ABSTRACT
Hyperpigmentation that manifests through melasma and solar lentigo (age spots), although mostly harmless for health, bothers many people. Controlling the rate-limiting activity of tyrosinase is most effective for suppressing excessive melanin formation and accordingly recent research has focused on the maturation of tyrosinase. Salacia, a medicinal plant, has been used to treat diabetes in India and Sri Lanka. Salacia extract reportedly contains components that inhibit the activity of α-glucosidase. Salacinol, the active ingredient in Salacia extract, has unique thiosugar sulphonium sulphate inner salt structure. Here, we observed that the salacinol component of Salacia extract possesses anti-melanogenic activity in comparison to various existing whitening agents. Although the anti-melanogenic mechanism of salacinol is presumably medicated by inhibition of tyrosinase activity, which is often found in existing whitening agents, salacinol did not inhibit tyrosinase activity in vitro. Analysis of the intracellular state of tyrosinase showed a decrease in the mature tyrosinase form due to inhibition of N-linked oligosaccharide processing. Salacinol inhibited the processing glucosidase I/II, which are involved in the initial stage of N-linked glycosylation. Owing to high activity, low cytotoxicity and high hydrophilicity, salacinol is a promising candidate compound in whitening agents aimed for external application on skin.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Melanoma/drug therapy , Monophenol Monooxygenase/antagonists & inhibitors , Oligosaccharides/antagonists & inhibitors , Skin Neoplasms/drug therapy , Sugar Alcohols/pharmacology , Sulfates/pharmacology , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Dose-Response Relationship, Drug , Glycosylation , Humans , Melanins/antagonists & inhibitors , Melanins/biosynthesis , Melanoma/metabolism , Melanoma/pathology , Mice , Molecular Conformation , Monophenol Monooxygenase/metabolism , Oligosaccharides/metabolism , Salacia/chemistry , Skin Neoplasms/metabolism , Skin Neoplasms/pathology , Structure-Activity Relationship , Sugar Alcohols/chemistry , Sugar Alcohols/isolation & purification , Sulfates/chemistry , Sulfates/isolation & purification , Tumor Cells, CulturedABSTRACT
The cause of hyperpigmentation, such as solar lentigo and seborrheic keratosis, is the excessive accumulation of melanin pigments in the epidermal basal layer. Melanin pigments are synthesized in the melanosomes, which are specific organelles produced by melanocytes in the basal layer. Melanosomes containing melanin pigments are transported to the neighboring keratinocytes. However, the behavior of melanosomes after being transported to the keratinocytes has been poorly understood. In this study, we focused on a lysosomal protease cathepsin V (CTSV) to clarify the mechanism underlying melanosome degradation in the keratinocytes. Using immunohistochemical observation, we found that CTSV was highly expressed across the entire epidermis in normal skin; however, CTSV expression levels were lower in the basal layer than those in the stratum corneum side in the hyperpigmented region. Moreover, we found that melanosome degradation was suppressed in CTSV knockdown cells. These results indicated that CTSV is involved in melanosome degradation.
Subject(s)
Cathepsins/metabolism , Cysteine Endopeptidases/metabolism , Epidermis/pathology , Keratinocytes/metabolism , Lysosomes/metabolism , Melanosomes/metabolism , Cell Line , Epidermis/metabolism , Female , Gene Knockdown Techniques , Humans , Hyperpigmentation/metabolism , Hyperpigmentation/pathology , Keratinocytes/pathology , MaleABSTRACT
The relation between the rheological properties and the swallowing characteristics of vegetable juices fortified with 0-30.0% carrot puree (CP) was evaluated. The apparent viscosity of vegetable juices increased with increasing CP concentrations, and a increases in yield stress were observed at and above 17.5% CP. In a sensory evaluation, texture perceived in the oral cavity varied as between vegetable juices with >17.5% CP and those with <12.5% CP. The maximum velocity in the pharyngeal region was classified into three same-quality subgroups: vegetable juices with 0-12.5% CP, with 10.0-25.0% CP, and with 17.5-30.0% CP. It significantly decreased with increasing CP concentrations.
Subject(s)
Beverages , Daucus carota , Deglutition/physiology , Food Handling , Food, Fortified , Rheology , Female , Food Storage , Humans , Malus , Pharynx/physiology , Sensation , Viscosity , Young AdultABSTRACT
Coronary artery spasm has an important function in the etiology of variant angina and other acute coronary syndromes. Abnormal activation of Rho-family GTPases has been observed in cardiovascular disorders, but the function of genetic variability in Rho-family GTPases remains to be evaluated in cardiovascular disorders. We examined the genetic variability of Rho-family GTPases and their regulators in coronary artery spasm. We performed a comprehensive candidate gene analysis of 67 single nucleotide polymorphisms with amino-acid substitution in Rho-family GTPases and their regulators in 103 unrelated Japanese patients with acetylcholine-induced coronary artery spasm and 102 control Japanese subjects without acetylcholine-induced coronary artery spasm. We noted an association of the single nucleotide polymorphism of ARHGAP9 (rs11544238, Ala370Ser) with coronary artery spasm (odds ratio =2.67). We found that ARHGAP9 inactivated Rac as RacGAP and that the mRNA level of ARHGAP9 was strongly detected in hematopoietic cells. ARHGAP9 negatively regulated cell migration. The Ala370Ser polymorphism counteracted ARHGAP9-reduced cell migration, spreading and adhesion. The Ala370Ser polymorphism in the ARHGAP9 gene is associated with coronary artery spasm. These data suggest that the polymorphism of ARHGAP9 has a critical function in the infiltration of hematopoietic cells into the endothelium and inflammation leading to endothelial dysfunction.
