Inhibitory Effects of Baicalein and Wogonin on Lipopolysaccharide‐Induced Nitric Oxide Production in Macrophages

Wakabayashi, Ichiro

doi:10.1111/j.1600-0773.1999.tb01496.x

Cited by 81 publications

(54 citation statements)

References 17 publications

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“…Baicalein (5,6,7-trihydroxyflavone) is a flavonoid derived from the root of Scutellaria baicalensis Georgi, a medicinal plant traditionally used in Oriental medicine . This flavonoid has been shown to exert anti-inflammatory effects; it inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in RAW264.7 mouse macrophages (Wakabayashi, 1999) and inhibited adhesion molecule expression induced by thrombin in cultured human umbilical vein endothelial cells (Kimura et al, 2001). In vivo anti-inflammatory effects of baicalein have been also demonstrated; baicalein ameliorated all the considered inflammatory symptoms in dextran sulfate sodium-induced colitis in mice (Hong et al, 2002).…”

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confidence: 91%

Flavonoid Baicalein Attenuates Activation-Induced Cell Death of Brain Microglia

Suk¹,

Lee²,

Kang³

et al. 2003

J Pharmacol Exp Ther

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Baicalein (5,6,7-trihydroxyflavone), a flavonoid originated from the root of Chinese medicinal herb Scutellaria baicalensis, has been shown to exert anti-inflammatory and antioxidant effects, and it is a well known inhibitor of 12-lipoxygenase. We have previously reported that neuroglia undergo nitric oxide (NO)-dependent and NO-independent apoptosis upon inflammatory activation. In the current work, we asked how anti-inflammatory baicalein influences autoregulatory apoptosis of activated microglia and their NO production. Baicalein attenuated NO production and apoptosis of lipopolysaccharide (LPS)-activated, but not interferon-␥-activated, BV-2 mouse microglial cells as well as rat primary microglia cultures. The inhibition of NO production by baicalein was due to the suppression of inducible NO synthase induction. Moreover, baicalein inhibited LPSinduced nuclear factor-B (NF-B) activity in BV-2 cells without affecting caspase-11 activation, interferon regulatory factor-1 induction, or signal transducer and activator of transcription-1 phosphorylation. Transfection of BV-2 cells with a p65 subunit of NF-B abolished the apoptosis-attenuating effects of baicalein, indicating that the inhibition of NF-B is a major mechanism of action. Baicalein, however, did not significantly affect NO donor-mediated cytotoxicity, and the apoptosis-attenuating effects of baicalein were independent of 12-lipoxygenase inhibition. Based on our previous findings that activation-induced cell death (AICD) of microglia occurs through two separate pathways (NO-dependent pathway and caspase-11-dependent pathway), our current results suggest that baicalein selectively inhibits the NO-dependent apoptotic pathway of activated microglia by suppressing cytotoxic NO production. Also, the AICD-inhibiting effects of baicalein were specific for the inflammatory stimulus that activated microglia.

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mentioning

confidence: 91%

Flavonoid Baicalein Attenuates Activation-Induced Cell Death of Brain Microglia

Suk¹,

Lee²,

Kang³

et al. 2003

J Pharmacol Exp Ther

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“…Wogonin was found to inhibit NO production by iNOS and PGE 2 production by COX-2 from LPSinduced macrophages (47,52,54,55,92). The IC 50 values of wogonin were 31 and 0.3 mM for NO and PGE 2 production, respectively, from LPS-induced RAW cells (52).…”

