Enhancing the efficacy of Hypericum perforatum in the treatment of an experimental model of multiple sclerosis using gold nanoparticles: an in vivo study.

Objective: Hypericum perforatum is a herbal medicine used in traditional medicine for the treatment of depression due to its antidepressant and anti-inflammatory activities. Therefore, we evaluated the therapeutic efficacy of H. perforatum extract (HPE) in combination with gold nanoparticles (HPE-GNP) against experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Materials and Methods: EAE was induced in C57BL/6 mice with subcutaneous injection of MOG35-55 emulsified in complete Freund's adjuvant, and intraperitoneal pertussis toxin. Mice were treated with drugs in free (HPE) and nano-form (HPE-GNP) preparations. Splenocytes were isolated from all mice and the level of inflammatory and anti-inflammatory cytokines were evaluated by ELISA. The expression of T cells' transcription factors was also assessed using Real-Time PCR. Results: Clinical score was reduced after HPE-GNP treatment. This change was associated with a decrease in the incidence and infiltration of inflammatory cells into the central nervous system. Additionally, treatment with HPE-GNP decreased the level of pro-inflammatory cytokines (IFN-γ, IL-17A and IL-6) and increased anti-inflammatory cytokines (TGF-ß, IL-10 and IL-4). The real-time analysis revealed a decrease in the level of T-bet and ROR-γt but an increase in FoxP3 and GATA3 expression. Conclusion: The current study demonstrated that HPE-GNP could potentially reduce clinical and pathological complications of EAE, but laboratory data showed that HPE-GNP was significantly more effective than HPE in the treatment of EAE.

Comparative assessment of immunomodulatory, proliferative, and antioxidant activities of crocin and crocetin on mesenchymal stem cells.

Saffron (Crocus sativus L) is a well-known spice with active pharmacologic components including crocin, crocetin, safranal, and picrocrocin. Similar to crocin/crocetin, mesenchymal stem cells (MSCs) have been shown to display immunomodulatory and antioxidant properties, which could be beneficial in treatment of various diseases. In the current study, we have evaluated the effects of crocin and crocetin on the functions of MSCs. We used the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay to evaluate MSCs proliferation, and flow cytometry assay to measure the percentage of apoptotic MSCs and Tregs populations. Furthermore, we used the real-time polymerase chain reaction method to quantify messenger RNA (mRNA) expression of inflammatory and anti-inflammatory cytokines. Antioxidant assay was employed to quantify antioxidant parameters including nitric oxide and malondialdehyde levels besides superoxide dismutase activity. Our findings indicated that both crocin and crocetin at low concentrations (2.5 and 5 µM) exhibited significant effects on increasing MSCs viability and on protecting them against apoptosis-induced death. Furthermore, crocin and crocetin at low concentrations (2.5 and 5 µM) displayed a better antioxidant function. Moreover, increased Treg population was observed at lower doses. In addition, crocin/crocetin at low concentrations caused an elevation in mRNA expression of anti-inflammatory cytokines (transforming growth factor-ß, interleukin-10 [IL-10], and IL-4), while at higher doses (25 and 50 µM) they led to lowering inflammatory cytokines (IL-1ß, IL-6, IL-17, and interferon gamma). Altogether, both crocin and crocetin at lower concentrations exhibited more efficacies on MSCs with a better effect toward crocin. It seems that crocin and crocetin may be considered as complementary treatments for the patients who undergo MSCs transplantation.

Evaluation of 1,25(OH)2D3 Effects on FOXP3, ROR-γt, GITR, and CTLA-4 Gene Expression in the PBMCs of Vitamin D-Deficient Women with Unexplained Recurrent Pregnancy Loss (URPL).

