Sonchus asper extract inhibits LPS-induced oxidative stress and pro-inflammatory cytokine production in RAW264.7 macrophages

  • Wang, Lan ;
  • Xu, Ming Lu ;
  • Liu, Jie ;
  • Wang, You ;
  • Hu, Jian He ;
  • Wang, Myeong-Hyeon
  • Received : 2015.03.06
  • Accepted : 2015.06.17
  • Published : 2015.12.01


BACKGROUND/OBJECTIVES: Sonchus asper is used extensively as an herbal anti-inflammatory for treatment of bronchitis, asthma, wounds, burns, and cough; however, further investigation is needed in order to understand the underlying mechanism. To determine its mechanism of action, we examined the effects of an ethyl acetate fraction (EAF) of S. asper on nitric oxide (NO) production and prostaglandin-E2 levels in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. MATERIALS/METHODS: An in vitro culture of RAW264.7 macrophages was treated with LPS to induce inflammation. RESULTS: Treatment with EAF resulted in significant suppression of oxidative stress in RAW264.7 macrophages as demonstrated by increased endogenous superoxide dismutase (SOD) activity and intracellular glutathione levels, decreased generation of reactive oxygen species and lipid peroxidation, and restoration of the mitochondrial membrane potential. To confirm its anti-inflammatory effects, analysis of expression of inducible NO synthase, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and the anti-inflammatory cytokines IL-$1{\beta}$ and IL-6 was performed using semi-quantitative RT-PCR. EAF treatment resulted in significantly reduced dose-dependent expression of all of these factors, and enhanced expression of the antioxidants MnSOD and heme oxygenase-1. In addition, HPLC fingerprint results suggest that rutin, caffeic acid, and quercetin may be the active ingredients in EAF. CONCLUSIONS: Taken together, findings of this study imply that the anti-inflammatory effect of EAF on LPS-stimulated RAW264.7 cells is mediated by suppression of oxidative stress.


