• Title/Summary/Keyword: Protein C deficiency

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Anti-wrinkle Effect of Safflower (Carthamus tinctorius L.) Seed Extract (II) (홍화씨추출물의 피부 주름개선 효과(II))

  • Kim Mi Jin;Kim Ja Young;Choi Sang-Won;Hong Jin Tae;Yoon Kyung-Sup
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.30 no.4 s.48
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    • pp.449-456
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    • 2004
  • Phytoestrogens derived from plants and foods, which are diphenolic compounds with structural similarities to natural and synthetic estrogens, have been shown to estrogenic and antiestrogenic actions. Particularly, recent study revealed that phenolic compounds in safflower seed, such as serotonin derivatives, lignans and flavonoids, could be acted as phytoestrogens. Safflower (Carthamus tinctorius L.) seed extract (SID C.SE), therefore, are receiving a renewed interest as potential therapeutic source against skin wrinkles induced by estrogen deficiency. This study was conducted to investigate the anti-wrinkle effect of SID C.SE on normal human fibroblasts through the expression of type I procollagen and UVA-induced MMP-1 in vitro. The SID C.SE increased the type I procollagen expression, comparable to trans-retinol and reduced UVA-induced MMP-1 expression in a dose-dependent manner. The clinical study indicated that cream group treated with $0.1\%$ SID C.SE significantly reduced a skin wrinkles, as compared with a control (non-treated cream group) (p<0.05). These results suggest that the safflower seed extract may be useful as potential source of anti-wrinkle cosmetics.

Abnormal Behavior Controlled via GPR56 Expression in Microglia (미세아교세포에서 GPR56 발현에 의한 이상 행동)

  • Hyunju Kim
    • Journal of Life Science
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    • v.33 no.6
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    • pp.455-462
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    • 2023
  • During pregnancy, maternal immune activation (MIA) from infection increases the risk of neurodevelopmental diseases, including schizophrenia and autism spectrum disorders. MIA induced by polyinosinic-polycytidylic acid (poly (I:C)) and lipopolysaccharide (LPS) in animal experiments has led to offspring with abnormal behaviors and brain development. In addition, it has recently been reported that microglia, which reside in the brain and function as immune cells, play an important role in behavioral abnormalities and brain development in MIA-induced offspring. However, the underlying mechanism remains unclear. In this study, we investigated whether microglia-specific inhibition of GPR56, a member of the G protein-coupled receptor (GPCR) family, causes behavioral abnormalities in brain development. First, MIA induction did not affect the microglia population, but when examining the expression of microglial GRP56 in MIA-induced fetuses, GPR56 expression was inhibited between embryonic days 14.5 (E14.5) and E18.5 regardless of sex. Furthermore, microglial GPR56-suppressed mice showed abnormal behaviors in the MIA-induced offspring, including sociability deficits, repetitive behavioral patterns, and increased anxiety levels. Although abnormal cortical development such as that in the MIA-induced offspring were not observed in the microglial GPR56-suppressed mice, their brain activity was observed through c-fos staining. These results suggest that microglia-specific GPR56 deficiency may cause abnormal behaviors and could be used as a biomarker for the diagnosis and/or as a therapeutic target of behavioral deficits in MIA offspring.

Determination of plasma C16-C24 globotriaosylceramide (Gb3) isoforms by tandem mass spectrometry for diagnosis of Fabry disease (패브리병(Fabry) 진단을 위한 혈장 중 Globotriaosylceramide (Gb3)의 탠덤매스 분석법 개발과 임상 응용)

