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Pharmacological Applications of Lucidone: A Naturally Occurring Cyclopentenedione

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Medicinal Plants - Recent Advances in Research and Development

Abstract

Lindera erythrocarpa, commonly known as spicewood or spicebush, has a long history of use as a traditional remedy and culinary spice. Recent studies have reported that lucidone, an active constituent of fruits and leaves of Lindera erythrocarpa, has various beneficial properties, such as antioxidant, anti-inflammatory, hepatoprotective, dermatoprotective, hypolipidemic, and skin-whitening effects. The pleiotropic activities of lucidone derive from its unique chemistry as well as its ability to modulate multiple signaling pathways, such as inflammatory signaling pathways regulated by NF-κB and MAPKs; cytoprotective pathway that depends on Nrf2 activation and inhibition of apoptosis; hypolipidemic pathway regulated by PPRγ and C/EBPα; and anti-melanogenic pathway modulated by MITF. Also, lucidone is remarkably low cytotoxic and exhibits limited bioavailability. These findings suggest that lucidone is a promising agent for the treatment of inflammatory and oxidative diseases.

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Abbreviations

AAPH:

2,2′-Azobis(2-amidinopropane) dihydrochloride

ALT:

Alanine aminotransferase

AP-1:

Activator protein-1

ARE:

Antioxidant response element

AST:

Aspartate aminotransferase

ATF-2:

Activating transcription factor-2

cAMP:

Cyclic adenosine monophosphate

COX-2:

Cyclooxygenase-2

EMSA:

Electrophoretic mobility shift assay

ERK:

Extracellular signal-regulated kinase

GSH:

Glutathione

HF:

High fat

HO-1:

Heme oxygenase-1

IκB:

Inhibitor of nuclear factor kappa-B

IKK:

IκB kinase

iNOS:

Inducible nitric oxide synthase

JNK:

c-JUN N-terminal kinase

LDH:

Lactate dehydrogenase

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MDA:

Malondialdehyde

MITF:

Microphthalmia-associated transcription factor

MKK:

Mitogen kinase kinase

NAFLD:

Nonalcoholic fatty liver diseases

NF-κB:

Nuclear factor kappa-B

NO:

Nitric oxide

Nrf2:

Nuclear factor E2-related factor-2

PGE2 :

Prostaglandin-E2

PPARγ:

Peroxisome proliferator-activated receptor-γ

ROS:

Reactive oxygen species

SAPK:

Stress-activated protein kinase

TGF-β:

Transforming growth factor-β

TNF-α:

Tumor necrosis factor alpha

TRP:

Tyrosinase-related proteins

UVA:

Ultraviolet A

α-MSH:

Alpha-melanocyte-stimulating hormone

References

  • Altalbawy FMA (2013) Synthesis and antimicrobial evaluation of some novel bis-α, β-unsaturated ketones, nicotinonitrile, 1,2-dihydropyridine-3-carbonitrile, fused thieno[2,3-b]pyridine and pyrazolo[3,4-b]pyridine derivatives. Int J Mol Sci 14(2):2967–2979. doi:10.1139/v02-194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Antkowiak R, Antkowiak WZ, Banczyk I et al (2003) A new phenolic metabolite, involutone, isolated from the mushroom Paxillus involutus. Can J Chem 81(1):118–124. doi:10.1139/v02-194

    Google Scholar 

  • Babu KS, Li XC, Jacob MR et al (2006) Synthesis, antifungal activity, and structure-activity relationships of coruscanone A analogues. J Med Chem 49(26):7877–7886. doi:10.1021/jm061123i

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bag S, Ghosh S, Tulsan R et al (2013) Design, synthesis and biological activity of multifunctional α, β- unsaturated carbonyl scaffolds for Alzheimer’s disease. Bioorg Med Chem Lett 23(9):2614–2618. doi:10.1016/j.bmcl.2013.02.103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bao W, Li K, Rong S et al (2010) Curcumin alleviates ethanol-induced hepatocytes oxidative damage involving heme oxygenase-1 induction. J Ethnopharmacol 128(2):549–553. doi:10.1016/j.jep.2010.01.029

