immunity

Suppressive effect of a standardized mistletoe extract on the expression of activatory NK receptors and function of human NK cells.: J Clin Immunol. 2007 Sep;27(5):477-85 Authors: Lee SJ, Son YO, Kim H, Kim JY, Park SW, Bae JH, Kim HH, Lee EY, Chung BS, Kim SH, Kang CD

Despite long-term use of mistletoe extracts for cancer treatment, their mode of action remains elusive. In this study, it was studied in vitro if mistletoe extract is able to modulate the expression of natural cytotoxic receptors (NCRs) and NKG2D receptor, which stimulate natural killer cell-mediated cytotoxicity. Unexpectedly, a mistletoe extract, ABNOBA viscum Fraxini, inhibited the expression level of NKp46 and NKG2D receptors in dose- and time-dependent manners. The levels of NKp30 and NKG2D receptors were remarkably induced and NKp44 was slightly induced after 48 h treatment with IL-2 and IL-15 in both mRNA and surface expression. The activatory NK receptors were not induced significantly after treatment with IL-12, IL-18, and IL-21 for 48 h. Induction of activatory NK receptors by IL-2 and IL-15 was suppressed almost to the untreated levels by treatment with mistletoe extract, which appeared to induce apoptosis of NK cells in a dose-dependent manner. However, the treatment with IL-2 and IL-15 did not prevent the mistletoe-induced NK-cell death. Mistletoe extract inhibited significantly the cytotoxic activity of resting and IL-2- or IL-15-stimulated NK cells. These results suggest that inhibition of survival and function of NK cells by mistletoe extract may curtail in part the therapeutic effects of mistletoe.

PMID: 17530391 [PubMed - indexed for MEDLINE]

Comparison of Echinacea alkylamide pharmacokinetics between liquid and tablet preparations.: Phytomedicine. 2007 Sep;14(9):587-90 Authors: Matthias A, Addison RS, Agnew LL, Bone KM, Watson K, Lehmann RP

The relative oral bioavailability of alkylamides from two different Echinacea dosage forms (liquid and tablet) were compared in a small two-way crossover study in humans (n=3). The liquid preparation investigated contained a mixture of Echinacea purpurea root (300 mg/ml) and Echinacea angustifolia root (200 mg/ml) extracted in 60% ethanol. The tablet preparation investigated was also a mixture of E. purpurea root (675 mg/tablet) and E. angustifolia root (600 mg/tablet), but was prepared from the dried 60% ethanolic extracts of these two Echinacea species. Alkylamides were found to be rapidly absorbed and measurable in plasma from both preparations. No significant differences in the tetraene alkylamide pharmacokinetic parameters for T(1/2), AUC(t-lin) and C(max) in the two different preparations were found. T(max) increased from 20 min for the liquid to 30 min for the tablet, which is not unexpected as the tablet required time for disintegration before absorption could occur. These results suggested that there was no significant difference in the bioavailability of alkylamides from the liquid and tablet Echinacea formulations. Furthermore, the results also indicated that the absorption site and any alkylamide loss due to digestive processes were similar in both preparations.

PMID: 17289362 [PubMed - indexed for MEDLINE]

The role of alkamides as an active principle of echinacea.: Planta Med. 2007 Jun;73(7):615-23 Authors: Woelkart K, Bauer R

Alkamides are the major lipophilic constituents of ECHINACEA preparations, which are widely used in some European countries and in North America for common colds. In earlier investigations they have been shown to possess stimulatory effects on phagocytosis. Recent experiments have demonstrated that alkamides are detectable in human blood in relevant concentrations after oral administration of Echinacea preparations. Alkamides show structural similarity with anandamide, an endogenous ligand of cannabinoid receptors. Consequently, it was found that alkamides bind significantly to CB (2) receptors, which is now considered as a possible molecular mode of action of Echinacea alkamides as immunomodulatory agents. It was also demonstrated recently in several studies that alkamide-containing Echinacea preparations trigger effects on the pro-inflammatory cytokines. They were therefore suggested as a new class of cannabinomimetics. However, the therapeutic relevance of these findings is still not clear as clinical studies on the common cold show contradictory results. Among the many pharmacological properties reported, investigations concerning herb-drug interactions have been neglected for a long time. Latest research concludes that prolonged use of Echinacea poses a minimal risk for co-medications metabolized by the P450 enzymes.

