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The activity-guided fractionation of the MeOH extract of the rhizomes and roots of Nardostachys chinensis led to the isolation of two new sesquiterpenoids, narchinol B (8) and narchinol C (9), along with 10 known compounds, ursolic acid (1), nardosinone (2), pinoresinol (3), desoxo-narchinol A (4), kanshone B (5), epoxyconiferyl alcohol (6), debilon (7), 4α,5-dimethyl-1,3-dioxo-1,2,3,4,4α,5,6,7-octahydronaphthalene (10), p-coumaric acid (11), and isoferulic acid (12). Their structures were determined using spectroscopic techniques, which included 1D- and 2D-NMR. Among the isolates, compounds 2, 4, 5, 8 and 9 showed inhibitory activity against LPS-induced NO production with IC(50) values of 4.6-21.6 μM., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Aerial parts of Artemisia asiatica (Compositae) have been traditionally used as an oriental medicine for the treatment of inflammatory and ulcerogenic diseases. In the present study, artemisolide was isolated as a nuclear factor (NF)-kappaB inhibitor from A. asiatica by activity-guided fractionation. Artemisolide inhibited NF-kappaB transcriptional activity in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 with an IC50 value of 5.8 microM. The compound was also effective in blocking NF-kappaB transcriptional activities elicited by the expression vector encoding the NF-kappaB p65 or p50 subunits bypassing the inhibitory kB degradation signaling NF-kappaB activation. The macrophages markedly increased their PGE2 and NO production upon exposure to LPS alone. Artemisolide inhibited LPS-induced PGE2 and NO production with IC50 values of 8.7 microM and 6.4 microM, respectively, but also suppressed LPS-induced synthesis of cyclooxygenase (COX)-2 or inducible NO synthase (iNOS). Taken together, artemisolide is a NF-kappaB inhibitor that attenuates LPS-induced production of PGE2 or NO via down-regulation of COX-2 or iNOS expression in macrophages RAW 264.7. Therefore, artemisolide could represent and provide the anti-inflammatory principle associated with the traditional medicine, A. asiatica.

The herb, Chrysanthemum zawadskii var, latilobum commomly known as Gu-Jul-Cho in Korea, used in traditional medicine to treat pneumonia, bronchitis, cough, common cold, pharyngitis, bladder-related disorders, gastroenteric disorders, and hypertension. Linarin is the main active compound and the biological mechanisms of its activity are unclear. It is believed that effects of this herb may be exerted through the pluripotent effectors of linarin due to its ability to treat a variety of afflictions. In this study, the effects of linarin on the mouse macrophages cell line, RAW 264.7, were investigated. It was found that linarin could activate macrophages by producing cytokines. Monocytes and tissue macrophages produce at least two groups of protein mediators of inflammation, interleukin 1 (IL-1) and the tumor necrosis factor (TNF). Recent studies have shown that TNF and IL-1 modulate the inflammatory function of endothelial cells, leukocytes, and fibroblasts. TNF-alpha production by macrophages treated with linarin occured in a dose dependent manner. However, IL-1 production was largely unaffected by this natural product. This study demonstrated the ability of linarin to activate macrophages both directly and indirectly. Linarin also affect both cytokine production and nitric oxide inhibition, in addition to the expression of some surface molecules. Nitric oxide (NO), derived from L-argin-ine, is produced by two forms(constitutive and inducible) of nitric oxide synthase (NOS). The NO produced in large amounts by inducible NOS is known to be responsible for the vasodilation and hypotension observed in septic shock. Linarin was found to inhibit NO production in the LPS-activated RAW 264.7 cells. Linarin may be a useful candidate as a new drug for treating endotoxemia and the inflammation accompanied by NO overproduction. The linarin-treated total lymphocytes exhibited cytotoxicity in a dose dependent manner between 20 microg/ml and 40 microg/ml. These results suggest that linarin may function through macrophage activation.

Auranofin (AF), a gold compound, is an orally active therapeutic agent used to treat rheumatoid arthritis (RA), a self-perpetuating inflammatory disease. RA is characterized by autoimmune-mediated proliferation of synovial cells that leads to inflammation, pain, and swelling in most major joints. However, the mechanism as to how AF relieves RA symptoms has not been fully elucidated. The object of this study was to examine the ability of AF to immunomodulate macrophages as antigen presenting cells (APCs). Macrophages are recognized as playing an important role in the pathogenesis of RA, in that there is a relative abundance of macrophage-derived cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in rheumatoid synovium. In this work, we tested whether AF (2.5–20 mM) could inhibit inflammatory activity in the macrophage cell line RAW 264.7. AF decreased production of nitric oxide (NO) and the pro-inflammatory cytokines, TNF-α, IL-1β and IL-6 in macrophages. Furthermore, AF inhibited cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2) production in a concentration-dependent manner. In conclusion, these findings may provide an explanation for the clinical effects of AF in patients with RA. [ABSTRACT FROM AUTHOR]