    Article  CAS  PubMed  Google Scholar 

  • Braudeau C, Bouchet D, Toquet C et al (2003) Generation of heme oxygenase-1-transgenic rats. Exp Biol Med (Maywood) 228(5):466–471

    CAS  Google Scholar 

  • Chang TS (2012) Natural melanogenesis inhibitors acting through the down-regulation of tyrosinase activity. Materials 5(9):1661

    Article  CAS  Google Scholar 

  • Chen WC, Wang SY, Chiu CC et al (2013) Lucidone suppresses hepatitis C virus replication by Nrf2-mediated heme oxygenase-1 induction. Antimicrob Agents Ch 57(3):1180–1191. doi:10.1128/AAC.02053-12

    Article  CAS  Google Scholar 

  • Chen S, Wang L, Zhang W et al (2015) Secondary metabolites from the root of Lindera reflexa Hemsl. Fitoterapia 105:222–227. doi:10.1016/j.fitote.2015.07.005

    Article  CAS  PubMed  Google Scholar 

  • Comai S, Dall’Acqua S, Grillo A et al (2010) Essential oil of Lindera neesiana fruit: chemical analysis and its potential use in topical applications. Fitoterapia 81(1):11–16. doi:10.1016/j.fitote.2009.06.017

    Google Scholar 

  • Davis RL, Dertien J, Syapin PJ (2002) Ethanol-induced modulation of inducible nitric-oxide synthase activity in human A172 astrocytoma cells. Alcohol Clin Exp Res 26(9):1404–1411. doi:10.1097/01.ALC.0000030841.92766.80

    Article  CAS  PubMed  Google Scholar 

  • Deng XS, Deitrich RA (2007) Ethanol metabolism and effects: nitric oxide and its interaction. Curr Clin Pharmacol 2(2):145–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deng Z, Zhong H, Cui S et al (2011) Cytotoxic sesquiterpenoids from the fruits of Lindera communis. Fitoterapia 82(7):1044–1046. doi:10.1016/j.fitote.2011.06.012

    Google Scholar 

  • Farombi EO, Shrotriya S, Na HK et al (2008) Curcumin attenuates dimethylnitrosamine-induced liver injury in rats through Nrf2-mediated induction of heme oxygenase-1. Food Chem Toxicol 46(4):1279–1287. doi:10.1016/j.fct.2007.09.095

    Article  CAS  PubMed  Google Scholar 

  • Ferguson BS, Nam H, Morrison RF (2016) Curcumin inhibits 3T3-L1 preadipocyte proliferation by mechanisms involving post-transcriptional p27 regulation. Biochem Biophys Rep 5:16–21. doi:10.1016/j.bbrep.2015.11.014

    PubMed  Google Scholar 

  • Fernández Checa JC, Bellentani S, Tiribelli C (2002) Alcohol-induced liver disease: from molecular damage to treatment. Rev Med Chil 130:681–690

    Article  PubMed  Google Scholar 

  • Fernandez-Checa JC, Colell A, Mari M et al (2005) Ceramide, tumor necrosis factor and alcohol-induced liver disease. Alcohol Clin Exp Res 29(11):151S–157S

    CAS  PubMed  Google Scholar 

  • Hong M, Li S, Tan HY (2015) Current status of herbal medicines in chronic liver disease therapy: the biological effects, molecular targets and future prospects. Int J Mol Sci 16(12):28705–28745. doi:10.3390/ijms161226126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsieh YH, Wang SY (2013) Lucidone from Lindera erythrocarpa Makino fruits suppresses adipogenesis in 3T3-L1 cells and attenuates obesity and consequent metabolic disorders in high-fat diet C57BL/6 mice. Phytomedicine 20(5):394–400. doi:10.1016/j.phymed.2012.11.007

