Herbal Science Research - immunity

Suppressive effect of a standardized mistletoe extract on the expression of activatory NK receptors and function [...]

Site Editor — Fri, 02 Nov 2007 05:51:27 -0700

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.

Site Editor — Fri, 02 Nov 2007 05:40:19 -0700

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.

Site Editor — Fri, 02 Nov 2007 05:39:07 -0700

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.

Site Editor — Mon, 22 Oct 2007 18:26:50 -0700

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 [...] autoimmune encephalomyelitis

Site Editor — Mon, 22 Oct 2007 18:09:34 -0700

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.

Site Editor — Thu, 27 Sep 2007 19:07:55 -0700

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, [...] Isolated from Boswellia Resin, Inhibits Nuclear Factor (NF)-kappa B Activation.

Site Editor — Thu, 27 Sep 2007 19:02:56 -0700

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.

Site Editor — Wed, 26 Sep 2007 19:08:52 -0700

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.

Site Editor — Wed, 26 Sep 2007 19:01:00 -0700

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.

Site Editor — Sat, 22 Sep 2007 18:10:56 -0700

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.

Use of traditional medicines in the management of HIV/AIDS opportunistic infections in Tanzania [...]

Site Editor — Sat, 22 Sep 2007 18:08:48 -0700

Use of traditional medicines in the management of HIV/AIDS opportunistic infections in Tanzania: a case in the Bukoba rural district.: J Ethnobiol Ethnomed. 2007; 3: 29 Kisangau DP, Lyaruu HV, Hosea KM, Joseph CC

BACKGROUND: Ethnobotanical surveys were carried out to document herbal remedies used in the management of HIV/AIDS opportunistic infections in Bukoba Rural district, Tanzania. The district is currently an epicenter of HIV/AIDS and although over 90% of the population in the district relies on traditional medicines to manage the disease, this knowledge is impressionistic and not well documented. The HIV/AIDS opportunistic conditions considered during the study were Tuberculosis (TB), Herpes zoster (Shingles), Herpes simplex (Genital herpes), Oral candidiasis and Cryptococcal meningitis. Other symptomatic but undefined conditions considered were skin rashes and chronic diarrhea. METHODS: An open-ended semi-structured questionnaire was used in collecting field information. Descriptive statistics were used to analyze the ethnobotanical data collected. Factor of informant consensus (Fic) was used to analyze the ethnobotanical importance of the plants. RESULTS: In the present study, 75 plant species belonging to 66 genera and 41 families were found to be used to treat one or more HIV/AIDS related infections in the district. The study revealed that TB and oral candidiasis were the most common manifestations of HIV/AIDS opportunistic infections affecting most of the population in the area. It unveils the first detailed account of ethnomedical documentation of plants focusing the management of HIV/AIDS related infections in the district. CONCLUSION: It is concluded that the ethnopharmacological information reported forms a basis for further research to identify and isolate bioactive constituents that can be developed to drugs for the management of the HIV/AIDS opportunistic infections.

Echinacea alkylamides modulate induced immune responses in T-cells.

Site Editor — Sat, 22 Sep 2007 17:51:48 -0700

Echinacea alkylamides modulate induced immune responses in T-cells.: Fitoterapia. 2007 Aug 11; Matthias A, Banbury L, Bone KM, Leach DN, Lehmann RP

The effects of Echinacea and several of its phytochemical components on NFkappaB expression by Jurkat cells (a human T-cell line) were investigated in vitro. In the absence of stimulation, Echinacea and its components exerted no significant effect on basal NFkappaB expression levels. In the presence of endotoxin (LPS), NFkappaB expression was decreased. However, this decrease was significantly reversed by treatment with cichoric acid, an Echinacea root extract (prepared from both Echinacea angustifolia and Echinacea purpurea) and the alkylamide fraction derived from this combination. For the phorbol myristate acetate stimulation of Jurkat cells, effects on NFkappaB expression were mixed. Depending on the concentration, cichoric acid and a 2,4-diene alkylamide significantly induced NFkappaB levels, whereas a 2-ene alkylamide caused a significant inhibition. In contrast, both the Echinacea and the mixed alkylamide fraction exerted no effect. The alkylamide results indicate that the two basic forms of these compounds present in Echinacea may have opposing effects. These opposing effects demonstrate the importance of a knowledge, not only of the phytochemical make-up of a herbal preparation, but also of the actions of each component and the consequences of differing relative amounts in the preparation being investigated.