  • Yoon, Hye-Ran;Cho, Kyung-Hee;Yoo, Han-Wook;Choi, Jin-Ho;Lee, Dong-Hwan;Zhang, Kate;Keutzer, Joan
    • Journal of Genetic Medicine
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    • v.4 no.1
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    • pp.45-52
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    • 2007
  • Purpose : A simple, rapid, and highly sensitive analytical method for Gb3 in plasma was developed without labor-ex tensive pre-treatment by electrospray ionization MS/ MS (ESI-MS/MS). Measurement of globotriaosy lceramide (Gb3, ceramide trihex oside) in plasma has clinical importance for monitoring after enzyme replacement therapy in Fabry disease patients. The disease is an X-linked lipid storage disorder that results from a deficiency of the enzyme ${\alpha}$-galactosidase A (${\alpha}$-Gal A). The lack of ${\alpha}$-Gal A causes an intracellular accumulation of glycosphingolipids, mainly Gb3. Methods : Only simple 50-fold dilution of plasma is necessary for the extraction and isolation of Gb3 in plasma. Gb3 in diluted plasma was dissolved in dioxane containing C17:0 Gb3 as an internal standard. After centrifugation it was directly injected and analyzed through guard column by in combination with multiple reaction monitoring mode of ESI-MS/MS. Results : Eight isoforms of Gb3 were completely resolved from plasma matrix. C16:0 Gb3 occupied 50% of total Gb3 as a major component in plasma. Linear relationship for Gb3 isoforms w as found in the range of 0.001-1.0 ${\mu}g$/mL. The limit of detection (S/N=3) was 0.001 ${\mu}g$/mL and limit of quantification was 0.01 ${\mu}g$/mL for C16:0 Gb3 with acceptable precision and accuracy. Correlation coefficient of calibration curves for 8 Gb3 isoforms ranged from 0.9678 to 0.9982. Conclusion : This quantitative method developed could be useful for rapid and sensitive 1st line Fabry disease screening, monitoring and/or diagnostic tool for Fabry disease.

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Antidepressant Effects of JG02 on Chronic Restraint Stress Animal Model (만성구속스트레스 동물모델에 대한 JG02의 항우울 효과)

  • You, Dong Keun;Seo, Young Kyung;Lee, Ji-Yoon;Kim, Ju Yeon;Jung, Jin-Hyeong;Choi, Jeong June;Jung, In Chul
    • Journal of Oriental Neuropsychiatry
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    • v.30 no.3
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    • pp.209-220
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    • 2019
  • Objectives: As a general emotion, everyone can temporarily experience depression, but depressive disorder is a disease that excessively affects daily life. Among the various causes of depression, the deficiency of monoamine-based neurotransmitters such as serotonin and epinephrine are considered significant. Thus, antidepressants that target monoamines are used frequently. However, side effects such as nausea, vomiting, insomnia, anxiety, and sexual dysfunction are observed. Thus, it is necessary to develop a new therapeutic agent with fewer side effects. In this study, we investigated the antidepressant effect of JG02, used to treat depression by normalizing the flow of qi (氣) in Korean medicine. Methods: C57BL/6 mice were selected and randomly divided into six groups: normal, control, amitriptyline, and JG02 (50, 125, 250 mg/kg), respectively. Except for normal, depression was induced by applying restraint stress at the same time for six hours daily for 14 consecutive days. Saline, amitriptyline or JG02 samples were orally administered two hours before applying the stress. After that, a forced swimming test and an open field test were performed. Additionally, serum corticosterone, serotonin mRNA, BDNF mRNA, and protein in the hippocampal region were measured and compared. Results: JG02 decreased immobility time rate in the FST and increased the zone transition number and travel distance in the OFT. Also, JG02 inhibited the release of serum corticosterone, and increased serotonin, BDNF gene expression, and BDNF protein in the hippocampus. Conclusions: In this study, JG02 showed significant antidepressant effects on the chronic restraint stress mice model. When further research is performed based on JG02, the development of a new antidepressant is considered highly possible.

Betulin Targets Lipin1/2-Meidated P2X7 Receptor as a Therapeutic Approach to Attenuate Lipid Accumulation and Metaflammation

  • Dou, Jia-Yi;Jiang, Yu-Chen;Hu, Zhong-He;Yao, Kun-Chen;Yuan, Ming-Hui;Bao, Xiao-Xue;Zhou, Mei-Jie;Liu, Yue;Li, Zhao-Xu;Lian, Li-Hua;Nan, Ji-Xing;Wu, Yan-Ling
    • Biomolecules & Therapeutics
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    • v.30 no.3
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    • pp.246-256
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    • 2022
  • The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 µM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7r-NLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.

