Temperate propolis has anti-inflammatory effects and is a potent inhibitor of nitric oxide formation in macrophages

Previous research has shown that propolis has immunomodulatory activity. Extracts from two UK propolis samples were assessed for their anti-inflammatory activities by investigating their ability to alter the production of the cytokines: tumour necrosis factor-ff (TNF-ff), interleukin-1 (IL-1), IL-6, and IL-10 from mouse bone marrow-derived macrophages co-stimulated with lipopolysaccharide (LPS). The propolis extracts suppressed the secretion of IL-1 and IL-6 with less effect on TNFff. In addition, propolis reduced the levels of nitric oxide formed by LPS-stimulated macrophages. Metabolomic profiling was carried out by liquid chromatography (LC) coupled with mass spectrometry (MS) on a ZIC-pHILIC column. LPS increased the levels of intermediates involved in nitric oxide biosynthesis; propolis lowered many of these. In addition, LPS produced an increase in itaconate and citrate, and propolis treatment increased itaconate still further while greatly reducing citrate levels. Moreover, LPS treatment increased levels of glutathione (GSH) and intermediates in its biosynthesis, while propolis treatment boosted these still further. In addition, propolis treatment greatly increased levels of uridine diphosphate (UDP)-sugar conjugates. Overall, the results showed that propolis extracts exert an anti-inflammatory effect by the inhibition of pro-inflammatory cytokines and by the metabolic reprogramming of LPS activity in macrophages

Chemical characterization of Saudi propolis and its antiparasitic and anticancer properties

Propolis, is a gummy material produced by honey bees from different parts of plants and is enriched with varied biological active compounds like flavonoids, phenolics and phenolic acids with wide applicability in the food, pharmaceutical and cosmetics industries. The current report is focused on the characterisation of propolis collected from Asir region, South-west of Saudi Arabia and its effect on Trypanosoma brucei (the causative organism of African sleeping sickness) and cytotoxic effect against U937 human leukemia cells. The Chemical composition and spectral characteristics of Saudi propolis was studied by Liquid Chromatography Mass Spectrometry (LC-MS) and High-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD).The two main active compounds isolated from Saudi propolis via column chromatography and size exclusion chromatography were fisetinidol and ferulic acid. High resolution electrospray ionization-mass spectrophotometer (HRESI-MS) and nuclear magnetic resonance (NMR) were used to elucidate the structures of the isolated compounds. All crudes extracts, fractions as well as isolated compounds were subjected for biological testing against Trypanosoma brucei (S427 WT), and their cytotoxicity against U937 human leukemia cells. Amongst the various samples investigated, S-6 fraction demonstrated highest anti-trypanosomal activity at 2.4 µg/ml MIC followed by fisetinidol at 4.7 µg/ml reflecting that the anti-trypanosomal activity is attributable to the presence of fisetinidol in the fraction. Similarly, all the tested samples exhibited cytotoxicity with an IC50 > 60 µg/ml. S-6 fractions exhibited highest cytotoxic activity against U937 cells with an IC50 of 58.7 µg/ml followed by ferulic acid with an IC50 87.7 µg/ml indicating that the cytotoxic effect of propolis might be due to the presence of ferulic acid. In conclusion, the biological activity of propolis could be attributed to the synergistic action of the two active compounds-ferulic acid and fisetinidol. The data obtained in the study is thus indicative of the role of propolis as potential anti-trypanosomal and anticancer agent for effective cancer therapy

Medicinal Plants as Therapeutic Alternatives to Combat Mycobacterium tuberculosis : A Comprehensive Review

Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis (MTB) and a significant health concern worldwide. The main threat to the elimination of TB is the development of resistance by MTB to the currently used antibiotics and more extended treatment methods, which is a massive burden on the health care system. As a result, there is an urgent need to identify new, effective therapeutic strategies with fewer adverse effects. The traditional medicines found in South Asia and Africa have a reservoir of medicinal plants and plant-based compounds that are considered another reliable option for human beings to treat various diseases. Abundant research is available for the biotherapeutic potential of naturally occurring compounds in various diseases but has been lagging in the area of TB. Plant-based compounds, or phytoproducts, are being investigated as potential anti-mycobacterial agents by reducing bacterial burden or modulating the immune system, thereby minimizing adverse effects. The efficacy of these phytochemicals has been evaluated through drug delivery using nanoformulations. This review aims to emphasize the value of anti-TB compounds derived from plants and provide a summary of current research on phytochemicals with potential anti-mycobacterial activity against MTB. This article aims to inform readers about the numerous potential herbal treatment options available for combatting TB.publishedVersionPeer reviewe

The effects of small molecule analogues of the anti-inflammatory parasitic worm product ES-62 on the metabolome of mouse bone marrow-derived macrophages

