Gifu-shi, Japan


Gifu-shi, Japan
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Takahashi T.,ICHIMARU PHARCOS Co. | Matsubara J.,ICHIMARU PHARCOS Co. | Wakamatsu K.,ICHIMARU PHARCOS Co. | Tanaka Y.T.,ICHIMARU PHARCOS Co. | And 5 more authors.
Immunology, Endocrine and Metabolic Agents in Medicinal Chemistry | Year: 2015

Background: Proteoglycan is one of the components of the extracellular matrix with various biological activities and has been used as the functional foods to improve knee joint health or skin condition. Objective: To examine the effect of ingestion of salmon (Oncorhynchus keta, Salmonidae) nasal cartilage-derived proteoglycan (sPG) on skin condition, we performed a randomized, double-blind, controlled study in healthy adult volunteers. Methods: Recruited subjects (n=156) were men and women, ages 21-62 years. From this population, we selected 19 subjects based on the exclusion criteria of the guidelines for evaluation of cosmetic functions of Japanese Cosmetic Science Society. Subjects were randomly divided into an sPG group (n=10; mean age, 39.1 years) and a placebo group (n=9; mean age, 39.6 years). The characteristics of the sPG used in this study were assessed by HPLC and electrophoresis analysis. Results: The safety was confirmed by the monitoring of all volunteer subjects for the development of adverse reactions. We found no negative information on the safety of proteoglycan ingestion and no evidence for an interaction between proteoglycan and other functional foods/medicine in several different databases. Viscoelasticity and recovery after deformation as the skin elasticity increased significantly in the sPG group compared to the placebo group (p<0.05). Skin looseness significantly decreased in the sPG group (p<0.05). Moreover, the number of wrinkles, conspicuous or darkened facial pores, and blotches significantly decreased in the sPG group (p<0.05). Measurements of skin conductance showed that sPG improved skin moisture and micrographs of facial corneocytes showed that sPG improved rough skin. Conclusion: Our results suggest the potential of sPG as a food ingredient to improve human skin condition, including skin elasticity, wrinkles, facial pores, blotches, moisture, and smoothness. © 2015 Bentham Science Publishers.

Tsuchiya Y.,Tohoku Women's College | Kawamata K.,Tohoku University | Tomita M.,Tohoku Women's College | Tsuboi M.,Ichimaru Pharcos Co. | And 2 more authors.
Journal of Nutritional Science and Vitaminology | Year: 2015

Recently, proteoglycan was purified from the nasal cartilage of salmon. Although several physiological effects have been reported, the effect of salmon nasal cartilage proteoglycan (salmon PG) on glucose metabolism remains unclear. We studied the effect of salmon PG on rat plasma glucose levels. Oral administration of 1% salmon PG significantly attenuated the increase in portal plasma glucose levels following an oral glucose tolerance test (OGTT). Additionally 1% salmon PG delayed the increase in peripheral glucose concentration induced by the OGTT. Mucosal administration of 1% salmon PG significantly decreased active glucose transport using the everted jejunal sac method. Furthermore, transmural potential difference (∆PD) measurements using the everted jejunum revealed that 1% salmon PG significantly decreased glucose-dependent and phlorhizin (inhibitor of sodium-glucose co-transporter 1; SGLT1)-sensitive ∆PD. These results suggest that salmon PG decreases glucose absorption via SGLT1 in the jejunum, thereby attenuating the increase in portal and peripheral plasma glucose levels in rats. © 2015, Center for Academic Publications Japan. All rights reserved.

