[Show abstract][Hide abstract] ABSTRACT: During our on-going screening program designed to isolate natural compounds from marine environments, we isolated isoketochabrolic acid (IKCA) from Sargassum micracanthum, an important brown algae distributed in Jeju Island, Korea. Furthermore, we evaluated the inhibitory effects of IKCA on nitric oxide (NO) production in lipopolysaccharide (LPS)-triggered macrophages. IKCA strongly inhibited NO production, with an IC50 value of 58.31 μM. Subsequent studies demonstrated that IKCA potently and concentration-dependently reduced prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 cytokine production. In conclusion, to the best of our knowledge, this is the first study to show that IKCA isolated from S. micracanthum has a potent anti-inflammatory activity. Therefore, IKCA might be useful as an anti-inflammatory health supplement or functional cosmetics.
[Show abstract][Hide abstract] ABSTRACT: In order to test the effectiveness of tangeretin at ameliorating melanoma and melanoma-associated depigmentation, western blotting was used to assess the melanin content of treated melanoma cells. Tangeretin, a 4',5,6,7,8-pentamethoxyflavone, was found to trigger intracellular melanin production in a concentration-dependent manner in B16/F10 murine melanoma cells. Melanin content increased 1.74-fold in response to treatment with 25 μM of tangeretin, compared to that in non-treated cells. Examination of melanogenic protein expression showed that tyrosinase, tyrosinase-related protein (TRP)-1, and extracellular signal-regulated kinase (ERK) 1/2 levels increased in a dose-dependent manner. Furthermore, the expression of cyclic adenosine monophosphate response element binding protein (CREB) and microphthalmia transcription factor (MITF) was increased by tangeretin in 1 h and 4 h, respectively. Tangeretin- upregulated melanogenesis was suppressed by ERK 1/2 inhibitor and not by ERK1 inhibitor. These results suggest that tangeretin has therapeutic potential for melanoma and melanoma-associated depigmentation because it can induce hyperpigmentation through the activation of melanogenic signaling proteins and initiation of sustained ERK2 expression.
No preview · Article · Mar 2015 · Natural product communications
[Show abstract][Hide abstract] ABSTRACT: As an approach to search for chemopreventive agents, we tested p-coumaric acid, 3-methoxy-p-coumaric acid (ferulic acid), and 3,5-dimethoxy-p-coumaric acid (sinapic acid) in B16/F10 melanoma cells. Intracellular melanin contents were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and cytotoxicity of the compounds were examined by lactate dehydrogenase (LDH) release. p-Coumaric acid showed inhibitory effect on melanogenesis, but ferulic acid increased melanin content, and sinapic acid had almost no effect on melanogenesis. Treatment with ferulic acid resulted in a 2 to 3 fold elevation in the production of melanin. Correlatively, cell viability decreased in a dose-dependent manner when treated with ferulic acid. However, ferulic acid did not affect the LDH release from the cells. Treatment with sinapic acid resulted in a 50~60% elevation in the release of LDH when treated with a 200 μg/mL concentration and showed neither cytostasis nor increase of melanin synthesis in a dose-dependent manner. Taken together, p-coumaric acid inhibits melanogenesis, ferulic acid induces melanogenesis, and sinapic acid exerts cytotoxic effects in B16/F10 murine melanoma cells. The results indicate that the addition of methoxy groups to p-coumaric acid shows the melanogenic or cytotoxic effects in melanoma cells compared to the original compound. Therefore, this study suggests the possibility that methoxylated p-coumaric acid, ferulic acid can be used as a chemopreventive agent.
Preview · Article · Mar 2015 · Preventive Nutrition and Food Science
[Show abstract][Hide abstract] ABSTRACT: Development of bioactive ingredients from natural sources has long been the research project of our laboratory. In this study, the extract from Corylus hallaisanensis Nakai branches was investigated and their anti-inflammatory constituents were identified. The prepared ethanol extract was successively partitioned into n-hexane, ethyl acetate, n-butanol and aqueous layers. Upon anti-inflammatory screenings, ethyl acetate fraction exhibited good nitric oxide production inhibitory activity in lipopolysaccharide-induced RAW 264.7 cells. Further phytochemical studies for the ethyl acetate fractions led to isolation of four constituents such as ß-sitosterol (1), 3,3',4'-tri-O-methylellagic acid (2), carpinontriol A (3) and carpinontriol B (4). All of the compounds were isolated for the first time from this plant. The isolates 2, 3 and 4 showed considerable inhibition on the production of nitric oxide in the RAW 264.7 cell without causing cell toxicities. And compounds 3 and 4 reduced the production of interleukin-6, an inflammatory cytokine, in dose-dependent manner in RAW 264.7 cells. Based on these results, C. hallaisanensis extracts could be potentially applicable as anti-inflammatory agents in pharmaceutical or cosmetic industries.