Research on Immune Responses Induced by Salmonella Typhimurium Infectionin CRIP1-Deficient Condition (CRIP1결손조건 하에서 Salmonella Typhimurium 감염에 의해 유도되는 면역반응에 관한 연구)

  • Dongju Seo;Se-Hui Lee;Sun Park;Hyeyun Kim;Jin-Young Yang
    • Journal of Life Science
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    • v.34 no.1
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    • pp.48-58
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    • 2024
  • Salmonella is a common food-borne intracellular bacterial pathogen that has triggered significant public health concerns. Salmonella hosts' genetic factors play a pivotal role in determining their susceptibility to the pathogen. Cysteine-rich intestinal protein 1 (CRIP1), a member of LIM/double zinc finger protein family, is widely expressed in humans, such as in the lungs, spleen, and especially the gut. Recently, CRIP1 has been reported as a key marker of several immune disorders; however, the effect of CRIP1 on bacterial infection remains unknown. We aimed to elucidate the relationship between Salmonella infection and CRIP1 gene deficiency, as Salmonella spp. is known to invade the Peyer's patches of the small intestine, where CRIP1 is highly expressed. We found that CRIP1-deficient conditions could not alter the characteristics of bone marrow-derived myeloid cells in terms of phagocytosis on macrophages and the activation of costimulatory molecules on dendritic cells using ex vivo differentiation. Moreover, flow cytometry data showed comparable levels of MHCII+CD11b+CD11c+ dendritic cells and MHCII+F4/80+CD11b+ macrophages between WT and CRIP1 knockout (KO) mice. Interestingly, the basal population of monocytes in the spleen and neutrophils in MLNs is more abundant in a steady state of CRIP1 KO mice than WT mice. Here, we demonstrated that the CRIP1 genetic factor plays dispensable roles in host susceptibility to Salmonella Typhimurium infections and the activation of myeloid cells. In addition, differential immune cell populations without antigen exposure in CRIP1 KO mice suggest that the regulation of CRIP1 expression may be a novel immunotherapeutic approach to various infectious diseases.

Characterization of Mutations in Bruton's Tyrosine Kinase(Btk) Gene from Unrelated 3 X-linked Agammaglobulinemia(XLA) Families in Korea (국내 X-관련성 범저감마글로불린혈증 세가족에 대한 Bruton's Tyrosine Kinase 단백질 발현 및 유전자 변이 분석)

  • Song, Chang-Hwa;Jo, Eun-Kyeong;Park, Jeong-Kyu;Kim, Jung-Soo;Hong, Soo-Jong;Lee, Jae-Ho
    • Clinical and Experimental Pediatrics
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    • v.45 no.3
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    • pp.302-310
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    • 2002
  • Purpose : X-linked agammaglobulinemia(XLA) is an immunodeficiency caused by abnormalities in Bruton's tyrosine kinase(Btk), and is characterized by a deficiency of peripheral blood B cells. We studied cytoplasmic expression of Btk protein and analyzed the Btk gene in peripheral blood mononuclear cells(PBMC) from three XLA families in Korea. Methods : Heparinized venous blood samples were collected from four XLA patients and additional family members in three unrelated XLA families. Mononuclear cells were separated from their blood and the intracellular Btk protein was characterized by a flow cytometry. The mutation analysis was performed using direct sequencing. Results : Cytoplasmic expression of Btk protein in monocytes was not detected in the patients with XLA. We observed a novel deletion and two point mutations within introns(intron 1 and intron 18) resulting in alternative splicings. In XLA family 2, a 980 bp deletion(from intron 9+191 T to intron 10-215 C) including exon 10 was found in patient P2. He was the only sporadic case in this study, because his mother and brother showed a normal Btk expression by flow cytometry. Conclusion : These identified genetic alterations support the molecular heterogeneity of Btk gene in XLA disease. Additionally, by means of flow cytometric analysis, we diagnosed three hypogammaglobulinemia patients as XLA. Advancements in diagnostic methods has facilitated a prompt and definite diagnosis of this disease.

Serum Zinc Concentration in Children with Acute Gasrtoenteritis (영유아의 급성 장염에서 혈청 아연농도)

