The mechanism of anti-inflammatory activity of 2'-hydroxychalcone derivatives

Suzuki, Katsuya; Seung, Ban Hyun; Sung, Lim Soon; Lee, Sang‐Hyun; Hoon, Jung Sang; Sil, Lee Yeon; Hyun, Shin Kuk; Ohuchi, Kazuo

doi:10.2492/jsir.25.130

Cited by 8 publications

(6 citation statements)

References 18 publications

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“…12,29 These particular chalcones were selected for their biological relevance, and also because the OH-2' group in general has been identified as being important in enhancing the biological properties of chalcones, especially anti-inflammatory and antibacterial activities. 30,31 In addition to altering the biological activity of the molecule, the presence of the OH-2' group allows for cyclization of chalcones to flavanones through the light-induced pathway depicted in Figure 1. 32 As a result, 2'-hydroxychalcones interconvert readily to their corresponding flavanones.…”

mentioning

confidence: 99%

Regiospecificity of Human UDP-glucuronosyltransferase Isoforms in Chalcone and Flavanone Glucuronidation Determined by Metal Complexation and Tandem Mass Spectrometry

Niemeyer

Brodbelt

2013

J. Nat. Prod.

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The glucuronidation of a series of chalcones (2'-hydroxychalcone, 2',4'-dihydroxychalcone, 3,2'-dihydroxychalcone, 4,2'-dihydroxychalcone, and cardamonin) and their corresponding cyclized flavanones (7-hydroxyflavanone, 3'-hydroxyflavanone, 4'-hydroxyflavanone, and alpinetin) by nine human UDP-glucuronosyltransferase (UGT) 1A enzymes was evaluated. A post-column metal complexation LC-MS/MS strategy was used successfully to produce characteristic mass spectrometric product ions that were utilized in combination with elution order trends to identify chalcone and flavanone monoglucuronides unambiguously, thus allowing determination of the regioselectivities of the UGT1A isoforms. The presence of hydroxy groups on the A or B-ring had a significant effect on the glucuronide product yield and the site where glucuronidation occurred. For example, for reaction with UGT1A9, formation of the 2'-O-glucuronide was increased for dihydroxychalcones with A-ring hydroxy substituents. In contrast, although UGT1A8 reacted with 3,2'-dihydroxychalcone and 4,2'-dihydroxychalcone to yield 2'-O-glucuronide products, the presence of a B-ring hydroxy group at the 4' position on cardamonin and 2',4'-dihydroxychalcone quenched the reaction at the OH-2' position. Moreover, the A-ring OH-4 group promoted glucuronidation at the 2' position for the reaction of 4,2'-dihydroxychalcone with UGT1A1 and 1A3. For UGT1A7, hydroxy group substituents on the chalcone A-ring also promoted cyclization and formation of the corresponding flavanone glucuronide.

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mentioning

confidence: 99%

Regiospecificity of Human UDP-glucuronosyltransferase Isoforms in Chalcone and Flavanone Glucuronidation Determined by Metal Complexation and Tandem Mass Spectrometry

Niemeyer

Brodbelt

2013

J. Nat. Prod.

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“…Chalcones are a group of aromatic enones that belong to the flavonoid family and have been widely investigated for various pharmacological activities such as anti-tumor, antioxidant, anti-inflammatory, anti-diabetic, and neuroprotective effects [ 2 , 3 ]. Many naturally occurring or synthetic chalcone derivatives have been reported for anti-inflammatory potentials [ 40 , 41 ]. Since chalcones are easy to synthesize, it is possible that naturally occurring chalcones may serve as lead compounds for the further enrichment of the structural diversity or the enhancement of its safety or efficacy for a targeted pharmacological profile.…”

Section: Discussionmentioning

confidence: 99%

The Antioxidant, Anti-Inflammatory, and Neuroprotective Properties of the Synthetic Chalcone Derivative AN07

