Antioxidant and Anti-Inflammatory Effects of Herbal Formula SCE 3 in Lipopolysaccharide-Stimulated RAW 264 . 7 Macrophages

SC-E3 is a novel herbal formula composed of five oriental medicinal herbs that are used to treat a wide range of inflammatory diseases in Korean traditional medicine. In this study, we sought to determine the effects of SC-E3 on free radical generation and inflammatory response in lipopolysaccharide(LPS-) treated RAW 264.7 macrophages and the molecular mechanism involved. The ethanol extract of SC-E3 showed good free radical scavenging activity and inhibited LPS-induced reactive oxygen species generation. SC-E3 significantly inhibited the production of the LPS-induced inflammatory mediators, nitric oxide and prostaglandin E2, by suppressing the expressions of inducible nitric oxide synthase and cyclooxygenase-2, respectively. SC-E3 also prevented the secretion of the proinflammatory cytokines, IL-1β, TNF-α, and IL-6, and inhibited LPS-induced NF-κB activation and themitogen-activated protein kinase (MAPK) pathway. Furthermore, SC-E3 induced the expression of heme oxygenase-1 (HO1) by promoting the nuclear translocation and transactivation of Nrf2. Taken together, these results suggest that SC-E3 has potent antioxidant and anti-inflammatory effects and that these effects are due to the inhibitions of NF-κB andMAPK and the induction of Nrf2-mediated HO-1 expression in macrophages. These findings provide scientific evidence supporting the potential use of SC-E3 for the treatment and prevention of various inflammatory diseases.

[1]  Nam-Hui Yim,et al.  Anti-Inflammatory Effect of Rhapontici Radix Ethanol Extract via Inhibition of NF-κB and MAPK and Induction of HO-1 in Macrophages , 2016, Mediators of inflammation.

[2]  M. Rhee,et al.  Antioxidant and Anti-Inflammatory Effects of Rhei Rhizoma and Coptidis Rhizoma Mixture on Reflux Esophagitis in Rats , 2016, Evidence-based complementary and alternative medicine : eCAM.

[3]  M. Rhee,et al.  Protective effect of Rhei Rhizoma on reflux esophagitis in rats via Nrf2-mediated inhibition of NF-κB signaling pathway , 2015, BMC Complementary and Alternative Medicine.

[4]  Lingbo Qu,et al.  Geniposide protects against acute alcohol-induced liver injury in mice via up-regulating the expression of the main antioxidant enzymes. , 2015, Canadian journal of physiology and pharmacology.

[5]  Jae Yong Ryu,et al.  A systems approach to traditional oriental medicine , 2015, Nature Biotechnology.

[6]  Xiaoling Li,et al.  Geniposide suppresses LPS-induced nitric oxide, PGE2 and inflammatory cytokine by downregulating NF-κB, MAPK and AP-1 signaling pathways in macrophages. , 2014, International immunopharmacology.

[7]  Xiao-yu Xu,et al.  Progress on the pharmacological research of puerarin: a review. , 2014, Chinese journal of natural medicines.

[8]  Yanning Liu,et al.  Resveratrol Reduces the Proinflammatory Effects and Lipopolysaccharide- Induced Expression of HMGB1 and TLR4 in RAW264.7 Cells , 2014, Cellular Physiology and Biochemistry.

[9]  Yunhe Fu,et al.  Geniposide Plays an Anti-inflammatory Role via Regulating TLR4 and Downstream Signaling Pathways in Lipopolysaccharide-Induced Mastitis in Mice , 2014, Inflammation.

[10]  R. Anand,et al.  Anti-inflammatory Potential of Alpha-Linolenic Acid Mediated Through Selective COX Inhibition: Computational and Experimental Data , 2014, Inflammation.

[11]  S. Reddy,et al.  Reactive oxygen species in inflammation and tissue injury. , 2014, Antioxidants & redox signaling.

[12]  E. Lim,et al.  Effects of Gardeniae Fructus on Cytokines in Mouse Macrophage , 2014 .

[13]  A. Pandey,et al.  Chemistry and Biological Activities of Flavonoids: An Overview , 2013, TheScientificWorldJournal.

[14]  Y. Kanaho,et al.  Garcinia vilersiana bark extract activates the Nrf2/HO-1 signaling pathway in RAW264.7 cells. , 2013, The Journal of toxicological sciences.

[15]  D. Choi,et al.  Traditional Korean East Asian Medicines and Herbal Formulations for Cognitive Impairment , 2013, Molecules.

