| Reference | [1]. Int Immunopharmacol. 2015 Mar;25(1):130-40. doi: 10.1016/j.intimp.2015.01.020. Epub 2015 Jan 28.<br />
Phytocomponent 4-hydroxy-3-methoxycinnamaldehyde ablates T-cell activation by targeting protein kinase C-θ and its downstream pathways.<br />
Akber U(1), Na BR(1), Ko YS, Lee HS(1), Kim HR(1), Kwon MS(1), Park ZY(1), Choi EJ(2), Han WC(3), Lee SH(4), Oh HM(5), Jun CD(6).<br />
Author information: (1)School of Life Sciences, Immune Synapse Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea. (2)Division of Sport Science, College of Natural Sciences, Konkuk University, Chungbuk 380-702, Korea. (3)Department of Pathology, Wonkwang University School of Medicine, Iksan, Chonbuk 570-749, Korea. (4)College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea. (5)Bioindustrial Process Research Center, KRIBB, Jeongeup 580-185, Korea. Electronic address: [email protected]. (6)School of Life Sciences, Immune Synapse Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea. Electronic address: [email protected].<br />
Erratum in Int Immunopharmacol. 2015 Jun;26(2):439. Ko, You-Seung [corrected to Ko, Yoo-Seung].<br />
Autoreactive T-cell responses have a crucial role in the pathology and clinical course of autoimmune diseases. Therefore, controlling the activation of these cells is an important strategy for developing therapies and therapeutics. Here, we identified that 4-hydroxy-3-methoxycinnamaldehyde (4H3MC) has a therapeutic potential for T-cell activation by modulating protein kinase C-θ (PKCθ) and its downstream pathways. Pre- and post-treatment with 4H3MC prevented IL-2 release from human transformed and untransformed T cells at the micromolar concentrations without any cytotoxic effects, in fact more efficiently than its structural analogue 4-hydroxycinnamic acid-a previously reported T-cell inhibitor. In silico analysis showed that 4H3MC is a potential inhibitor of PKC isotypes, including PKCθ-a crucial PKC isotype in T cells. Consistently, 4H3MC significantly blocked PKC activity in vitro and also inhibited the phosphorylation of PKCθ in T cells. 4H3MC had no effect on TCR-mediated membrane-proximal-signalling events such as phosphorylation of Zap70. Instead, it attenuated the phosphorylation of mitogen-activated protein kinases (ERK and p38) and promoter activities of NF-κB, AP-1 and NFAT. Taken together, our results provide the evidences that 4H3MC may have curative potential as a novel immune modulator in a broad range of immunopathological disorders by modulating PKCθ activity.<br />
DOI: 10.1016/j.intimp.2015.01.020 PMID: 25637768 [Indexed for MEDLINE]<br />
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[2]. PLoS One. 2015 Dec 10;10(12):e0144521. doi: 10.1371/journal.pone.0144521. eCollection 2015.<br />
Oral Administration of 4-Hydroxy-3-Methoxycinnamaldehyde Attenuates Atopic Dermatitis by Inhibiting T Cell and Keratinocyte Activation.<br />
Lee HS(1), Choi EJ(2), Choi H(2), Lee KS(1), Kim HR(1), Na BR(1), Kwon MS(1), Jeong GS(3), Choi HG(4), Choi EY(5), Jun CD(1).<br />
Author information: (1)School of Life Sciences, Immune Synapse Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea. (2)Division of Sport Science, College of Natural Sciences, Konkuk University, Chungju, Republic of Korea. (3)College of Pharmacy, Keimyung University, Daegu, Republic of Korea. (4)College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea. (5)Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.<br />
Atopic dermatitis (AD) is a skin condition caused by an imbalance of distinct subsets of T helper cells. Previously, we showed that 4-hydroxy-3-methoxycinnamaldehyde (4H3MC) inhibits T cell activation but does not induce apoptosis. Here, we examined the mechanism underlying the inhibitory effect of 4H3MC on AD both in vivo and in vitro. We sought to test the pharmacological effects of 4H3MC using a mouse model of 2, 4-'2,4-dinitrocholorobenzene' (DNCB)- and mite-induced AD. Also, we determined whether 4H3MC affects T cell differentiation and proliferation. Oral administration of 4H3MC attenuated the symptoms of DNCB- and mite-induced AD, including increased ear thickness, serum IgE levels, immune cell infiltration into inflammatory lesions, and pathogenic cytokine expression in ear tissues. In vitro, 4H3MC blocked T cell differentiation into Th1 and Th2 subtypes, as reflected by suppression of T-bet and GATA3, which are key transcription factors involved in T cell differentiation. In addition, 4H3MC downregulated T cell proliferation during Th1 and Th2 differentiation and keratinocyte activation. Collectively, these findings suggest that 4H3MC ameliorates AD symptoms by modulating the functions of effector T cells and keratinocytes.<br />
DOI: 10.1371/journal.pone.0144521 PMCID: PMC4675532 PMID: 26656486 [Indexed for MEDLINE]<br />