  • Lee, Hyun Joo;Yom, Hye Won;Seo, Jeong Wan
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.9 no.1
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    • pp.14-22
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    • 2006
  • Purpose: To identify factors that influence serum zinc concentrations in children with acute gastroenteritis. Methods: Thirty-two children under 5 years of age (15 boys and 17 girls) were selected randomly among those who visited to an pediatric emergency room of Ehwa Womans University Mokdong Hospital with acute gastroenteritis from May to August 2005. This study estimated the association between serum zinc concentrations and clinical, biochemical variables in patients with acute gastroenteritis. Results: Serum zinc concentration was lower in febrile patients than afebrile patients with acute gastroenteritis ($67.5{\pm}25.3$ vs $85.5{\pm}14.2$, p<0.05). It also was lower in patients with positive C-reactive protein (CRP) than those with negative CRP ($63.9{\pm}25.4$vs $86.7{\pm}13.8$, p<0.05). Serum zinc concentration was negatively correlated (r=-0.494, p<0.05) with CRP concentration, whereas positively correlated with hematocrit (r=0.370, p<0.05), total protein (r=0.474, p<0.05), and albumin (r=0.636, p<0.05). Twelve patients (37.5%) showed very low serum zinc concentration (< $70{\mu}g/dL$) without clinical symptoms of deficiency or growth retardation. Frequency of febrile illness or positive CRP is significantly greater in group with zinc < $70{\mu}g/dL$ than the group with zinc ${\geq}70{\mu}g/dL$ (91.7% vs 55%, p<0.05; 91.7% vs 40%, p<0.05, respectively). Conclusion: In patients with acute gastroenteritis, serum zinc concentration was influenced by various factors such as fever, CRP, and biochemical factors. For evaluating zinc status in the body. factors.

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Research on Proper Dietary Recommendations for Korea (한국인(韓國人)의 균형식(均衡食) 권장에 관한 연구(硏究) -한국인(韓國人)의 식생활(食生活)의 추이(해방후 30년간)-)

  • Lee, Ki-Yull;Leekim, Yang-Cha
    • Journal of Nutrition and Health
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    • v.10 no.2
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    • pp.59-70
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    • 1977
  • This study was designed to evaluate the changes and improvements in the Korean diet during the last thirty years (since independence in 1945), and to make recommendations for the improvement of their nutritional status, consequently contributing to the physical and mental welfare of the Korean people. The results and recommendations are as follows: 1. The total calorie and carbohydrate intake decreased by $8{\sim}12%$ in the 1970's, as compared with the 1940's and the 1950's. 2. The intake of calcium and vitamiu A increased $30{\sim}50%$ and $20{\sim}60%$ respectively in the 1960's and 1970's as compared with the 1940,s. But this intake level is still lower than the RDA values. 3. The vitamin C intake was somewhat higher in the mountainous and farming areas than in urban areas. 4. In the 1970's, the decrease of untriend intake due to seasonal variation was marked especially for protein, niacin, vitamin $B_1$, and vitamin C. 5. The consumption of protein foods (meats and legumes) increased in an amount of $15{\sim}36g$ per day. There was a marked increase in the intake of meat in farming areas and of milk in urban areas in the 1970's. This increased intake of animal proteins is a very desirable dietary change. 6. The cereal consumption was lowest in urban areal, but there was a general decrease in the intake of the cereal group in the entire area in the 1970's. For the farmers, the intake of cereal food decreased most, from 750 g to 576 g, but cereals still composed a high proportion of the entire diet. 7. Fruits and vegetables showed the highest intake for the urban people, as expected. For the whole area, this food group showed an increase of 8.7% in the 1970's, as compared with the 1960's. 8. The gradual ihcrease in the intake of the fats and oil group was a desirable dietary change. but the absolute amount was too low. 9. A 7% increase in height and a 9% incrrase in weight for growing children and adolescents was observed in the 1970's as compared with the 1940's, but several kinds of deficiency diseases, such as nutritional anemia and dental caries were still apparent in many areas. 10. To improve cur food life and to cope with food shortages faced in Korea, an efficient and nationwide nutrition education program should be implemented. This would maximize efficiency of intake from the limited food sources for a balanced diet. 11. As it is of utmost importance to provide growing children with a desirable physical, sccial mental, and especially nutritional environment, a well-planned and organized school feeding program should be practiced widely and efficiently. 12. Young mothers and pregnant women should be educated on the importance of their children's nutrition, especially for the critical fetal and infancy periods. 13. More thorough and continuous nutritional survey studies on the changes in dietary patterns for the entire nation should be pursued, evaluated and documented. This would Provide a good information guide for future nutritional study programs. 14. It is the nutritionistist's strong desire that national leaders, especially decision makers recognize the fact that improvement of the nutritional status of the People is one of the most economic and preventative ways of improving their physical and mental health. This is closely related to the economic development and strength of the nation.

