Abstract
p-Hydroxyacetophenone (HAP) is a crucial chemical compound present in plants of the genus Artemisia, which are used in traditional therapies for treating jaundice, hepatitis, and inflammatory diseases. Nevertheless, the bioactivity of HAP remains to be identified in order to prove its importance in the plants of genus Artemisia. This study investigated the antioxidative, antinociceptive, and anti-inflammatory effects of HAP, and probed its possible molecular mechanisms. Our results revealed that HAP (80 mg/kg, intraperitoneally) in vivo reduced the acetic acid-induced writhing response and formalin-induced licking time. Moreover, in the λ-carrageenan-induced acute-inflammatory paw edema model in mice, HAP significantly improved hind paw swelling and neutrophil infiltration. In a homogenized paw tissue examination, HAP attenuated pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-1β, and interleukin-6. Simultaneously, HAP also inhibited the production of nuclear factor kappa B, cyclooxygenase-2, and nitric oxide (NO). Another examination revealed that HAP exerted anti-inflammatory activity by decreasing malondialdehyde levels in the edematous paw through increasing the activities of superoxide dismutase, glutathione peroxidase, and glutathione reductase in the liver. These findings may be beneficial in understanding the therapeutic effects of some plants of the genus Artemisia in the pretreatment of inflammation-associated diseases.
Similar content being viewed by others
References
Chang CW, Chang WT, Liao JC, Chiu YJ, Hsieh MT, Peng WH, Lin YC (2012) Analgesic and anti-Inflammatory activities of methanol extract of Cissus repens in mice. Evid Based Complement Alternat Med 2012:135379
Wang C, Sun J, Li H, Yang X, Liu H, Chen J (2016) In vivo anti-inflammatory activities of the essential oil from Radix Angelicae dahuricae. J Nat Med 70:563–570
Chou SC, Chiu YJ, Chen CJ, Lin YC, Wu CH, Chao CT, Chang CW, Peng WH (2012) Analgesic and anti-inflammatory activities of the ethanolic extract of Artemisia morrisonensis hayata in mice. Evid Based Complement Alternat Med 2012:138954
Lim DW, Kim YT, Jang YJ, Kim YE, Han D (2013) Anti-obesity effect of Artemisia capillaris extracts in high-fat diet-induced obese rats. Molecules 18:9241–9252
Islam MN, Ishita IJ, Jung HA, Choi JS (2014) Vicenin 2 isolated from Artemisia capillaris exhibited potent anti-glycation properties. Food Chem Toxicol 69:55–62
Masuda Y, Asada K, Satoh R, Takada K, Kitajima J (2015) Capillin, a major constituent of Artemisia capillaris Thunb. flower essential oil, induces apoptosis through the mitochondrial pathway in human leukemia HL-60 cells. Phytomedicine 22:545–552
Huang TJ, Liu SH, Kuo YC, Chen CW, Chou SC (2014) Antiviral activity of chemical compound isolated from Artemisia morrisonensis against hepatitis B virus in vitro. Antiviral Res 101:97–104
Zhao Y, Geng CA, Chen H, Ma YB, Huang XY, Cao TW, He K, Wang H, Zhang XM, Chen JJ (2015) Isolation, synthesis and anti-hepatitis B virus evaluation of p-hydroxyacetophenone derivatives from Artemisia capillaris. Bioorg Med Chem Lett 25:1509–1514
Alvarez ME, Rotelli AE, Pelzer LE, Saad JR, Giordano O (2000) Phytochemical study and anti-inflammatory properties of Lampaya hieronymi Schum. ex Moldenke. Farmaco 55:502–505
Medzhitov R (2010) Inflammation 2010: new adventures of an old flame. Cell 140:771–776