Section: Wogonin As An Anti-inflammatory Agentmentioning

confidence: 99%

Anti-inflammatory Plant Flavonoids and Cellular Action Mechanisms

et al. 2004

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Abstract. Plant flavonoids show anti-inflammatory activity in vitro and in vivo. Although not fully understood, several action mechanisms are proposed to explain in vivo anti-inflammatory action. One of the important mechanisms is an inhibition of eicosanoid generating enzymes including phospholipase A 2 , cyclooxygenases, and lipoxygenases, thereby reducing the concentrations of prostanoids and leukotrienes. Recent studies have also shown that certain flavonoids, especially flavone derivatives, express their anti-inflammatory activity at least in part by modulation of proinflammatory gene expression such as cyclooxygenase-2, inducible nitric oxide synthase, and several pivotal cytokines. Due to these unique action mechanisms and significant in vivo activity, flavonoids are considered to be reasonable candidates for new anti-inflammatory drugs. To clearly establish the therapeutic value in inflammatory disorders, in vivo anti-inflammatory activity, and action mechanism of varieties of flavonoids need to be further elucidated. This review summarizes the effect of flavonoids on eicosanoid and nitric oxide generating enzymes and the effect on expression of proinflammatory genes. In vivo anti-inflammatory activity is also discussed. As natural modulators of proinflammatory gene expression, certain flavonoids have a potential for new anti-inflammatory agents.

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“…Interest is increasing in the protective biological effects of some natural antioxidants, especially from edible plants, which are candidates for preventing various inflammatory disorders and extending the life span of humans (Unno et al 1997;Yang et. al 1998;Virgili et al 1998;Wakabayashi 1999). Many of the natural antioxidants reported in the literature are related to the polyphenol or flavonoid families having potent antioxidant properties including the scavenging of oxygen radicals, nitric oxide and lipid radicals (Nowak et al 1993).…”

Section: Discussionmentioning

confidence: 99%

Effects of Apocynin and Natural Antioxidant from Spinach on Inducible Nitric Oxide Synthase and Cyclooxygenase‐2 Induction in Lipopolysaccharide‐Induced Hepatic Injury in Rat

Lomnitski

Foley

Grossman

et al. 2000

Pharmacology & Toxicology

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Abstract:The immunoreactivity of inducible nitric oxide synthase, and cyclooxygenase-2 was compared among groups of male Wistar rats comprising those injected with lipopolysaccharide following pretreatment with either natural antioxidant from spinach or the antioxidant apocynin, with lipopolysaccharide without pretreatment with antioxidants, with each of the two antioxidants alone, and untreated controls. The grade of staining of both inducible nitric oxide synthase and cyclooxygenase-2 increased with the severity of the inflammatory reaction in the lipopolysaccharide-treated animals, compared to the antioxidant-treated groups. Interpretation of the results of the immunostained tissues indicated that pretreatment with either antioxidant significantly (P∞0.05) attenuated the lipopolysaccharide-stimulated inducible nitric oxide synthase induction. Analysis of the cycloxygenase-2-stained liver samples indicated that the pretreatment with the natural antioxidant NAO significantly (P∞0.05) attenuated lipopolysaccharide-stimulated cycloxygenase-2 induction; whereas, in animals pretreated with apocynin, there was a trend of reduction in the cyclooxygenase-2 expression, but not statistically significant (P±0.05). The negative nitrotyrosine immunoreactivity of the lipopolysaccharide-related hepatic lesions may indicate that there was relatively low interaction between superoxide anions and nitric oxide to form peroxynitrite or that the expression levels of the nitrotyrosine were below the limit of detection. In all treatment groups a positive correlation (P∞0. 05, rΩ0.86) found between the inducible nitric oxide synthase and cyclooxygenase-2 scores suggests a strong relationship between these two parameters. The results indicate the possible therapeutic efficacy of NAO and apocynin in the prevention of liver damage related to clinical endotoxemia known to be associated with oxidative stress.

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Inhibitory Effects of Baicalein and Wogonin on Lipopolysaccharide‐Induced Nitric Oxide Production in Macrophages

Cited by 81 publications

References 17 publications

Flavonoid Baicalein Attenuates Activation-Induced Cell Death of Brain Microglia

Flavonoid Baicalein Attenuates Activation-Induced Cell Death of Brain Microglia

Anti-inflammatory Plant Flavonoids and Cellular Action Mechanisms

Effects of Apocynin and Natural Antioxidant from Spinach on Inducible Nitric Oxide Synthase and Cyclooxygenase‐2 Induction in Lipopolysaccharide‐Induced Hepatic Injury in Rat

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