Use of Quantitative Flow Cytometry to Measure Ex Vivo Immunostimulant Activity of Echinacea: The Case for Polysaccharides.

Site Editor — Sat, 22 Sep 2007 17:50:54 -0700

Use of Quantitative Flow Cytometry to Measure Ex Vivo Immunostimulant Activity of Echinacea: The Case for Polysaccharides.: J Altern Complement Med. 2007 Aug; 13(6): 625-634 Pillai S, Pillai C, Mitscher LA, Cooper R

Introduction: When directly exposed to various echinacea fractions, human leukocytes ex vivo are strongly stimulated to proliferate and to produce immunostimulation and inflammatory cytokines. A comparison of fractions containing lipoidal small molecules and high-molecular-weight water-soluble polysaccharides indicates that the latter are substantially more potent as immunostimulants. Echinacea purpurea (L.) Moench, E. angustifolia DC, and E. pallida (Nutt.), Nutt. extracts, and each plant part contain significantly potent constituents. Flow cytometric techniques were utilized. Objectives: This study was undertaken to determine whether flow cytometry could measure immunostimulant activity present in echinacea and, if so, which species produced more activity, which plant part was the most active, and whether the organic soluble or the aqueous extractables were more active. Ex vivo human clinical material was employed. Design: Echinacea extracts were analyzed using flow cytometric techniques. The immunostimulation assays were measured in triplicate. Methods: Samples dissolved in dimethyl sulfoxide (DMSO) were added to 200 muL of heparinized blood mixed with 50 muL of phosphate buffer, vortexed, and incubated to allow adequate time for immune-cell stimulation. Fifty (50) muL of the stimulated blood samples were added to each of a reagent cocktail consisting of 20 muL of CD4FITC/CD69PE/CD3PerCP expressed on the helper/inducer T-lymphocyte subset; CD8FITC/CD69/PE/ CD3PerCP expressed on the human suppresser/cytotoxic T-lymphocytes and on a subset of natural killer lymphocytes; CD19FITC/CD69PE/CD45PerCP expressed on B-lymphocytes; or CD56FITC/CD69PE/CD45PerCP expressed on NK lymphocytes. Four hundred and fifty (450) muL of 1 X FACS lysing solution was added and incubated in the dark (rt, 30 minutes) and then subjected to flow cytometric analysis. All reported readings are the average of several determinations. Positive controls consisted of phorbol myristyl acetate (PMA) (50 ng/mL), phytohemagglutinin (10 mug/mL), CD2/CD2R (positive activation control)(5 muL/250 muL of reaction), and negative controls consisted of dimethyl sulfoxide (2% in RPMI-1640), RPMI-1640 medium, and cyclosporin A (10 mug/mL). Results: The main immunostimulatory activity of echinacea resides in the water-soluble materials rather than the lipoidal small molecules. E. purpurea, E. Pallida, and E. angustifolia leaves, stems, flowering tops, and roots all produce substantial immunostimulatory activity. Conclusions: The use of flow cytometry demonstrates a link between the polysaccharides in echinacea and the biologic immunostimulatory effect that has therapeutic relevance, and strong evidence for this immunostimulant property is presented.

The effect of Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra on CD25 expression in humans: a pilot study.