PubMed | Nihon Pharmaceutical University, University of Shizuoka and Ichimaru Pharcos Co.
Type: | Journal: Scientific reports | Year: 2015

The production of melanin is regulated by -melanocyte-stimulating hormone (-MSH), which is produced from proopiomelanocortin (POMC). Keratinocytes release POMC along with lower levels of -MSH and ACTH. To clarify the mechanism of melanogenesis after ultraviolet (UV)-irradiation, this study focused on the expression of POMC and POMC-derived peptides after UV-irradiation. Western blot analysis and immunoassays indicated that both POMC and -MSH-like immunoreactivity (-MSH-LI) increased after UV-irradiation. However, other POMC-derived products were very low. In hypophysectomized mice, -MSH-LI increased to the same level as in control mice after UV-irradiation. Structural analysis revealed that the major -MSH-LI product was ACTH(1-8). Furthermore, ACTH(1-8) competed with [(125)I]--MSH for receptor binding and increased melanin production via a melanocortin-1 receptor. These results suggested that melanin was produced through ACTH(1-8) after UV-irradiation. Trypsin-like enzymatic activity, which is responsible for POMC activation, increased after UV-irradiation and was identified as tryptase. In mast cell-deficient mice, which do not produce tryptase, -MSH-LI levels were unchanged after UV-irradiation. The present study demonstrates the production of ACTH(1-8) from POMC by tryptase, which is a novel peptide-processing mechanism in the extracellular compartment of the skin.

Masutani T.,Gifu University | Masutani T.,Ichimaru Pharcos Co. | Tanaka Y.T.,Ichimaru Pharcos Co. | Kojima H.,Ichimaru Pharcos Co. | And 3 more authors.
Life Sciences | Year: 2016

Aims The molecular mechanism of osteoarthritis (OA) has never been understood clearly, but it has been suggested that imbalance of degradation and synthesis in cartilage contribute to the underlying mechanisms of OA. In this study, we investigated the effectiveness in the cartilage metabolism of the artichoke extract that includes the compound cynaropicrin. Main methods We evaluated the efficacy of the artichoke extract or cynaropicrin in the cartilage metabolism factors and NF-κB signaling activity stimulated by inflammatory cytokine in chondrogenic cell lines, OUMS-27 and SW1353, using qRT-PCR, immunofluorescence and immunoblotting. Key findings We initially found that an artichoke extract and cynaropicrin both inhibited the increase of cartilage degradation factor MMP13 and further decreased the synthesis factor aggrecan induced by TNF-α in OUMS-27. In addition, cynaropicrin suppressed the enhancement of master regulator HIF-2α on cartilage degradation and further reduced the master regulator Sox9 on cartilage synthesis induced by TNF-α. We observed that cynaropicrin suppresses NF-κB signaling, which controls HIF-2α and Sox9. Since, HIF-2α is induced by p65 (RelA), we evaluated the effect of cynaropicrin and observed that it suppressed the nuclear transport of p65 (RelA) by inhibiting phosphorylation of IκBα. Moreover, cynaropicrin not only suppressed TNF-α stimulation, it had a similar effect on IL-1β stimulation. No significant cytotoxicity with cynaropicrin was observed. Significance These finding suggest that cynaropicrin is an effective substance that can improve the balance of cartilage metabolism, by altering the equilibrium of cartilage degradation and synthesis induced by multiple mediators know to contribute to OA. © 2016 Elsevier Inc.

Tanaka Y.T.,Gifu University | Tanaka Y.T.,Ichimaru Pharcos Co. | Tanaka K.,Ichimaru Pharcos Co. | Kojima H.,Ichimaru Pharcos Co. | And 5 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2013

Aging of skin is characterized by skin wrinkling, laxity, and pigmentation induced by several environmental stress factors. Histological changes during the photoaging of skin include hyperproliferation of keratinocytes and melanocytes causing skin wrinkles and pigmentation. Nuclear factor kappa B (NF-κB) is one of the representative transcription factors active in conjunction with inflammation. NF-κB is activated by stimulation such as ultraviolet rays and inflammatory cytokines and induces the expression of various genes such as those of basic fibroblast growth factor (bFGF) and matrix metalloprotease-1 (MMP-1). We screened several plant extracts for their possible inhibitory effect on the transcriptional activity of NF-κB. One of them, an extract from Cynara scolymus L., showed a greatest effect on the suppression of NF-κB transactivation. As a result, we found that cynaropicrin, which is a sesquiterpene lactone, inhibited the NF-κB-mediated transactivation of bFGF and MMP-1. Furthermore, it was confirmed that in an in vivo mouse model cynaropicrin prevented skin photoaging processes leading to the hyperproliferation of keratinocytes and melanocytes. These findings taken together indicate that cynaropicrin is an effective antiphotoaging agent that acts by inhibiting NF-κB-mediated transactivation. © 2012 Elsevier Ltd. All rights reserved.