No preview · Article · Jan 2015 · Journal of Applied Pharmaceutical Science
[Show abstract][Hide abstract] ABSTRACT: The ethanol extract of Tilia taquetii Schneider leaves was investigated for its anti-wrinkle properties and for the relevant chemical constituents. Phytochemical studies led to the identification of five known compounds, viz. phytol (1), isoquercitrin (2), oleanderolide (3), arjunolic acid (4) and maslinic acid (5) from the extract. Of these, compounds 4 and 5 inhibited the expression of matrix metalloproteinase-1 (MMP-1), an enzyme responsible for the breakdown of collagen fiber. Moreover, compound 5 showed inhibition activity on elastase, a protease enzyme capable of degrading elastin. These results suggest that the extract of T. taquetii containing the triterpenes 4 and 5 could be applied as anti-wrinkle ingredients in cosmetic preparations.
No preview · Article · Dec 2014 · Natural product communications
[Show abstract][Hide abstract] ABSTRACT: To investigate the suitability of the green alga Cladophora wrightiana, grown in the southern regions of the Korean Peninsula, as a source of anti-inflammatory agents for human use. Anti-inflammatory effects of the ethyl acetate extracts of C. wrightiana (CWE) were evaluated on lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. CWE were examined for their ability to inhibit pro-inflammatory mediators and cytokines, such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-lβ. To elucidate its inflammatory mechanisms, CWE was investigated as an inhibitor of mitogenactivated protein kinase (MAPK) in US-stimulated RAW 264.7 cells. Our results demonstrate that CWE potently inhibited LPS-induced NO production, with IC50 values of 61.25 μg/mL. Consistent with these findings, CWE reduced the LPS-induced expression of inducible NO synthase (iNOS) protein in a concentration-dependent manner, as determined using western blot analysis. Furthermore, the levels of PGE2, TNF-α, IL-6, and IL-1β released into media were reduced by CWE in a concentration-dependent manner. In addition, CWE also induced a dosedependent inhibition of the phosphorylation of mitogen activated protein kinases (MAPKs, JNK, and ERK). Collectively, the results of this study demonstrate that CWE reduces the levels of pro-inflammatory mediators and cytokines including NO, PGE2, IL-1β, TNF-α, and IL-6 via suppression of)NK and ERK phosphorylation in RAW 264.7 cells. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of CWE.
No preview · Article · Sep 2014 · Biosciences Biotechnology Research Asia
[Show abstract][Hide abstract] ABSTRACT: In this study, we investigated the ability of 6,7-dimethoxy-4-methylcoumarin (DMC) to inhibit lipopolysaccharide (LPS)-induced expression of pro-inflammatory mediators in mouse macrophage (RAW 264.7) cells, and the molecular mechanism through which this inhibition occurred. Our results indicated that DMC downregulated LPS-induced nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, thereby reducing the production of NO and prostaglandin E2 (PGE2) in LPS-activated RAW 264.7 cells. Furthermore, DMC suppressed LPS-induced production of pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α. To elucidate the mechanism underlying the anti-inflammatory activity of DMC, we assessed its effects on the mitogen-activated protein kinase (MAPK) pathway and the activity and expression of nuclear transcription factor kappa-B (NF-κB). The experiments demonstrated that DMC inhibited LPS-induced phosphorylation of extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinase (JNK), and p38. In addition, it attenuated LPS-induced NF-κB activation via the inhibition of IκB-α phosphorylation. Taken together, these data suggest that DMC exerts its anti-inflammatory effects in RAW 264.7 cells through the inhibition of LPS-stimulated NF-κB and MAPK signaling, thereby downregulating the expression of pro-inflammatory mediators.
[Show abstract][Hide abstract] ABSTRACT: Objective:
To investigate the anti-inflammatory effects of Jeju seaweeds on macrophage RAW 264.7 cells under lipopolysaccharide (LPS) stimulation.
Ethyl acetate fractions were prepared from five different types of Jeju seaweeds, Dictyopteris divaricata (D. divaricata), Dictyopteris prolifera (D. prolifera), Prionitis cornea (P. cornea), Grateloupia lanceolata (G. lanceolata), and Grateloupia filicina (G. filicina). They were screened for inhibitory effects on proinflammatory mediators and cytokines such as nitric oxide (NO), prostaglandin E2, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6).
