Lucidone, a novel melanin inhibitor from the fruit of <i>Lindera erythrocarpa</i> Makino

Kumar, K. J. Senthil; Yang, Jeong-Mo; Chu, Feng-Hua; Chang, Shang-Tzen; Wang, Sheng-Yang

doi:10.1002/ptr.3018

Cited by 40 publications

(27 citation statements)

References 27 publications

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“…The lucidone derivatives, such as methyllinderone and methyllucidone, also exhibited anti-inflammation activity and anti-farnesyl protein transferase (16,17). Recent in vitro and animal model studies have demonstrated that lucidone exerts anti-inflammatory activity with significant suppression of iNOS and COX-2 production (16,18) and antimelanogenic activity (19). In the present study, we characterize the anti-HCV activity of lucidone and evaluate its possible mechanism of action against HCV replication.…”

mentioning

confidence: 92%

Lucidone Suppresses Hepatitis C Virus Replication by Nrf2-Mediated Heme Oxygenase-1 Induction

Chen

Wang

Chiu

et al. 2013

Antimicrob Agents Chemother

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dUpon screening of plant-derived natural products against hepatitis C virus (HCV) in the replicon system, we demonstrate that lucidone, a phytocompound, isolated from the fruits of Lindera erythrocarpa Makino, significantly suppressed HCV RNA levels with 50% effective concentrations of 15 ؎ 0.5 M and 20 ؎ 1.1 M in HCV replicon and JFH-1 infectious assays, respectively. There was no significant cytotoxicity observed at high concentrations, with a 50% cytotoxic concentration of 620 ؎ 5 M. In addition, lucidone significantly induced heme oxygenase-1 (HO-1) production and led to the increase of its product biliverdin for inducing antiviral interferon response and inhibiting HCV NS3/4A protease activity. Conversely, the anti-HCV activity of lucidone was abrogated by blocking HO-1 activity or silencing gene expression of HO-1 or NF-E2-related factor 2 (Nrf2) in the presence of lucidone, indicating that the anti-HCV action of lucidone was due to the stimulation of Nrf-2-mediated HO-1 expression. Moreover, the combination of lucidone and alpha interferon, the protease inhibitor telaprevir, the NS5A inhibitor BMS-790052, or the NS5B polymerase inhibitor PSI-7977, synergistically suppressed HCV RNA replication. These findings suggest that lucidone could be a potential lead or supplement for the development of new anti-HCV agent in the future.A pproximately 170 million people across the world are infected with hepatitis C virus (HCV). The virus causes chronic inflammation of the liver that ultimately leads to severe consequences such as cirrhosis and hepatocellular carcinoma (1). The HCV genome is a 9.6-kb positive single-strand RNA molecule encoding a single polyprotein of 3,000 amino acids that is processed by viral and cellular proteases to produce structural (C, E1, and E2) and nonstructural (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) proteins (2). Pegylated alpha interferon (PEG-IFN-␣) combined with ribavirin is the only recommended standard therapy for hepatitis C patients at present. However, the current therapeutic regimens only achieve a 40 to 50% cure rate in genotype 1 HCV-infected patients (3). In addition, the severe side effects of the current treatments, including depression, fatigue, flu-like symptoms, and hemolytic anemia, often lead to treatment discontinuation (4). Despite recent advancement of therapeutics with the approval of NS3/4A protease inhibitors, telaprevir and boceprevir, in combination with PEG-IFN-␣ and ribavirin, viral resistance and side effect to both inhibitors was still observed in clinical studies (5-7). Therefore, it is essential to develop new anti-HCV agents for therapeutic purposes.Heme oxygenase-1 (HO-1), the rate-limiting enzyme in the oxidative degradation of heme, protects against oxidative stress and liver inflammation (8). Its reaction products including biliverdin, carbon monoxide, and ferrous iron are regarded as potential cytoprotectants (9). Among the various intracellular molecules capable of inducing HO-1, BTB and CNC homolog 1 (Bach1) and nuclear factor erythroid-derived 2 r...

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confidence: 92%

Lucidone Suppresses Hepatitis C Virus Replication by Nrf2-Mediated Heme Oxygenase-1 Induction

Chen

Wang

Chiu

et al. 2013

Antimicrob Agents Chemother

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“…The synthesis of novel CPDs is often devoted to modification of natural CPDs resulting in structure-activity relationship (SAR) studies and subsequent discoveries of novel bioactives with applicability in chemical technologies, biotechnology and biomedicine fields. Among well studied CPD representatives are lucidone and linderone with anti-inflammatory activities [2][3][4][5], cytostatic compound TX-1123 [6], involutone constituent of fungi Paxillus involutus [7][8][9], madindolines [10][11][12][13] and nostotrebin 6 [14][15][16] attributed to enzyme inhibitory effects. The novel synthetic approaches are primarily focused on total synthesis of above-mentioned CPDs and also on strategies for development of structurally simplified CPDs with biological, especially antibacterial and antifungal activities.…”

