Lipopolysaccharide-induced Nitric Oxide Production Research Articles

Lipopolysaccharide-induced nitric oxide production in BV2 microglial cells

Lipopolysaccharide-induced nitric oxide production in BV2 microglial cells

HPPO-Derived Meroterpenoids from the Marine-Derived Fungus Penicillium sp. SCSIO 41691.

Seven new 4-hydroxy-6-phenyl-2H-pyran-2-one (HPPO) derived meroterpenoids, 1-methyl-12a,12b-epoxyarisugacin M (1), 1-methyl-4a,12b-epoxyarisugacin M (2), 2,3-dihydroxy-3,4a-epoxy-12a-dehydroxyisoterreulactone A (3), 2-hydroxy-12a-dehydroxyisoterreulactone A (4), 3'-demethoxyterritrems B' (5), 4a-hydroxyarisugacin P (6), and 1-epi-arisugacin H (7), together with two known analogues (8 and 9), were isolated from the marine-derived fungal strain Penicillium sp. SCSIO 41691. Their structures were elucidated by spectroscopic methods, and the absolute configurations of compounds 1 and 3 were determined by single-crystal X-ray diffraction. Among them, 1 and 2 had a unique methyl migration in the basic meroterpenoid skeleton with a 12a,12b-epoxy or 4a,12b-epoxy group, and 3 was a highly oxygenated HPPO-derived meroterpenoid featuring a rare 6/5/6/6/6/6 hexacyclic system with a 3,4a-epoxy group. Biologically, 5 exhibited inhibitory activity against lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells with an IC50 value of 21 μM, more potent than the positive control indomethacin.

Anti-inflammatory monoterpenes from morinda (Morinda officinalis How.)

Morinda (Morinda officinalis How.) is widely consumed as a functional food owing to its potential to promote health. This study investigated the anti-inflammatory phytochemicals of morinda and isolated 30 monoterpenes, including 6 undescribed iridoids (1, 6, 9–11 and 25), 2 undescribed acyclic monoterpenoids (28, 29), a known acyclic monoterpenoid and 21 known iridoids. Their chemical and stereo-structures were elucidated based on HR–ESI–MS, NMR, 13C-NMR calculations, ECD data and ECD calculations. Notably, compounds 11, 12 and 20 exerted pronounced inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages, with IC50 values of 28.51 ± 1.70, 25.45 ± 4.17 and 29.17 ± 3.71 μM respectively (indomethacin, IC50 of 33.68 ± 2.19 μM). The same compounds exert anti-inflammatory effects by blocking nuclear translocation of nuclear factor κ-B, and down-regulating the expression of inflammatory cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-1β and interleukin-6 at mRNA and protein levels in a dose-dependent manner. These results suggest that moderate consumption of morinda helps prevent and reduce the occurrence of inflammatory-related diseases.

Acylated flavonoid glycosides from Barringtonia pendula and their inhibition on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells

Six new acylated flavonoid glycosides namely barringosides J − O (1–6) along with tephrokaempferoside and barringoside D were isolated from the branches and leaves of Barringtonia pendula. The structural elucidation was confirmed by extensive analysis of their spectroscopic data including HRQTOFMS, 1D and 2D NMR experiments. Moderate inhibitory effects on LPS-induced NO production in RAW264.7 cells were observed for barringosides M (4) and N (5) with IC50 values of 48.40 ± 3.01 and 56.61 ± 3.87 μM, whereas weak inhibition was found for compounds 1–3, 6, and 7 with IC50 values ranging from 64.91 ± 3.68 to 79.80 ± 3.90 μM.

Polyoxygenated cyclohexene derivatives and other constituents of Uvaria rufa stem

Six undescribed compounds, uvarirufols D and E, (+)-uvarigranol B, (−)-uvarigranol E, 6-acetoxy-5-hydroxy-7-methoxyflavanone and cherrevenaphthalene D, along with twelve known compounds, including polyoxygenated cyclohexenes, flavonoids, and lignans, were isolated from the methanol extract of Uvaria rufa stems. Their structures were elucidated by spectroscopic analyses and the absolute configurations were determined using electronic circular dichroism. Several isolates were evaluated for cytotoxic, antitubercular and anti-inflammatory potentials. (−)-6-Acetylzeylenol showed moderate inhibitory activity against Mycobacterium tuberculosis, with MIC value of 47.10 μg/mL. Cherrevenaphthalene D exhibited weak antimycobacterial activity and potent inhibitory effect on lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 cells (EC50 = 8.54 μM). 8-Hydroxy-5,7-dimethoxyflavanone displayed moderate level of NO inhibition (EC50 = 43.62 μM) with little cytotoxicity. The polyoxygenated cyclohexenes and lignans were inactive against HCT 116 and 22Rv1 cancer cells (IC50 > 100 μM).