Aerial parts of Artemisia asiatica (Compositae) have been traditionally used as an oriental medicine for the treatment of inflammatory and ulcerogenic diseases. In the present study, artemisolide was isolated as a nuclear factor (NF)-κB inhibitor from A. asiatica by activity-guided fractionation. Artemisolide inhibited NF-κB transcriptional activity in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 with an IC50 value of 5.8 μM. The compound was also effective in blocking NF-κB transcriptional activities elicited by the expression vector encoding the NF-κB p65 or p50 subunits bypassing the inhibitory kB degradation signaling NF-κB activation. The macrophages markedly increased their PGE2 and NO production upon exposure to LPS alone. Artemisolide inhibited LPS-induced PGE2 and NO production with IC50 values of 8.7 μM and 6.4 μM, respectively, but also suppressed LPS-induced synthesis of cyclooxygenase (COX)-2 or inducible NO synthase (iNOS). Taken together, artemisolide is a NF-κB inhibitor that attenuates LPS-induced production of PGE2 or NO via down-regulation of COX-2 or iNOS expression in macrophages RAW 264.7. Therefore, artemisolide could represent and provide the anti-inflammatory principle associated with the traditional medicine, A. asiatica. [ABSTRACT FROM AUTHOR]

Abstract: Several types of immunomodulatory polysaccharides originated from plants or mushrooms have been used as immunotherapeutic agents in the treatment of cancers. Here, we describe an immunomodulatory polysaccharide that cannot only activate monocytic cells strongly, but also induce differentiation of monocytic cells into macrophages. High molecular weight substances, SHE, were isolated from Salicornia herbacea, which has been used to treat a variety of diseases including cancers in traditional oriental remedy. The immunomodulatory activities of SHE were examined on a mouse monocytic cell line, RAW 264.7 cells. We found that SHE activated RAW cells to produce cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and nitric oxide (NO) dose dependently. SHE also induced the expression of co-stimulatory molecules such as B7-1 and CD40, and increased phagocytic activity on opsonized sheep red blood cells. While increasing these parameters of macrophage activation, SHE inhibited the growth of RAW cells dose dependently inducing morphological changes from slightly adherent monocytic cells to strongly adherent macrophages. The active components of SHE appeared to be polysaccharides, and not an endotoxin. These results show that polysaccharides originated from S. herbacea possess potent immunomodulatory activity on monocyte/macrophage lineage cells. [Copyright &y& Elsevier]

Abstract: Three new diterpenes (7, 15 and 17) and two new neolignans (19 and 20) along with nineteen known compounds have been isolated from the fruits of Vitex rotundifolia. Their structures were elucidated by a combination of 1D and 2D NMR, HRESI-MS, and CD data. All isolates were tested for their inhibitory activities on LPS-induced nitric oxide production in RAW264.7 cells. Of these, compounds 3, 4, 7, 13, 15, 19, and 24 found to inhibit nitric oxide production with the IC50 values ranging from 11.3 to 24.5 μM. [Copyright &y& Elsevier]

Abstract: Resveratrol (trans-3,4′,5-trihydroxystilbene) is one of nonflavonoid polyphenolic phytoalexins found in various plant species, a number of which are components of human diet including grapes and red wines. Resveratrol has exerted several beneficial effects with anti-inflammation, cardioprotection and cancer chemoprevention. However, its mechanisms of action are not completely understood. In this study, we investigated effects of resveratrol on inflammatory gene expression in interferon (IFN)-γ alone-stimulated macrophages and proposed a molecular basis underlying the action. Resveratrol inhibited IFN-γ-induced production of nitric oxide (NO), IFN-γ-inducible protein-10 (IP-10), or the monokine induced by IFN-γ (MIG) in RAW 264.7 macrophages and also that of NO in primary macrophages derived from bone marrows of C3H/HeJ (toll-like receptor-4−/−) mice. Moreover, resveratrol diminished IFN-γ-induced protein levels of inducible NO synthase (iNOS), attenuated mRNA levels of iNOS, IP-10 or MIG as well as inhibited IFN-γ-induced promoter activity of iNOS gene, indicating that the phytoalexin could down-regulate inflammatory genes at the transcription level. To understand a mechanism of the action, we tested resveratrol could affect the signal transducers and activation of transcription-1 (STAT-1), a pivotal transcription factor in IFN-γ-induced expression of inflammatory genes. Resveratrol inhibited IFN-γ-induced transcriptional activity of STAT-1 in macrophages and also IFN-γ-induced Tyr701 or Ser727 phosphorylation of STAT-1. We then focused on protein kinases upstream STAT-1 phosphorylation. Resveratrol inhibited IFN-γ-induced activation of Janus kinase-2 (JAK-2) and also the extracellular signal-regulated kinase, in which JAK-2 was more sensitive. Taken together, this study proposes a new mechanism of resveratrol, blocking JAK/STAT-1 pathway that controls inflammatory responses in IFN-γ-activated macrophages. [Copyright &y& Elsevier]