Takagi M.,Nihon University | Tachi Y.,Nihon University | Zhang J.,Nihon University | Shinozaki T.,Nihon University | And 6 more authors.
Chemistry and Biodiversity | Year: 2014

Seventeen limonoids (tetranortriterpenoids), 1-17, including three new compounds, i.e., 17-defurano-17-(2,5-dihydro-2-oxofuran-3-yl)-28-deoxonimbolide (14), 17-defurano-17-(2ξ-2,5-dihydro-2-hydroxy-5-oxofuran-3-yl)-28- deoxonimbolide (15), and 17-defurano-17-(5ξ-2,5-dihydro-5-hydroxy-2-oxofuran- 3-yl)-2′,3′-dehydrosalannol (17), were isolated from an EtOH extract of the leaf of neem (Azadirachta indica). The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines, seven compounds, i.e., 1-3, 12, 13, 15, and 16, exhibited potent cytotoxicities with IC50 values in the range of 0.1-9.9 μM against one or more cell lines. Among these compounds, cytotoxicity of nimonol (1; IC50 2.8 μM) against HL60 cells was demonstrated to be mainly due to the induction of apoptosis by flow cytometry. Western blot analysis suggested that compound 1 induced apoptosis via both the mitochondrial and death receptor-mediated pathways in HL60 cells. In addition, when compounds 1-17 were evaluated for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α-melanocyte-stimulating hormone (α-MSH), seven compounds, 1, 2, 4-6, 15, and 16, exhibited inhibitory activities with 31-94% reduction of melanin content at 10 μM concentration with no or low toxicity to the cells (82-112% of cell viability at 10 μM). All 17 compounds were further evaluated for their inhibitory effects against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13- acetate (TPA) in Raji cells. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.

Akazawa H.,Nihon University | Fujita Y.,Ichimaru Pharcos Co. | Banno N.,Ichimaru Pharcos Co. | Watanabe K.,Nihon University | And 4 more authors.
Journal of Oleo Science | Year: 2010

Ten cyclic diarylheptanoids (1-10), including three new compounds: myricanone 5-O-a-Larabinofuranosyl-(1→6)-b-D-glucopyranoside (7), myricanone 17-O-β-D-(6'-O-galloyl)-glucopyranoside (8), and 16-methoxy acerogenin B 9-O-β-D-apiofuranosyl-(1→6)-b-D-glucopyranoside (10), along with two flavonoids (11, 12), were isolated from the extracts of Myrica rubra (Myricaceae) bark. The structures of new compounds were determined on the basis of spectroscopic methods. On evaluation of compounds 1-12 against the melanogenesis in the B16 melanoma cells, six compounds, 3, 5, 7, 8, 10, and 12, exhibited inhibitory effects with 30-56% reduction of melanin content at 25 μg/mL with no or very weak toxicity to the cells (82-103% of cell viability at 25 μg/mL). In addition, upon evaluation of compounds 1-12 against the scavenging activities of free radicals [against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical], seven compounds, 1, 3, 5, 6, 8, 11, and 12, showed potent scavenging activity [IC50 2-21 μM (0.6-7.3 μg/mL)]. © 2010 by Japan Oil Chemists' Society.