anti-inflammatory;NO production;oxidative stress;Sonchus asper


  1. Leopold JA, Loscalzo J. Oxidative mechanisms and atherothrombotic cardiovascular disease. Drug Discov Today Ther Strateg 2008;5:5-13.
  2. Turrens JF, Boveris A. Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem J 1980;191:421-7.
  3. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 2000;86:494-501.
  4. Romano M, Claria J. Cyclooxygenase-2 and 5-lipoxygenase converging functions on cell proliferation and tumor angiogenesis: implications for cancer therapy. FASEB J 2003;17:1986-95.
  5. Kinnula VL, Crapo JD. Superoxide dismutases in the lung and human lung diseases. Am J Respir Crit Care Med 2003;167:1600-19.
  6. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 2000;87:840-4.
  7. Lakshmi SV, Padmaja G, Kuppusamy P, Kutala VK. Oxidative stress in cardiovascular disease. Indian J Biochem Biophys 2009;46:421-40.
  8. Benz CC, Yau C. Ageing, oxidative stress and cancer: paradigms in parallax. Nat Rev Cancer 2008;8:875-9.
  9. Yung LM, Leung FP, Yao X, Chen ZY, Huang Y. Reactive oxygen species in vascular wall. Cardiovasc Hematol Disord Drug Targets 2006;6:1-19.
  10. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 2010;49:1603-16.
  11. Balasundram N, Sundram K, Samman S. Phenolic compounds in plants and agro industrial by-products: antioxidant activity, occurrence, and potential uses. Food Chem 2006;99:191-203.
  12. Jeruto P, Lukhoba C, Ouma G, Otieno D, Mutai C. An ethnobotanical study of medicinal plants used by the Nandi people in Kenya. J Ethnopharmacol 2008;116:370-6.
  13. Sabeen M, Ahmad SS. Exploring the folk medicinal flora of Abbotabad City, Pakistan. Ethnobot Leafl 2009;13:810-33.
  14. Khan RA, Khan MR, Sahreen S, Bokhari J. Prevention of CCl4-induced nephrotoxicity with Sonchus asper in rat. Food Chem Toxicol 2010;48:2469-76.
  15. Wang L, Xu ML, Hu JH, Rasmussen SK, Wang MH. Codonopsis lanceolata extract induces G0/G1 arrest and apoptosis in human colon tumor HT-29 cells--involvement of ROS generation and polyamine depletion. Food Chem Toxicol 2011;49:149-54.
  16. Tiwari M, Dwivedi UN, Kakkar P. Suppression of oxidative stress and pro-inflammatory mediators by Cymbopogon citratus D. Stapf extract in lipopolysaccharide stimulated murine alveolar macrophages. Food Chem Toxicol 2010;48:2913-9.
  17. Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 1984;21:130-2.
  18. Cho JY, Baik KU, Jung JH, Park MH. In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa. Eur J Pharmacol 2000;398:399-407.
  19. Lee HJ, Hyun EA, Yoon WJ, Kim BH, Rhee MH, Kang HK, Cho JY, Yoo ES. In vitro anti-inflammatory and anti-oxidative effects of Cinnamomum camphora extracts. J Ethnopharmacol 2006;103:208-16.
  20. Enayat S, Banerjee S. Comparative antioxidant activity of extracts from leaves, bark and catkins of Salix aegyptiaca sp. Food Chem 2009;116:23-8.
  21. Rahman I, MacNee W. Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches. Free Radic Biol Med 2000;28:1405-20.
  22. Kleinert H, Euchenhofer C, Ihrig-Biedert I, Forstermann U. Glucocorticoids inhibit the induction of nitric oxide synthase II by down-regulating cytokine-induced activity of transcription factor nuclear factor-kappa B. Mol Pharmacol 1996;49:15-21.
  23. Hennebert O, Pelissier MA, Le Mee S, Wülfert E, Morfin R. Anti-inflammatory effects and changes in prostaglandin patterns induced by 7beta-hydroxy-epiandrosterone in rats with colitis. J Steroid Biochem Mol Biol 2008;110:255-62.
  24. Afolayan AJ, Jimoh FO. Nutritional quality of some wild leafy vegetables in South Africa. Int J Food Sci Nutr 2009;60:424-31.
  25. Helal AM, Nakamura N, El-Askary H, Hattori M. Sesquiterpene lactone glucosides from Sonchus asper. Phytochemistry 2000;53:473-7.
  26. Kim KM, Kwon YG, Chung HT, Yun YG, Pae HO, Han JA, Ha KS, Kim TW, Kim YM. Methanol extract of Cordyceps pruinosa inhibits in vitro and in vivo inflammatory mediators by suppressing NF-kappaB activation. Toxicol Appl Pharmacol 2003;190:1-8.

Cited by

  1. Agmatine Reduces Lipopolysaccharide-Mediated Oxidant Response via Activating PI3K/Akt Pathway and Up-Regulating Nrf2 and HO-1 Expression in Macrophages vol.11, pp.9, 2016,
  2. An ethanol extract of Aster yomena (Kitam.) Honda inhibits lipopolysaccharide-induced inflammatory responses in murine RAW 264.7 macrophages vol.11, pp.1, 2017,
  3. Fucoidan inhibits lipopolysaccharide-induced inflammatory responses in RAW 264.7 macrophages and zebrafish larvae vol.13, pp.4, 2017,
  4. Advance of antioxidants in asthma treatment vol.7, pp.1, 2017,
  5. Inhibitory effects on the production of inflammatory mediators and reactive oxygen species by Mori folium in lipopolysaccharide-stimulated macrophages and zebrafish vol.89, pp.1 suppl, 2017,
  6. Antinociceptive and Antibacterial Properties of Anthocyanins and Flavonols from Fruits of Black and Non-Black Mulberries vol.23, pp.1, 2017,
  7. Maxim Ethanol Extract vol.21, pp.7, 2018,
  8. In vitro evaluation of the synergistic antioxidant and anti-inflammatory activities of the combined extracts from Malaysian Ganoderma lucidum and Egyptian Chlorella vulgaris vol.18, pp.1, 2018,
  9. Spermidine Protects against Oxidative Stress in Inflammation Models Using Macrophages and Zebrafish vol.26, pp.2, 2018,
  10. Attenuate Inflammatory and Oxidative Mediators vol.2018, pp.1741-4288, 2018,


Supported by : University of Henan Province