Anti-Inflammatory and Antinociceptive Activities of Anthraquinone-2-Carboxylic Acid

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2016 Apr 9

PMID 27057092

Citations 21

Authors

Jae Gwang Park

Seung Cheol Kim

Yun Hwan Kim

Woo Seok Yang

Yong Kim

Sungyoul Hong

Kyung-Hee Kim

Byong Chul Yoo

Shi Hyung Kim

Jong-Hoon Kim

Jae Youl Cho

Affiliations

Soon will be listed here.

Abstract

Anthraquinone compounds are one of the abundant polyphenols found in fruits, vegetables, and herbs. However, the in vivo anti-inflammatory activity and molecular mechanisms of anthraquinones have not been fully elucidated. We investigated the activity of anthraquinones using acute inflammatory and nociceptive experimental conditions. Anthraquinone-2-carboxylic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA), one of the major anthraquinones identified from Brazilian taheebo, ameliorated various inflammatory and algesic symptoms in EtOH/HCl- and acetylsalicylic acid- (ASA-) induced gastritis, arachidonic acid-induced edema, and acetic acid-induced abdominal writhing without displaying toxic profiles in body and organ weight, gastric irritation, or serum parameters. In addition, AQCA suppressed the expression of inflammatory genes such as cyclooxygenase- (COX-) 2 in stomach tissues and lipopolysaccharide- (LPS-) treated RAW264.7 cells. According to reporter gene assay and immunoblotting analyses, AQCA inhibited activation of the nuclear factor- (NF-) κB and activator protein- (AP-) 1 pathways by suppression of upstream signaling involving interleukin-1 receptor-associated kinase 4 (IRAK1), p38, Src, and spleen tyrosine kinase (Syk). Our data strongly suggest that anthraquinones such as AQCA act as potent anti-inflammatory and antinociceptive components in vivo, thus contributing to the immune regulatory role of fruits and herbs.

Citing Articles

9,10-Dioxoanthracenyldithiocarbamates effectively inhibit the proliferation of non-small cell lung cancer by targeting multiple protein tyrosine kinases.

Olszewski M, Stasevych M, Zvarych V, Maciejewska N J Enzyme Inhib Med Chem. 2023; 39(1):2284113.

PMID: 38078360 PMC: 11721965. DOI: 10.1080/14756366.2023.2284113.

Safety and tolerability of Pau d' Arco ( for primary dysmenorrhea: A single-arm, open-label trial on adults ages 18-45.

McClure C, Bollen M, Buttolph L, Stack E, Langley B, Hanes D Adv Integr Med. 2023; 9(3):159-166.

PMID: 36960315 PMC: 10032363. DOI: 10.1016/j.aimed.2022.04.003.

2-Bromoanthraquinone as a highly efficient photocatalyst for the oxidation of -aromatic alcohols: experimental and DFT study.

Liao S, Liu J, Yan L, Liu Q, Chen G, Ma L RSC Adv. 2022; 10(61):37014-37022.

PMID: 35521235 PMC: 9057153. DOI: 10.1039/d0ra06414a.

Adjusting the Structure of β-Cyclodextrin to Improve Complexation of Anthraquinone-Derived Drugs.

Krzak A, Swiech O, Majdecki M, Garbacz P, Gwardys P, Bilewicz R Molecules. 2021; 26(23).

PMID: 34885787 PMC: 8659250. DOI: 10.3390/molecules26237205.

Anthraquinones as Potential Antibiofilm Agents Against Methicillin-Resistant .

Song Z, Zhang J, Zhou K, Yue L, Zhang Y, Wang C Front Microbiol. 2021; 12:709826.

PMID: 34539607 PMC: 8446625. DOI: 10.3389/fmicb.2021.709826.

References

Motobu M, Amer S, Koyama Y, Hikosaka K, Sameshima T, Yamada M . Protective effects of sugar cane extract on endotoxic shock in mice. Phytother Res. 2006; 20(5):359-63. DOI: 10.1002/ptr.1860. View

Byeon S, Chung J, Lee Y, Kim B, Kim K, Cho J . In vitro and in vivo anti-inflammatory effects of taheebo, a water extract from the inner bark of Tabebuia avellanedae. J Ethnopharmacol. 2008; 119(1):145-52. DOI: 10.1016/j.jep.2008.06.016. View

Tanaka T, Morito K, Kinoshita M, Ohmoto M, Urikura M, Satouchi K . Orally administered phosphatidic acids and lysophosphatidic acids ameliorate aspirin-induced stomach mucosal injury in mice. Dig Dis Sci. 2012; 58(4):950-8. DOI: 10.1007/s10620-012-2475-y. View

Zhao Z, Kim Y, Wu Y, Zhang J, Lee J, Li X . Korean Red Ginseng attenuates anxiety-like behavior during ethanol withdrawal in rats. J Ginseng Res. 2014; 38(4):256-63. PMC: 4213848. DOI: 10.1016/j.jgr.2014.05.010. View