PMID: 17538868 [PubMed - indexed for MEDLINE]

Epigallocatechin gallate affects human dendritic cell differentiation and maturation.: J Allergy Clin Immunol. 2007 Oct 10; Authors: Yoneyama S, Kawai K, Tsuno NH, Okaji Y, Asakage M, Tsuchiya T, Yamada J, Sunami E, Osada T, Kitayama J, Takahashi K, Nagawa H

BACKGROUND: Epigallocatechin gallate (EGCG), a component of green tea catechin with the strongest biological activity, has been focused in recent years because of its anti-inflammatory and immunomodulatory activities. Dendritic cells (DCs) are professional antigen-presenting cells, capable of priming naive T cells, and play the key roles in the activation of T-cell-mediated immune responses. OBJECTIVE: We aimed to investigate the effect of EGCG on human monocyte-derived DCs (MODCs) and, consequently, on the T-cell-mediated immune response. METHODS: The induction of apoptosis, and the detailed phenotypic and functional changes of MODCs, generated by culture of peripheral blood monocytes in the presence of GM-CSF and IL-4, induced by EGCG was investigated and compared with the effects of dexamethasone. RESULTS: Epigallocatechin gallate induced apoptosis and affected the phenotype of the developing DCs. The expressions of CD83, CD80, CD11c, and MHC class II, which are molecules essential for antigen presentation by DCs, were downregulated by EGCG. EGCG also suppressed the endocytotic ability of immature DCs, whereas dexamethasone-treated DCs had higher endocytotic ability than control DCs. Most importantly, mature DCs treated with EGCG inhibited stimulatory activity toward allogeneic T cells while secreting high amounts of IL-10. CONCLUSION: Epigallocatechin gallate induces immunosuppressive alterations on human MODCs, both by induction of apoptosis and suppression of cell surface molecules and antigen presentation. CLINICAL IMPLICATIONS: These alterations should be considered promising new immunosuppressive and anti-inflammatory agents to treat autoimmune and allergic diseases and to prevent the graft rejection in organ transplantation.

PMID: 17935769 [PubMed - as supplied by publisher]

Anti-inflammatory properties and regulatory mechanism of a novel derivative of artemisinin in experimental autoimmune encephalomyelitis.: J Immunol. 2007 Nov 1;179(9):5958-65 Authors: Wang Z, Qiu J, Guo TB, Liu A, Wang Y, Li Y, Zhang JZ

Ethyl 2-[4-(12-beta-artemisininoxy)]phenoxylpropionate (SM933) is a novel derivative of artemisinin, an herbal compound approved for the treatment of malaria. In this study, we show that SM933 has unique anti-inflammatory properties through regulation of signaling pathways, leading to amelioration of experimental autoimmune encephalomyelitis. The anti-inflammatory properties of SM933 were characterized by inhibition of encephalitogenic T cell responses that were altered to exhibit a Th2 immune deviation and reduced activity and concentration of NO and inducible NO synthase. The observed effect of SM933 was mediated through regulatory mechanisms involving the NFkappaB and the Rig-G/JAB1 signaling pathways. SM933 was found to inhibit the activity of NFkappaB by up-regulating IkappaB, which accounted for various down-stream anti-inflammatory actions. Furthermore, it up-regulated Rig-G through the action of IFN-alpha and prevented JAB1, a master cell cycle regulator, from entering the nucleus to promote p27 degradation, resulting in down-regulation of CDK2 and cyclin A and cell cycle progression. Regulation of the Rig-G/JAB1 pathway by SM933 led to altered cell cycle activity of encephalitogenic T cells as a result of its selective effect on activated, but not resting, T cells. The study indicates that SM933 is a novel anti-inflammatory agent acting through defined signaling mechanisms and provides regulatory mechanisms required for effective drug targeting in treatment of autoimmune disease and inflammation.