Chen

Gao

et al. 2020

Molecules

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Chalcones belong to a class of biologically active polyphenolic natural products. As a result of their simple chemical nature, they are easily synthesized and show a variety of promising biological activities. 2-Hydroxy-4′-methoxychalcone (AN07) is a synthetic chalcone derivate with potential anti-atherosclerosis effects. In this study, we demonstrated the novel antioxidant, anti-inflammatory, and neuroprotective effects of AN07. In RAW 264.7 macrophages, AN07 attenuated lipopolysaccharide (LPS)-induced elevations in reactive oxygen species (ROS) level and oxidative stress via down-regulating gp91phox expression and stimulating the antioxidant system of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) pathways, which were accompanied by increased glutathione (GSH) levels. Additionally, AN07 attenuated LPS-induced inflammatory factors, including NO, inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and phosphorylated inhibitor of nuclear factor kappa B-alpha (p-IκBα) in RAW 264.7 macrophages. However, the effects of AN07 on promoting nuclear Nrf2 levels and decreasing COX-2 expressions were significantly abrogated by the peroxisome proliferator-activated receptor-γ (PPARγ) antagonist GW9662. In human dopaminergic SH-SY5Y cells treated with or without methylglyoxal (MG), a toxic endogenous by-product of glycolysis, AN07 up-regulated neurotrophic signals including insulin-like growth factor 1 receptor (IGF-1R), p-Akt, p-GSK3β, glucagon-like peptide 1 receptor (GLP-1R), and brain-derived neurotrophic factor (BDNF). AN07 attenuated MG-induced apoptosis by up-regulating the B-cell lymphoma 2 (Bcl-2) protein and down-regulating the cytosolic expression of cytochrome c. AN07 also attenuated MG-induced neurite damage via down-regulating the Rho-associated protein kinase 2 (ROCK2)/phosphorylated LIM kinase 1 (p-LIMK1) pathway. Moreover, AN07 ameliorated the MG-induced down-regulation of neuroprotective Parkinsonism-associated proteins parkin, pink1, and DJ-1. These findings suggest that AN07 possesses the potentials to be an anti-inflammatory, antioxidant, and neuroprotective agent

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“…Compound 13 and other 2 0 -hydroxychalcone derivatives inhibited PGE 2 production through the suppression of COX-2 and inhibited both NO and TNF-a production through the inhibition of the expression of iNOS and TNF-a mRNA in RAW264.7 cells. They also suppressed the LPSinduced activation of NF-jB and AP-1, indicating that inhibition of production of PGE 2 , NO and TNF-a is due to inhibition of NF-jB and AP-1 activation (Suzuki et al 2005).…”

Section: Chemoprevetive Properties Of Natural Chalconesmentioning

confidence: 97%

Naturally occurring chalcones and their biological activities

2014

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The aim of this review is to summarize the various naturally occurring chalcone compounds which have been isolated from different plants. Chalcones considered as obligate intermediated in flavonoid biosynthesis but they do not accumulate to appreciable degree in most plants. The largest number of natural chalcones has been isolated from species of the Leguminosae, Asteraceae and Moraceae families. Chalcone accumulating plants have often been used in traditional medicine and chalcones have therefore been studied and reported to possess many beneficial biological effects including anti-inflammatory, antimicrobial, antifungal, antioxidant, cytotoxic, antitumor and chemopreventive activities. Previously published reviews on this topic survey the biological activities of natural and synthetic chalcones but there are no comprehensive contributions on occurrence and biological activities of natural chalcones. The present study provides an overview of hydroxy or/and methoxy-substituted chalcones, methylated, prenylated, geranylated and other monomeric derivatives, chromeno-and furanochalcones, dimeric chalcones and dihydrochalcone derivatives focusing on their biosynthesis, natural sources and biological activities. On the basis of 608 references, this review covers the phytochemistry and biological activity of natural chalcones, describing 646 compounds have been appeared in the literature since 1975. The summary is aimed to initiate further pharmacobotanical, biotechnological and medicinal studies on the field of chalcone research.

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The mechanism of anti-inflammatory activity of 2'-hydroxychalcone derivatives

Cited by 8 publications

References 18 publications

Regiospecificity of Human UDP-glucuronosyltransferase Isoforms in Chalcone and Flavanone Glucuronidation Determined by Metal Complexation and Tandem Mass Spectrometry

Regiospecificity of Human UDP-glucuronosyltransferase Isoforms in Chalcone and Flavanone Glucuronidation Determined by Metal Complexation and Tandem Mass Spectrometry

The Antioxidant, Anti-Inflammatory, and Neuroprotective Properties of the Synthetic Chalcone Derivative AN07

Naturally occurring chalcones and their biological activities

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