Section: Introductionmentioning

confidence: 99%

Dimeric cyanobacterial cyclopent-4-ene-1,3-dione as selective inhibitor of Gram-positive bacteria growth: Bio-production approach and preparative isolation by HPCCC

et al. 2016

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a b s t r a c tThe need for new antimicrobial agents is greater than ever because of the emergence of multidrug resistance in common pathogens and incidence of new infections. Cyclopent-4-ene-1,3-diones (CPDs) have been reported as a new class of compounds with promising antimicrobial and antifungal properties. Herein we report the selective antibiotic properties of nostotrebin 6, a phenolic CPD produced biotechnologically by the culture of cyanobacterium Nostoc sp. str. Lukešová 27/97. High performance countercurrent chromatography (HPCCC) combined with gel permeation chromatography (GPC) was used for the isolation of nostotrebin 6 with a relatively high 0.53 ± 0.1% yield (calculated from dried biomass) and final purity higher than 96%. Nostotrebin 6 was tested for its antimicrobial and antifungal activities by using standard micro-dilution method, and the results were expressed as minimal inhibitory concentrations (MICs). Nostotrebin 6 unequivocally inhibited the growth of Gram-positive reference (Enterococcus faecalis CCM 4224, Staphylococcus aureus CCM 4223 and Staphylococcus aureus CCM 3953) and multidrug-resistant (Staphylococcus haemolyticus A/16568, Staphylococcus aureus MRSA 4591 and Enterococcus faecium VanA 419/ana) strains. Its strongest effect was exerted against the Gram-positive bacteria with MICs ranging between 6.25 and 15.6 μg/mL. There was no effect on Gram-negative strains tested and yeasts. Our results suggest that nostotrebin 6 could serve as basic nucleus for further design of novel antibiotic agents and demonstrate that the bio-production approach based on HPCCC/GPC isolation endpoint is an efficient methodology for obtaining nostotrebin 6 in multi-gram scale. Furthermore, the presented isolation method can be easily up-scaled to process kilograms of the cyanobacterial biomass.

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“…Smalley et al 12) reported that the levels of ERK1/2 phosphorylation in B16 cells were enhanced by α-MSH (10 nM) treatment. In contrast, according to the paper by Kumar et al,18) the level of phosphorylation was not affected in the presence of α-MSH (100 nM). In our experiment, phosphorylation was suppressed time-dependently at 6 and 12 h, regardless of the presence or absence of α-MSH (Fig.…”

Section: Effect Of Noni Extracts On Melanogenesis In α-Mshstimulated mentioning

confidence: 73%

Inhibitory Effects of Morinda citrifolia Extract and Its Constituents on Melanogenesis in Murine B16 Melanoma Cells

Masuda

Itoh

Murata

et al. 2012

Biological & Pharmaceutical Bulletin

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The objective of this study was to examine the effects of Morinda citrifolia (noni) extract and its constituents on α-melanocyte stimulating hormone (α-MSH)-stimulated melanogenesis in cultured murine B16 melanoma cells (B16 cells). A 50% ethanolic extract of noni seeds (MCS-ext) showed significant inhibition of melanogenesis with no effect on cell proliferation. MCS-ext was more active than noni leaf and fruit flesh extracts. Activity guided fractionation of MCS-ext led to the isolation of two lignans, 3,3′-bisdemethylpinoresinol (1) and americanin A (2), as active constituents. To elucidate the mechanism of melanogenesis inhibition by the lignans, α-MSH-stimulated B16 cells were treated with 1 (5 μM) and 2 (200 μM). Time-dependent increases of intracellular melanin content and tyrosinase activity, during 24 to 72 h, were inhibited significantly by treatment with the lignans. The activity of 1 was greater than that of 2. Western blot analysis suggested that the lignans inhibited melanogenesis by down regulation of the levels of phosphorylation of p38 mitogenactivated protein kinase, resulting in suppression of tyrosinase expression.Key words Morinda citrifolia; noni seed; B16 melanoma cell; tyrosinase; 3,3′-bisdemethylpinoresinol; americanin A Melanogenesis is a multistage process involving melanin synthesis, melanin transport, and melanosome release. Tyrosinase is one of the key enzymes in the melanin biosynthetic pathway. Abnormal deposition of melanin pigment causes hyperpigmentary disorders, such as melasma, freckles and age spots. Tyrosinase inhibitor is one of the candidates for reduction of melanogenesis. 1,2) In the development of novel and useful cosmetic agents and functional foods, we have continued to research melanin hyperpigmentation inhibitors from natural sources. The fruit, roots, bark and leaves of a tropical tree, Morinda citrifolia L. (Rubiaceae), commonly known as "noni" in Hawaii and Tahiti, have long been used throughout Polynesia as a folk medicine in the treatment of many diseases, e.g. hypertension and diabetes.3) Recently, the noni fruit juice and tea made from noni leaves have been introduced into the functional food market. Noni fruit contains a large number of seed throughout its flesh. During the production of noni fruit juice, these seeds are removed and discarded. Consequently, we have investigated the utility of noni seeds. In a previous paper, 4) we reported the tyrosinase inhibitory activity and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity of 50% ethanolic extracts of noni seeds, fruit flesh and leaves. A 50% ethanolic extract from noni seeds (MCS-ext) inhibited tyrosinase activity and scavenged the DPPH radical more potently than extracts from the leaves or fruit. Activity-guided fractionation, followed by chromatography of MCS-ext, led to the isolation of 3,3′-bisdemethylpinoresinol (1), americanin A (2) and quercetin (3), as active constituents with both tyrosinase inhibitory and radical scavenging activities. 4) After the publication of our previous pa...

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Lucidone, a novel melanin inhibitor from the fruit of Lindera erythrocarpa Makino

Cited by 40 publications

References 27 publications

Lucidone Suppresses Hepatitis C Virus Replication by Nrf2-Mediated Heme Oxygenase-1 Induction

Lucidone Suppresses Hepatitis C Virus Replication by Nrf2-Mediated Heme Oxygenase-1 Induction

Dimeric cyanobacterial cyclopent-4-ene-1,3-dione as selective inhibitor of Gram-positive bacteria growth: Bio-production approach and preparative isolation by HPCCC

Inhibitory Effects of Morinda citrifolia Extract and Its Constituents on Melanogenesis in Murine B16 Melanoma Cells

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