Lyonensinols A - C, 24-Norursane-Type Triterpenoids from the Twigs and Leaves of Lyonia doyonensis and Their Potential Anti-inflammatory and PTP1B Inhibitory Activities.

Lyonia doyonensis is a deciduous shrub native to high-altitude regions of Asia. So far, there is no report on any chemical and biological properties of L.doyonensis. An EtOH extract of L.doyonensis twigs and leaves showed inhibitory activities on protein tyrosine phosphatase 1B and lipopolysaccharide-induced inflammation in BV-2 microglial cells. A phytochemical investigation of this extract led to the isolation of a, so far only ambiguously described, 24-norursane-type triterpenoid, now named lyonensinol A (1: ), along with its two new derivatives, lyonensinols B and C (2: and 3: ), and six known triterpenoids (4 - 9: ). Their structures were elucidated by detailed analysis of spectroscopic data. A combination of chemical conversions, electronic circular dichroism, and Mo2(OAc)4-induced electronic circular dichroism was used to confirm their absolute configurations. Lyonensinols B (2: ) and C (3: ) represent the first examples of norursane-type triterpenoids acylated with a p-coumaroyl moiety. The potential anti-inflammatory and protein tyrosine phosphatase 1B inhibitory activities of all the isolates were evaluated. Compounds 3, 7: , and 8: at 10 µM showed potent inhibitory activities on lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells, with nitric oxide levels decreasing to 31.5, 41.9, and 27.1%, respectively, while compounds 3, 4, 7: , and 8: exhibited notable inhibitory activities against protein tyrosine phosphatase 1B, with IC50 values ranging from 1.7 to 18.2 µM. Interestingly, compounds 3: and 8: , bearing a C-3 trans-p-coumaroyl group, showed not only more potent anti-inflammatory effects, but also exhibited stronger protein tyrosine phosphatase 1B inhibition than their respective stereoisomers (2: and 7: ) with a cis-p-coumaroyl group.

Three New Benzophenone Derivatives from Selaginella tamariscina.

Six compounds including three new benzophenones, selagibenzophenones D-F (1-3), two known selaginellins (4-5) and one known flavonoid (6), were isolated from Selaginella tamariscina. The structures of new compounds were established by 1D-, 2D-NMR and HR-ESI-MS spectral analyses. Compound 1 represents the second example of diarylbenzophenone from natural sources. Compound 2 possesses an unusual biphenyl-bisbenzophenone structure. Their cytotoxicity against human hepatocellular carcinoma HepG2 and SMCC-7721 cells and inhibitory activities on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells were evaluated. Compound 2 showed moderate inhibitory activity against HepG2 and SMCC-7721 cells, and compounds 4 and 5 showed moderate inhibitory activity to HepG2 cells. Compounds 2 and 5 also exhibited inhibitory activities on lipopolysaccharide-induced nitric oxide (NO) production.

Five Sesquiterpenes from Paraconiothyrium sp. and Their Anti-inflammatory Activity.

Five eremophilane sesquiterpenes including three new ones, named paraconions A-C (1-3), were isolated from an endophytic fungus, Paraconiothyrium sp. from Artemisia selengensis. The structures of these new compounds were established based on spectroscopic methods, including nuclear magnetic resonance (NMR), ultraviolet (UV), and infrared (IR) spectroscopy, as well as high resolution electrospray ionization mass spectrometry (HR-ESI-MS). An anti-inflammatory assay indicated that paraconion B (2) inhibited lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 cells, with an IC50 value of 51.7 μM. The compounds discovered in this study will enrich the structural types of secondary metabolites of the endophytic fungus Paraconiothyrium sp.