Our results revealed that D. divaricata, D. prolifera, P. cornea, G. lanceolata, and G. filicina potently inhibited LPS-stimulated NO production (IC50 values were 18.0, 38.36, 38.43, 32.81 and 37.14 µg/mL, respectively). Consistent with these findings, D. divaricata, D. prolifera, P. cornea, and G. filicina also reduced the LPS-induced and prostaglandin E2 production in a concentration-dependent manner. Expectedly, they suppressed the expression of inducible NO synthase and cyclooxygenase-2 at the protein level in a dose-dependent manner in the RAW 264.7 cells, as determined by western blotting. In addition, the levels of TNF-α and IL-6, released into the medium, were also reduced by D. divaricata, D. prolifera, P. cornea, G. lanceolata, and G. filicina in a dose-dependent manner (IC50 values for TNF-α were 16.11, 28.21, 84.27, 45.52 and 74.75 µg/mL, respectively; IC50 values for IL-6 were 37.35, 80.08, 103.28, 62.53 and 84.28 µg/mL, respectively). The total phlorotannin content was measured by the Folin-Ciocalteu method and expressed as phloroglucinol equivalents. The content was 92.0 µg/mg for D. divaricata, 151.8 µg/mg for D. prolifera, 57.2 µg/mg for P. cornea, 53.0 µg/mg for G. lanceolata, and 40.2 µg/mg for G. filicina.
Thus, these findings suggest that Jeju seaweed extracts have potential therapeutic applications for inflammatory responses.
Preview · Article · Jul 2014 · Asian Pacific Journal of Tropical Biomedicine
[Show abstract][Hide abstract] ABSTRACT: A number of seaweed species are used as traditional foods and medicine in different parts of the world, including Asian countries. However, very few data on the anti-melanogenic effect of seaweed have been published. Undaria pinnatifida (Dolmiyeok), a brown alga, is a traditional food in Jeju Island, the southern regions of the Korea peninsula. In this study, ethylacetate extracts of U. pinnatifida (UPE) were examined for their anti-melanogenic potentials. Our results supports the finding that UPE down-regulated melanin content in a dose-dependent pattern. To clarify the target of UPE action in melanogenesis, we performed Western blotting for tyrosinase and microphthalmia-associated transcription factor (MITF), which are key melanogenic enzymes. UPE inhibited tyrosinase and MITF expressions in a dose-dependent manner. These results indicate that treatment with UPE significantly inhibits the melanogenesis in B16 cells, and may be effective in the whitening agent for the skin.
Preview · Article · Jun 2014 · Interdisciplinary toxicology
[Show abstract][Hide abstract] ABSTRACT: In order to develop a skin-whitening agent, melanin contents and intracellular tyrosinase activity were determined by western blotting. Ethyl acetate fractions of 80% ethanol extracts from lily (Lilium Oriental Hybrid 'Siberia') bulbs (R-EA) inhibited melanin synthesis in a dose-dependent manner in α-melanocyte stimulating hormone (α-MSH)- treated B16/F10 murine melanoma cells. Intracellular tyrosinase activity and melanin contents were suppressed by 45% and 74%, respectively, in response to treatment with 100 μg/mL of R-EA. Examination of protein expression associated with α-MSH-induced melanogenesis showed that tyrosinase related protein (TRP)-1 was inhibited more strongly than tyrosinase, and these results were correlated with stronger inhibition of melanin synthesis than intracellular tyrosinase activity. Taken together, R-EA containing p-coumaric acid and resveratrol could be used as a hypopigmentation agent through suppression of sustained extracellular signal-regulated kinase (ERK) activation via melanogenic induction.
No preview · Article · May 2014 · Journal of the Korean Society of Food Science and Nutrition
[Show abstract][Hide abstract] ABSTRACT: Though many essential oils from citrus peels are claimed to have several medicinal functions, the chemical composition and biological activities of the essential oils of Citrus flowers have not been well described. Therefore, this study intended to investigate the chemical composition and anti-inflammatory potential of essential oils from C. unshiu flower (CEO) to support its purported beneficial health effects. The chemical constituents of the CEO, analyzed by gas chromatography-mass spectrometry (GC-MS), included y-terpinene (24.7%), 2-beta-pinene (16.6%), 1-methyl-2-isopropylbenzene (11.5%), L-limonene (5.7%), beta3-ocimene (5.6%), and alpha-pinene (4.7%). The effects of the CEO on nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages were also examined. The results indicate that the CEO is an effective inhibitor of LPS-induced NO and PGE2 production in RAW 264.7 cells. Additionally, CEO was shown to suppress the production of inflammatory cytokines including interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6. Based on these results, CEO may be considered a potential anti-inflammatory candidate with human health benefits.