Background: Vitamin D insufficiency and deficiency can be associated with adverse effects on fetus and pregnancy outcomes. This study aimed at evaluating the effect of 1,25VitD3 on specific transcription factor and markers of Tregs and T helper 17 (Th17) cells in peripheral blood mononuclear cells (PBMCs) of women with unexplained recurrent pregnancy loss (URPL) as a case group and PBMCs of healthy women as a control group. Methods: Samples from 20 non-pregnant patients with a history of URPL were compared to 20 normal non-pregnant women. PBMCs were divided into three wells for each subject in the presence of 1,25VitD3 (50 nM, for 16 hours), phytohemagglutinin (10 µM; positive control), and without any treatment (negative control). By Real-time PCR (Taqman assay), specific transcription factors of Tregs and Th17 cells, forkhead box P3 (FOXP3), retinoic acid-related orphan receptor γt (ROR-γt), glucocorticoid-induced tumor necrosis factor receptor-related (GITR), and CTLA-4 mRNA expressions in two groups were measured. Results: FOXP3/ROR-γt mRNA expression in PBMCs decreased significantly in women experiencing URPL compared to the control group (p = 0.0001). Although 1,25VitD3 (50 nM) increased FOXP3 gene expression (p = 0.0001), it did not significantly affect ROR-γt gene expression. Besides, 1,25VitD3 treatment significantly increased FOXP3/ROR-γt mRNA expression from baseline in PBMCs of the fetal loss group compared to that of the control group (p = 0.01). The 1,25VitD3 also increased GITR gene expression (p = 0.017) in PBMCs of URPL women compared to the controls. Conclusion: Vitamin D deficiency may be a contributor to recurrent pregnancy loss and suggests that the supplementation of women with Vitamin D pre-pregnancy may be protective against URPL via affecting Tregs signature genes, FOXP3 and GITR.

Evaluation of the Effects of 1,25 Vitamin D3 on Regulatory T Cells and T Helper 17 Cells in Vitamin D-deficient Women with Unexplained Recurrent Pregnancy Loss.

BACKGROUND: Vitamin D insufficiency and deficiency can be associated with adverse effects on pregnancy outcomes, which may include recurrent pregnancy loss through the mechanisms that are yet unknown. The aim of this study was to evaluate the effect of 1,25VitD3 on regulatory T cells (Tregs) and T helper17 (Th17) cell populations In vitro in unexplained recurrent pregnancy loss (URPL) patients and healthy women. METHODS: Samples from 20 non-pregnant women with a history of URPL were compared to 20 normal non-pregnant women. Peripheral blood mononuclear cells (PBMC) were divided into 3 wells for each subject: in the presence of 1, 25 VitD3 (50 nM, for 16 hours), PHA (positive control) (10µM), and without any treatment (as a baseline or negative control). The percentage of regulatory T cells and Th17 cells was measured by flow cytometry at baseline and then after cell culture experiments. RESULTS: Our study indicated that the percentage of Tregs in patients with URPL was significantly lower than the control group (2.42 ± 0.27 vs. 3.41 ± 0.29, P= 0.01). The percentage of Th17 cells was significantly greater in URPL patients compared to the control group (2.91 ± 0.33 vs. 1.18± 0.15, P=0.001). 1, 25VitD3 treatment significantly increased the percentage of Tregs from the baseline in the URPL group compared to that in the control group (1.23 ± 0.03 vs. 1.00 ± 0.03, P= 0.01). CONCLUSION: Vitamin D deficiency may be a contributor to recurrent pregnancy loss and suggests supplementation of women with Vit D pre-pregnancy may be protective against URPL.

In vivo study: Th1-Th17 reduction in pristane-induced systemic lupus erythematosus mice after treatment with tolerogenic Lactobacillus probiotics.

Uncontrolled inflammation in systemic lupus erythematosus (SLE) could cause dysfunction in multiple organs. T helper 17 (Th17) cells are a main branch of inflammatory responses in the pathogenesis of SLE, and by producing interleukin 17 (IL-17), represent a major functional tool in the progression of inflammation. Animal models provide a special field for better studies of the pathogenesis of diseases. Tolergenic probiotics could decrease inflammation in autoimmune diseases by modulating the immune system and maintaining homeostasis. The aim of this project was to evaluate the effects of Lactobacillus rhamnosus and Lactobacillus delbrueckii on Th17 cells and their related mediators in a pristane-induced BALB/c mice model of SLE. The mice were divided into pretreatment groups, which received probiotics or prednisolone at Day 0, and treatment groups, which received probiotics and prednisolone 2 months after injection. The presence of antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), and anti-ribonucleoprotein (anti-RNP) and lipogranuloma was evaluated; also, the population of Th1-Th17 cells as well as interferon Î³ (IFN-γ), IL-17, and IL-10 levels, and the expression of RAR-related orphan related receptor gamma (RORγt) and IL-17 were determined. We observed that probiotics and prednisolone could delay SLE in pretreatment and treatment mice groups, with a reduction in ANA, anti-dsDNA, anti-RNP, and mass of lipogranuloma. Probiotics and prednisolone decreased the population of Th1-Th17 cells and reduced IFN-γ and IL-17 as inflammatory cytokines in the pretreatment and treatment groups in comparison with SLE-induced mice. Our results indicated that, due to their anti-inflammatory properties and reduction of Th17, Th1, and cytotoxic T lymphocyte (CTL) cells, the use of these probiotics could probably represent a new tool for the better management of SLE.

