Ethanolic Extract from Pteris wallichiana Alleviates DSS-Induced Intestinal Inflammation and Intestinal Barrier Dysfunction by Inhibiting the TLR4/NF-κB Pathway and Regulating Tight Junction Proteins

The aim of the research was to determine the protective effect and mechanism of Pteris wallichiana J. Agardh extract (PWE) on DSS-induced ulcerative colitis (UC) in mice. In this research, PWE is rich in flavonoids and diterpenoids by UPLC-MS/MS analysis. In LPS-induced RAW264.7 cells, PWE reduced the productions of inflammatory factors (i.e., NO, TNF-α, IL-6, and IL-1β). In DSS-induced UC in mice, PWE improved disease activity index (DAI) score, attenuated oxidative stress by decreasing MPO and MDA activities and activating GSH and SOD levels, and inhibited TNF-α, IL-6, and IL-1β expressions in the colonic tissues. PWE also improved the intestinal barrier by upregulating the expressions of tight junction proteins, including occludin and ZO-1. Moreover, PWE extract alleviated intestinal inflammation by suppressing the TLR4/MyD88/NF-κB signaling pathway. Conclusion: PWE can alleviate DSS-induced UC in mice by increasing the expressions of intestinal tight junction proteins and inhibiting the TLR4/NF-κB inflammatory pathway.     

Quercetin-Rich Ethanolic Extract of Polygonum odoratum var Pakphai Leaves Decreased Gene Expression and Secretion of Pro-Inflammatory Mediators in Lipopolysaccharide-Induced Murine RAW264.7 Macrophages

Polygonum odoratum var. Pakphai has been used in traditional Thai medicine for the treatment of flatulence and constipation and to relieve the inflammation caused by insect bites. Quercetin (Q), which is abundant in plant-based foods, has been found to exert anti-inflammatory properties. This study evaluated the anti-inflammatory activity of P. odoratum ethanolic extract in RAW264.7 macrophage cells. Leaves were extracted with 50% ethanol, phenolics and flavonoids were then analyzed using UHPLC-QTOF-MS and HPLC-DAD. RAW264.7 cells were induced with lipopolysaccharides (LPSs). They were then treated with the extract and prostaglandin E₂ (PGE₂), and interleukin-6 (IL-6) and tumor necrotic factor-alpha (TNF-α) concentrations were determined. Levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), IL-6 and TNF-α mRNAs were analyzed using qRT-PCR. Chemical analysis demonstrated that the extract was abundant with Q while also containing catechin, gallic acid, epicatechin gallate and coumarin. The extract increased the viability of RAW264.7 cells and dose-dependently decreased nitric oxide production, PGE₂, IL-6 and TNF-α levels in the medium from the LPS-induced RAW264.7 cell culture. Consistently, COX-2, iNOS, IL-6 and TNF-α mRNA levels were decreased in a concentration-dependent manner (p < 0.05). Thus, the quercetin-rich ethanolic extract derived from P. odoratum var Pakphai leaves can exert anti-inflammatory activity in LPS-induced RAW264.7 cells through a reduction of the pro-inflammatory mediator response.     

Antioxidant and Anti-Inflammatory Activities of Six Flavonoids from Smilax glabra Roxb

This study aimed to isolate, prepare and identify the main flavonoids from a standardized Smilax glabra flavonoids extract (SGF) using preparative HPLC, MS, ¹H NMR and ¹³C NMR, determine the contents of these flavonoids using UPLC, then compare their pharmacological activities in vitro. We obtained six flavonoids from SGF: astilbin (18.10%), neoastilbin (11.04%), isoastilbin (5.03%), neoisoastilbin (4.09%), engeletin (2.58%) and (−)-epicatechin (1.77%). The antioxidant activity of six flavonoids were evaluated by determining the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2′-Azinobis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS⁺) radical scavenging activity and ferric reducing antioxidant power (FRAP). In addition, the anti-inflammatory activity of six flavonoids were evaluated by determining the production of cytokines (IL-1β, IL-6), nitric oxide (NO) using enzyme linked immunosorbent assay and the NF-κB p65 expression using Western blotting in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results showed that (−)-epicatechin, astilbin, neoastilbin, isoastilbin and neoisoastilbin had strong antioxidant activities, not only in DPPH and ABTS⁺ radicals scavenging capacities, but in FRAP system. Furthermore, all the six flavonoids could significantly inhibit the secretion of IL-1β, IL-6, NO (p < 0.01) and the protein expression of NF-κB p-p65 (p < 0.01) in LPS-stimulated RAW264.7 cells. This study preliminarily verified the antioxidant and anti-inflammatory activities of six flavonoids in S. glabra.     