Site Editor — Sat, 22 Sep 2007 17:48:35 -0700

The effect of Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra on CD25 expression in humans: a pilot study.: Phytother Res. 2007 Jul 27;
Zwickey H, Brush J, Iacullo CM, Connelly E, Gregory WL, Soumyanath A, Buresh R

This phase 0, double-blind, repeated within subject, randomized pilot study examined CD25 expression on T cells after ingestion of three commonly used herbs: Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra, administered singly and in combination. CD25 expression on T cells was significantly increased for subjects ingesting Echinacea at 24 h with notable increases in activation from Astragalus and Glycyrrhiza. CD25 expression remains elevated with daily use of Echinacea for at least 7 days. Copyright (c) 2007 John Wiley & Sons, Ltd.

Effects of herbal products and their constituents on human cytochrome P450(2E1) activity.

Site Editor — Sat, 22 Sep 2007 17:46:51 -0700

Effects of herbal products and their constituents on human cytochrome P450(2E1) activity.: Food Chem Toxicol. 2007 Jun 15;
Raner GM, Cornelious S, Moulick K, Wang Y, Mortenson A, Cech NB

Ethanolic extracts from fresh Echinacea purpurea and Spilanthes acmella and dried Hydrastis canadensis were examined with regard to their ability to inhibit cytochrome P450(2E1) mediated oxidation of p-nitrophenol in vitro. In addition, individual constituents of these extracts, including alkylamides from E. purpurea and S. acmella, caffeic acid derivatives from E. purpurea, and several of the major alkaloids from H. canadensis, were tested for inhibition using the same assay. H. canadensis (goldenseal) was a strong inhibitor of the P450(2E1), and the inhibition appeared to be related to the presence of the alkaloids berberine, hydrastine and canadine in the extract. These compounds inhibited 2E1 with K(I) values ranging from 2.8muM for hydrastine to 18muM for berberine. The alkylamides present in E. purpurea and S. acmella also showed significant inhibition at concentrations as low as 25muM, whereas the caffeic acid derivatives had no effect. Commercial green tea preparations, along with four of the individual tea catechins, were also examined and were found to have no effect on the activity of P450(2E1).

Effect of Echinacea purpurea tincture and its polysaccharide complex on the efficacy of cytostatic therapy of transferred tumors

Site Editor — Sat, 22 Sep 2007 17:46:05 -0700

[Effect of Echinacea purpurea tincture and its polysaccharide complex on the efficacy of cytostatic therapy of transferred tumors]: Eksp Klin Farmakol. 2007 May-Jun; 70(3): 33-5 Razina TG, Lopatina KA, Zueva AM, Gur'ev AM, Krylova SG, Amosova EN

Experiments on C57LB/6 mice with transplanted Luis lung carcinoma showed that the officinal Echinacea purpurea preparation did not influence the efficacy of cytostatic therapy. This echinacea preparation did not change the development of metastases and even stimulated the tumor growth. In contrast, a hydrophilic polysaccharide complex isolated from echinacea increased the antitumor and antimetastatic activity of cyclophosphamide.

Alkamides from Echinacea inhibit cyclooxygenase-2 activity in human neuroglioma cells.

Site Editor — Sat, 22 Sep 2007 17:45:09 -0700

Alkamides from Echinacea inhibit cyclooxygenase-2 activity in human neuroglioma cells.: Biochem Biophys Res Commun . 2007 Aug 24; 360(2): 441-6 Hinz B, Woelkart K, Bauer R

During past years inhibition of the cyclooxygenase-2 (COX-2) enzyme has been proven as an effective strategy to suppress pain and inflammation. Based on this and other mechanistic findings, interest has also renewed in the molecular pathways underlying the anti-inflammatory effects of herbal drugs. The present study addressed this issue and investigated the impact of several polyunsaturated alkamides isolated from a CO2 extract of the roots of Echinacea angustifolia DC. on both activity and expression of COX-2. A 48-h treatment of H4 human neuroglioma cells with the CO2 extract led to a significant suppression of prostaglandin (PG) E2 formation. Analysis of eight different alkamides revealed a contribution of undeca-2Z-ene-8,10-diynoic acid isobutylamide (A5), dodeca-2E-ene-8,10-diynoic acid isobutylamide (A7), and dodeca-2E,4Z-diene-8,10-diynoic acid 2-methylbutylamide (A8) to this response. Using an established short-term COX-2 activity assay, all three alkamides were shown to interfere with COX-2 activity. In contrast, none of the COX-2-suppressing nor any other tested alkamide was found to inhibit COX-2 mRNA and protein expression. Instead, increased COX-2 mRNA and protein levels were registered in the presence of the CO2 extract and most of the analyzed alkamides which caused, however, no stimulation of PG formation. Overall, our results suggest that certain alkamides derived from E. angustifolia roots may contribute to the pharmacological action of the herbal extract by inhibiting COX-2-dependent PGE2 formation at sites of inflammation.