Effects of heat degradation of betanin in red beetroot (Beta vulgaris L.) on biological activity and antioxidant capacity.

Betanin is a red pigment of red beetroot (Beta vulgaris L.), providing the beneficial effects to maintain human health. Betanin is involved in the characteristic red color of red beetroot, and used as an edible dye. Betanin is known to be a highly unstable pigment, and water solutions of betanin are nearly fully degraded after heating at 99°C for 60 min in the experimental conditions of this study. The present study investigated the effects of red beetroot juice (RBJ) and betanin on immune cells, and found that stimulation with RBJ and betanin induces interleukin (IL)-1β, IL-8, and IL-10 mRNA in a human monocyte derived cell line, THP-1 cells. This mRNA induction after stimulation with RBJ and betanin was not significantly changed after heat treatment when attempting to induce degradation of the betanin. Following these results, the effects of heat degradation of betanin on the inhibition of lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264 cells and the antioxidant capacity were investigated. The results showed that the inhibition activity of RBJ and betanin with the LPS induced NO production is not altered after heat degradation of betanin. In addition, the results of FRAP (ferric reducing antioxidant power) and DPPH (1,1-Diphenyl-2-picrylhydrazyl) assays indicate that a not inconsiderable degree of the antioxidant capacity of RBJ and betanin remained after heat degradation of betanin. These results suggest that it is important to consider the effects of degradation products of betanin in the evaluation of the beneficial effects of red beetroot on health.

The Effects of 1-O-Acetylbritannilactone Isolated from Inula britannica Flowers on Human Neutrophil Elastase and Inflammation of RAW 264.7 Cells and Zebrafish Larvae.

During a search for natural inflammatory inhibitors, 1-O-acetylbritannilactone (ABL), a sesquiterpene lactone, was isolated from the flowers of Inula britannica. ABL significantly inhibited human neutrophil elastase (HNE) with a half-maximal inhibitory concentration (IC50) of 3.2 ± 0.3 µM, thus did so more effectively than the positive control material (epigallocatechin gallate) (IC50 7.2 ± 0.5 µM). An enzyme kinetic study was performed. ABL noncompetitively inhibited HNE with an inhibition constant Ki of 2.4 µM. ABL inhibited lipopolysaccharide-induced nitric oxide and prostaglandin E2 production by RAW 264.7 cells in a dose-dependent manner, as well as the protein-level expression of inducible nitric oxide synthase and cyclooxygenase-2. The anti-inflammatory effect of ABL was confirmed using a transgenic Tg(mpx:EGFP) zebrafish larval model. The exposure of the larvae to ABL inhibited neutrophil recruitment to the site of injury after tail fin amputation.

Four new Polyhydroxy Cyclohexanes from the Stems of Fissistigma tientangense.

Four undescribed polyhydroxy cyclohexanes, fissistexanes A-D (1-4), together with two known biogenetically related polyhydroxy cyclohexanes (5 and 6) were isolated from the stems of Fissistigma tientangense. The structures of these polyhydroxy cyclohexanes were determined by comprehensive spectroscopic analyses. The absolute configuration of 1 was confirmed by X-ray crystallographic. The absolute configurations of 2-4 were confirmed by chemical reaction and optical rotations. Compound 4 represent the first example of a no substituent polyhydroxy cyclohexanes from natural products. All isolated compounds were evaluated for their anti-inflammatory activities. Compounds 3 and 4 showed inhibitory activities against the nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro.

Volatile Components and Biological Activities of n-Hexane Extract From Rhizomes of Homalomena cochinchinensis

In this study, we analyzed the volatile constituents of the n-hexane extract from the rhizomes of Homalomena cochinchinensis Engl. by gas chromatography-mass spectrometry (GC-MS). We also investigated the anti-inflammatory, acetylcholinesterase (AChE) inhibitory, and cytotoxic activities of this extract. GC-MS analysis revealed the presence of 25 compounds, of which linalool was the primary component (17.6%). The extract significantly inhibited lipopolysaccharide-induced production of nitric oxide in RAW264.7 cells (IC50 = 21.08 ± 1.80 µg/mL); displayed weak cytotoxic activity against SK-LU-1, HepG2, and MCF7 cancer cell lines (IC50 values ranged from 154.60 to 184.25 µg/mL); and exhibited a weak capacity for AChE inhibition (IC50 = 131.10 ± 9.76 µg/mL). This report is the first to examine the volatile components and biological activities of the n-hexane extract from rhizomes of Homalomena cochinchinensis.