Adsorption and Desorption Characteristics of Total Flavonoids from Acanthopanax senticosus on Macroporous Adsorption Resins

We examined the application of six different resins with the aim of selecting a macroporous resin suitable for purifying Acanthopanax senticosus total flavonoids (ASTFs) from Acanthopanax senticosus crude extract (EAS) by comparing their adsorption/desorption capacities, which led to the selection of HPD-600. Research on the adsorption mechanism showed that the adsorption process had pseudo-second-order kinetics and fit the Freundlich adsorption model. Moreover, the analysis of thermodynamic parameters indicated that the adsorption process is spontaneous and endothermic. The optimal conditions for purification of ASTFs were determined as sample pH of 3, 60% ethanol concentration, and 3 BV·h⁻¹ flow rate, for both adsorption and desorption, using volumes of 2.5 and 4 BV, respectively. The application of macroporous resin HPD-600 to enrich ASTFs resulted in an increase in the purity of total flavonoids, from 28.79% to 50.57%. Additionally, the antioxidant capacity of ASTFs was higher than that of EAS, but both were lower than that of L-ascorbic acid. The changes in ASTFs compositions were determined using ultra-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS), with the results illustrating that the levels of seven major flavonoids of ASTFs were increased compared to that in the crude extract.     

Antioxidant and Anti-Inflammatory Activity of Filipendula glaberrima Nakai Ethanolic Extract and Its Chemical Composition

Many countries are endeavoring to strengthen the competitiveness of their biological resources by exploring and developing wild endemic plants. This study examined the effects of Filipendula glaberrima Nakai (FG) on the antioxidant and anti-inflammatory activity using an in vitro system. The bioactive components were also examined using chromatographic techniques. The ethanol extract of Filipendula glaberrima Nakai (FGE) exerted antioxidant activities in the radical scavenging and reducing power assays and had high amounts of total polyphenolic compounds. The qRT-PCR results suggested that FGE significantly downregulated the levels cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) 2, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in LPS-stimulated RAW 264.7 cells. The FGE treatment also decreased the production of nitric oxide, TNF-α, and IL-6 significantly in a dose-dependent manner. In addition, FGE downregulated phosphorylation of MAPK and NF-κB signaling pathway-related proteins. The chromatographic and mass spectrometry results showed that FGE contained bioactive flavonoids such as (+)-catechin, miquelianin, quercitrin, and afzelin, which may be active compounds with antioxidant and anti-inflammatory activities. This study provides fundamental data on the anti-inflammatory activity of the FG and can serve as a good starting point for developing a novel natural anti-inflammatory agent using FGE-containing bioactive flavonoids.     

Characterization of βN-Octadecanoyl-5-hydroxytryptamide Anti-Inflammatory Effect

Background: N-octadecanoyl-5-hydroxytryptamide (C₁₈-5HT) is an amide that can be obtained by the coupling of serotonin and octadecanoic acid. This study aims to characterize the in vivo and in vitro anti-inflammatory activity of C₁₈-5HT. Methods: A subcutaneous air pouch model (SAP) was used. The exudates were collected from SAP after carrageenan injection to assess cell migration and inflammatory mediators production. RAW 264.7 cells were used for in vitro assays. Results: C₁₈-5HT significantly inhibited leukocyte migration into the SAP as well as nitric oxide (NO) and cytokines production and protein extravasation. We also observed an reduction in some cytokines and an increase in IL-10 production. Assays conducted with RAW 264.7 cells indicated that C₁₈-5HT inhibited NO and cytokine produced. Conclusions: Taken together, our data suggest that C₁₈-5HT presents a significant effect in different cell types (leukocytes collected from exudate, mainly polumorphonuclear leukocytes and cell culture macrophages) and is a promising compound for further studies for the development of a new anti-inflammatory drug.     