Oral Echinacea purpurea extract in low-grade, steroid-dependent, autoimmune idiopathic uveitis: a pilot study.

Site Editor — Sat, 22 Sep 2007 17:44:14 -0700

Oral Echinacea purpurea extract in low-grade, steroid-dependent, autoimmune idiopathic uveitis: a pilot study.: J Ocul Pharmacol Ther. 2006 Dec; 22(6): 431-6
Neri PG, Stagni E, Filippello M, Camillieri G, Giovannini A, Leggio GM, Drago F

AIM: The aim of to test efficacy and safety of Echinacea purpurea (echinacea) extract in the control of low-grade uveitis. METHODS: Fifty-one (51) patients with low-grade, steroid dependent, autoimmune uveitis were recruited; posterior uveitis was excluded. The start therapy was represented by topical desamethazone for anterior uveitis and oral prednisone, rapidly tapered, for anterior uveitis with inflammatory scores equal to +2 and in all cases of intermediate uveitis. Best-corrected visual acuity (BCVA) decrease or improvement was defined as a reduction or increase of 2 or more letters seen from the initial BCVA; ETDRS chart was used. Thirty-two (32) patients (21 with anterior uveitis and 11 with intermediate uveitis) received Echinacea (150 mg twice/day) as add-on therapy, whereas 20 patients (10 with anterior uveitis and 9 with intermediate uveitis) were treated with the conventional steroid therapy alone. RESULTS: Thirty-one (31) patients showed anterior uveitis and 20 intermediate uveitis. The follow-up duration was 9 months. At the last follow-up, 19/21 patients with anterior uveitis and 9/11 with intermediate uveitis treated with echinacea presented uveitis settled, with a steroid-off time of 209 and 146 days, respectively. BCVA was stable or improved in 19/21 of anterior uveitis and 9/11 of intermediate uveitis. No adverse reactions supposed to be resulting from commercial-grade echinacea were recorded. Patients who did not receive echinacea required a longer treatment period with steroids with a steroid-off time of 121 and 87 days. CONCLUSIONS: Systemic echinacea appears safe and effective in the control of low-grade autoimmune idiopathic uveitis.

Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical: a nutrigenetics proof of concept.

Site Editor — Sat, 22 Sep 2007 17:12:00 -0700

Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical: a nutrigenetics proof of concept.: Nutrition. 2007 Sep 18; Authors: Kornman K, Rogus J, Roh-Schmidt H, Krempin D, Davies AJ, Grann K, Randolph RK

OBJECTIVE: Although observational studies have shown that genotype may influence nutritional effects on target outcomes, there are few reported studies that stratified subjects by genotype before a nutritional intervention. This proof-of-concept trial determined whether specifically formulated botanical mixtures reduced inflammation in individuals with genetic variations that predispose to overexpression of interleukin-1beta (IL-1beta) and early heart disease. METHODS: Healthy adults with elevated C-reactive protein (CRP) were stratified into genetic groups based on being positive (IL1(Pos)) or negative (IL1(Neg)) for the at-risk IL-1 gene variations. IL1(Pos) (n = 39) and IL1(Neg) (n = 40) subjects were then randomized to the candidate botanical formulation or placebo. The botanical formulation included rose hips, a blueberry and blackberry mixture, and a grapevine extract. RESULTS: At 12 wk of dosing with the botanical formulation, IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects. Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects. At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels. However, in IL1(Pos) subjects, significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo. No CRP effect was observed in the IL1(Neg) subjects. CONCLUSION: This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes.