Huston JM, Tracey KJ (2011) The pulse of inflammation: heart rate variability, the cholinergic anti-inflammatory pathway and implications for therapy. J Intern Med 269:45–53
Sumantran VN, Tillu G (2012) Cancer, inflammation, and insights from Ayurveda. Evid Based Complement Alternat Med 2012:306346
Jeon IH, Mok JY, Park KH, Hwang HM, Song MS, Lee D, Lee MH, Lee WY, Chai KY, Jang SI (2012) Inhibitory effect of dibutyryl chitin ester on nitric oxide and prostaglandin E2 production in LPS stimulated RAW 264.7 cells. Arch Pharm Res 35:1287–1292
Ge YB, Wang ZG, Xiong Y, Huang XJ, Mei ZN, Hong ZG (2016) Anti-inflammatory and blood stasis activities of essential oil extracted from Artemisia argyi leaf in animals. J Nat Med 70:531–538
Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G (2006) Inflammation and cancer: how hot is the link? Biochem Pharmacol 72:1605–1621
Lu Y, Na MK, Suh SJ, Li X, Kim GJ, Chao GH, Jeong YT, Kim DS, Chang YC, Murakami M, Kang W, Kim CH, Chang HW (2013) Anti-inflammatory activity of hexane extracts from bones and internal organs of Anguilla japonica suppresses cyclooxygenase-2-dependent prostaglandin D2 generation in mast cells and anaphylaxis in mice. Food Chem Toxicol 57:307–313
Killeen MJ, Linder M, Pontoniere P, Crea R (2014) NF-κB signaling and chronic inflammatory diseases: exploring the potential of natural products to drive new therapeutic opportunities. Drug Discov Today 19:373–378
Armutcu F, Akyol S, Ustunsoy S, Turan FF (2015) Therapeutic potential of caffeic acid phenethyl ester and its anti-inflammatory and immunomodulatory effects (Review). Exp Ther Med 9:1582–1588
Janero DR (1990) Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 9:515–540
Cuzzocrea S, Costantino G, Zingarelli B, Mazzon E, Micali A, Caputi AP (1999) The protective role of endogenous glutathione in carrageenan induced pleurisy in the rat. Eur J Pharmacol 372:187–197
Koster R, Anderson M, Beer DEJ (1959) Acetic acid for analgesic screening. Fed Proc 18:412–415
Tjølsen A, Berge OG, Hunskaar S, Rosland JH, Hole K (1992) The formalin test: an evaluation of the method. Pain 51:5–17
Vinegar R, Schreiber W, Hugo R (1969) Biphasic development of carrageenan edema in rats. J Pharmacol Exp Ther 166:96–103
Lin YC, Chang CW, Wu CR (2015) Anti-nociceptive, anti-inflammatory and toxicological evaluation of Fang-Ji-Huang-Qi-Tang in rodents. BMC Complement Altern Med. doi:10.1186/s12906-015-0527-5
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Ataoğlu T, Ungör M, Serpek B, Haliloğlu S, Ataoğlu H, Ari H (2002) Interleukin-1β and tumour necrosis factor-α levels in periapical exudates. Int Endod J 35:181–185
Petrovic N, Murray M (2010) Using N,N,N′,N′-tetramethyl-p-phenylene-diamine (TMPD) to assay cyclooxygenase activity in vitro. Methods Mol Biol 594:129–140
Moshage H, Kok B, Huizenga JR, Jansen PL (1995) Nitrite and nitrate determinations in plasma: a critical evaluation. Clin Chem 41:892–896
Tatum VL, Changchit C, Chow CK (1990) Measurement of malondialdehyde by high performance liquid chromatography with fluorescence detection. Lipids 25:226–229
Vani M, Reddy GP, Reddy GR, Thyagaraju K, Reddanna P (1990) Glutathione-S-transferase, superoxide dismutase, xanthine oxidase, catalase, glutathione peroxidase and lipid peroxidation in the liver of exercised rats. Biochem Int 21:17–26
Ceballos-Picot I, Trivier JM, Nicole A, Sinet PM, Thevenin M (1992) Age-correlated modifications of copperzinc superoxide dismutase and glutathione-related enzyme activities in human erythrocytes. Clin Chem 38:66–70