Curcumin Modifies the Activity of Plasmatic Antioxidant Enzymes and the Hippocampal Oxidative Profile in Rats upon Acute and Chronic Exposure to Ozone

Ozone (O₃) is an oxidating tropospheric pollutant. When O₃ interacts with biological substrates, reactive oxygen and nitrogen species (RONS) are formed. Severe oxidative damage exhausts the endogenous antioxidant system, which leads to the decreased activity of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Curcumin (CUR) is a natural polyphenol with well-documented antioxidant and anti-inflammatory properties. The aim of this work is to evaluate the effects of curcumin on CAT, GPx, and SOD activity and the inhibition of oxidative damage after the acute and chronic exposure to O₃. Fifty male Wistar rats were divided into five experimental groups: the intact control, CUR-fed control, exposed-to-O₃ control, CUR-fed (preventive), and CUR-fed (therapeutic) groups. These two last groups received a CUR-supplemented diet while exposed to O₃. These experiments were performed during acute- and chronic-exposure phases. In the preventive and therapeutic groups, the activity of plasma CAT, GPx, and SOD was increased during both exposure phases, with slight differences; concomitantly, lipid peroxidation and protein carbonylation were inhibited. For this reason, we propose that CUR could be used to enhance the activity of the antioxidant system and to diminish the oxidative damage caused by exposure to O₃.     

Aurones and Flavonols from Coreopsis lanceolata L. Flowers and Their Anti-Oxidant,Pro-Inflammatory Inhibition Effects,and Recovery Effects on Alloxan-Induced Pancreatic Islets in Zebrafish

(1) Background: Many flavonoids have been reported to exhibit pharmacological activity; a preparatory study confirmed that Coreopsis lanceolata flowers (CLFs) contained high flavonoid structure content; (2) Methods: CLFs were extracted in aqueous methanol (MeOH:H₂O = 4:1) and fractionated into acetic ester (EtOAc), normal butanol (n-BuOH), and H₂O fractions. Repeated column chromatographies for two fractions led to the isolation of two aurones and two flavonols; (3) Results: Four flavonoids were identified based on a variety of spectroscopic data analyses to be leptosidin (1), leptosin (2), isoquercetin (3), and astragalin (4), respectively. This is the first report for isolation of 2–4 from CLFs. High-performance liquid chromatography (HPLC) analysis determined the content levels of compounds 1–4 in the MeOH extract to be 2.8 ± 0.3 mg/g (1), 17.9 ± 0.9 mg/g (2), 3.0 ± 0.2 mg/g (3), and 10.9 ± 0.9 mg/g (4), respectively. All isolated compounds showed radical scavenging activities and recovery activities in Caco-2, RAW264.7, PC-12, and HepG2 cells against reactive oxygen species. MeOH extract, EtOAc fraction, and 1–3 suppressed NO formation in LPS-stimulated RAW 264.7 cells and decreased iNOS and COX-2 expression. Furthermore, all compounds recovered the pancreatic islets damaged by alloxan treatment in zebrafish; (4) Conclusions: The outcome proposes 1–4 to serve as components of CLFs in standardizing anti-oxidant, pro-inflammatory inhibition, and potential anti-diabetic agents.     

Oxyresveratrol Ameliorates Dextran Sulfate Sodium-Induced Colitis in Rats by Suppressing Inflammation

Colitis causes destruction of the intestinal mucus layer and increases intestinal inflammation. The use of antioxidants and anti-inflammatory agents derived from natural sources has been recently highlighted as a new approach for the treatment of colitis. Oxyresveratrol (OXY) is an antioxidant known to have various beneficial effects on human health, such as anti-inflammatory, antibacterial activity, and antiviral activity. The aim of this study was to investigate the therapeutic effect of OXY in rats with dextran sulfate sodium (DSS)-induced acute colitis. OXY ameliorated DSS-induced colitis and repaired damaged intestinal mucosa. OXY downregulated the expression of pro-inflammatory cytokine genes (TNF-α, IL-6, and IL-1β) and chemokine gene MCP-1, while promoting the production of anti-inflammatory cytokine IL-10. OXY treatment also suppressed inflammation via inhibiting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in the colon, as well as the activity of myeloperoxidase (MPO). OXY exhibited anti-apoptotic effects, shifting the Bax/Bcl-2 balance. In conclusion, OXY might improve DSS-induced colitis by restoring the intestinal mucus layer and reducing inflammation within the intestine.     