PMID: 17947669 [PubMed - in process]

Immunostimulating activity of crude polysaccharide extract isolated from Curcuma xanthorrhiza Roxb.: Biosci Biotechnol Biochem. 2007 Jun;71(6):1428-38 Authors: Kim AJ, Kim YO, Shim JS, Hwang JK

Curcuma xanthorrhiza Roxb., commonly known as Javanese turmeric, has been reported to possess a variety of biological activities, including anti-inflammatory effects, anticarcinogenic effects, wound healing effects, and serum cholesterol-lowering effects. CPE, crude polysaccharide extract isolated from the rhizome of C. xanthorrhiza using 0.1 N NaOH, consisted of arabinose (18.69%), galactose (14.0%), glucose (50.67%), mannose (12.97%), rhamnose (2.73%), and xylose (0.94%), with an average molecular weight of 33,000 Da. In the present study, we investigated the effect of CPE on nitric oxide (NO), hydrogen peroxide (H2O2), tumor necrosis factor-alpha (TNF-alpha), and prostaglandin E2 (PGE2) production in RAW 264.7 cells. The uptake of fluorescein-labeled Escherichia coli was measured to determine whether CPE stimulates the phagocytic activity of RAW 264.7 cells. CPE significantly increased the phagocytosis of macrophages and the release of NO, H2O2, TNF-alpha, and PGE2 in a dose-dependent manner, and showed a similar activity to lipopolysaccharide (LPS). To study the mechanisms of CPE, we examined induction of iNOS and COX-2. NO and PGE2 were produced as a result of stimulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) respectively. Both modulations of iNOS and COX-2 expression by CPE were evaluated by Western immunoblotting and RT-PCR. Since transcription of these enzymes is under the control of nuclear factor-kappa B (NF-kappaB), we assessed the phosphorylation of inhibitor kappaBalpha (IkappaBalpha) through Western immunoblotting. CPE clearly induced phosphorylation of IkappaBalpha, suggesting a role as an NF-kappaB activator. Taking all this together, we conclude that CPE isolated from Curcuma xanthorrhiza stimulates the immune functions of macrophages, which is mediated in part by specific activation of NF-kappaB.

PMID: 17587672 [PubMed - indexed for MEDLINE]

Incensole Acetate, a Novel anti-inflammatory compound Isolated from Boswellia Resin, Inhibits Nuclear Factor (NF)-kappa B Activation.: Mol Pharmacol. 2007 Sep 25; Authors: Moussaieff A, Shohami E, Kashman Y, Fride E, Schmitz ML, Renner F, Fiebich BL, Munoz E, Ben-Neriah Y, Mechoulam R

Boswellia resin is a major anti-inflammatory agent in herbal medical tradition, as well as a common food supplement. Its anti-inflammatory activity has been attributed to boswellic acid and its derivatives. Here, we re-examined the anti-inflammatory effect of the resin, using IkappaBalpha degradation in TNFalpha-stimulated HeLa cells as a read-out for a bioassay-guided fractionation. We thus isolated two novel NF-kappaB inhibitors from the resin, their structures elucidated as incensole acetate (IA) and its non-acetylated form, incensole (IN). IA inhibited TAK/TAB-mediated IkappaB kinase (IKK) activation loop phosphorylation, resulting in the inhibition of cytokine and LPS mediated NF-kappaB activation. It had no effect on IKK activity in vitro, nor did it suppress IkappaBalpha phosphorylation in costimulated T-cells, indicating that the kinase inhibition is neither direct, nor is it affecting all NF-kappaB activation pathways. The inhibitory effect appears specific as IA did not interfere with TNFalpha-induced activation of JNK and p38 MAPK. IA treatment had a robust anti-inflammatory effect in a mouse inflamed paw model. Cembrenoid diterpenoids, and specifically IA and its derivatives may thus constitute a potential novel group of NF-kappaB inhibitors, originating from an ancient anti-inflammatory herbal remedy.

PMID: 17895408 [PubMed - as supplied by publisher]

Enhancement of innate and adaptive immune functions by multiple echinacea species.: J Med Food. 2007 Sep;10(3):423-34 Authors: Zhai Z, Liu Y, Wu L, Senchina DS, Wurtele ES, Murphy PA, Kohut ML, Cunnick JE