PMID: 17884346 [PubMed - as supplied by publisher]

Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis.

Site Editor — Fri, 13 Jul 2007 18:40:51 -0700

Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis.: Lancet Infect Dis. 2007 Jul; 7(7): 473-80 Shah SA, Sander S, White CM, Rinaldi M, Coleman CI

Echinacea is one of the most commonly used herbal products, but controversy exists about its benefit in the prevention and treatment of the common cold. Thus, we did a meta-analysis evaluating the effect of echinacea on the incidence and duration of the common cold. 14 unique studies were included in the meta-analysis. Incidence of the common cold was reported as an odds ratio (OR) with 95% CI, and duration of the common cold was reported as the weighted mean difference (WMD) with 95% CI. Weighted averages and mean differences were calculated by a random-effects model (DerSimonian-Laird methodology). Heterogeneity was assessed by the Q statistic and review of L'Abbé plots, and publication bias was assessed through the Egger weighted regression statistic and visual inspection of funnel plots. Echinacea decreased the odds of developing the common cold by 58% (OR 0.42; 95% CI 0.25-0.71; Q statistic p<0.001) and the duration of a cold by 1.4 days (WMD -1.44, -2.24 to -0.64; p=0.01). Similarly, significant reductions were maintained in subgroup analyses limited to Echinaguard/Echinacin use, concomitant supplement use, method of cold exposure, Jadad scores less than 3, or use of a fixed-effects model. Published evidence supports echinacea's benefit in decreasing the incidence and duration of the common cold.

Alkamides from Echinacea inhibit cyclooxygenase-2 activity in human neuroglioma cells.

Site Editor — Fri, 13 Jul 2007 18:39:55 -0700

Alkamides from Echinacea inhibit cyclooxygenase-2 activity in human neuroglioma cells.: >Biochem Biophys Res Commun. 2007 Jun 19; Hinz B, Woelkart K, Bauer R

During past years inhibition of the cyclooxygenase-2 (COX-2) enzyme has been proven as an effective strategy to suppress pain and inflammation. Based on this and other mechanistic findings, interest has also renewed in the molecular pathways underlying the anti-inflammatory effects of herbal drugs. The present study addressed this issue and investigated the impact of several polyunsaturated alkamides isolated from a CO(2) extract of the roots of Echinacea angustifolia DC on both activity and expression of COX-2. A 48-h treatment of H4 human neuroglioma cells with the CO(2) extract led to a significant suppression of prostaglandin (PG) E(2) formation. Analysis of eight different alkamides revealed a contribution of undeca-2Z-ene-8,10-diynoic acid isobutylamide (A5), dodeca-2E-ene-8,10-diynoic acid isobutylamide (A7), and dodeca-2E,4Z-diene-8,10-diynoic acid 2-methylbutylamide (A8) to this response. Using an established short-term COX-2 activity assay, all three alkamides were shown to interfere with COX-2 activity. In contrast, none of the COX-2-suppressing nor any other tested alkamide was found to inhibit COX-2 mRNA and protein expression. Instead, increased COX-2 mRNA and protein levels were registered in the presence of the CO(2) extract and most of the analyzed alkamides which caused, however, no stimulation of PG formation. Overall, our results suggest that certain alkamides derived from E. angustifolia roots may contribute to the pharmacological action of the herbal extract by inhibiting COX-2-dependent PGE(2) formation at sites of inflammation.

In vitro and in vivo antiallergic effects of Glycyrrhiza glabra and its components.