Pharmacological bioactivity of enzymatically bio-transformed ginsenosides

Many ginsenosides have shown positive effects, including anti-cancer potential and anti-inflammatory effects. Of note, protopanaxadiol (PPD) and protopanaxatriol (PPT) are not easily absorbed by the body through the digestive tract due to their hydrophilicity. From this point of view, the cytotoxic potencies of the hydrolysates of PPD and PPT on CRC are much stronger than their source compounds. Moreover, several minor ginsenosides that are absent naturally but have high disease ameliorative efficacy can be obtained from major ginsenoside by enzymatic hydrolysis. Therefore, the first aim of this study was to determine the effectiveness of the biotransformation of ginsenosides via enzymatic hydrolysis to improve their bioactivity. Second, the anti-inflammatory and anti-cancer effects of the raw and bio-transformed ginseng metabolites were determined in vitro. The results suggest that enzymes can effectively biotransform major ginsenosides (i.e., PPD and PPT) into minor ginsenosides (i.e., compound K) by hydrolyzing the β-glucosidic linkage. Moreover, the bio-transformed ginsenosides were effective in inhibiting the proliferation of HCT-116 cells and suppressing lipopolysaccharide-induced nitric oxide production in RAW 264.7 murine macrophages. Therefore, the enzymatic hydrolysis of ginsenosides can be employed to functionally produce hydrolysates with increased bioactivity.

Prenylated sulfonyl amides from the leaves of Glycosmis pentaphylla and their potential anti-proliferative and anti-inflammatory activities

Six previously undescribed sulfur-containing amides were isolated from the leaves of Glycosmis pentaphylla. Their structures were delineated by HRESIMS, 1D and 2D NMR, electronic circular dichroism (ECD) calculations, and DP4+ analyses based on gauge-independent atomic orbital (GIAO) NMR calculations. Compounds 1–4 belong to the type of methylsulfonylpropenoic acid amides. Through different cyclization pathways of geranyloxy, compounds 1 and 2 carry uncommon cyclohexane-1, 3-diol and cyclohex-3-en-1-ol moiety, respectively. Compound 3 is the oxidation product of the double bond Δ6′′(7′′) of geranyloxy. Compound 5 is elucidated as the type of methylsulfonylpropanoic acid amide. Compound 6 represents a rare sulfur-containing amide possessing a morpholin-3-one moiety. All isolated compounds were evaluated for their anti-inflammatory and anti-proliferative activities. Compound 4 significantly inhibited lipopolysaccharide-induced nitric oxide (NO) production in mouse macrophage RAW 264.7 cells with the IC50 value of 0.55 µM. Moreover, compounds 3 and 4 exhibited different anti-proliferative activities against HepG-2 with IC50 values ​​of 11.52 and 9.41 µM, respectively.

Guide isolation of guaiane-type sesquiterpenoids from Daphne tangutica maxim. And their anti-inflammatory activities

Using liquid chromatography with tandem mass spectrometry guided molecular networking, 12 undescribed guaiane-type sesquiterpenoids, namely tanguticatins A-L, 19 known analogs and a previously undescribed triterpene (tanguticatin M) were obtained from Daphne tangutica Maxim and characterized. Their planar structures and configurations were elucidated and unequivocally assigned by detailed spectroscopic analyses, electronic circular dichroism spectral calculations and single single-crustal X-ray diffraction analysis. All the isolated compounds were evaluated for lipopolysaccharide-induced nitric oxide production in murine microglial BV2 cells. Tanguticatin E and K exhibited more potent inhibitory effects than minocycline (positive control).

Isoschaftoside Inhibits Lipopolysaccharide-Induced Inflammation in Microglia through Regulation of HIF-1α-Mediated Metabolic Reprogramming.