[16]  C. Glass,et al.  Analysis of inflammatory and lipid metabolic networks across RAW264.7 and thioglycolate-elicited macrophages[S] , 2013, Journal of Lipid Research.

[17]  Yun-Tai Kim,et al.  Anti-Inflammatory Effects of Total Isoflavones from Pueraria lobata on Cerebral Ischemia in Rats , 2013, Molecules.

[18]  F. Gallyas,et al.  Antioxidant and Anti-Inflammatory Effects in RAW264.7 Macrophages of Malvidin, a Major Red Wine Polyphenol , 2013, PloS one.

[19]  Q. Ma Role of nrf2 in oxidative stress and toxicity. , 2013, Annual review of pharmacology and toxicology.

[20]  Guan-Jhong Huang,et al.  Involvement of Heme Oxygenase-1 Participates in Anti-Inflammatory and Analgesic Effects of Aqueous Extract of Hibiscus taiwanensis , 2012, Evidence-based complementary and alternative medicine : eCAM.

[21]  Wei Zhang,et al.  α-Linolenic acid intake attenuates myocardial ischemia/reperfusion injury through anti-inflammatory and anti-oxidative stress effects in diabetic but not normal rats. , 2011, Archives of medical research.

[22]  Russell J. Mumper,et al.  Plant Phenolics: Extraction, Analysis and Their Antioxidant and Anticancer Properties , 2010, Molecules.

[23]  A. Remppis,et al.  Rhizoma Coptidis Inhibits LPS-Induced MCP-1/CCL2 Production in Murine Macrophages via an AP-1 and NFκB-Dependent Pathway , 2010, Mediators of inflammation.

[24]  T. Lawrence The nuclear factor NF-kappaB pathway in inflammation. , 2009, Cold Spring Harbor perspectives in biology.

[25]  H. Biesalski Polyphenols and inflammation: basic interactions , 2007, Current opinion in clinical nutrition and metabolic care.

[26]  Y. Hwang,et al.  Protective effects of puerarin on carbon tetrachloride-induced hepatotoxicity , 2007, Archives of pharmacal research.

[27]  Jie Ren,et al.  Anti-inflammatory Effect of α-Linolenic Acid and Its Mode of Action through the Inhibition of Nitric Oxide Production and Inducible Nitric Oxide Synthase Gene Expression via NF-κB and Mitogen-Activated Protein Kinase Pathways , 2007 .

[28]  E. Ainsworth,et al.  Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin–Ciocalteu reagent , 2007, Nature Protocols.

[29]  Y. Fujii,et al.  Pharmacology and Toxicology of Bupleurum Root-Containing Kampo Medicines in Clinical Use , 2006, Human & experimental toxicology.

[30]  R. Devlin,et al.  Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: further mechanistic studies. , 2005, Toxicology and applied pharmacology.

[31]  Kazuo Kobayashi,et al.  Macrophages in inflammation. , 2005, Current drug targets. Inflammation and allergy.

[32]  K. Itoh,et al.  Transcription Factor Nrf2 Regulates Inflammation by Mediating the Effect of 15-Deoxy-Δ12,14-Prostaglandin J2 , 2004, Molecular and Cellular Biology.

[33]  J. Avruch,et al.  Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. , 2001, Physiological reviews.

[34]  G. Cantelli-forti,et al.  Comparison between chinese medical herb Pueraria lobata crude extract and its main isoflavone puerarin antioxidant properties and effects on rat liver CYP-catalysed drug metabolism. , 2000, Life sciences.

[35]  M. Gyamfi,et al.  Free-radical scavenging action of medicinal herbs from Ghana: Thonningia sanguinea on experimentally-induced liver injuries. , 1999, General pharmacology.

[36]  R. W. Davis,et al.  Discovery and analysis of inflammatory disease-related genes using cDNA microarrays. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[37]  V. Ooi,et al.  Free radical scavenging activities of mushroom polysaccharide extracts. , 1997, Life sciences.

[38]  Z. Ďuračková Some current insights into oxidative stress. , 2010, Physiological research.

[39]  B. Choo,et al.  Comparative Study of Extracts from Rhubarb on Inflammatory Activity in Raw 264.7 Cells , 2009 .

[40]  S. Tabish Complementary and Alternative Healthcare: Is it Evidence-based? , 2008, International journal of health sciences.

[41]  P. Tak,et al.  NF-κB: a key role in inflammatory diseases , 2001 .

[42]  D. Willis,et al.  Heme oxygenase: A novel target for the modulation of inflammatory response , 1996, Nature Medicine.