Zhang J.,Nihon University | Koike R.,Nihon University | Yamamoto A.,Nihon University | Ukiya M.,Nihon University | And 6 more authors.
Chemistry and Biodiversity | Year: 2013

A new flavonoid glycoside, chrysin 6-C-β-rutinoside (chrysin α-L-rhamnopyranosyl-(1→6)-C-β-glucopyranoside; 2), and two new triterpene glycosides, (31R)-31-O-methylpassiflorine (7) and (31S)-31-O-methylpassiflorine (8), along with 14 known glycosides, including three flavonoid glycosides, 1, 3, and 4, six triterpene glycosides, 5, 6, and 9-12, three cyano glycosides, 13-15, and two other glycosides, 16 and 17, were isolated from a MeOH extract of the leaves of Passiflora edulis (passion flower; Passifloraceae). The structures of new compounds were elucidated on the basis of extensive spectroscopic analysis and comparison with literature data. Upon evaluation of compounds 1-17 against the melanogenesis in the B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH), three compounds, isoorientin (1), 2, and (6S,9R)-roseoside (17), exhibited inhibitory effects with 37.3-47.2% reduction of melanin content with no, or almost no, toxicity to the cells (90.8-100.2% cell viability) at 100 μM. Western blot analysis showed that compound 2 reduced the protein levels of MITF, TRP-1, and tyrosinase, in a concentration-dependent manner while exerted almost no influence on the level of TRP-2, suggesting that this compound inhibits melanogenesis on the α-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of TRP-1 and tyrosinase. In addition, compounds 1-17 were evaluated for their inhibitory effects against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.

PubMed | Akihisa Medical Clinic, Ichimaru Pharcos Co., Nihon University and China Pharmaceutical University
Type: Journal Article | Journal: Chemistry & biodiversity | Year: 2016

Seven triterpenoids, 1-7, two diarylheptanoids, 8 and 9, four phenolic compounds, 10-13, and three other compounds, 14-16, were isolated from the hexane and MeOH extracts of the bark of Myrica cerifera L. (Myricaceae). Among these compounds, betulin (1), ursolic acid (3), and myricanol (8) exhibited cytotoxic activities against HL60 (leukemia), A549 (lung), and SK-BR-3 (breast) human cancer cell lines (IC

Tanaka K.,Nagoya City University | Tanaka K.,Ichimaru Pharcos Co. | Asamitsu K.,Nagoya City University | Uranishi H.,Nagoya City University | And 4 more authors.
Current Drug Metabolism | Year: 2010

The skin photoaging is an inevitable process that occurs in daily life. It is characterized by acceralated keratinocyte proliferation and degradation of collagen fibers, causing skin wrinkling and laxity, and melanocyte proliferation that leads to pigmentation. Ultraviolet (UV) is considered to be a major cause of such skin changes. It is well established that nuclear factor κ B (NF-κB) is activated upon UV irradiation and induces various genes including interleukin-1 (IL-1), tumor necrosis factor α (TNFα), and matrix metalloprotease-1 (MMP-1). It is also known that production of basic fibroblast growth factor (bFGF) is induced in skin tissues by UV irradiation and it promotes the proliferation of skin keratinocytes and melanocytes. We found that either UVB, IL-1 or TNFα could induce NF-κB by activating its signal transduction pathway. The activated NF-κB produces MMP-1 and bFGF in skin fibroblasts and human keratinocyte cell line HaCaT. In this experiment, we examined whether parthenolide and magnolol, NF-κB inhibitors, could block such UVB-mediated skin changes. We found that either parthenolide or magnolol could effectively inhibit the gene expression mediated by NF-κB and the production of bFGF and MMP-1 from cells overexpressing p65, a major subunit of NF-κB. We also found that these NF-κB inhibitors could inhibit the UVB-induced proliferation of keratinocytes and melanocytes in the mouse skin. These findings suggest that NF-κB inhibitors are useful in preventing the skin photoaging. © 2010 Bentham Science Publishers Ltd.

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