Isoschaftoside is a C-glycosyl flavonoid extracted from the root exudates of Desmodium uncinatum and Abrus cantoniensis. Previous studies suggested that C-glycosyl flavonoid has neuroprotective effects with the property of reducing oxidative stress and inflammatory markers. Microglia are key cellular mediators of neuroinflammation in the central nervous system. The aim of this study was to investigate the effect of isoschaftoside on lipopolysaccharide-induced activation of BV-2 microglial cells. The BV-2 cells were exposed to 10 ng/ml lipopolysaccharide and isoschaftoside (0-1000 μM). Isoschaftoside effectively inhibited lipopolysaccharide-induced nitric oxide production and proinflammatory cytokines including iNOS, TNF-α, IL-1β, and COX2 expression. Isoschaftoside also significantly reduced lipopolysaccharide-induced HIF-1α, HK2, and PFKFB3 protein expression. Induction of HIF-1α accumulation by CoCl2 was inhibited by isoschaftoside, while the HIF-1α specific inhibitor Kc7f2 mitigated the metabolic reprogramming and anti-inflammatory effect of isoschaftoside. Furthermore, isoschaftoside attenuated lipopolysaccharide-induced phosphorylation of ERK1/2 and mTOR. These results suggest that isoschaftoside can suppress inflammatory responses in lipopolysaccharide-activated microglia, and the mechanism was partly due to inhibition of the HIF-1α-mediated metabolic reprogramming pathway.

Antioxidant, anti-inflammatory, and antibacterial activities of a 70% ethanol-Symphyocladia linearis extract

Research on the potential biological activity of red alga Symphyocladia spp. has been limited to Symphyocladia latiuscula, which is widely used as a food ingredient in Korea. Here, we examined the biological activity of another species, Symphyocladia linearis, which is found in Korea and was reported as a new species in 2013. The aim of this study was to evaluate the antioxidant, anti-inflammatory, and antibacterial properties of a 70% ethanol extract of S. linearis. Antioxidant activity, which was evaluated using radical scavenging assays, revealed half maximal inhibitory concentration values for 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) of 34.57 and 11.70 μg/mL algal extract, respectively. Anti-inflammatory activity of the S. linearis ethanolic extract was evaluated using RAW 264.7 cells by measuring the inhibition of lipopolysaccharide-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production. The potential cytotoxicity of NO and PGE2 was first examined, confirming no toxicity at concentrations ranging from 10-100 μg/mL. NO production was inhibited 61.1% and 78.0% at 50 and 100 μg/mL S. linearis extract, respectively; and PGE2 production was inhibited 69.1%, 83.2%, and 94.8% at 25, 50, and 100 μg/mL S. linearis extract, respectively. Thus, the S. linearis extract showed very strong efficacy against PGE2 production. The cellular production of reactive oxygen species, measured using 2′,7′-dichlorofluorescin diacetate fluorescence, was inhibited 48.8% by the addition of 100 μg/mL S. linearis extract. Antibacterial activity was evaluated using the disc diffusion method and minimum inhibitory concentration (MIC). S. linearis was effective only against gram-positive bacteria, exhibiting antibacterial activity against Staphylococcus aureus with a MIC of 256 μg/mL extract and against Bacillus cereus with a MIC of 1,024 μg/mL extract. Based on these results, we infer that a 70% ethanolic extract of S. linearis possesses strong anti-inflammatory properties, and therefore has the potential to be used in the prevention and treatment of inflammatory and immune diseases.

Carbon monoxide-releasing molecule-401, a water-soluble manganese-based metal carbonyl, suppresses Prevotella intermedia lipopolysaccharide-induced production of nitric oxide in murine macrophages