Expression of Th1 and Th2 Cytokine and Associated Transcription Factors in Peripheral Blood Mononuclear Cells and Correlation with Disease Severity.

BACKGROUND: Psoriasis is a T cell-mediated autoimmune disease in patients with elevated levels of proinflammatory cytokines belonging mainly to the Th1 pathway. We investigated whether treatment of psoriasis patients with methotrexate (MTX), along with micronutrients, modulated mRNA expression of Th1 and Th2 components and whether expression of these components correlated with psoriasis severity. METHODS: Thirty plaque-type psoriasis patients with Psoriasis Area and Severity Index (PASI) scores greater than 10 were recruited; these were 15 non-micronutrients taking- (NMT) patients treated with MTX daily (0.2-0.3 mg/kg/week), and 15 micronutrients taking- (MT) patients treated with MTX plus a micronutrient supplement daily, for 12 weeks. Blood samples were collected immediately before treatment (baseline) and after 12 weeks of treatment. Taqman quantitative real-time polymerase chain reaction (qPCR) was applied to analyze the expression of the Th1 components T-bet, interleukin-12 (IL-12), and interferon-gamma (IFN-Υ), and the Th2 components GATA-3 and interleukin-4 (IL-4). Disease severity was measured using the PASI scoring system. RESULTS: Significant clinical improvement in the MT group coincided with significant down-regulation of Th1 and up-regulation of Th2 markers (P<0.05). With respect to the PASI-75, (defined as a 75% or greater reduction in the PASI score) cut-off point, expression of IFN-γ in the MT group with PASI scores above 75 was significantly less than that of patients in the NMT group (P=0.05). Also, GATA3 and IL-4 mRNA expression in the MT group with PASI scores greater than above 75 was significantly greater than that of patients in the NMT group (P=0.05 and 0.04, respectively). CONCLUSION: Based on significant attenuation of the PASI score, which correlated with upregulation of Th2 pathway markers in the MT group, we recommend administration of micronutrients combined with MTX for psoriasis patients. Our results contribute to a better understanding of methotrexate immunepathogenesis mechanisms and their correlations to clinical responses in psoriasis.

Investigation of dietary supplements prevalence as complementary therapy: Comparison between hospitalized psoriasis patients and non-psoriasis patients, correlation with disease severity and quality of life.

OBJECTIVES: Psoriasis patients are often displeased with traditional medical treatments and they may self-prescribe dietary supplements as an alternative or complementary treatments. We aimed to investigate the prevalence of self-medication of dietary supplements among psoriasis and non-psoriasis cases and its impact on disease severity and quality of life. DESIGN AND SETTING: This case-control study evaluated 252 records of psoriasis patients and 245 non-psoriasis cases. Dietary supplementation over last 30days and characteristics, including age, age at onset of disease, co-morbidities, smoking and education were recorded. Psoriasis area and severity index (PASI) and dermatology quality of life index (DLQI) were calculated. P value less than 0.05 was considered as significant level. RESULTS: This study consisted 138 psoriasis (females; 54) and 138 non-psoriasis cases (females; 50), aged between 21 and 91 years. Among psoriasis patients, 72% reported using at least one of dietary supplements, which was different from non-psoriasis cases (25.36%, P=0.01). Multivitamin/mineral supplements (MVM) were the most frequent used dietary supplements (26.81%) and the most common reasons for the consumption of these supplements were to maintain and improve health. The consumption of folic acid (21.73%), omega-3 fatty acids or fish oil (10.14%), herbs (12.31%) and vitamin E (1.44%) had the most frequencies after MVM. No significant differences in PASI and DLQI were found among patients with consumption of different supplements (P>0.05). There was non-significant and negative correlation between education and use of supplements (P=0.21, r=-0.02). CONCLUSIONS: Self-medicating of MVM over last 30days was prevalent among studied psoriasis patients. They took dietary supplements in order to improve and maintain their health.

Evaluation of psoriasis severity and inflammatory responses under concomitant treatment with methotrexate plus micronutrients for psoriasis vulgaris: a randomized double blind trial.