Site Editor — Fri, 13 Jul 2007 18:29:45 -0700

In vitro and in vivo antiallergic effects of Glycyrrhiza glabra and its components.: Planta Med. 2007 Mar;73(3):257-61 Authors: Shin YW, Bae EA, Lee B, Lee SH, Kim JA, Kim YS, Kim DH

Licorice (Glycyrrhiza glabra L., Leguminosae) is frequently used in traditional medicine to treat inflammatory and allergic diseases. In this study, the main components (glycyrrhizin, 18beta-glycyrrhetinic acid, isoliquiritin, and liquiritigenin) were isolated from licorice, and their anti-allergic effects, such as antiscratching behavior and IgE production-inhibitory activity, were evaluated both in vitro and in vivo. Liquiritigenin and 18beta-glycyrrhetinic acid most potently inhibited the degranulation of RBL-2H3 cells induced by IgE with the antigen (DNP-HSA) and rat peritoneal mast cells induced by compound 48/80. Liquiritigenin and 18beta-glycyrrhetinic acid potently inhibited the passive cutaneous anaphylactic reaction as well as the scratching behavior in mice induced by compound 48/80. These components inhibited the production of IgE in ovalbumin-induced asthma mice but liquiritigenin had little effect. This suggests that the antiallergic effects of licorice are mainly due to glycyrrhizin, 18beta-glycyrrhetinic acid, and liquiritigenin, which can relieve IgE-induced allergic diseases such as dermatitis and asthma.

PMID: 17327992 [PubMed - indexed for MEDLINE]

Anti-TB activity of Evodia elleryana bark extract.

Site Editor — Fri, 13 Jul 2007 17:58:23 -0700

Anti-TB activity of Evodia elleryana bark extract.: Fitoterapia. 2007 Apr;78(3):250-2 Authors: Barrows LR, Powan E, Pond CD, Matainaho T

An ethyl acetate extract of bark from Evodia elleryana produced significant growth inhibition of Mycobacterium tuberculosis at concentrations only minimally inhibitory to human T cells. The crude extract yielded 95% inhibition of TB at 50 microg/ml. The crude extract yielded 29% growth inhibition of human T-cells in culture at that concentration.

PMID: 17350179 [PubMed - indexed for MEDLINE]

Curcumin and autoimmune disease.

Site Editor — Fri, 13 Jul 2007 17:48:50 -0700

Curcumin and autoimmune disease.: Adv Exp Med Biol. 2007;595:425-51 Authors: Bright JJ

The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

PMID: 17569223 [PubMed - in process]

Ethnotherapeautic management of skin diseases among the Kikuyus of Central Kenya.

Site Editor — Sat, 23 Jun 2007 05:17:53 -0700

Ethnotherapeautic management of skin diseases among the Kikuyus of Central Kenya.:

Ethnotherapeautic management of skin diseases among the Kikuyus of Central Kenya.

J Ethnopharmacol. 2007 May 4;111(2):303-7

Authors: Njoroge GN, Bussmann RW

Skin health is increasingly becoming an important aspect of primary health care among many communities particularly because of the increased challenge of HIV-AIDS, skin conditions being among the common opportunistic diseases in immuno-compromised individuals. This study investigated the use of traditional remedies in managing various skin conditions in the Central Province of Kenya. Fifty-seven plant species in 31 families were identified as regularly utilized. Of these plants 27 species had a frequency of three and above. Some of the highly utilized plant species include: Croton megalocarpus Hutch., Senna didymobotrya (Fresen.) Irwin & Barneby, Vernonia lasiopus O. Hoffm., Croton macrostachyus Del. and Aloe secundifolia Engl. In the majority of the cases the sap or occasionally the latex was applied directly on the affected areas. In other cases the plant parts were heated and used as poultice. Only in few conditions were the plant parts boiled and the extract used for washing affected areas, probably acting as antiseptic. This study found that 14 skin conditions were commonly managed using herbal preparations. Of these conditions nine (9) had informant consensus of 0.5 and above, with the highest consensus found in management of swellings and skin sores. Soils were also cited as an important non-plant resource for management of skin conditions especially those associated with measles. Since most skin conditions are caused by microorganisms such as bacteria, viruses and fungi, the medicinal plants and other resources reported in this study form a justifiable basis for antimicrobial trials, pharmacological and phytochemical analysis, with promising results.