No preview · Article · May 2014 · Natural product communications
[Show abstract][Hide abstract] ABSTRACT: Hypochoeris radicata, an invasive plant species, is a large and growing threat to ecosystem integrity on Jeju Island, a UNESCO
World Heritage site. Therefore, research into the utilization of H. radicata is important and urgently required in order to solve this invasive plant problem in Jeju Island. The broader aim of our research is to elucidate the biological activities of
H. radicata, which would facilitate the conversion of this invasive species into high value added products. The present study was undertaken to identify the pharmacological effects of H. radicata
flower on the production of inflammatory
mediators in macrophages. The results indicate that the ethyl acetate fraction of
H. radicata extract (HRF-EA) inhibited the production of pro-inflammatory molecules such as NO, iNOS, PGE2, and COX-2, and cytokines such as TNF-α, IL-1β, and IL-6 in LPS-stimulated RAW 264.7 cells. Furthermore, the phosphorylation of MAPKs such as p38, ERK, and JNK was suppressed by HRF-EA in a concentration-dependent manner. In addition, through HPLC and UPLC fingerprinting, luteolins were also identified and quantified as extract constituents. On the basis of these results, we suggest that
H. radicata may be considered possible anti-inflammatory candidates for pharmaceutical and/or cosmetic applications.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the in vitro inhibitory effects of acanthoic acid (ACAN), isolated from Acanthopanax koreanum, on melanogenesis and its related enzymes such as tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 in B16 melanoma cells. We found that ACAN significantly attenuates melanin synthesis and reduces the activity of intracellular tyrosinase, the rate-limiting melanogenic enzyme. Western blot analysis showed that ACAN also decreases tyrosinase, TRP-1, and TRP-2 protein expression. In addition, ACAN significantly decreased the expression of microphthalmia-associated transcription factor (MITF), a key regulator of melanogenesis. These results indicate that ACAN effectively inhibits melanin biosynthesis through down-regulation of MITF and thus could be useful as a new skin-whitening agent.
Full-text · Article · Oct 2013 · Natural product communications
[Show abstract][Hide abstract] ABSTRACT: During our ongoing screening program designed to determine the anti-inflammatory potential of natural compounds, we isolated sargachromenol from Sargassum micracanthum. In the present study, we investigated the anti-inflammatory effects of sargachromenol on lipopolysaccharide (LPS)-induced inflammation in murine RAW 264.7 macrophage cells and the underlying mechanisms. Sargachromenol significantly inhibited the LPS-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) in a dose-dependent manner. It also significantly inhibited the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner in LPS-stimulated macrophage cells. Further analyses showed that sargachromenol decreased the cytoplasmic loss of inhibitor κ B α (I κ B α ) protein. These results suggest that sargachromenol may exert its anti-inflammatory effects on LPS-stimulated macrophage cells by inhibiting the activation of the NF- κ B signaling pathway. In conclusion, to our knowledge, this is the first study to show that sargachromenol isolated from S. micracanthum has an effective anti-inflammatory activity. Therefore, sargachromenol might be useful for cosmetic, food, or medical applications requiring anti-inflammatory properties.
Preview · Article · Sep 2013 · The Scientific World Journal
[Show abstract][Hide abstract] ABSTRACT: To investigate the suitability of citrus-press cakes, by-products of the juice industry as a source for the whitening agents for cosmetic industry.
Ethylacetate extracts of citrus-press cakes (CCE) were examined for their anti-melanogenic potentials in terms of the inhibition of melanin production and mechanisim of melanogenesis by using Western Blot analysis with tyrosinese, tyrosinase-related protein-1 (TRP-1), TRP2, and microphthalmia-associated transcription factor (MITF) proteins. To apply the topical agents, citrus-press cakes was investigated the safety in human skin cell line. Finally flavonoid analysis of CCE was also determined by HPLC analysis.
Results indicated that CCE were shown to down-regulate melanin content in a dose-dependent pattern. The CCE inhibited tyrosinase, TRP-2, and MITF expressions in a dose-dependent manner. To test the applicability of CCE to human skin, we used MTT assay to assess the cytotoxic effects of CCE on human keratinocyte HaCaT cells. The CCE exhibited low cytotoxicity at 50 µg/mL. Characterization of the citrus-press cakes for flavonoid contents using HPLC showed varied quantity of rutin, narirutin, and hesperidin.
Considering the anti-melanogenic activity and human safety, CCE is considered as a potential anti-melanogenic agent and may be effective for topical application for treating hyperpigmentation disorders.