Anti-Inflammatory Comparison of Melatonin and Its Bromobenzoylamide Derivatives in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells and Croton Oil-Induced Mice Ear Edema

The pineal gland is a neuroendocrine organ that plays an important role in anti-inflammation through the hormone melatonin. The anti-inflammatory effects of melatonin and its derivatives have been reported in both in vitro and in vivo models. Our previous study reported the potent antioxidant and neuroprotective activities of bromobenzoylamide substituted melatonin. In silico analysis successfully predicted that melatonin bromobenzoylamid derivatives were protected from metabolism by CYP2A1, which is a key enzyme of the melatonin metabolism process. Therefore, the anti-inflammatory activities of melatonin and its bromobenzoylamide derivatives BBM and EBM were investigated in LPS-induced RAW 264.7 macrophages and croton oil-induced ear edema in mice. The experiments showed that BBM and EBM significantly reduced production of the inflammatory mediators interleukin-6 (IL-6), prostaglandin E2 (PGE₂), and nitric oxide (NO) in a dose-dependent manner, but only slightly affected TNF-α in LPS-induced RAW 264.7 macrophages. This suggests that modifying melatonin at either the N1-position or the N-acetyl side chain affected production of NO, PGE₂ and IL-6 in in vitro model. In the croton oil-induced mouse ear edema model, BBM, significantly decreased ear edema thickness at 2–4 h. It leads to conclude that bromobenzoylamide derivatives of melatonin may be one of the potential candidates for a new type of anti-inflammatory agent.     

Antioxidant product analysis of Folium Hibisci Mutabilis

Folium Hibisci Mutabilis, a new member of Chinese Pharmacopoeia, can treat some diseases induced by reactive oxygen species. The study prepared a lyophilized aqueous extract of Folium Hibisci Mutabilis (LAFHM). LAFHM was found to enrich eight flavonoids (i.e., quercetin, luteolin, hyperoside, isoquercitrin, rutin, kaempferol, tiliroside, and vitexin) by HPLC analysis. These flavonoids were further compared using antioxidant assays, where triliroside and vitexin always exhibited higher IC₅₀ values than the others. In ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry analysis, these flavonoids could basically give two characteristic m/z values (226 and 196) and their corresponding double m/z values (i.e., 602, 570, 926, 926, 570, 1186, and 862), when treated by 1,1-diphenyl-2-picryl-hydrazl radical (DPPH^?). Finally, the coupling products of DPPH^?-treated triliroside were investigated using computational chemistry. It was found that the –OH in para-coumaroyl moiety to have the lowest bond disassociation energy among all phenolic -OHs in the triliroside. In conclusion, Folium Hibisci Mutabilis contains the above eight antioxidant flavonoids. Despite of the different antioxidant levels, they can generally produce flavonoid-radical coupling product and flavonoid-flavonoid homodimer during antioxidant process. Especially, tiliroside uses para-coumaroyl as linker to construct a tiliroside-radical coupling product at the meta-carbon atom.     