    Article  CAS  PubMed  Google Scholar 

  • Joshi SC, Mathela CS (2012) Antioxidant and antibacterial activities of the leaf essential oil and its constituents furanodienone and curzerenone from Lindera pulcherrima (Nees.) Benth. ex Hook. f. Phcog Res 4(2):80–84. doi:10.4103/0974-8490.94721

    Google Scholar 

  • Kang MC, Ko RK, Lee JY, et al (2008) Antioxidant activity and whitening effect of Lindera erythrocarpa extract. www.earticle.net/article.aspx?sn=99232

  • Kim YJ, Uyama H (2005) Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future. Cell Mol Life Sci 62(15):1707–1723. doi:10.1007/s00018-005-5054-y

    Article  CAS  PubMed  Google Scholar 

  • Kumar KJS, Yang JC, Chu FH et al (2010) Lucidone, a novel melanin inhibitor from the fruit of Lindera erythrocarpa Makino. Phytother Res 24(8):1158–1165. doi:10.1002/ptr.3018

    CAS  PubMed  Google Scholar 

  • Kumar KJS, Yang HL, Tsai YC et al (2013) Lucidone protects human skin keratinocytes against free radical-induced oxidative damage and inflammation through the up-regulation of HO-1/Nrf2 antioxidant genes and down-regulation of NF-kappaB signaling pathway. Food Chem Toxicol 59:55–66. doi:10.1016/j.fct.2013.04.055

    Article  PubMed  Google Scholar 

  • Lee JY, Park HR, Oh YK et al (2007) Effects of transcription factor activator protein-1 on interleukin-8 expression and enteritis in response to Clostridium difficile toxin A. J Mol Med 85(12):1393–1404. doi:10.1007/s00109-007-0237-7

    Google Scholar 

  • Lin JK (2007) Molecular targets of curcumin. Adv Exp Med Biol 595:227–243. doi:10.1007/978-0-387-46401-5_10

    Article  PubMed  Google Scholar 

  • Lin CT, Chu FH, Chang ST et al (2007) Secoaggregatalactone-A from Lindera aggregata induces apoptosis in human hepatoma hep G2 cells. Planta Med 73(15):1548–1553. doi:10.1055/s-2007-993739

    Google Scholar 

  • Majano PL, Medina J, Zubia I et al (2004) N-Acetyl-cysteine modulates inducible nitric oxide synthase gene expression in human hepatocytes. J Hepatol 40(4):632–637. doi:10.1016/j.jhep.2003.12.009

    Article  CAS  PubMed  Google Scholar 

  • Marks MS, Seabra MC (2001) The melanosome: membrane dynamics in black and white. Nat Rev Mol Cell Biol 2(10):738–748

    Article  CAS  PubMed  Google Scholar 

  • Moon HS, Chung CS, Lee HG et al (2007) Inhibitory effect of (-)-epigallocatechin-3-gallate on lipid accumulation of 3T3-L1 cells. Obesity 15(11):2571–2582. doi:10.1038/oby.2007.309

    Article  CAS  PubMed  Google Scholar 

  • Ng S, Lee HH, Bennett GJ (1990) 13C NMR study on linderones and lucidones. Magn Reson Chem 28(4):337–342. doi:10.1002/mrc.1260280411

    Article  CAS  Google Scholar 

  • Noble M, Noble D, Fletton RA (1978) G2201-C, a new cyclopentenedione antibiotic, isolated from the fermentation broth of Streptomyces cattleya. J Antibiot 31(1):15–18

    Google Scholar 

  • Oh HM, Choi SK, Lee JM et al (2005) Cyclopentenediones, inhibitors of farnesyl protein transferase and anti-tumor compounds, isolated from the fruit of Lindera erythrocarpa Makino. Bioorg Med Chem 13(22):6182–6187. doi:10.1016/j.bmc.2005.06.029