INTRODUCTION: We evaluated the effectiveness of concomitant treatment with methotrexate (MTX) plus micronutrients in comparison with monotherapy with MTX only in psoriasis patients. Plasma levels of interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) were also measured and their association with clinical severity was evaluated. METHODS: Thirty psoriasis patients 20 to 50 years old with a PASI score > 10 were divided randomly into two groups. Both groups were given oral methotrexate (0.2-0.3 mg/kg/week) for 12 weeks. In addition, Group B received one tablet of micronutrient supplement daily. Disease severity was calculated using the psoriasis area and severity index (PASI) score before and after 12 weeks. Levels of IL-1ß and TNF-α were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: We found that 13 (86.6%) patients in Group B and 8 (53.3%) patients in Group A attained a mild PASI score (≤ 10% body involvement). IL-1ß and TNF-α levels were significantly decreased in favor of Group B (p < 0.05). There was a significant correlation between changes in both IL-1ß and TNF-α levels and PASI score after the study (p < 0.05). CONCLUSION: The results obtained were positive, and therefore double-blind randomized trials with a larger sample size are highly suggested to confirm or reject these results.

Hesperidin ameliorates immunological outcome and reduces neuroinflammation in the mouse model of multiple sclerosis.

Multiple sclerosis (MS) is the most abundant central nervous system (CNS) inflammatory disease, which is due to the reaction of auto reactive T cells with own myelin proteins, leading to physical disorder and paralysis among people suffering the disease. Hesperidin, a flavanone glycoside found abundantly in citrus fruits possesses a wide range of pharmacological properties including potential anti-inflammatory and anti-cancer effects. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of hesperidin on MS alleviation. Female C57BL/6 mice were immunized with MOG35-55. Clinical scores and other parameters were monitored daily for the 21days. At the end of the period, brain/spinal cord histology was performed to measure lymphocyte infiltration; T-cell profiles were determined through ELISA, flow cytometry, and real-time PCR. Transcription factor expression levels in the CNS were assessed using real-time PCR; T cell differentiation was evaluated via flow cytometry. The results demonstrated that hesperidin inhibited development of EAE. Histological studies revealed limited leukocyte infiltration into the CNS. Hesperidin increased Treg cells production of interleukin IL-10 and transforming growth factor (TGF)-ß, but concurrently resulted in a significant reduction in production of IL-17 and IL-6. Flow cytometry revealed there were also significant decreases in the percentages of Th17 cells, as well as significant increase in percentages of Treg cells in the spleen and lymph nodes. Real-time PCR results indicated hesperidin treatment reduced ROR-γt factor expression, but enhanced Foxp3 expression. Collectively, these results demonstrated that hesperidin could reduce the incidence and severity of disease.

Effects of 1,25-dihydroxyvitamin D3 on IL-17/IL-23 axis, IFN-γ and IL-4 expression in systemic lupus erythematosus induced mice model.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a multi-factorial autoimmune disease which may be characterized by T lymphocytes dysfunctions. Th17 cells have been identified as new effector cells, which play an important role in the pathogenesis. In recent years, immunomodulatory effect of vitamin D3 has been noticed. In the present experiment, the effect of vitamin D3 on the expression of IL-17, IL-23, IL-4 and IFN-γ were assessed in activated chromatin-induced mouse model for SLE. MATERIALS AND METHODS: Five groups of mice were included in this study; Group one received active chromatin +CFA + PBS; Group 2 received vitamin D3 starting 2 weeks before disease induction; Group 3 received vitamin D3 (50 ng/day) starting with the disease establishment; Group 4 received non active chromatin +CFA + PBS; Group 5 received CFA + PBS. On day 56 splenocytes were isolated and gene expression of interleukin IL-17, IL-23, IL-4 and IFN-γ were analyzed by Real-Time PCR method. Proteinuria and serum anti-dsDNA and Th17 levels were measured using commercial kits. RESULTS: The results showed that IL-17, IL-23, and IFN-γ mRNA expression, and IL-17 titers were decreased remarkably and that of IL-4 increased in mice which received vitamin D3 before SLE induction. Administration of vitamin D3 after the establishment of SLE failed to affect the IL-17 or IL-23 mRNA levels. Lastly, pre-treatment of mice with vitamin D3 decreased the anti-ds DNA antibody titer. CONCLUSION: Our findings showed that vitamin D3 supplementation in lupus induced mice through modulating the expression rate of some inflammatory cytokines diminished the inflammatory conditions in SLE.

