Inhibitory effects of methanol extracts of selected plants on proliferation of two human melanoma cell lines

Purpose: The aim of the current study was to investigate the in vitro antiproliferative activity of methanolic extracts of six plants regardless of their claimed ethnopharmacological application.Methods: Methanol extracts of different parts of Glycyrrhizaglabra L. (Licorice), Matricaria chamomilla L. (Chamomile), Salvia triloba L. (Sage), Rheum palmatum L. (Rhubarb), Trigonella foenum-graecum L. (Fenugreek) and Sambucusebulus L. (Dwarf Elder) were prepared. The antiproliferative effects of the extracts were tested on two skin cancer melanoma cell lines namely A375.S2 (low tyrosinase expression) and WM 136.1A (high tyrosinase expression) using MTT assay. The IC50 values for the active extracts were determined against the two melanoma cell lines.Results: The methanolic extracts of G.glabra, M. chamomilla, S. triloba, R. palmatum inhibited the melanotic WM1361A proliferation in a dose-dependent manner revealing IC50 values of 35.2, 25.2, 20.6, 17.8, μg/ml, respectively but not A375.S2 cell line. However, the extracts of T. foenum-graecum and S. ebulus did not exhibit any significant cytotoxic activity on both melanoma cell lines.Conclusion: The results of these experiments show that methanol extracts of licorice, chamomile, sage and rhubarb have significant antiproliferative activity onWM1361A cell line; a representative human melanotic melanocyte tumor cell line. This renders these plants as potential sources of new lead compounds for the development of new drugs for melanoma cancer.Keywords: Melanoma, Plant extract, tyrosinase, Licorice, Chamomile, Sage, Rhubarb, WM1361

Inhibitory effects of methanol extracts of selected plants on the proliferation of two human melanoma cell lines

Purpose: To investigate the in vitro antiproliferative activity of methanol extracts of six plants regardless of their claimed ethnopharmacological application.Methods: Methanol extracts of different parts of Glycyrrhiza glabra L. Licorice), Matricaria chamomilla L. (Chamomile), Salvia triloba L. (Sage), Rheum palmatum L. (Rhubarb), Trigonella foenum-graecum L (Fenugreek) and Sambucus ebulus L. (Dwarf Elder)were prepared. The antiproliferative effects of the extracts weretestedon two skin cancer melanoma cell lines namely A375.S2 (low tyrosinase expression) and WM 136.1A (high tyrosinase expression) using MTT assay.The IC50 values for the active extracts were determined against the two melanoma cell lines.Results: The methanol extracts of G. glabra, M. chamomilla, S.triloba, R. palmatum inhibited the melanotic WM1361A proliferation in a dose-dependent manner revealing IC50 values of 35.2, 25.2, 20.6, 17.8, μg/ml, respectively but not A375.S2 cell line. However, the extracts of T. foenum-graecum and S. ebulus did not exhibit any significant cytotoxic activity on both melanoma cell lines.Conclusion: Methanol extracts of Licorice, Chamomile, Sage and Rhubarb have significantantiproliferative activity on WM1361A cell line; a representative human melanotic melanocyte tumor cell line. This renders these plants as potential sources of new lead compounds for the development of new drugs for melanoma cancer.Keywords: Melanoma, Plant extract, tyrosinase, Licorice, Chamomile, Sage, Rhubarb, WM1361A

Immunomodulatory effects of tigecycline in Balb/c mice

Tigecycline is a glycylcycline antibiotic approved by the FDA for the treatment of complicated infections. Despite its effectiveness, the FDA announced a warning of increasing mortality associated with its use. There is, however, no clear explanation for this side effect. Previous reports found a possible effect of tigecycline on leukocyte proliferation and proinflammatory cytokine release. We therefore investigated the effect of tigecycline on the immune components and response in Balb/c mice in vivo and in vitro. It was found that tigecycline enhanced lymphocyte proliferation and significantly increased cellular infiltration within the footpad, as based on DTH testing, but reduced the hemagglutination titer. In splenocyte cultures, tigecycline suppressed splenocyte proliferation with IC50 3–5 mol L–1, significantly increased IL-2 secretion and reduced IL-17 secretion in a dose dependent mode. In conclusion, tigecycline is safe at therapeutic and sub-therapeutic doses, but it could still have an immunomodulatory effect at higher doses. Use of higher doses of tigecycline requires further investigation