    Article  CAS  PubMed  Google Scholar 

  • Pan MH, Chiou YS, Wang YJ et al (2011) Multistage carcinogenesis process as molecular targets in cancer chemoprevention by epicatechin-3-gallate. Food Funct 2(2):101–110. doi:10.1039/c0fo00174k

    Article  CAS  PubMed  Google Scholar 

  • Pang B, Zhao LH, Zhou Q et al (2015) Application of berberine on treating type 2 diabetes mellitus. Int J Entocrinol 2015:905749. doi:10.1155/2015/905749

    Google Scholar 

  • Park G, Kim HG, Sim Y et al (2013) Sauchinone, a lignan from Saururus chinensis, protects human skin keratinocytes against ultraviolet B-induced photoaging by regulating the oxidative defense system. Biol Pharm Bull 36(7):1134–1139

    Article  CAS  PubMed  Google Scholar 

  • Patani GA, LaVoie EJ (1996) Bioisosterism: a rational approach in drug design. Chem Rev 96(8):3147–3176

    Article  CAS  PubMed  Google Scholar 

  • Pirola L, Frojdo S (2008) Resveratrol: one molecule, many targets. IUBMB Life 60(5):323–332. doi:10.1002/iub.47

    Article  CAS  PubMed  Google Scholar 

  • Senthil Kumar KJ, Wang SY (2009) Lucidone inhibits iNOS and COX-2 expression in LPS-induced RAW 264.7 murine macrophage cells via NF-kappaB and MAPKs signaling pathways. Planta Med 75(5):494–500. doi:10.1055/s-0029-1185309

    Google Scholar 

  • Senthil Kumar KJ, Hsieh HW, Wang SY (2010) Anti-inflammatory effect of lucidone in mice via inhibition of NF-kappaB/MAP kinase pathway. Int Immunopharmacol 10(4):385–392. doi:10.1016/j.intimp.2009.12.013

    Google Scholar 

  • Senthil Kumar KJ, Liao JW, Xiao JH et al (2012) Hepatoprotective effect of lucidone against alcohol-induced oxidative stress in human hepatic HepG2 cells through the up-regulation of HO-1/Nrf-2 antioxidant genes. Toxicol in Vitro 26(5):700–708. doi:10.1016/j.tiv.2012.03.012

    Google Scholar 

  • Sevcikova Z, Pour M, Novak D et al (2014) Chemical properties and biological activities of cyclopentenediones: a review. Mini Rev Med Chem 14(4):322–331

    Article  CAS  PubMed  Google Scholar 

  • Stauber RE, Stadlbauer V (2006) Novel approaches for therapy of chronic hepatitis C. J Clin Virol 36(2):87–94. doi:10.1016/j.jcv.2006.02.003

    Article  CAS  PubMed  Google Scholar 

  • Surh YJ (2003) Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 3(10):768–780. doi:10.1038/nrc1189

    Article  CAS  PubMed  Google Scholar 

  • Surh YJ, Han S, Keum YS et al (2000) Inhibitory effects of curcumin and capsaicin on phorbol ester-induced activation of eukaryotic transcription factors, NF-kappaB and AP-1. Biofactors 12(1–4):107–112

    Article  CAS  PubMed  Google Scholar 

  • Tichotova L, Matousova E, Spulak M et al (2011) Synthesis and biological activity of desmethoxy analogues of coruscanone A. Bioorg Med Chem Lett 21(20):6062–6066. doi:10.1016/j.bmcl.2011.08.059

    Article  CAS  PubMed  Google Scholar 

  • Wang SY, Lan XY, Xiao JH et al (2008) Antiinflammatory activity of Lindera erythrocarpa fruits. Phytother Res 22(2):213–216. doi:10.1002/ptr.2289