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[3]. J Invest Dermatol. 2014 Feb;134(2):551-553. doi: 10.1038/jid.2013.341. Epub 2013 Aug 7.<br />
Downregulation of melanocyte-specific facultative melanogenesis by 4-hydroxy-3-methoxycinnamaldehyde acting as a cAMP antagonist.<br />
Roh E(1), Jeong IY(1), Shin H(1), Song S(1), Doo Kim N(2), Jung SH(3), Tae Hong J(1), Ho Lee S(4), Han SB(1), Kim Y(5).<br />
Author information: (1)College of Pharmacy, Chungbuk National University, Cheongju, Korea. (2)New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea. (3)College of Pharmacy, Chungnam National University, Daejeon, Korea. (4)College of Pharmacy, Yeungnam University, Gyeongsan, Korea. (5)College of Pharmacy, Chungbuk National University, Cheongju, Korea. Electronic address: [email protected].<br />
DOI: 10.1038/jid.2013.341 PMID: 23934066 [Indexed for MEDLINE]<br />
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[4]. ChemSusChem. 2020 Sep 7;13(17):4400-4408. doi: 10.1002/cssc.202001242. Epub 2020 Aug 6.<br />
Importance of Lignin Coniferaldehyde Residues for Plant Properties and Sustainable Uses.<br />
Yamamoto M(1), Blaschek L(2), Subbotina E(3), Kajita S(1), Pesquet E(2).<br />
Author information: (1)Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, Tokyo, 184-8588, Japan. (2)Arrhenius laboratories Department of Ecology, Environment and Plant Sciences, Stockholm University, 106 91, Stockholm, Sweden. (3)Arrhenius laboratories, Department of Organic Chemistry, Stockholm University, 106 91, Stockholm, Sweden.<br />
Increases in coniferaldehyde content, a minor lignin residue, significantly improves the sustainable use of plant biomass for feed, pulping, and biorefinery without affecting plant growth and yields. Herein, different analytical methods are compared and validated to distinguish coniferaldehyde from other lignin residues. It is shown that specific genetic pathways regulate amount, linkage, and position of coniferaldehyde within the lignin polymer for each cell type. This specific cellular regulation offers new possibilities for designing plant lignin for novel and targeted industrial uses.<br />
DOI: 10.1002/cssc.202001242 PMCID: PMC7539997 PMID: 32692480<br />
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[5]. Theranostics. 2020 Jan 1;10(1):179-200. doi: 10.7150/thno.36722. eCollection 2020.<br />
Coniferaldehyde attenuates Alzheimer's pathology via activation of Nrf2 and its targets.<br />
Dong Y(1), Stewart T(2), Bai L(1), Li X(1), Xu T(1), Iliff J(3), Shi M(2), Zheng D(4), Yuan L(1), Wei T(5), Yang X(1), Zhang J(2)(4).<br />
Author information: (1)The State Key Laboratories of Natural and Biomimetic Drugs and Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China. (2)Department of Pathology, University of Washington School of Medicine, Seattle, WA 98104, United States. (3)Department of Anesthesiology and Perioperative Medicine, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, United States. (4)Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. (5)National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.<br />
Background: Alzheimer's disease (AD) currently lacks a cure. Because substantial neuronal damage usually occurs before AD is advanced enough for diagnosis, the best hope for disease-modifying AD therapies likely relies on early intervention or even prevention, and targeting multiple pathways implicated in early AD pathogenesis rather than focusing exclusively on excessive production of β-amyloid (Aβ) species. Methods: Coniferaldehyde (CFA), a food flavoring and agonist of NF-E2-related factor 2 (Nrf2), was selected by multimodal in vitro screening, followed by investigation of several downstream effects potentially involved. Furthermore, in the APP/PS1 AD mouse model, the therapeutic effects of CFA (0.2 mmol kg-1d-1) were tested beginning at 3 months of age. Behavioral phenotypes related to learning and memory capacity, brain pathology and biochemistry, including Aβ transport, were assessed at different time intervals. Results: CFA promoted neuron viability and showed potent neuroprotective effects, especially on mitochondrial structure and functions. In addition, CFA greatly enhanced the brain clearance of Aβ in both free and extracellular vesicle (EV)-contained Aβ forms. In the APP/PS1 mouse model, CFA effectively abolished brain Aβ deposits and reduced the level of toxic soluble Aβ peptides, thus eliminating AD-like pathological changes in the hippocampus and cerebral cortex and preserving learning and memory capacity of the mice. Conclusion: The experimental evidence overall indicated that Nrf2 activation may contribute to the potent anti-AD effects of CFA. With an excellent safety profile, further clinical investigation of coniferaldehyde might bring hope for AD prevention/therapy.<br />
DOI: 10.7150/thno.36722 PMCID: PMC6929631 PMID: 31903114 [Indexed for MEDLINE]<br />
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