PMID: 17207950 [PubMed - indexed for MEDLINE]

[Prevention and alternative methods for prophylaxis of recurrent urinary tract infections in women]

Site Editor — Mon, 11 Jun 2007 06:43:56 -0700

[Prevention and alternative methods for prophylaxis of recurrent urinary tract infections in women]: Urologe A. 2006 Apr;45(4):443-4, 446-50 Authors: Vahlensieck W, Bauer H

General recommendations to prevent recurrent urinary tract infections (rUTI) result in about one-third of patients remaining free of recurrences. Oral and parenteral immunotherapy were effective in several controlled studies for prevention of rUTI. These therapies can be combined with acute antibiotic therapy. Vaginal prophylaxis with oestriol has proven its positive effect without serious gynaecological side effects. Also there is increasing evidence that cranberries prevent rUTI. The exact mode (juice, tablets or preserved berries), dosage and duration of this therapy remain to be defined. There are also promising therapy modalities such as changing bacterial gut flora, general immune response (acupuncture, inpatient rehabilitation) and urine acidity.

Sufficiently important difference for common cold: severity reduction.

Site Editor — Mon, 11 Jun 2007 05:28:03 -0700

Sufficiently important difference for common cold: severity reduction.: Ann Fam Med. 2007 May-Jun;5(3):216-23 Authors: Barrett B, Harahan B, Brown D, Zhang Z, Brown R

PURPOSE: We undertook a study to estimate the sufficiently important difference (SID) for the common cold. The SID is the smallest benefit that an intervention would require to justify costs and risks. METHODS: Benefit-harm tradeoff interviews (in-person and telephone) assessed SID in terms of overall severity reduction using evidence-based simple-language scenarios for 4 common cold treatments: vitamin C, the herbal medicine echinacea, zinc lozenges, and the unlicensed antiviral pleconaril. RESULTS: Response patterns to the 4 scenarios in the telephone and in-person samples were not statistically distinguishable and were merged for most analyses. The scenario based on vitamin C led to a mean SID of 25% (95% confidence interval [CI] 0.23-0.27). For the echinacea-based scenario, mean SID was 32% (95% CI, 0.30-0.34). For the zinc-based scenario, mean SID was 47% (95% CI, 0.43-0.51). The scenario based on preliminary antiviral trials provided a mean SID of 57% (95% CI, 0.53-0.61). Multivariate analyses suggested that (1) between-scenario differences were substantive and reproducible in the 2 samples, (2) presence or severity of illness did not predict SID, and (3) SID was not influenced by age, sex, tobacco use, ethnicity, income, or education. Despite consistencies supporting the model and methods, response patterns were diverse, with wide spreads of individual SID values within and among treatment scenarios. CONCLUSIONS: Depending on treatment specifics, people want an on-average 25% to 57% reduction in overall illness severity to justify costs and risks of popular cold treatments. Randomized trial evidence does not support benefits this large. This model and these methods should be further developed for use in other disease entities.

The Role of Alkamides as an Active Principle of Echinacea.

Site Editor — Wed, 06 Jun 2007 00:22:32 -0700

The Role of Alkamides as an Active Principle of Echinacea.: Planta Med. 2007 May 31; 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.

Chinese medicinal herbs for the common cold.

Site Editor — Fri, 25 May 2007 02:26:59 -0700

Chinese medicinal herbs for the common cold.: Cochrane Database Syst Rev. 2007;(1):CD004782 Authors: Wu T, Zhang J, Qiu Y, Xie L, Liu GJ