    Article  CAS  PubMed  Google Scholar 

  • Watt KD, Charlton MR (2010) Metabolic syndrome and liver transplantation: a review and guide to management. J Hepatol 53(1):199–206. doi:10.1016/j.jhep.2010.01.040

    Article  PubMed  Google Scholar 

  • Wijeratne EM, Turbyville TJ, Zhang Z et al (2003) Cytotoxic constituents of Aspergillus terreus from the rhizosphere of Opuntia versicolor of the Sonoran Desert. J Nat Prod 66(12):1567–1573. doi:10.1021/np030266u

    Article  CAS  PubMed  Google Scholar 

  • Wu L, Xiao F, Hu X (2013) Concise synthesis of lucidone and methyl lucidone. Chin J Org Chem 33(7):1587

    Article  Google Scholar 

  • Yang CP, Huang GJ, Huang HC et al (2013) The effect of the aerial part of Lindera akoensis on lipopolysaccharides (LPS)-induced nitric oxide production in RAW264.7 cells. Int J Mol Sci 14(5):9168–9181. doi:10.3390/ijms14059168

    Google Scholar 

  • Yao P, Nussler A, Liu L et al (2007) Quercetin protects human hepatocytes from ethanol-derived oxidative stress by inducing heme oxygenase-1 via the MAPK/Nrf2 pathways. J Hepatol 47(2):253–261. doi:10.1016/j.jhep.2007.02.008

    Article  CAS  PubMed  Google Scholar 

  • Zelik P, Lukesova A, Cejka J et al (2010) Nostotrebin 6, a bis(cyclopentenedione) with cholinesterase inhibitory activity isolated from Nostoc sp. str. Lukesova 27/97. J Enzym Inhib Med Chem 25(3):414–420. doi:10.3109/14756360903213481

    Article  CAS  Google Scholar 

  • Zhao Q, Zhao Y, Wang K (2006) Antinociceptive and free radical scavenging activities of alkaloids isolated from Lindera angustifolia Chen. J Ethnopharmacol 106(3):408–413. doi:10.1016/j.jep.2006.01.019

    Google Scholar 

  • Zhao YY, Xiao M, Zhang CL et al (2015) Associations between the tumor necrosis factor-alpha gene and interleukin-10 gene polymorphisms and risk of alcoholic liver disease: a meta-analysis. Clin Res Hepatol Gastroenterol. doi:10.1016/j.clinre.2015.10.007

    Google Scholar 

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Authors and Affiliations

  1. Department of Forestry, National Chung Hsing University, Taichung, Taiwan

    K. J. Senthil Kumar & Sheng-Yang Wang

  2. Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan

    Sheng-Yang Wang

Authors
  1. K. J. Senthil Kumar
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  2. Sheng-Yang Wang
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Corresponding author

Correspondence to Sheng-Yang Wang .

Editor information

Editors and Affiliations

  1. Department of Applied Chemistry, Chaoyang University of Technology, Taichung, Taiwan

    Hsin-Sheng Tsay

  2. Agricultural Biotechnology Research Center, Taipei, Taiwan

    Lie-Fen Shyur

  3. Department of Applied Chemistry, Chaoyang University of Technology, Taichung, Taiwan

    Dinesh Chandra Agrawal

  4. School of Pharmacy and Chinese Herbal Medicine Research Center, China Medical University, Taichung, Taiwan

    Yang-Chang Wu

  5. College of Agriculture and Natural Resources, Department of Forestry, National Chung Hsing University, Taichung, Taiwan

    Sheng-Yang Wang

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Senthil Kumar, K.J., Wang, SY. (2016). Pharmacological Applications of Lucidone: A Naturally Occurring Cyclopentenedione. In: Tsay, HS., Shyur, LF., Agrawal, D., Wu, YC., Wang, SY. (eds) Medicinal Plants - Recent Advances in Research and Development. Springer, Singapore. https://doi.org/10.1007/978-981-10-1085-9_11

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