Hyperforin-loaded gold nanoparticle alleviates experimental autoimmune encephalomyelitis by suppressing Th1 and Th17 cells and upregulating regulatory T cells.

Hyperforin an herbal compound, is commonly used in traditional medicine due to its anti-inflammatory activities. The aim of this study was to use a hyperforin loaded gold nanoparticle (Hyp-GNP) in the treatment of experimental autoimmune encephalomyelitis (EAE) an animal model of multiple sclerosis (MS). Hyp-GNP and hyperforin significantly reduced clinical severity of EAE, which was accompanied by a decrease in the number of inflammatory cell infiltration in the spinal cord. Additionally, treatment with Hyp-GNP significantly inhibited disease-associated cytokines as well as an increase in the anti-inflammatory cytokines in comparison to all groups including the free-hyp group. Furthermore, hyperforin and Hyp-GNP inhibited the differentiation of Th1 and Th17 cells while promoting Treg and Th2 cell differentiation via regulating their master transcription factors. The current study demonstrated the although, free-hyp improved clinical and laboratory data Hyp-GNP is significantly more efficient than free hyperforin in the treatment of EAE.

St. John's wort and its component hyperforin alleviate experimental autoimmune encephalomyelitis through expansion of regulatory T-cells.

Multiple sclerosis (MS) is a central nervous system disorder mainly characterized by inflammation, demyelination and axonal injury. Anti-inflammatory agents can be used to ameliorate the disease process. Hypericum perforatum L or St. John's wort is widely used as an anti-depressant and anti-inflammatory remedy in traditional and herbal medicine. Based on St. John's wort properties, the therapeutic potentials of an H. perforatum extract (HPE) and a single component, hyperforin were evaluated for effectiveness against MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Female C57BL/6 mice were immunized with specific antigen MOG35-55 and then administered different doses of hyperforin or HPE post-immunization. Clinical symptoms/other relevant parameters were assessed daily. Histological analysis of the spinal cord was performed. T-cell proliferative activity was also evaluated using a BrdU assay. The effect of hyperforin on regulatory T-cells (Treg cells) was assessed using flow cytometry. The results indicate hyperforin and HPE reduced the incidence and severity of EAE, an outcome that closely correlated with an inhibition of pathological features (leukocyte infiltration and demyelination) and antigen-specific T-cell proliferation. The study also showed that hyperforin caused increased Treg cell levels in the spleen. These results indicated that hyperforin and HPE could attenuate EAE autoimmune responses by inhibiting immune cell infiltration and expansion of Treg cell and could eventually be considered as a potential candidate for use in the treatment of MS.

Anti-cancer properties of a sesquiterpene lactone-bearing fraction from Artemisia khorassanica.

BACKGROUND: Artemisia species are important medicinal plants throughout the world. The present in vitro study, using a sesquiterpene lactone-bearing fraction prepared from Artemisia khorassanica (SLAK), sought to investigate anti-cancer properties of this plant and elucidate potential underlying mechanisms for the effects. MATERIALS AND METHODS: Anti-cancer potential was evaluated by toxicity against human melanoma and fibroblast cell lines. To explore the involved pathways, pattern of any cell death was determined using annexin-V/PI staining and also the expression of Bax and cytochrome c was investigated by Western blotting. RESULTS: The results showed that SLAK selectively caused a concentration-related inhibition of proliferation of melanoma cells that was associated with remarkable increase in early events and over-expression of both Bax and cytochrome c. CONCLUSIONS: The current experiment indicates that Artemisia may have anti-cancer activity. We anticipate that the ingredients may be employed as therapeutic candidates for melanoma.

Anti-inflammatory effect of garlic 14-kDa protein on LPS-stimulated-J774A.1 macrophages.

