Chemical Constituents Identified from Fruit Body of Cordyceps bassiana and Their Anti-Inflammatory Activity.

Cordyceps bassiana is one of Cordyceps species with anti-oxidative, anti-cancer, anti-inflammatory, anti-diabetic, anti-obesity, anti-angiogenic, and anti-nociceptive activities. This mushroom has recently demonstrated to have an ability to reduce 2,4-dinitrofluorobenzene-induced atopic dermatitis symptoms in NC/Nga mice. In this study, we further examined phytochemical properties of this mushroom by column chromatography and HPLC analysis. By chromatographic separation and spectroscopic analysis, 8 compounds, such as 1,9-dimethylguanine (1), adenosine (2), uridine (3), nicotinamide (4), 3-methyluracil (5), 1,7-dimethylxanthine (6), nudifloric acid (7), and mannitol (8) were identified from 6 different fractions and 4 more subfractions. Through evaluation of their anti-inflammatory activities using reporter gene assay and mRNA analysis, compound 1 was found to block luciferase activity induced by NF-κB and AP-1, suppress the mRNA levels of cyclooxygenase (COX)-2 and tumor necrosis factor (TNF)-α. Therefore, our data strongly suggests that compound 1 acts as one of major principles in Cordyceps bassiana with anti-inflammatory and anti-atopic dermatitis activities.

In vitro and in vivo anti-inflammatory effect of Rhodomyrtus tomentosa methanol extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhodomyrtus tomentosa (Aiton) Hassk. is a representative Thai medicinal plant traditionally used in South Asian countries to relieve various inflammatory symptoms. However, no systematic studies on its anti-inflammatory activity and mechanisms have been reported. MATERIALS AND METHODS: The effect of the methanol extract from the leaves of this plant (Rt-ME) on the production of inflammatory mediators [nitric oxide (NO) and prostaglandin E2 (PGE2)] and the molecular mechanism of Rt-ME-mediated inhibition, including target enzymes, were studied with RAW264.7, peritoneal macrophage, and HEK293 cells. Additionally, the in vivo anti-inflammatory activity of this extract was evaluated with mouse gastritis and colitis models. RESULTS: Rt-ME clearly inhibited the production of NO and PGE2 in lipopolysaccharide (LPS)-activated RAW264.7 cells and peritoneal macrophages in a dose-dependent manner. According to RT-PCR, immunoblotting and immunoprecipitation analyses and a kinase assay with mRNA, whole cell extract, and nucleus lysates from RAW264.7 cells and mice, it was revealed that Rt-ME was capable of suppressing the activation of both nuclear factor (NF)-κB and activator protein (AP)-1 pathways by directly targeting Syk/Src and IRAK1/IRAK4. CONCLUSION: Rt-ME could have anti-inflammatory properties by suppressing Syk/Src/NF-kB and IRAK1/IRAK4/AP-1 pathways and will be further developed as a herbal remedy for preventive and/or curative purposes in various inflammatory diseases.

AP-1 pathway-targeted inhibition of inflammatory responses in LPS-treated macrophages and EtOH/HCl-treated stomach by Archidendron clypearia methanol extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Archidendron clypearia Jack. (Fabaceae) is a representative ethnomedicinal herbal plant prescribed for various inflammatory diseases such as pharyngolaryngitis and tonsillitis. However, the pharmacology behind this plant's anti-inflammatory properties has not been fully understood. Therefore, in this study, the anti-inflammatory mechanism of a 95% methanol extract (Ac-ME) was explored. MATERIALS AND METHODS: The anti-inflammatory mechanism of Ac-ME on the AP-1 activation pathway, which plays a critical role in the production of prostaglandin (PG)E2 in RAW264.7 cells and peritoneal macrophages and in induction of acute gastritis caused by HCl/EtOH, was investigated using immunoblotting, immunoprecipitation analyses, and reporter gene activity assays. In particular, enzyme assays and HPLC analysis were employed to identify direct target enzymes of Ac-ME and to detect active chemical components from the plant extract. RESULTS: Ac-ME clearly reduced the nuclear levels of total and phospho-forms of c-Jun, FRA-1, and ATF-2. Consequently, this extract suppressed both the production of PGE2 in lipopolysaccharide (LPS)-activated RAW264.7 and peritoneal macrophage cells and PGE2-dependent induction of gastritis lesion in stomach under EtOH/HCl exposure. Analysis of AP-1 upstream signalling revealed that the AP-1 activation pathway consisting of IRAK1, TRAF6, TAK1, MKK3/6, and p38 was predominantly inhibited by Ac-ME. Similarly, this extract directly blocked the enzyme activity of IRAK1, indicating that this enzyme is an inhibitory target of Ac-ME and is involved in the suppression of the AP-1 pathway. HPLC analysis showed that quercetin, which inhibits PGE2 production, is an active component in Ac-ME. CONCLUSION: Ac-ME is an ethnomedicinal remedy with an IRAK1/p38/AP-1-targeted inhibitory property. Since AP-1 is a major inflammation-inducing transcription factor, the therapeutic potential of Ac-ME in other AP-1-mediated inflammatory symptoms will be further tested.

Methanol extract of Evodia lepta displays Syk/Src-targeted anti-inflammatory activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Evodia lepta (Spreng.) Merr., in the Rutaceae family, is a medicinal plant traditionally used to treat inflammatory symptoms such as in meningitis and hepatitis. However, no study has systematically investigated its anti-inflammatory activities including its molecular mechanism. MATERIALS AND METHODS: The effects of a methanol extract from the roots Evodia lepta (El-ME) were evaluated using lipopolysaccharide (LPS)-treated RAW264.7 cells producing nitric oxide (NO) and prostaglandin E2 (PGE2), and an HCl/ethanol-induced mouse gastritis model. Target molecules were identified by analyzing the activation of transcription factors and their upstream kinases. RESULTS: El-ME reduced the production of NO and PGE2 from LPS-activated RAW264.7 cells in a dose-dependent manner. El-ME also ameliorated the gastritis symptoms of EtOH/HCl-treated mice. The extract suppressed production of mRNA for the inducible NO synthase (iNOS) and cyclooxygenase (COX)-2; the nuclear translocation of nuclear factor (NF)-κB; the phosphorylation of upstream kinases that activate NF-κB; and the kinase activities of Syk and Src. CONCLUSION: The anti-inflammatory effects of El-ME might be due to its suppression of Syk/Src and NF-κB. Considering the in vitro and in vivo efficacy of El-ME, Evodia lepta could be developed into an anti-inflammatory herbal remedy.