Anti-inflammatory effect of fucoxanthin on dextran sulfate sodium-induced colitis in mice

Abstract

The anti-inflammatory activities of fucoxanthin, a marine carotenoid derived from the macroalgae and microalgae, have been demonstrated in the previous studies. However, the effect of fucoxanthin on ulcerative colitis (UC), an inflammatory bowel disease, was still unclear. In this study, we evaluated the in vivo anti-inflammatory effect of fucoxanthin on dextran sulfate sodium(DSS)-induced colitis in mice. Fucoxanthin at the doses of 50 and 100?mg/kg/day significantly protected against DSS-induced gradual loss of body weight, exhibited inhibitory effects on the DSS-induced increase of disease activity index and colon shortening. Moreover, fucoxanthin treatment resulted in a marked amelioration of the histological damage in the colon, and reduced the colonic PGE₂ levels in colitic mice. In addition, the DSS-induced overexpressions of inflammation-related molecules including COX‐2 and NF-κB were significantly decreased in fucoxanthin-treated mice. These finding suggested that the use of fucoxanthin provides a new and attractive alternative to control UC.     

Self‐Assembly of Multi‐nanozymes to Mimic an Intracellular Antioxidant Defense System

In this work, for the first time, we constructed a novel multi‐nanozymes cooperative platform to mimic intracellular antioxidant enzyme‐based defense system. V₂O₅ nanowire served as a glutathione peroxidase (GPx) mimic while MnO₂ nanoparticle was used to mimic superoxide dismutase (SOD) and catalase (CAT). Dopamine was used as a linker to achieve the assembling of the nanomaterials. The obtained V₂O₅@pDA@MnO₂ nanocomposite could serve as one multi‐nanozyme model to mimic intracellular antioxidant enzyme‐based defense procedure in which, for example SOD, CAT, and GPx co‐participate. In addition, through assembling with dopamine, the hybrid nanocomposites provided synergistic antioxidative effect. Importantly, both in vitro and in vivo experiments demonstrated that our biocompatible system exhibited excellent intracellular reactive oxygen species (ROS) removal ability to protect cell components against oxidative stress, showing its potential application in inflammation therapy.     

Study of the Antioxidant and Anti-Inflammatory Properties of the Biological Extracts of Psophocarpus tetragonolobus Using Two Extraction Methods

Psophocarpus tetragonolobus has long been used in traditional medicine and cuisine. In this study, Psophocarpus tetragonolobus extracts were isolated by maceration and ultrasound-assisted extraction and were evaluated for their antioxidant and anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The obtained results show that both extracts (maceration and ultrasound) were rich in bioactive molecules and exerted substantial antioxidant and anti-inflammatory effects. The P. tetragonolobus extracts’ treatment in LPS-stimulated RAW264.7 macrophages resulted in a significant downregulation of the expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β mRNA. In addition, the P. tetragonolobus extracts’ treatment attenuated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression. Our observations indicate that there is no significant difference between the two studied extracts of P. tetragonolobus in terms of biological properties (specifically, antioxidant and anti-inflammatory effects. Regardless of the extraction method, P. tetragonolobus could be used for treating diseases related to oxidative stress and inflammatory reactions.     

Effects of Holdfast of Laminaria japonica on Listeria Invasion on Enterocyte-Like Caco-2 Cells and NO Production of Macrophage RAW 264.7 Cells

Listeria monocytogenes (Lm) causes food poisoning in humans mainly through consumption of ready-to-eat foods. Immunocompromised persons are at the highest risk for infection. We investigated effects of crude soluble polysaccharides (SPS) and ethanolic extract (EE) fractions of frond (kombu) and holdfast (ganiashi) parts of Laminaria japonica on Lm invasion into human enterocyte-like Caco-2 cells and immune and/or inflammatory reactions of murine macrophage RAW 264.7 cells. Recovery and viscosity were high in kombu SPS. Total phenolic content and antioxidant activities (2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity and Fe-reducing power) were higher in ganiashi EE. EE of ganiashi, rather than kombu, suppressed the Lm invasion into the differentiated Caco-2 cells, though the inhibitory effect of SPS was not significant. Ganiashi SPS increased the nitric oxide (NO) production of intact RAW 264.7 cells. On the other hand, the NO production from Escherichia coli O111 lipopolysaccharide-activated cells was suppressed by kombu SPS and ganiashi EE. These results suggest that L. japonica, particularly ganiashi, might suppress the invasion and infection of Lm and also the inflammation.     