Echinacea preparations are commonly used as nonspecific immunomodulatory agents. Alcohol extracts from three widely used Echinacea species, Echinacea angustifolia, Echinacea pallida, and Echinacea purpurea, were investigated for immunomodulating properties. The three Echinacea species demonstrated a broad difference in concentrations of individual lipophilic amides and hydrophilic caffeic acid derivatives. Mice were gavaged once a day (for 7 days) with one of the Echinacea extracts (130 mg/kg) or vehicle and immunized with sheep red blood cells (sRBC) 4 days prior to collection of immune cells for multiple immunological assays. The three herb extracts induced similar, but differential, changes in the percentage of immune cell populations and their biological functions, including increased percentages of CD49+ and CD19+ lymphocytes in spleen and natural killer cell cytotoxicity. Antibody response to sRBC was significantly increased equally by extracts of all three Echinacea species. Concanavalin A-stimulated splenocytes from E. angustifolia- and E. pallida-treated mice demonstrated significantly higher T cell proliferation. In addition, the Echinacea treatment significantly altered the cytokine production by mitogen-stimulated splenic cells. The three herbal extracts significantly increased interferon-alpha production, but inhibited the release of tumor necrosis factor-gamma and interleukin (IL)-1beta. Only E. angustifolia- and E. pallida-treated mice demonstrated significantly higher production of IL-4 and increased IL-10 production. Taken together, these findings demonstrated that Echinacea is a wide-spectrum immunomodulator that modulates both innate and adaptive immune responses. In particular, E. angustifolia or E. pallida may have more anti-inflammatory potential.

PMID: 17887935 [PubMed - in process]

A randomized, placebo-controlled, double-blind clinical trial of curcuminoids in oral lichen planus.: Phytomedicine. 2007 Aug;14(7-8):437-46 Authors: Chainani-Wu N, Silverman S, Reingold A, Bostrom A, Mc Culloch C, Lozada-Nur F, Weintraub J

We studied the efficacy of curcuminoids in the treatment of oral lichen planus (OLP), a chronic, mucocutaneous, immunological disease. Curcuminoids are components of turmeric (Curcuma longa) that have anti-inflammatory activity. Turmeric has been used in Ayurveda (Indian traditional medicine) for centuries. A randomized, double-blind, placebo-controlled trial was conducted. In all, 100 consecutive, eligible patients with OLP presenting to the oral medicine clinic at the University of California, San Francisco, were to be selected. Two interim analyses were to be conducted during the trial. The trial was conducted between February 2003 and September 2004. The first interim analysis was conducted in October 2004 using data from the first 33 subjects. Study subjects were randomized to receive either placebo or curcuminoids at 2000 mg/day for 7 weeks. In addition, all subjects received prednisone at 60 mg/day for the first 1 week. The primary outcome was a change in symptoms from baseline. Secondary outcomes were changes in clinical signs and occurrence of side effects. The first interim analysis did not show a significant difference between the placebo and curcuminoids groups. Conditional power calculations suggested a less than 2% chance that the curcuminoids group would have a significantly better outcome as compared with the placebo group if the trial were continued to completion. Therefore, the study was ended early for futility. Reaching a conclusion regarding the efficacy of curcuminoids based on the results of this study is not possible as it was ended early for futility. Curcuminoids at this dose were well tolerated and the results suggest that for future studies a larger sample size, a higher dose and/or longer duration of curcuminoids administration should be considered; however, for the next step, an RCT of a shorter duration, using a higher dose of curcuminoids, and without an initial course of prednisone, should be considered.

PMID: 17604143 [PubMed - indexed for MEDLINE]

The use of herbal medicines in early drug development for the treatment of HIV infections and AIDS.: Expert Opin Investig Drugs. 2007 Sep; 16(9): 1355-64 Liu J

This review systematically assesses the beneficial and harmful effects of herbal medicines in people with HIV infection and AIDS. Based on a Cochrane review and updated searches, the author identifies the available evidence on herbal medicines compared with placebo or antiretroviral drugs in patients with HIV infection, HIV-related disease or AIDS. There are ten randomised controlled trials, involving 571 individuals with HIV infection or AIDS, that met the inclusion criteria. Some herbal medicines, such as IGM-1 seem to be effective in symptom improvement, but generally no significant effect on antiviral or immunity enhancement among reviewed herbs was seen. Combined treatment of Chinese herbal medicine, SH and antiretroviral agents showed increased antiviral benefit compared with antiretrovirals alone. These findings suggest beneficial effects from some of the tested herbs but more evidence from larger studies are needed to support this evidence in the future.