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Additive anti-inflammation by a combination of conjugated linoleic acid and α-lipoic acid through molecular interaction between both compounds

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Abstract

Alpha lipoic acid (LA) and conjugated linoleic acid (CLA) have been well-documented on a variety of functional effects in health foods. The main purpose of this study was focused on the additive anti-inflammatory activity of the combination of LA and CLA in vitro. Raw 264.7 cells induced by lipopolysaccharide were treated with LA and CLA individually or in combination at a variety of concentration ranges. Co-treating 25 μM of LA and 25 μM of CLA significantly inhibited pro-inflammatory cytokines compared to the same concentration of single LA- or CLA-treated group. The molecular mechanism of anti-inflammation by a combination of these compounds was attributed to extracellular signal-regulated kinase-1 (ERK1) and peroxisome proliferator-activated receptor gamma (PPARγ). Also, the molecular interaction between both compounds was confirmed by NMR. Our findings suggested that the combination of CLA and LA showed potential additive effect on anti-inflammation through the molecular interaction of both compounds.

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Abbreviations

AP-1:

Activator protein 1

BCA:

Bicinchoninic acid

CDCl3 :

Deuterated chloroform

CLA:

Conjugaeted linoleic acid

DMEM:

Dulbecco’s modified Eagle’s Media

DMSO:

Dimethyl sulfoxide

ELISA:

Enzyme linked Immunosorbent Assay

ERK:

Extracellular signal-regulated kinase

EtOH:

Ethanol

IL:

Interleukin

iNOS:

inducible nitric oxide synthase

LA:

Lipoic acid

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MEK:

Mitogen-activated protein kinase kinase

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NMR:

Nuclear magnetic resonance

NO:

Nitric oxide

NF-κB:

Nuclear factor kappa-light chain-enhancer of activated B cells

PBS:

Phosphate buffered saline

PPARγ:

Peroxisome proliferator-activated receptor gamma

qRT-PCR:

Quantitative real-time polymerase chain reaction

RIPA:

Radioimmunoprecipitation assay

SEM:

Standard error of the mean

SUMO:

Small ubiquitin-like modifier

TMS:

Tetramethylsilane

TNF-α:

Tumor necrosis factor alpha

TRAF:

Tumor necrosis factor receptor-associated factor

References

  • Baschant U, Tuckermann J. The role of the glucocorticoid receptor in inflammation and immunity. J. Steroid Biochem. Mol. Biol. 120: 69-75 (2010)

    Article  CAS  Google Scholar 

  • Bottomley PA, Foster TH, Argersinger RE, Pfeifer LM. A review of normal tissue hydrogen NMR relaxation times and relaxation mechanisms from 1 to 100 MHz: dependence on tissue type, NMR frequency, temperature, species, excision, and age. Med. Phys. 11: 425-448 (1984)

    Article  CAS  Google Scholar 

  • Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G. A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nat. Cell Biol. 6: 97-105 (2004)

    Article  CAS  Google Scholar 

  • Chen CY, Peng WH, Tsai KD, Hsu SL. Luteolin suppresses inflammation-associated gene expression by blocking NF-kappaB and AP-1 activation pathway in mouse alveolar macrophages. Life Sci. 81: 1602-1614 (2007)

    Article  CAS  Google Scholar 

  • Chen XM, Kitts DD. Determining conditions for nitric oxide synthesis in Caco-2 cells using Taguchi and factorial experimental designs. Anal. Biochem. 381: 185-192 (2008)

    Article  CAS  Google Scholar 

  • Cheng WL, Lii CK, Chen HW, Lin HW, Liu KL. Contribution of conjugated linoleic acid to the suppression of inflammatory responses through the regulation of the NF-kappaB pathway. J. Agric. Food Chem. 52: 71-78 (2004)

    Article  CAS  Google Scholar 

  • Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30: 1073-1081 (2009)

    Article  CAS  Google Scholar 

  • Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu. Rev. Med. 62: 141-155 (2011)

    Article  CAS  Google Scholar 

  • Demarco VG, Scumpia PO, Bosanquet JP, Skimming JW. Alpha-lipoic acid inhibits endotoxin-stimulated expression of iNOS and nitric oxide independent of the heat shock response in RAW 264.7 cells. Free Radic. Res. 38: 675-682 (2004)

    Article  CAS  Google Scholar 

  • Hara T, Kimura I, Inoue D, Ichimura A, Hirasawa A. Free fatty acid receptors and their role in regulation of energy metabolism. Rev. Physiol. Biochem. Pharmacol. 164: 77-116 (2013)

    Article  CAS  Google Scholar 

  • Ibarguren M, Lopez DJ, Escriba PV. The effect of natural and synthetic fatty acids on membrane structure, microdomain organization, cellular functions and human health. Biochim. Biophys. Acta 1838: 1518-1528 (2014)

    Article  CAS  Google Scholar 

  • Karin M. The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem. 270: 16483-16486 (1995)