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Melanogenesis regulatory constituents from Premna serratifolia wood collected in Myanmar

  • WOO, SO-YEUN
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.04a
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    • pp.21-22
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    • 2019
  • Melanin is a mixture of pigmented biopolymers synthesized by epidermal melanocytes that determine the skin, eye, and hair colors. Melanocytes produce two different kinds of melanin, eumelanin (dark brown/black insoluble pigments found in dark skin and dark hair and pheomelanin (lighter red/yellow). The biological role of melanin is to prevent skin damage by ultraviolet (UV) radiation. However, the overproduction or deficiency of melanin synthesis could lead to serious dermatological problems, which include melasma, melanoderma, lentigo, and vitiligo. Therefore, regulating melanin production is important to prevent the pigmentation disorders. Myanmar has a rich in natural resources. However, the chemical constituents of these natural resources in Myanmar have not been fully investigated. In the effort to search for compounds with anti-melanin deposition activity from Myanmar natural resources, five plants were collected in Myanmar. Extracts of these collected five plants were tested for anti-melanin deposition activity against a mouse melanoma cell line (B16-F10) induced with ${\alpha}$-melanocyte-stimulating hormone (${\alpha}$-MSH) and 3-isobutyl-1-methylxanthine (IBMX), and their anti-melanin deposition activities were compared with the positive control, arbutin. Among the tested extracts, the CHCl3 extracts of the Premna serratifolia (syn: P. integrifolia) wood showed anti-melanin deposition activities with IC50 values of $81.3{\mu}g/mL$. Hence, this study aims to identify secondary metabolites with anti-melanin deposition activity from P. serratifolia wood of Myanmar. P. serratifolia belongs to the Verbenaceae family and is widely distributed in near western sea coast from South Asia to South East Asia, which include India, Malaysia, Vietnam, Cambodia, and Sri Lanka. People in Tanintharyi region located in the southern part of Myanmar utilize the P. serratifolia, Sperethusa crenulata, Naringi crenulata, and Limonia acidissima as Thanaka, traditional cosmetics in Myanmar. Thanaka is applied in the form of paste onto skins to make it smooth and clear, as well as to prevent wrinkles, skin aging, excessive facial oil, pimples, blackheads, and whiteheads. However, the chemical constituents responsible for their cosmetic properties are yet to be identified. Moreover, the chemical constituents of P. serratifolia was almost uncharacterized. Investigation of the P. serratifolia chemical constituents is thus an attractive endeavor to discover new anti-melanin deposition active compounds. The investigation of the chemical constituents of the active CHCl3 extract of P. serratifolia led to isolation of four new lignoids, premnan A (1), premnan B (2), taungtangyiol C (3), and 7,9-dihydroxydolichanthin B (4), together with premnan C (5) (assumed to be an artifact), one natural newlignoid,(3R,4S)-4-(1,3-benzodioxol-5-ylcarbonyl)-3-[(R)-1-(1,3-benzo dioxol-5-yl)-1-hydroxy methyl]tetrahydro-2-furanone (6), and five known compounds (7-11)1,2). The structures of all isolated compounds were determined on the basis of their spectroscopic data and by comparison with the reported literatures. The absolute configurations of 1-3 and 5 were also determined by optical rotation and circular dichroism (CD) data analyses1). The anti-melanin deposition activities of all the isolated compounds were evaluated against B16-F10 cell line. 7,9-Dihydroxydolichanthin B (4) and ($2{\alpha},3{\alpha}$)-olean-12-en-28-oic acid (11) showed strong anti-melanin deposition activities with IC50 values of 18.4 and $11.2{\mu}M$, respectively, without cytotoxicity2). On the other hand, compounds 1-3, 5, and 7 showed melanogenesis enhancing activities1). To better understand their anti-melanin deposition mechanism, the effects of 4 and 11 on tyrosinase activities were investigated. The assay indicated that compounds 4 and 11 did not inhibit tyrosinase. Furthermore, we also examined the mRNA expression of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). Compounds 4 and 11 down-regulated the expression of Tyr and Mitf mRNAs, respectively. Although the P. serratifolia wood has been used as traditional cosmetics in Myanmar for centuries, there are no scientific evidences to support its effectiveness as cosmetics. Investigation of the anti-melanin deposition activity of the chemical constituents of P. serratifolia thus provided insight into the effectiveness of the P. serratifolia wood as a cosmetic agent.

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