No preview · Article · Aug 2013 · Asian Pacific Journal of Tropical Biomedicine
[Show abstract][Hide abstract] ABSTRACT: The marine environment is a unique source of bioactive natural products, of which Sargassum muticum (Yendo) Fensholt is an important brown algae distributed in Jeju Island, Korea. S. muticum is a traditional Korean food stuff and has pharmacological functions including anti-inflammatory effects. However, the active ingredients from S. muticum have not been characterized.
Bioguided fractionation of the ethanolic extract of S. muticum, collected from Jeju island, led to the isolation of a norisoprenoid. Its structure was determined by analysis of the spectroscopic data. In vitro anti-inflammatory activity and mechanisms of action of this compound were examined using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells through ELISA assays and Western blot analysis.
Apo-9[prime]-fucoxanthinone, belonging to the norisoprenoid family were identified. Apo-9[prime]-fucoxanthinone effectively suppressed LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production. This compound also exerted their anti-inflammatory actions by down-regulating of NF-kappaB activation via suppression of IkappaB-alpha in macrophages.
This is the first report describing effective anti-inflammatory activity for apo-9[prime]-fucoxanthnone isolated from S. muticum. Apo-9[prime]-fucoxanthinone may be a good candidate for delaying the progression of human inflammatory diseases and warrants further studies.
Full-text · Article · Jul 2013 · DARU-JOURNAL OF FACULTY OF PHARMACY
[Show abstract][Hide abstract] ABSTRACT: This study was conducted to identify the anti-melanogenesis constituents from a seaweed Dictyota coriacea (Holmes). Three known compounds, viz. 1,9-dihydroxycrenulide (1), epiloliolide (2) and D-mannitol (3), were isolated from the ethanol extract. The melanin synthesis inhibition activities were evaluated using B16F10 melanoma cells for the isolates. Compared with the positive control, arbutin, compounds 1 and 2 exhibited more potency, showing 27.8 and 22.6% inhibition activities at a substrate concentration of 30 microg/mL. Our studies also indicate that these compounds are not cytotoxic. Hence, they might prove to be useful therapeutic agents for treating hyperpigmentation and effective components of whitening cosmetics.
[Show abstract][Hide abstract] ABSTRACT: Essential oils, volatile compounds from plants, are attractive natural ingredients possessing wide range of applications in cosmetics, foods, household products and alternative medicines. In this study, the three different oils from Prunus yedoensis (PYE), Saururus chinensis (SCE), Zanthoxylum piperitum (ZPE) were prepared by supercritical carbon dioxide extraction and their chemical components were analyzed. In addition, their anti-inflammatory activities were investigated by measuring the inhibition of pro-inflammatory cytokines. Monoteipenes alpha-Pinene (22.4%), 2-beta-pinene (20.1%) and camphor (13.1%) were found as the major components in PYE. In the case of SCE, sesquiterpenes delta-cadinol (22.5%) and delta-cadinene (19.7%) as well as a diterpene trans-phytol (13.7%) were mainly identified. The major chemical constituents of ZYE were in the order of octanoic acid (13.4%), n-heptanol (9.8%) and 1-octanol (8.1%). As a bioactivity study, the effects of PYE, SCE and ZPE on nitric oxide (NO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 production in lipopolysaccharide-activated RAW 264.7 macrophages were examined. These essential oils (PYE, SCE, ZPE) were appeared to considerably suppress the production of pro-inflammatory cytokine and mediators in dose-dependent manner. The results indicate that PYE, SCE and ZPE can be useful natural agents to manage inflammatory symptoms and diseases.
No preview · Article · Apr 2013 · International Journal of Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Development of natural products possessing anti-inflammatory activities has been the focus of research in our laboratory. In this study, the extract from Carpinus turczaninowii branches was studied and their anti-inflammatory constituents were identified. The aqueous ethanol extract was fractionated successively to afford n-hexane, ethyl acetate, n-butanol and aqueous layers. Upon anti-inflammatory tests for Nitric Oxide (NO) production, using RAW 264.7 cells, the ethyl acetate fraction exhibited potent inhibitory activities without causing cell toxicities. The ethyl acetate fraction was subjected to further purification to isolate carpinontriol A and carpinontriol B as active constituents. These diarylheptanoid compounds were isolated for the first time from this plant. The isolates reduced the lipopolysaccharide (LPS)-induced secretion of NO and IL-6 productions in a dose-dependent manner in RAW 264.7 cells which indicates their anti-inflammatory effects. Based on these results, it was suggested that C. turczaninowii extracts containing carpinontriols A and B could be considered potential anti-inflammatory agents for pharmaceuticals or cosmetics.
No preview · Article · Feb 2013 · International Journal of Pharmacology