BACKGROUND: Chinese herbal medicines are frequently used to treat the common cold in China. Until now, their efficacy has not been systematically reviewed. OBJECTIVES: To assess the effectiveness and safety of Chinese herbal medicines for the common cold. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2006) which contains the Acute Respiratory Infections Group's specialised register; MEDLINE (1966 to July 2006); EMBASE (1980 to March 2006); AMED (1985 to July 2006); and the Chinese Biomedical Database (CBM) (1975 to July 2005). SELECTION CRITERIA: Randomised controlled trials (RCTs) studying the efficacy of Chinese herbal medicine(s) for the treatment of the common cold were included, irrespective of publication status or language. DATA COLLECTION AND ANALYSIS: Four review authors telephoned original trial authors of the RCTs identified by our searches to verify the randomisation procedure. Two review authors extracted and analysed data from the trials which met the inclusion criteria. MAIN RESULTS: Fourteen studies involving 2440 patients were included. The methods of all studies were rated of poor quality (category C). Included studies used "effective drugs" as controls; however, the efficacy of these control drugs was not reported. Different Chinese herbal preparations were tested in nearly all trials; in only one was a Chinese herbal preparation tested twice. In six studies, five herbal preparations were found to be more effective at enhancing recovery than the control; and in the other eight studies, five herbal preparations were shown to be equal to the control. There was a strong probability of different biases in all of the included studies. AUTHORS' CONCLUSIONS: Chinese herbal medicines may shorten the symptomatic phase in patients with the common cold. However, the lack of high quality clinical trials means we are unable to recommend any kind of Chinese herbal preparation for the common cold.

Comparative studies of various ganoderma species...with regard to their antitumor and immunomodulating activities in vitro

Site Editor — Thu, 01 Feb 2007 16:56:49 -0800

Comparative studies of various ganoderma species and their different parts with regard to their antitumor and immunomodulating activities in vitro.: J Altern Complement Med. 2006 Oct;12(8):777-89 Authors: Yue GG, Fung KP, Tse GM, Leung PC, Lau CB

OBJECTIVES: Ganoderma lucidum (Lingzhi or Reishi) has been commonly suggested in East Asia as a potential candidate for prevention and treatment of different diseases, including cancer. Ganoderma extracts, in particular Ganoderma lucidum (extracts or isolated components), have previously been shown to possess antitumor activities. The present study aimed at comparing three different species of Ganoderma, wildly grown versus cultivated, as well as the different parts of the fruiting body (whole fruiting body, pileus, and stipe), with regard to their antitumor effects in human breast cancer cells and immunomodulatory activities in mouse splenic lymphocytes in vitro. METHODS: The aqueous extracts (12.5-400 microg/mL) of G. lucidum, G. sinense, and G. tsugae were examined for their antiproliferative activities in human breast cancer cell lines, MCF-7 and MDA-MB-231, as well as in normal human mammary epithelial cells (primary culture). The immunomodulatory effects of the extracts were evaluated in mouse splenic lymphocytes. The proliferative responses of the mentioned cell types were determined by MTT [3-(4,5-dimethylthiazolyl)-2,5-diphenyl-tetrazolium bromide] assay. RESULTS: The present results demonstrated that the extracts of all tested Ganoderma samples could significantly inhibit cell proliferation in human breast cancer cell lines MCF-7 and MDA-MB-231, with G. tsugae being the most potent. The extracts, however, did not exert any significant cytotoxic effect on human normal mammary epithelial cells. Within the species G. sinense, the inhibitory effects of wildly grown samples were not significantly different from those of the cultivated samples, except at 400 microg/mL. Most of the tested extracts of Ganoderma stimulated mouse splenic lymphocytes proliferation. The extracts from the stipes of the G. tsugae and wildly grown G. sinense showed much stronger inhibitory effects than the other parts of the fruiting body in both cancer cell lines, whereas the extracts from the stipes of G. lucidum and wildly grown G. sinense showed stronger immunopotentiating activities in mouse splenic lymphocytes. CONCLUSIONS: These results indicate that the aqueous extracts of these commonly available Ganoderma fruiting bodies, G. lucidum, G. sinense, and G. tsugae have antitumor activities in human breast cancer cells and immunomodulatory activities in murine lymphocytes. In addition, the present findings also suggest that the stipes of fruiting bodies of Ganoderma species should be included in the preparation of extract of these fungi in order to obtain the most comprehensive active ingredients. To the best of the authors' knowledge, this is the first detailed comparison among the different parts of the fruiting bodies of Ganoderma.