to a significantly greater (P<0·01) level than that of the BAT-negative group. Placebo ingestion produced no significant change in EE. These results suggest that oral ingestion of GP extract increases whole-body EE through the activation of BAT in human subjects.

Novel effects of diosgenin on skin aging.

Extracts of Dioscorea coomposita or Dioscorea villosa are consumed as supplemental health foods at the time of climacteric. The extracts contain large amounts of the plant steroid, diosgenin. Here, we studied the safety and efficacy of diosgenin against skin aging at the time of climacteric. In vitro, diosgenin enhanced DNA synthesis in a human 3D skin equivalent model, and increased bromodeoxyuridine uptake and intracellular cAMP level in adult human keratinocytes. The increase of bromodeoxyuridine uptake by diosgenin was blocked by an adenylate cyclase inhibitor, but not by antisense oligonucleotides against estrogen receptor alpha, estrogen receptor beta or an orphan G-protein-coupled receptor, GPR30, indicating the involvement of cAMP but not estrogen receptor alpha, estrogen receptor beta or GPR30. In vivo, administration of diosgenin improved the epidermal thickness in the ovariectomized mice, a climacteric model, without altering the degree of fat accumulation. In order to examine the safety of diosgenin, diosgenin and 17beta-estradiol were administered to breast cancer-burdened mice. The results revealed that while 17beta-estradiol accelerated the tumor growth, diosgenin did not show this effect. Our finding, a restoration of keratinocyte proliferation in aged skin, suggests that diosgenin may have potential as a safe health food for climacteric.

Changes in responses of UVB irradiated skin of brownish guinea pigs with aging.

It is known that skin often shows irregular pigmentation during aging, which is frequently associated with hyperpigmentation. Many studies have utilized brownish A1 guinea pigs to investigate the pathogenesis of ultraviolet B (UVB)-induced skin pigmentation, however, responses associated with aging following UVB irradiation have not been elucidated. To characterize those responses, dorsal skin of A1 guinea pigs from 14-weeks to 5-yr old were investigated. The minimal erythema dose was found to increase with aging. Further, in pigmentation induced by UVB radiation, skin brightness (DeltaL*-value) decreased equally in both the 14-week old (young) group and in the 3-yr old (old) group of guinea pigs. The DeltaL*-value recovered in the young group from 21 d after UVB irradiation, whereas no such recovery was seen in the old group. In addition, the amount of melanin and the number of melanocytes returned near pre-irradiation levels in the young group, while they remained high in the old group. Our results therefore demonstrate for the first time that skin responses following UVB irradiation change with aging in A1 guinea pigs.

Human epidermal basal cell responses to ultraviolet-B differ according to their location in the undulating epidermis.

BACKGROUND: Exposure of skin to excessive ultraviolet-B (UVB) radiation causes epidermal hyperproliferation that leads to epidermal hyperplasia, however, it is not yet clear exactly how these responses progress. OBJECTIVES: We attempted to clarify the response patterns involved with epidermal hyperproliferation following UVB radiation. METHODS: UVB was irradiated at 2 minimal erythema doses (MED) to human back skin and epidermal morphologic changes were evaluated using in vivo confocal laser microscopy. Skin biopsy specimens were collected from exposed and from non-exposed regions, and were subjected to histochemical and immunohistochemical analysis. RESULTS: The in vivo confocal laser microscopic analysis showed that UVB-induced epidermal hyperplasia was prominent at the epidermal rete ridges. Further, 3 days after UVB exposure, numerous Ki67-positive epidermal cells were observed in the epidermal rete ridges, but not in the epidermis at the top of the dermal papilla. These results suggest that cells highly responsive to UVB exist in the epidermal rete ridges and that their hyperproliferation leads to elongation of the epidermal rete ridges. In contrast, the number of keratin 10-positive basal cells, known as transitional cells, was increased throughout the epidermis, suggesting that an upward migration of keratinocytes from the epidermal basal layer occurred regardless of their location. However, diffusion of melanin to the suprabasal layers was markedly observed in epidermal regions above the dermal papillae, suggesting the occurrence of strong upper cell movement at this position. CONCLUSION: Based on our results, we conclude that differences in keratinocyte responses to UVB radiation exist in cells located in the undulating epidermal basal layer.

Pigmentation in intrinsically aged skin of A1 guinea pigs.