Evaluation of immunomodulatory effects of lamotrigine in BALB/c mice

Modulation of the immune system has recently been shown to be involved in the pharmacological effects of old antiepileptic drugs and in the pathogenesis of epilepsy. Therefore, the most recent guidelines for immunotoxicological evaluation of drugs were consulted to investigate the immunomodulatory effects of lamotrigine, a newer antiepileptic drug, in BALB/c mice. These included the in vivo effects of lamotrigine on delayed-type hypersensitivity (DTH) response to sheep red blood cell (SRBC) antigens, hemagglutination titer assays and hematological changes. In vitro effects of lamotrigine on ConA-induced splenocyte proliferation and cytokine secretion were assessed. The results showed that lamotrigine treatment significantly increased the DTH response to SRBC in the mouse model of this study. This was accompanied by a significant increase in relative monocyte and neutrophil counts and in spleen cellularity. Lamotrigine significantly inhibited ConA-induced splenocyte proliferation in vitro and it significantly inhibited IL-2 and TNF-α secretion in ConA-stimulated splenocytes. In conclusion, the results demonstrated significant immunomodulatory effects of lamotrigine in BALB/c mice. These data could expand the understanding of lamotrigine-induced adverse reactions and its role in modulating the immune system in epilepsy

Evaluation of Antiproliferative Activity of Some Traditional Anticancer Herbal Remedies from Jordan

Purpose: To evaluate the in vitro antiproliferative activity of the extracts of the three plants against a panel of human tumor cell lines representing the most common types of cancer in Jordan, viz, breast and colorectal and skin cancers.Methods: The methanol extracts of the aerial parts of the three plants (Arbutus andrachne L., Chrysanthemum coronarium L., and Teucrium polium L.) were prepared and assessed for antiproliferative activity against six human tumor cell lines (A375.S2, WM1361A, CACO-2, HRT18, MCF-7, T47D) using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide MTT cell proliferation assay.Results: C. coronarium extract, at the concentration range of 25 to 400 μg/mL, significantly inhibited (10 – 50 %) the proliferation of the 6 cell lines in a dose-dependent manner, whilst the extracts of the other two plants exhibited weak antiproliferative activity (2 – 10 % inhibition). The half-maximal inhibitory concentration (IC50) values of C. coronarium extract against the six cell lines were in the range of 75.8 to 138.5 μg/mL.Conclusion: The methanol extract of the aerial parts C. coronarium possesses a relatively potent antiproliferative activity and therefore might be a potential source of natural compounds that can be developed into new antineoplastic agents.Keywords: Antiproliferative, Arbutus andrachne L., Chrysanthemum coronarium L., Teucrium polium L. Jordan flora, Medicinal plants, Cancer, Antineoplasti

The role of toll-like receptor 9 on B-cell activating factor expression and function in normal human B-cells

B-cell autoreactivity is a characteristic abnormality in several autoimmune diseases. In systemic lupus erythematosus (SLE), inappropriate activation of TLR7 and TLR9, accompanied by high serum levels of BAFF, are implicated in disease pathogenesis. In murine B-cells, TLR9 activation resulted in up-regulating BAFF expression, while such a direct effect has not yet been established in normal human B-cells (nhB-cells). Therefore, the effect of CpG-2006, a synthetic TLR9 ligand, on the expression and function of BAFF and its receptors (BAFF-R, TACI and BCMA) in nhB-cells was studied. BAFF expression, in response to CpG-2006, was significantly upregulated at the level of mRNA, intracellular and membrane-bound protein in nhB-cell. In contrast, enhancement of BAFF secretion in culture supernatants of CpG-2006-stimulated nhB-cells was not detected. CpG-2006 treatment of nhB-cells significantly enhanced the expression of TACI and BCMA, but did not affect BAFF-R expression. CpG-2006-stimulated B-cells, in co-cultures with freshly isolated nhB-cells, co-stimulated B-cell receptor-induced cellular proliferation of the freshly isolated nhB-cells. This effect was completely blocked by a BAFF-specific monoclonal antibody. CpG-2006 treatment of nhB-cells sensitised them to proliferate in response to exogenous BAFF, whereas exogenous BAFF per se had no effect on the proliferation of untreated nhB-cells. This effect was inhibited by an anti-BAFF-R blocking antibody, but was not inhibited by anti-TACI or anti-BCMA antibodies. CpG-2006 mediated BAFF expression through NF-κB and ERK1/2 pathways, and partially through p38MAPK. Simultaneous treatment of nhB-cells with CpG-2006 and either of the inhibitory ODNs (ODN-TTAGGG or ODN-2088), at 1:5 ratio (CpG-2006: INH-ODN), inhibited CpG-2006-induced BAFF expression in nhB-cells. Finally, BJAB, RPMI and RAMOS B-cell tumour lines failed to represent nhB-cell’s responses to CpG-2006 treatment. Taken together, these novel findings demonstrate a functional cross-talk between TLR9 and BAFF in nhB-cells, and have possible implications for the roles of TLR9 and BAFF in the pathogenesis of SLE

The impact of pharmacist-led educational intervention on pneumococcal vaccine awareness and acceptance among elderly in Jordan