Study on Extraction and Antioxidant Activity of Flavonoids from Hemerocallis fulva (Daylily) Leaves

Hemerocallis fulva is a medical and edible plant. In this study, we optimized the ultrasound-assisted extraction (UAE) process of extracting flavonoids from Hemerocallis fulva leaves by single-factor experiments and response surface methodology (RSM). The optimum extraction conditions generating the maximal total flavonoids content was as follows: 70.6% ethanol concentration; 43.9:1 mL/g solvent to sample ratio; 61.7 °C extraction temperature. Under the optimized extraction conditions, the total flavonoid content (TFC) in eight Hemerocallis fulva varieties were determined, and H. fulva (L.) L. var. kwanso Regel had the highest TFC. The cytotoxicity of the extract was studied using the Cell Counting Kit-8 (CCK-8 assay). When the concentration was less than 1.25 mg/mL, the extract had no significant cytotoxicity to HaCaT cells. The antioxidant activity was measured via chemical antioxidant activity methods in vitro and via cellular antioxidant activity methods. The results indicated that the extract had a strong ABTS and •OH radical scavenging activity. Additionally, the extract had an excellent protective effect against H₂O₂-induced oxidative damage at a concentration of 1.25 mg/mL, which could effectively reduce the level of ROS to 106.681 ± 9.733% (p < 0.001), compared with the 163.995 ± 6.308% of the H₂O₂ group. We identified five flavonoids in the extracts using high-performance liquid chromatography (HPLC). Infrared spectroscopy indicated that the extract contained the structure of flavonoids. The results showed that the extract of Hemerocallis fulva leaves had excellent biocompatibility and antioxidant activity, and could be used as a cheap and potential source of antioxidants in the food, cosmetics, and medicine industries.     

Anti-Inflammatory Effects of Mitrephora sirikitiae Leaf Extract and Isolated Lignans in RAW 264.7 Cells

Mitrephora sirikitiae Weeras., Chalermglin & R.M.K. Saunders has been reported as a rich source of lignans that contribute to biological activities and health benefits. However, cellular anti-inflammatory effects of M. sirikitiae leaves and their lignan compounds have not been fully elucidated. Therefore, this study aimed to investigate the anti-inflammatory activities of methanol extract of M. sirikitiae leaves and their lignan constituents on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 mouse macrophage cells. Treatment of RAW 264.7 cells with the methanol extract of M. sirikitiae leaves and its isolated lignans, including (−)-phylligenin (2) and 3′,4-O-dimethylcedrusin (6) significantly decreased LPS-induced prostaglandin E₂ (PGE₂) and nitric oxide (NO) productions. These inhibitory effects of the extract and isolated lignans on LPS-induced upregulation of PGE₂ and NO productions were derived from the suppression of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) production, respectively. In addition, treatment with 2-(3,4-dimethoxyphenyl)-6-(3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane (3) and mitrephoran (5) was able to suppress LPS-induced tumor necrosis factor alpha (TNF-α) secretion and synthesis in RAW 264.7 cells. These results demonstrated that M. sirikitiae leaves and some isolated lignans exhibited potent anti-inflammatory activity through the inhibition of secretion and synthesis of PGE₂, NO, and TNF-α.     

Differential regulation of inducible nitric oxide synthase and cyclooxygenase-2 expression by superoxide dismutase in lipopolysaccharide stimulated RAW 264.7 cells

Inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) have been known to be involved in various pathophysiological processes such as inflammation. This study was performed to determine the regulatory function of superoxide dismutase (SOD) on the LPS-induced expression of iNOS, and COX-2 in RAW 264.7 cells. When a cell-permeable SOD, Tat-SOD, was added to the culture medium of RAW 264.7 cells, it rapidly entered the cells in a dose-dependent manner. Treatment of RAW 264.7 cells with Tat-SOD led to decrease in LPS-induced ROS generation. Pretreatment with Tat-SOD significantly inhibited LPS-induced expression of iNOS and NO production but had no effect on the expression of COX-2 and PGE₂ production in RAW 264.7 cells. Tat-SOD inhibited LPS-induced NF-κB DNA binding activity, IκBα degradation and activation of MAP kinases. These data suggest that SOD differentially regulate expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells.