The impact of Hyssop (Hyssopus officinalis) extract on activation of endosomal toll like receptors and their downstream signaling pathways.

OBJECTIVES: From the ancient, medicinal benefits of Hyssop (Hyssopus officinalis L.) have been implicated for respiratory and digestive diseases despite the effects of Hyssop on viral infections have not been mechanistically investigated. In this study, we examined whether the Hyssop extract activated anti-viral innate immunity, as a sentinel for immune system, through activation of endosomal TLRs recognizing nucleic acids and their downstream signaling. The Hyssop herb extracts was prepared and co-cultured with healthy individual's peripheral blood mononuclear cells (PBMCs). After viability assay, gene expression levels of TLR3,7,8,9, as well as MyD88 and NF-κB, were evaluated in treated PBMCs using Real-time PCR. Next, the secretion level of immune related cytokines was quantified via ELISA. RESULTS: Post 24 h, 40 µg/ml of the extract significantly inhibited the viability of less than 50% of cells compared to the control and had a maximum effect on cellular function. The Hyssop-treated PBMCs demonstrated an elevated expression of endosomal TLRs genes, as well as MyD88 and NF-κB. Moreover, the release of INF-α and ß notably enhanced in cell culture supernatant, while the content of inflammatory cytokines remarkably diminished (P < 0.05). The Hyssop extract was capable of inducing antiviral innate immune responses so can be promising in antiviral drug strategies.

Management of pain using magnesium sulphate: a narrative review.

Pain is one of the most complex and unpleasant sensory and emotional human experiences. Pain relief continues to be a major medical challenge. The application of systemic opioid and regional analgesia techniques has facilitated a decrease in the occurrence and gravity of pain. Magnesium has an evolving role in pain management. Magnesium sulfate (MgSO4), the pharmacological form of magnesium, is a physiological voltage-dependent blocker of N-methyl-D-aspartate (NMDA)-coupled channels. In terms of its antinociceptive role, magnesium blocks calcium influx, which inhibits central sensitization and decreases preexisting pain hypersensitivity. These properties have encouraged the research of magnesium as an adjuvant agent for intra- and post-operative analgesia. Moreover, the mentioned magnesium impacts are also detected in patients with neuropathic pain. Intravenous magnesium sulfate, followed by a balanced analgesia, decreases opioid consumption. This review has focussed on the existing evidence concerning the role of magnesium sulfate in pain management in situations including neuropathic pain, postherpetic neuralgia, trigeminal neuralgia, migraine, and post-operative pain. Additional studies are required to improve the use of magnesium sulfate for pain to increase the quality of life of patients.

The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double-blind, placebo-controlled clinical trial.

AIM: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with increased bone mass in the main sites of inflammation. Regulatory T (Treg) cells have been reported to involve in pathology of AS. This study designed at investigating the effects of nanocurcumin on Treg cell responses in peripheral blood (PB) of AS patients. METHODS: Test group including 12 AS patients received nanocurcumin daily for 4 months and control group including 12 patients received placebo. The frequency of Treg was measured by flow cytometry. The expression levels of FoxP3 and several associated microRNAs (miRNAs; miR-27, miR-17, and miR-146a) and cytokines including Interleukin-10 (IL-10), TGF-ß, and IL-6 were assessed by real-time polymerase chain reaction. Furthermore, enzyme-linked immunosorbent assay was done to determine the secretion levels of cytokines. RESULTS: After treatment with nanocurcumin the frequency of Treg cells in AS patients increased significantly. The RT-PCR data indicated that the expression of miR-17 and miR-27 were significantly decreased following nanocurcumin treatment while miR-146a and FoxP3 were significantly increased. Moreover, nanocurcumin-treated group had high levels of IL-10 and TGF-ß and low levels of IL-6 production than control group. CONCLUSION: The findings suggested that dysregulation of Treg cells in PB influences the AS development and nanocurcumin therapy could regulate the Treg cells, and so could be useful in the treatment of AS and may be other autoimmune diseases. This study is registered with IRCT.ir, number IRCT2017052927520N7.

Nanocurcumin improves regulatory T-cell frequency and function in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis is a chronic incapacitating disease of the central nervous system, it has been reported that the disturbance in the development and function of Treg subpopulations is associated with the disability status in the RRMS. Accordingly, in the current study, the objective was to specify nanocurcumin effects on Treg cells frequency, and function in patients with RRMS. METHODS AND MATERIALS: 50 patients with RRMS were enrolled in this study in which 25 were treated for at least six months with nanocurcumin capsules while the other half received placebo capsules as the control group. The blood sample was collected prior to the administration of nanocurcumin and placebo capsules and following six months. At baseline and after a six-month treatment, the frequency of Treg lymphocytes, the expression of transcription factor related to these cells and the secretion levels of cytokines were assessed by flowcytometry, real-time PCR and ELISA, respectively. RESULTS: A significant reduction was observed in the proportion of peripheral Treg cell frequency, and the levels of TGF-ß, IL-10 and FoxP3 expression in patients with RRMS. Our data revealed that the frequency of Treg cells (p = .0027), the expression of FoxP3 (p = .0005), TGF-ß (p = .0005), and IL-10 (p = .0002) and the secretion levels of the TGF-ß (p = .033), and IL-10 (p = .029) in cultured PBMCs are increased in nanocurcumin-treated group compared to placebo group. CONCLUSION: The results of the current work indicated that nanocurcumin is capable of restoring the frequency and function of Treg cells in MS patients.

Nanocurcumin is a potential novel therapy for multiple sclerosis by influencing inflammatory mediators.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Inflammation has ever been thought as disadvantageous in the pathophysiology of MS. Nanocurcumin has been used as an anti-inflammatory compound. The aim of this study was to identify effects of nanocurcumin on inflammatory mediators in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Fifty MS patients were randomly divided into two groups. The test group received nanocurcumin capsule daily for 6 months. Simultaneously, the control group received placebo. Real-Time PCR was employed to detect the probable changes in gene expression levels of miRNAs, and miRNA-dependent targets, and also transcription factors and pro-inflammatory cytokines in blood samples. ELISA was used to determine the alterations in these cytokines secretion levels. We have also examined EDSS score in MS patients in two groups. RESULTS: According to the results, a significant decrease in mRNA expression levels of miR-145 (p<0.0001), miR-132 (p=0.004), miR-16 (p=0.0034), STAT1 (p=0.0002), NF-κB (p<0.0001), AP-1 (p=0.0007), IL-1ß (p=0.0017), IL-6 (p=0.017), IFN-γ (p<0.0001), CCL2 (p=0.0067), CCL5 (p=0.0034), TNF-α (p<0.0001) and also significant increase in expression levels of miRNAs targets; Sox2 (p=0.0001), sirtuin-1(p=0.0007), Foxp3 (p=0.0082), PDCD1 (p=0.003) was evident in nanocurcumin treated group compared with before treatment. The secretion levels of IFN-γ (p=0.0025), CCL2 (p=0.0029), and CCL5 (p=0.0003) were reduced dramatically in test group compared with placebo group. CONCLUSION: In conclusion, nanocurcumin may be more effective on the inflammatory features of MS. According to present results, nanocurcumin may inhibit neuroinflammation in MS patients.

Changes in Th17 cells function after nanocurcumin use to treat multiple sclerosis.

BACKGROUND: MS is a chronic inflammatory disease that causes to brain inflammation and Th17 cells are considered to be important in multiple sclerosis pathogenesis. In the current study, we aimed to identify nanocurcumin effects on Th17 cells frequency, cytokines secretion, and expression of transcription factor of patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: In this study we investigated frequency of Th17 lymphocytes; the expression of transcription factor, associated cytokines and the concentration of them in 35 healthy controls, and from 25 patients at baseline and after 6 months of nanocurcumin treatment and also from 25 patients whose received placebo by flowcytometry, real-time PCR and ELISA, respectively. RESULTS: Our analysis revealed that the proportions of Th17 were increased dramatically, along with increases in the levels of IL-17A, IL-23, and RORγt expression in MS patients in compared with healthy control group. Post-treatment evaluation of the nanocurcumin group revealed a significant decrease in Th17 associated parameters such as Th17 frequency (p = 0.029), expression levels of RORγt (p < 0.0001) and IL-17 (p = 0.0044) and also secretion level of IL-17 (p = 0.0011), but IL-23 mRNA expression levels and IL-23 concentration were not influenced by nanocurcumin. However, in the placebo group there is no significant changes in these factors. CONCLUSION: Our study suggests that the increase in proportion of Th17 cells might contribute to the pathogenesis of RRMS. The results of the current work indicated that nanocurcumin is able to restore the dysregulated of Th17 cells in MS patients.