Limited data exist regarding pneumococcal vaccination coverage among the elderly in Middle Eastern countries including Jordan. The pharmacists’ role in improving vaccine acceptance has become increasingly evident. Yet, large-scale studies of the assessment of the pharmacists’ role on pneumococcal vaccines acceptance among the elderly are scarce. Hence, we assessed for the first time the current state of knowledge and pneumococcal vaccination coverage among the elderly and the role of pharmacist-led educational intervention on the attitude, awareness, vaccine acceptance, and prompts for physician consultation regarding pneumococcal vaccines in Jordan. This interventional study enrolled 916 randomly selected adults aged ≥ 65 years in Amman, Jordan. We showed that only 3.9% of the participants have ever heard about pneumococcal disease with 0.5% vaccination coverage. Immediately after educational intervention, 21.7% of the participants perceived pneumococcal disease as a threat, 52.1% of them believed in the importance of the vaccine, and 93.9% of them were willing to consult a physician in this regard. At a two-month follow-up, 30.5% had a positive attitude toward the vaccine and 36% consulted their physician regarding the vaccine. Vaccination coverage was significantly increased to 1.9% (P value = 0.008). The main obstacles against vaccination were a negative attitude and that physicians had not recommended the vaccine. Vaccine uptake was significantly associated with physician consultation (P value = 0.011). Insurance, employment, attitude, and reading the booklet significantly predicted physician consultation. In conclusion, very low pneumococcal vaccination coverage was observed among the elderly in Jordan. Enrollment of pharmacists in immunization education and recommendation is suggested to improve pneumococcal vaccine coverage among the elderly in Jordan

Travelers to U.S.: Zika Virus Knowledge, Attitudes, and Determinants of Practices in the Middle East—Insights for Future Awareness Campaigns

Travelers act as sentinels for the spread of Zika virus. Imported Zika cases and the presence of Zika virus-transmitting mosquitoes have been documented in the Middle East. However, data on travelers’ knowledge, attitude and practices regarding Zika and its prevention measures within the Middle East are scarce. This study aimed to address this issue in a sample of Jordanian and non-Jordanian travelers to U.S. in Jordan. A paper-based questionnaire was distributed to 301 travelers to U.S. in Queen Alia International airport, Amman, Jordan. Only 2.7% of the travelers knew that Zika is associated with birth defects. A total of 10.4% of the participants knew that the bite of infected mosquitoes is a route of Zika transmission. Only 12.6% of respondents correctly identified Zika prevention measures. The level of education and future plans for pregnancy were significantly associated with a high knowledge score (R2 = 0.140, p-value < 0.005). Although 76.2% of the travelers perceived Zika as a health threat, only 11.2% believed in the efficacy of the prevention measures. Formulation of educational campaigns within Middle Eastern countries and development of awareness strategies regarding Zika and its prevention within the airports are required. This is particularly essential with the upcoming 2022 FIFA World Cup in Qatar

Diagnosing Parkinsons disease and monitoring its progression: Biomarkers from combined GC-TOF MS and LC-MS/MS untargeted metabolomics.

Parkinsons disease (PD) is a prevalent neurodegenerative disorder with a poorly understood etiology. An accurate diagnosis of idiopathic PD remains challenging as misdiagnosis is common in routine clinical practice. Moreover, current therapeutics focus on symptomatic management rather than curing or slowing down disease progression. Therefore, identification of potential PD biomarkers and providing a better understanding of the underlying disease pathophysiology are urgent. Herein, hydrophilic interaction liquid chromatography-mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-TOF MS) based metabolomics approaches were used to profile the serum metabolome of 50 patients with different stages of idiopathic PD (early, mid and advanced) and 45 age-matched controls. Levels of 57 metabolites including cysteine-S-sulfate and N-acetyl tryptophan were significantly higher in patients with PD compared to controls, with lower amounts of additional 51 metabolites including vanillic acid, and N-acetylaspartic acid. Xanthines, including caffeine and its downstream metabolites, were lowered in patients with PD relative to controls indicating a potential role caffeine and its metabolites against neuronal damage. Seven metabolites, namely cysteine-S-sulfate, 1-methylxanthine, vanillic acid, N-acetylaspartic acid, 3-N-acetyl tryptophan, 5-methoxytryptophol, and 13-HODE yielded a ROC curve with a high classification accuracy (AUC 0.977). Comparison between different PD stages showed that cysteine-S-sulfate levels were significantly increasing with the advancement of PD stages while LPI 20:4 was significantly decreasing with disease progression. Our findings provide new biomarker candidates to assist in the diagnosis of PD and monitor its progression. Unusual metabolites like cysteine-S-sulfate might point to therapeutic targets that could enhance the development of novel PD treatments, such as NMDA antagonists