It is known that skin often shows irregular pigmentation during aging which is frequently associated with hyperpigmentation. Many studies have utilized brownish A1 guinea pigs to investigate the pathogenesis of ultraviolet (UV)-induced skin pigmentation, however, changes associated with intrinsic aging in A1 guinea pig skin have not been documented. To characterize such changes, skin from the dorsal and neck areas of 20-week, 1-, 2-, 3- and 5-yr-old guinea pigs was examined. Skin color was measured using a colorimeter, and biopsy specimens were stained with Masson-Fontana, L-3,4-dihydroxyphenylalanine (DOPA), and antibodies against KIT (ACK-45), gp100 (HMB-45) and S-100 proteins. The L* value of skin color decreased with aging and melanin deposits increased in the epidermis. Further, DOPA+, gp100+ and S-100+ melanocytes increased, indicating that the number of melanocytes had increased with age, whereas KIT+ melanocytes did not increase in dorsal skin and actually decreased in neck skin with aging. Further, rippled pigmented areas appeared in the neck skin of the 3-yr-old animals, and in the dorsal and neck skin of 5-yr-old guinea pigs in the absence of UV irradiation. Melanocytes were distributed uniformly in younger skin, whereas they were clustered in older skin. UV irradiation caused an increase in the number of melanocytes, although they were not clustered. These results are the first to provide evidence that pigmentation is induced in the skin of intrinsically aged A1 guinea pigs in the absence of UV irradiation, a process that differs from that elicited by UV irradiation.

Relationship between NMF (lactate and potassium) content and the physical properties of the stratum corneum in healthy subjects.

Natural moisturizing factor (NMF) of the stratum corneum (SC) has been established to play important roles in the physical properties of the SC. Few studies, however, have investigated the specific influences of NMF components other than the amino acids. In this study, therefore, we focus on the relationship between the ion content and physical properties of the SC in 40 healthy subjects. Changes in the physical properties of the SC induced by the extraction of NMF were equivalent to the changes that took place from summer to winter, demonstrating the important role of NMF in the physical properties of the SC in healthy subjects. The seasonal changes in the physical properties of the SC from summer to winter were accompanied by significant decreases in the levels of lactate, potassium, sodium, and chloride in the SC. Lactate and potassium were the only components found to correlate significantly with the state of hydration, stiffness, and pH in the SC. Interestingly, the levels of lactate and potassium in the SC were also significantly correlated. Moreover, potassium lactate restored the SC hydration state decreased by extraction of NMF. These results suggest that lactate and potassium may play roles in maintaining the physical properties of the SC in healthy subjects.

Down-regulation of melanin synthesis by a biphenyl derivative and its mechanism.

Down-regulation of melanin synthesis is required for recovery of pigmentary disorders and it is known that direct inhibitors of tyrosinase, the key enzyme in melanin synthesis, such as hydroquinone with a phenol structure, suppress melanin synthesis. We screened several phenolic derivatives using B16 melanoma cells and found that a biphenyl derivative, 2,2'-dihydroxy-5,5'-dipropyl-biphenyl (DDB), down-regulated melanin synthesis effectively. Although DDB has a phenol structure, it did not inhibit tyrosinase in vitro, thus we examined its mechanism in detail. Western blotting revealed that the amount of tyrosinase was decreased by DDB, and pulse-chase labeling and immunoprecipitation analysis showed a decrease of mature tyrosinase and acceleration of tyrosinase degradation in its presence. These results suggest that DDB down-regulates melanin synthesis by inhibiting the maturation of tyrosinase, leading to acceleration of tyrosinase degradation.

Histamine is involved in ultraviolet B-induced pigmentation of guinea pig skin.

We previously reported that histamine induced melanogenesis in cultured human melanocytes and that the stimulatory effect was mediated by protein kinase A activation via H2 receptors. It is well-known that ultraviolet B irradiation causes acute inflammation, known as erythema, and subsequent pigmentation, and there are several reports demonstrating an elevation of the histamine levels in ultraviolet B-irradiated skin. Thus, to evaluate the involvement of histamine in ultraviolet B-induced skin pigmentation, we examined the effect of an H2 antagonist in brownish guinea pig skin. Daily exposure to 200 mJ per cm2 ultraviolet B for 3 d evoked erythema and subsequent pigmentation in the skin samples tested. Moreover, a remarkable increase in dopa-positive melanocytes was observed in the pigmented area, which showed an increase in melanin synthesis. Topical application of famotidine, an H2 antagonist, significantly reduced pigmentation and moderated the increase of dopa-positive melanocytes in the ultraviolet B-irradiated skin. Even when the initiation of famotidine application was delayed to day 2 after irradiation, an inhibitory activity on ultraviolet B-induced pigmentation was observed; however, the ultraviolet B-induced erythema was not suppressed by topically applied famotidine. Thus, we concluded that histamine is involved in ultraviolet B-induced pigmentation and that famotidine suppressed the pigmentation by the prevention of histamine binding to H2 receptors in melanocytes but not by prevention of ultraviolet B permeability and inflammation.