    Article  CAS  Google Scholar 

  • Maeng YS, Min JK, Kim JH, Yamagishi A, Mochizuki N, Kwon JY, Park YW, Kim YM, Kwon YG. ERK is an anti-inflammatory signal that suppresses expression of NF-kappaB-dependent inflammatory genes by inhibiting IKK activity in endothelial cells. Cell. Signal. 18: 994-1005 (2006)

    Article  CAS  Google Scholar 

  • Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 6: 13 (2014)

    Article  Google Scholar 

  • Moura FA, de Andrade KQ, dos Santos JC, Goulart MO. Lipoic Acid: its antioxidant and anti-inflammatory role and clinical applications. Curr. Top Med. Chem. 15: 458-483 (2015)

    Article  CAS  Google Scholar 

  • Nanny MA, Maza JP. Noncovalent interactions between monoaromatic compounds and dissolved humic acids: a deuterium NMR T1 relaxation study. Environ. Sci. Technol. 35: 379-384 (2001)

    Article  CAS  Google Scholar 

  • O’Quinn PR, Nelssen JL, Goodband RD, Tokach MD. Conjugated linoleic acid. Anim. Health Res. Rev. 1: 35-46 (2000)

    Article  Google Scholar 

  • Ochoa JJ, Farquharson AJ, Grant I, Moffat LE, Heys SD, Wahle KW. Conjugated linoleic acids (CLAs) decrease prostate cancer cell proliferation: different molecular mechanisms for cis-9, trans-11 and trans-10, cis-12 isomers. Carcinogenesis 25: 1185-1191 (2004)

    Article  CAS  Google Scholar 

  • Onakpoya IJ, Posadzki PP, Watson LK, Davies LA, Ernst E. The efficacy of long-term conjugated linoleic acid (CLA) supplementation on body composition in overweight and obese individuals: a systematic review and meta-analysis of randomized clinical trials. Eur. J. Nutr. 51: 127-134 (2012)

    Article  CAS  Google Scholar 

  • Parimisetty A, Dorsemans AC, Awada R, Ravanan P, Diotel N, d’Hellencourt CL. Secret talk between adipose tissue and central nervous system via secreted factors-an emerging frontier in the neurodegenerative research. J. Neuroinflamm. 13: 67 (2016)

    Article  Google Scholar 

  • Pascual G, Fong AL, Ogawa S, Gamliel A, Li AC, Perissi V, Rose DW, Willson TM, Rosenfeld MG, Glass CK. A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437: 759-763 (2005)

    Article  CAS  Google Scholar 

  • Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim. Biophys. Acta 1790: 1149-1160 (2009)

    Article  CAS  Google Scholar 

  • Stachowska E, Dolegowska B, Dziedziejko V, Rybicka M, Kaczmarczyk M, Bober J, Rac M, Machalinski B, Chlubek D. Prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) synthesis is regulated by conjugated linoleic acids (CLA) in human macrophages. J. Physiol. Pharmacol. 60: 77-85 (2009)

    CAS  PubMed  Google Scholar 

  • Suzuki YJ, Aggarwal BB, Packer L. Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells. Biochem. Biophys. Res. Commun. 189: 1709-1715 (1992)

    Article  CAS  Google Scholar 

  • Teichert J, Hermann R, Ruus P, Preiss R. Plasma kinetics, metabolism, and urinary excretion of alpha-lipoic acid following oral administration in healthy volunteers. J. Clin. Pharmacol. 43: 1257-1267 (2003)

    Article  Google Scholar 

  • Vane J, Botting R. Inflammation and the mechanism of action of anti-inflammatory drugs. FASEB J. 1: 89-96. (1987)

    Article  CAS  Google Scholar 

  • Wang A, Al-Kuhlani M, Johnston SC, Ojcius DM, Chou J, Dean D. Transcription factor complex AP-1 mediates inflammation initiated by Chlamydia pneumoniae infection. Cell. Microbiol. 15: 779-794 (2013a)

    Article  CAS  Google Scholar 

  • Wang KC, Tsai CP, Lee CL, Chen SY, Lin GJ, Yen MH, Sytwu HK, Chen SJ. alpha-Lipoic acid enhances endogenous peroxisome-proliferator-activated receptor-gamma to ameliorate experimental autoimmune encephalomyelitis in mice. Clin. Sci. (Lond) 125: 329-340 (2013b)

    Article  CAS  Google Scholar 

  • Zhang WJ, Frei B. Alpha-lipoic acid inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J. 15: 2423-2432 (2001)

    Article  CAS  Google Scholar 

  • Zwirner NW, Ziblat A. Regulation of NK Cell Activation and Effector Functions by the IL-12 Family of Cytokines: The Case of IL-27. Front. Immunol. 8: 25 (2017)

    Article  Google Scholar 

Download references

Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) and Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through Agri-Bio Industry Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (115084-2). Ki-June Lee was supported by Brain Korea 21 Plus program.

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Lee, KJ., Ko, YJ., Kang, SK. et al. Additive anti-inflammation by a combination of conjugated linoleic acid and α-lipoic acid through molecular interaction between both compounds. Food Sci Biotechnol 29, 419–429 (2020). https://doi.org/10.1007/s10068-019-00677-7

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