Shen T, Lee J, Park M, Lee Y, Rho H, Kwak Y . Ginsenoside Rp1, a Ginsenoside Derivative, Blocks Promoter Activation of iNOS and COX-2 Genes by Suppression of an IKKβ-mediated NF-кB Pathway in HEK293 Cells. J Ginseng Res. 2013; 35(2):200-8. PMC: 3659523. DOI: 10.5142/jgr.2011.35.2.200. View

Kim J, Lee Y, Kim M, Byeon S, Rhee M, Park J . Src-mediated regulation of inflammatory responses by actin polymerization. Biochem Pharmacol. 2009; 79(3):431-43. DOI: 10.1016/j.bcp.2009.09.016. View

Kim M, Kim S, Lee M, Lee J, Jung W, Moon S . Tetramethylpyrazine, a natural alkaloid, attenuates pro-inflammatory mediators induced by amyloid β and interferon-γ in rat brain microglia. Eur J Pharmacol. 2014; 740:504-11. DOI: 10.1016/j.ejphar.2014.06.037. View

Feng Y, Huang S, Dou W, Zhang S, Chen J, Shen Y . Emodin, a natural product, selectively inhibits 11beta-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice. Br J Pharmacol. 2010; 161(1):113-26. PMC: 2962821. DOI: 10.1111/j.1476-5381.2010.00826.x. View

Deretic V . Links between autophagy, innate immunity, inflammation and Crohn's disease. Dig Dis. 2009; 27(3):246-51. PMC: 2788938. DOI: 10.1159/000228557. View

10.

Yu T, Li Y, Bian A, Zuo H, Zhu T, Ji S . The regulatory role of activating transcription factor 2 in inflammation. Mediators Inflamm. 2014; 2014:950472. PMC: 4090481. DOI: 10.1155/2014/950472. View

11.

Taiwo Y, Levine J . Effects of cyclooxygenase products of arachidonic acid metabolism on cutaneous nociceptive threshold in the rat. Brain Res. 1990; 537(1-2):372-4. DOI: 10.1016/0006-8993(90)90389-s. View

12.

Yi Y, Son Y, Ryou C, Sung G, Kim J, Cho J . Functional roles of Syk in macrophage-mediated inflammatory responses. Mediators Inflamm. 2014; 2014:270302. PMC: 4090447. DOI: 10.1155/2014/270302. View

13.

Li D, Zhang N, Cao Y, Zhang W, Su G, Sun Y . Emodin ameliorates lipopolysaccharide-induced mastitis in mice by inhibiting activation of NF-κB and MAPKs signal pathways. Eur J Pharmacol. 2013; 705(1-3):79-85. DOI: 10.1016/j.ejphar.2013.02.021. View

14.

Byeon S, Yi Y, Oh J, Yoo B, Hong S, Cho J . The role of Src kinase in macrophage-mediated inflammatory responses. Mediators Inflamm. 2012; 2012:512926. PMC: 3504478. DOI: 10.1155/2012/512926. View

15.

Koshihara Y, Fujimoto Y, Inoue H . A new 5-lipoxygenase selective inhibitor derived from Artocarpus communis strongly inhibits arachidonic acid-induced ear edema. Biochem Pharmacol. 1988; 37(11):2161-5. DOI: 10.1016/0006-2952(88)90576-x. View

16.

Lee Y, Chain B, Cho J . Distinct role of spleen tyrosine kinase in the early phosphorylation of inhibitor of kappaB alpha via activation of the phosphoinositide-3-kinase and Akt pathways. Int J Biochem Cell Biol. 2008; 41(4):811-21. DOI: 10.1016/j.biocel.2008.08.011. View

17.

Lee C, Kim J . A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases. J Ginseng Res. 2014; 38(3):161-6. PMC: 4213864. DOI: 10.1016/j.jgr.2014.03.001. View

18.

Balint G . A possible molecular basis for the effect of gastric anti-ulcerogenic drugs. Trends Pharmacol Sci. 1998; 19(10):401-3. DOI: 10.1016/s0165-6147(98)01191-2. View

19.

Hofmanova J, Strakova N, Hyrslova Vaculova A, Tylichova Z, Safarikova B, Skender B . Interaction of dietary fatty acids with tumour necrosis factor family cytokines during colon inflammation and cancer. Mediators Inflamm. 2014; 2014:848632. PMC: 4021685. DOI: 10.1155/2014/848632. View

20.

Naruse N, Goto M, Watanabe Y, Terasawa T, Dobashi K . K1115 A, a new anthraquinone that inhibits the binding of activator protein-1 (AP-1) to its recognition sites. II. Taxonomy, fermentation, isolation, physico-chemical properties and structure determination. J Antibiot (Tokyo). 1998; 51(6):545-52. DOI: 10.7164/antibiotics.51.545. View