Anti-inflammatory activity of AP-SF, a ginsenoside-enriched fraction, from Korean ginseng.

BACKGROUND: Korean ginseng is an ethnopharmacologically valuable herbal plant with various biological properties including anticancer, antiatherosclerosis, antidiabetic, and anti-inflammatory activities. Since there is currently no drug or therapeutic remedy derived from Korean ginseng, we developed a ginsenoside-enriched fraction (AP-SF) for prevention of various inflammatory symptoms. METHODS: The anti-inflammatory efficacy of AP-SF was tested under in vitro inflammatory conditions including nitric oxide (NO) production and inflammatory gene expression. The molecular events of inflammatory responses were explored by immunoblot analysis. RESULTS: AP-SF led to a significant suppression of NO production compared with a conventional Korean ginseng saponin fraction, induced by both lipopolysaccharide and zymosan A. Interestingly, AP-SF strongly downregulated the mRNA levels of genes for inducible NO synthase, tumor necrosis factor-α, and cyclooxygenase) without affecting cell viability. In agreement with these observations, AP-SF blocked the nuclear translocation of c-Jun at 2 h and also reduced phosphorylation of p38, c-Jun N-terminal kinase, and TAK-1, all of which are important for c-Jun translocation. CONCLUSION: Our results suggest that AP-SF inhibits activation of c-Jun-dependent inflammatory events. Thus, AP-SF may be useful as a novel anti-inflammatory remedy.

In vitro and in vivo anti-inflammatory activity of Phyllanthus acidus methanolic extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus acidus (L.) Skeels (Phyllanthaceae) has traditionally been used to treat gastric trouble, rheumatism, bronchitis, asthma, respiratory disorders, and hepatitis. Despite this widespread use, the pharmacological activities of this plant and their molecular mechanisms are poorly understood. Therefore, we evaluated the immunopharmacological activities of the methanolic extract of the aerial parts of this plant (Pa-ME) and validated its pharmacological targets. MATERIALS AND METHODS: Lipopolysaccharide (LPS)-treated macrophages, an HCl/EtOH-induced gastritis model, and an acetic acid-injected capillary permeability mouse model were employed to evaluate the anti-inflammatory activity of Pa-ME. Potentially active anti-inflammatory components of this extract were identified by HPLC. The molecular mechanisms of the anti-inflammatory activity were studied by kinase assays, reporter gene assays, immunoprecipitation analysis, and overexpression of target enzymes. RESULTS: Pa-ME suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and prevented morphological changes in LPS-treated RAW264.7 cells. Moreover, both HCl/EtOH-induced gastric damage and acetic acid-triggered vascular permeability were restored by orally administered Pa-ME. Furthermore, this extract downregulated the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 and reduced the nuclear levels of NF-κB. Signalling events upstream of NF-κB translocation, such as phosphorylation of Src and Syk and formation of Src/Syk signalling complexes, were also inhibited by Pa-ME. The enzymatic activities of Src and Syk were also suppressed by Pa-ME. Moreover, Src-induced and Syk-induced luciferase activity and p85/Akt phosphorylation were also inhibited by Pa-ME. Of the identified flavonoids, kaempferol and quercetin were revealed as partially active anti-inflammatory components in Pa-ME. CONCLUSION: Pa-ME exerts anti-inflammatory activity in vitro and in vivo by suppressing Src, Syk, and their downstream transcription factor, NF-κB.

Antiproliferative and Apoptosis-Inducing Activities of 4-Isopropyl-2,6-bis(1-phenylethyl)phenol Isolated from Butanol Fraction of Cordyceps bassiana.