Ahmad FB, Holdsworth DK (1994) Medicinal plants of Sabah, Malaysia, Part II. The Muruts. Int J Pharmacogn 32:378–383
Woolf CJ, Salter MW (2000) Neuronal plasticity: increasing the gain in pain. Science 288:1765–1769
Duarte ID, Nakamura M, Ferreira SH (1998) Participation of the sympathetic system in acetic acid-induced writhing in mice. Braz J Med Biol Res 21:341–343
Hunskaar S, Hole K (1987) The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain 30:103–114
Reeve AJ, Dickenson AH (1995) The roles of spinal adenosine receptors in the control of acute and more persistent nociceptive response of dorsal horn neurons in the anaesthetized rat. Br J Pharmacol 116:2221–2228
Hyuga S, Hyuga M, Oshima N, Maruyama T, Kamakura H, Yamashita T, Yoshimura M, Amakura Y, Hakamatsuka T, Odaguchi H, Goda Y, Hanawa T (2016) Ephedrine alkaloids-free Ephedra Herb extract: a safer alternative to ephedra with comparable analgesic, anticancer, and anti-influenza activities. J Nat Med 70:571–583
Missimo DR (1972) Biological properties of carrageenan. J Pharm Pharmacol 24:89–102
Vazquez E, Navarro M, Salazar Y, Crespo G, Bruges G, Osorio C, Tortorici V, Vanegas H, López M (2015) Systemic changes following carrageenan-induced paw inflammation in rats. Inflamm Res 64:333–342
Loram LC, Fuller A, Fick LG, Cartmell T, Poole S, Mitchell D (2007) Cytokine profiles during carrageenan-induced inflammatory hyperalgesia in rat muscle and hind paw. J Pain 8:127–136
Lu TC, Ko YZ, Huang HW, Hung YC, Lin YC, Peng WH (2007) Analgesic and anti-inflammatory activities of aqueous extract from Glycine tomentella root in mice. J Ethnopharmacol 113:142–148
El-Shitanya NA, El-Masrya SA, El-Ghareib MA, El-Desoky K (2010) Thioctic acid protects against carrageenaninduced acute inflammation in rats by reduction in oxidative stress, downregulation of COX-2 mRNA and enhancement of IL-10 mRNA. Fundam Clin Pharmacol 24:91–99
Schütze S, Wiegmann K, Machleidt T, Krönke M (1995) TNF-induced activation of NF-kappaB. Immunobiology 193:193–203
Ghosh S, Karin M (2002) Missing pieces in the NF-kappaB puzzle. Cell 109:S81–S96
Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, Lee L, Isakson P (1994) Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci USA 91:12013–12017
Vodovotz Y, Kim PK, Bagci EZ, Ermentrout GB, Chow CC, Bahar I, Billiar TR (2004) Inflammatory modulation of hepatocyte apoptosis by nitric oxide: in vivo, in vitro, and in silico studies. Curr Mol Med 4:753–762
Bogdan C (2001) Nitric oxide and the immune response. Nat Immunol 2:907–916
Yusufoglu HS (2014) Analgesic, antipyretic, anti-inflammatory, hepatoprotective and ephritic effects of the aerial parts of pulicaria arabica (Family: Compositae) on rats. Asian Pac J Trop Med doi:10.1016/S1995-7645(14)60293-5
Acknowledgements
This study was supported in part by the Department of Chinese Medicine and Pharmacy, Ministry of Health and Welfare (MOHW104-CMAP-M-114-000423, MOHW105-CMAP-M-114-000418).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare no conflicts of interest.
Rights and permissions
About this article
Cite this article
Ching-Wen, C., Yun-Chieh, C., Yu-Chin, L. et al. p-Hydroxyacetophenone suppresses nuclear factor-κB-related inflammation in nociceptive and inflammatory animal models. J Nat Med 71, 422–432 (2017). https://doi.org/10.1007/s11418-017-1074-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11418-017-1074-9