Context Many reports in the literature have suggested the therapeutic value of carbon monoxide-releasing molecules (CORMs) against various diseases. However, to date, little is known about their possible influence on periodontal disease. Objective This study was performed to investigate the influence of CORM-401 on the generation of nitric oxide (NO) in murine macrophage cells activated with lipopolysaccharide (LPS) derived from Prevotella intermedia, a pathogen associated with periodontal disease. Materials and methods LPS was isolated by the hot phenol-water method. Culture supernatants were analyzed for NO. Real-time PCR and immunoblotting were conducted to quantify mRNA and protein expression, respectively. NF-κB-dependent SEAP levels were estimated by reporter assay. DNA-binding of NF-κB was also analyzed. Results CORM-401 caused an apparent suppression of NO production through inhibition of iNOS at both the mRNA and protein levels in RAW264.7 cells stimulated with P. intermedia LPS. CORM-401 upregulated the expression of both the HO-1 gene and its protein in LPS-activated cells, and treatment with the HO-1 inhibitor significantly reversed the attenuating influence of CORM-401 against LPS-induced generation of NO. CORM-401 caused an apparent attenuation of NF-κB-dependent SEAP release induced by LPS. IκB-α degradation and nuclear translocation of NF-κB p50 subunit induced by LPS were significantly reduced by CORM-401. Additionally, CORM-401 significantly attenuated DNA-binding of p65 and p50 induced by LPS. CORM-401 attenuated NO generation induced by P. intermedia LPS independently of PPAR-γ, JNK, p38 and STAT1/3. Conclusion The modulation of host inflammatory response by CORM-401 might be of help in the therapy of periodontal disease.

NO Release Inhibitory Activity of Flavonoids from Aesculus Wilsonii Seeds through MAPK (P38), NF-κB, and STAT3 Cross-Talk Signaling Pathways.

The flavonoid constituents of Aesculus wilsonii, a source of the Chinese medicinal drug Suo Luo Zi, and their in vitro anti-inflammatory effects were investigated. Fifteen flavonoids, including aeswilflavonosides IA-IC (1: - 3: ) and aeswilflavonosides IIA-IIE (4: - 8: ), along with seven known derivatives were isolated from a seed extract. Their structures were elucidated by extensive spectroscopic methods, acid and alkaline hydrolysis, and calculated electronic circular dichroism spectra. Among them, compounds 3: and 7: possess a 5-[2-(carboxymethyl)-5-oxocyclopent-yl]pent-3-enylate or oleuropeoylate substituent, respectively, which are rarely reported in flavonoids. Compounds 2, 3, 7: , and 12: - 15: were found to inhibit lipopolysaccharide-induced nitric oxide production in RAW 264.7 cell lines. In a mechanistic assay, the flavonoid glycosides 2, 3: , and 7: reduced the expressions of interleukin-6 and tumor necrosis factor-alpha induced by lipopolysaccharide. Further investigations suggest that 2: and 3: downregulated the protein expression of tumor necrosis factor-alpha and interleukin-6 by inhibiting the phosphorylation of p38. Compound 7: was found to reduce the production of inducible nitric oxide synthase, and the secretion of tumor necrosis factor-alpha and interleukin-6 through inhibiting nuclear factor kappa-light-chain-enhancer of activated B signaling pathway. Compounds 2, 3: , and 7: possessed moderate inhibitory activity on the expression of signal transducer and activator of transcription-3. Taken together, the data indicate that the flavonoid glycosides of A.wilsonii seeds exhibit nitric oxide release inhibitory activity through mitogen-activated protein kinase (p38), nuclear factor kappa-light-chain-enhancer of activated B, and signal transducer and activator of transcription-3 cross-talk signaling pathways.

Preparation of chitosan-rosmarinic acid derivatives with enhanced antioxidant and anti-inflammatory activities

In present study, several chitosan derivatives grafted with rosmarinic acid，including chitosan-rosmarinic acid conjugate (CS-RA), chitosan rosmarinic acid salt (CSRA), N,N,N-trimethylated chitosan rosmarinic acid salt (TMCRA), and N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan rosmarinic acid salt (HACRA), were prepared and the effects of different grafting methods on bioactivity of these derivatives were investigated. The structural characterization was identified by FTIR and 1H NMR spectroscopy. The chitosan derivatives were also evaluated biologically for antioxidant, cytotoxic, and anti-inflammatory activities. Derivatives CSRA, TMCRA, and HACRA prepared through ion exchange method exhibited significant antioxidant ability. All derivatives remarkably inhibited lipopolysaccharide-induced nitric oxide and TNF-α production in RAW 264.7 cells without cytotoxicity, especially derivative TMCRA, whose inhibition rate was >50 % at only 250 μg/mL. The results suggested that chitosan quaternary ammonium derivatives grafted with rosmarinic acid possessed better antioxidant and anti-inflammatory properties than chitosan, which could be used as drug materials against oxidative and inflammation-related pathological processes.