The Cordyceps species have been widely used for treating various cancer diseases. Although the Cordyceps species have been widely known as an alternative anticancer remedy, which compounds are responsible for their anticancer activity is not fully understood. In this study, therefore, we examined the anticancer activity of 5 isolated compounds derived from the butanol fraction (Cb-BF) of Cordyceps bassiana. For this purpose, several cancer cell lines such as C6 glioma, MDA-MB-231, and A549 cells were employed and details of anticancer mechanism were further investigated. Of 5 compounds isolated by activity-guided fractionation from BF of Cb-EE, KTH-13, and 4-isopropyl-2,6-bis(1-phenylethyl)phenol, Cb-BF was found to be the most potent antiproliferative inhibitor of C6 glioma and MDA-MB-231 cell growth. KTH-13 treatment increased DNA laddering, upregulated the level of Annexin V positive cells, and altered morphological changes of C6 glioma and MDA-MB-231 cells. In addition, KTH-13 increased the levels of caspase 3, caspase 7, and caspase 9 cleaved forms as well as the protein level of Bax but not Bcl-2. It was also found that the phosphorylation of AKT and p85/PI3K was also clearly reduced by KTH-13 exposure. Therefore, our results suggest KTH-13 can act as a potent antiproliferative and apoptosis-inducing component from Cordyceps bassiana, contributing to the anticancer activity of this mushroom.

21-O-angeloyltheasapogenol E3, a novel triterpenoid saponin from the seeds of tea plants, inhibits macrophage-mediated inflammatory responses in a NF-κB-dependent manner.

21-O-Angeloyltheasapogenol E3 (ATS-E3) is a triterpenoid saponin recently isolated from the seeds of the tea tree Camellia sinensis (L.) O. Kuntze. ATS-E3 has several beneficial properties including anti-inflammatory, antidiabetic, antiatherosclerotic, and anticancer effects. Unlike other phenolic compounds isolated from tea plants, there are no studies reporting the pharmacological action of ATS-E3. In this study, we therefore aimed to explore the cellular and molecular inhibitory activities of ATS-E3 in macrophage-mediated inflammatory responses. ATS-E3 remarkably diminished cellular responses of macrophages such as FITC-dextran-induced phagocytic uptake, sodium nitroprusside- (SNP-) induced radical generation, and LPS-induced nitric oxide (NO) production. Analysis of its molecular activity showed that this compound significantly suppressed the expression of inducible NO synthase (iNOS), nuclear translocation of nuclear factor- (NF-) κB subunits (p50 and p65), phosphorylation of inhibitor of κB kinase (IKK), and the enzyme activity of AKT1. Taken together, the novel triterpenoid saponin compound ATS-E3 contributes to the beneficial effects of tea plants by exerting anti-inflammatory and antioxidative activities in an AKT/IKK/NF-κB-dependent manner.

IKK ß -Targeted Anti-Inflammatory Activities of a Butanol Fraction of Artificially Cultivated Cordyceps pruinosa Fruit Bodies.

The inhibitory activities of the Cordyceps pruinosa butanol fraction (Cp-BF) were investigated by determining inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells and by evaluating HCl/ethanol (EtOH)-triggered gastric ulcers in mice. The molecular mechanisms of the inhibitory effects of Cp-BF were investigated by identifying target enzymes using biochemical and molecular biological approaches. Cp-BF strongly inhibited the production of NO and TNF-α, release of reactive oxygen species (ROS), phagocytic uptake of FITC-dextran, and mRNA expression levels of interleukin (IL)-6, inducible NO synthase (iNOS), and tumour necrosis factor-alpha (TNF)-α in activated RAW264.7 cells. Cp-BF also strongly downregulated the NF-κB pathway by suppressing IKKß according to luciferase reporter assays and immunoblot analysis. Furthermore, Cp-BF blocked both increased levels of NF-κB-mediated luciferase activities and phosphorylation of p65/p50 observed by IKKß overexpression. Finally, orally administered Cp-BF was found to attenuate gastric ulcer and block the phosphorylation of IκBα induced by HCl/EtOH. Therefore, these results suggest that the anti-inflammatory activity of Cp-BF may be mediated by suppression of IKKα and its downstream NF-κB activation. Since our group has established the mass cultivation conditions by developing culture conditions for Cordyceps pruinosa, the information presented in this study may be useful for developing new anti-inflammatory agents.