CONTEXT: Garlic 14-kDa protein is purified from garlic (Allium sativum L.) which is used in traditional medicine and exerts various immunomodulatory activities. OBJECTIVE: The present study investigated the suppressive effect of garlic 14-kDa protein on LPS-induced expression of pro-inflammatory mediators and underlying mechanism in inflammatory macrophages. MATERIALS AND METHODS: J774A.1 macrophages were treated with 14-kDa protein (5-30 µg/ml) with/without LPS (1 µg/ml) and the production of inflammatory mediators such as prostaglandin E2 (PGE2), TNF-α, and IL-1ß released were measured using ELISA. Nitric oxide (NO) production was determined using the Griess method. The anti-inflammatory activity of 14-kDa protein was examined by measuring inducible nitric oxide synthase and cyclooxygenase-2 proteins using western blot. The expression of nuclear NF-κB p65 subunit was assessed by western blot. RESULTS: Garlic 14-kDa protein significantly inhibited the excessive production of NO, PGE, TNF-α, and IL-1ß in lipopolysaccharide (LPS)-activated J774A.1 macrophages in a concentration-related manner without cytotoxic effect. Western blot analysis demonstrated that garlic 14-kDa protein suppressed corresponding inducible NO synthase expression and activated cyclooxygenase-2 protein expression. The inhibitory effect was mediated partly by a reduction in the activity and expression of transcription factor NF-κB protein. CONCLUSION: Our results suggested, for the first time, garlic 14-kDa protein exhibits anti-inflammatory properties in macrophages possibly by suppressing the inflammatory mediators via the inhibition of transcription factor NF-κB signaling pathway. The traditional use of garlic as anti-inflammatory remedy could be ascribed partly to 14-kDa protein content. This protein might be a useful candidate for controlling inflammatory diseases and further investigations in vivo.

Assessment of 1,25-dihydroxyvitamin D3 effects on Treg cells in a mouse model of systemic lupus erythematosus.

CONTEXT: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which is characterized by the presence of auto-reactive T cell and anti-ds DNA antibodies. Treg cells are crucial for maintaining immunologic self-tolerance and are shown to be reduced in SLE patients. 1,25-Dihydroxyvitamin D3 has immunomedulatory effects on the immune system and has recently received substantial attention. OBJECTIVE: In this study we evaluated the effects of 1,25-dihydroxyvitamin D3 on Treg cells and related cytokines in lupus-like induced mice model. MATERIALS AND METHODS: Female Balb/c mice were divided into four groups: Group one: injected with PBS and Freund's adjuvant; Group two: injected with non-activated chromatin; Group three: Lupus-like disease was induced with activated chromatin; Group four: Mice were initially treated for two weeks with 1,25-dihydroxyvitamin D3 and then lupus-like disease was induced. Group five: Four mice from group one were treated with 1,25-dihydroxyvitamin D3 for two weeks after disease establishment. Ten weeks after the last injection the mice were killed and spleens were studied for Treg percentages and expression of cytokine genes. RESULTS: We found that treatment with 1,25-dihydroxyvitamin D3 reduces IL-6 and IL-10 mRNA expression and increases TGF-ß and Foxp3 mRNA expression levels, and also enhances spleen Treg percentage. CONCLUSIONS: The remarkable reduction of IL-6 and IL-10 gene expressions, significant enhancement of TGF-ß and Foxp3 gene expressions, along with an increase in Treg cell population after oral 1,25-dihydroxyvitamin D3 administration suggest a possible role for this vitamin as a prophylactic supplement in SLE.

In vitro immunomodulatory properties of a sesquiterpene lactone-bearing fraction from Artemisia khorassanica.

Artemisia species are important medicinal plants throughout the world. The present in vitro study, using a sesquiterpene lactone-bearing fraction prepared from Artemisia khorassanica (SLAK), sought to investigate immunomodulatory/anti-inflammatory properties of this plant and elucidate potential underlying mechanisms for the actions. Effects of the SLAK on mitogen-induced murine splenocyte proliferation and interleukin (IL)-4 and interferon (IFN)-γ secretion were evaluated. To assess anti-inflammatory activities, levels of inducible of nitric oxide (NO) and prostaglandin E2 (PGE2), as well as expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in peritoneal macrophages was examined. The results showed that SLAK noticeably was capable of suppressing PHA/LPS-stimulated splenocyte proliferation and of up-regulating production of the T-helper (TH)-2 cell cytokine IL-4 while down-regulating formation of TH1 IFNγ. In addition, while SLAK caused negligible proliferation inhibition, peritoneal macrophages displayed considerable decrease in NO and PGE2 production along with iNOS and COX-2 expression. The current experiment shows Artemisia khorasanica - a traditionally used herb - may have immunomodulatory and anti-inflammatory effects. It is anticipated that the ingredients may be employed as therapeutic candidates in the regulation of some immune responses implicated in various conditions and ailments.