Lipopolysaccharide (LPS) and Cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) cause macrophages to produce the proinflammatory cytokines IL-12, IL-6 and TNF-α. Pre-treatment of the macrophages with ES-62, an anti-inflammatory glycoprotein secreted by the parasitic filarial nematode Acanthocheilonema viteae suppresses the production of these cytokines.;Although able to prevent disease development in mouse models of allergy and autoimmunity, ES-62 is not suitable for drug therapy due to its potential immunogenicity. A library of small molecule analogues (SMAs) therefore was designed and tested for the previously mentioned inhibitory effects. SMAs 11a and 12b among library members were found to mimic ES-62's anti-inflammatory effects. These findings rationalised further testing in order to determine their mechanism of action based on their effects on the metabolome of primary macrophages.;From analysis of cellular extracts using hydrophilic interaction chromatography in combination with high resolution mass spectrometry it could be seen that stimulation of macrophages with either LPS or CpG produced metabolic changes in various pathways. Stimulation of macrophages with LPS or CpG in the presence of SMAs 11a and 12b revealed that many of the metabolic shifts were the same as observed with LPS and CpG alone. However, there were clear effects of the SMAs in producing downregulation in creatine metabolism/uptake and upregulation in glutathione biosynthesis.;By downregulating creatine metabolism/uptake, the SMAs may be controlling the availability of creatine for transporting high energy phosphate from the mitochondria to where it is required for biological functions including cell signalling, phagocytosis and motility. By causing an upregulation of the glutathione biosynthesis pathway the SMAs may be protecting the cells from oxidative stress and of note SMA12b has been previously linked to increased activity of the Nrf2/ARE/HO-1 anti-oxidant pathway. The SMAs may be downregulating the availability of the energy produced by oxidative phosphorylation in general without targeting the TCA cycle directly since they do not affect NADH levels in comparison with LPS or CpG stimulation alone. Finally, in the process of examining the response of the cells to LPS and CpG additional potential anti-inflammatory targets were revealed.Lipopolysaccharide (LPS) and Cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) cause macrophages to produce the proinflammatory cytokines IL-12, IL-6 and TNF-α. Pre-treatment of the macrophages with ES-62, an anti-inflammatory glycoprotein secreted by the parasitic filarial nematode Acanthocheilonema viteae suppresses the production of these cytokines.;Although able to prevent disease development in mouse models of allergy and autoimmunity, ES-62 is not suitable for drug therapy due to its potential immunogenicity. A library of small molecule analogues (SMAs) therefore was designed and tested for the previously mentioned inhibitory effects. SMAs 11a and 12b among library members were found to mimic ES-62's anti-inflammatory effects. These findings rationalised further testing in order to determine their mechanism of action based on their effects on the metabolome of primary macrophages.;From analysis of cellular extracts using hydrophilic interaction chromatography in combination with high resolution mass spectrometry it could be seen that stimulation of macrophages with either LPS or CpG produced metabolic changes in various pathways. Stimulation of macrophages with LPS or CpG in the presence of SMAs 11a and 12b revealed that many of the metabolic shifts were the same as observed with LPS and CpG alone. However, there were clear effects of the SMAs in producing downregulation in creatine metabolism/uptake and upregulation in glutathione biosynthesis.;By downregulating creatine metabolism/uptake, the SMAs may be controlling the availability of creatine for transporting high energy phosphate from the mitochondria to where it is required for biological functions including cell signalling, phagocytosis and motility. By causing an upregulation of the glutathione biosynthesis pathway the SMAs may be protecting the cells from oxidative stress and of note SMA12b has been previously linked to increased activity of the Nrf2/ARE/HO-1 anti-oxidant pathway. The SMAs may be downregulating the availability of the energy produced by oxidative phosphorylation in general without targeting the TCA cycle directly since they do not affect NADH levels in comparison with LPS or CpG stimulation alone. Finally, in the process of examining the response of the cells to LPS and CpG additional potential anti-inflammatory targets were revealed

Quantification of Methylisothiazolinone and Methylchloroisothiazolinone Preservatives by High-Performance Liquid Chromatography

Isothiazolinone preservatives (methylisothiazolinone (MIT) and methylchloroisothiazolinone (CMIT) are commonly used in cosmetics, industrial and household products. However, these isothiazolinone derivatives are known to cause allergic contact dermatitis. Hence, a sensitive, accurate, and reliable method for the detection of these compounds is thus warranted. The study aims to analyze concentrations of MIT and CMIT by high performance liquid chromatography. The analytical method used for quantification of MIT and CMIT in cosmetic products (leave-on-baby wet wipes) complies with the validation acceptance criteria (international standards ISO 5725, EU25 European Union for cosmetic regulations). MIT and CMIT were extracted and analyzed in leave-on baby wet-wipes collected from different stores in Riyadh city. Extraction was performed by ultrasonication of the samples, solid-phase extraction, and liquid-liquid extraction. Ten (10) µL of the sample was injected into the HPLC system and samples were analyzed with a mixture of acetic acid and methanol (80:20 v/v) in an isocratic mode. The flow rate was maintained at 1 mL/min. UV detection was performed at 274 nm. The results demonstrated recoveries between 90 and 106%, measurement uncertainty of C +/− 0.4% for methylisothiazolinone and C +/− 0.03% for methylchloroisothiazolinone, repeatability limit (r = 0.2%) and intermediate precision limit; R = 2% and R2 of 0.9996

An Insight into the Impact of Serum Tellurium, Thallium, Osmium and Antimony on the Antioxidant/Redox Status of PCOS Patients: A Comprehensive Study

Humans exploit heavy metals for various industrial and economic reasons. Although some heavy metals are essential for normal physiology, others such as Tellurium (Te), Thallium (TI), antimony (Sb), and Osmium (Os) are highly toxic and can lead to Polycystic Ovarian Syndrome (PCOS), a common female factor of infertility. The current study was undertaken to determine levels of the heavy metals TI, Te, Sb and Os in serum of PCOS females (n = 50) compared to healthy non-PCOS controls (n = 56), and to relate such levels with Total Antioxidant Capacity (TAC), activity of key antioxidant enzymes, oxidative stress marker levels and redox status. PCOS serum samples demonstrated significantly higher levels of TI, Te, Sb and Os and diminished TAC compared to control (p < 0.001). Furthermore, there was significant inhibition of SOD, CAT and several glutathione-related enzyme activities in sera of PCOS patients with concurrent elevations in superoxide anions, hydrogen and lipid peroxides, and protein carbonyls, along with disrupted glutathione homeostasis compared to those of controls (p < 0.001 for all parameters). Additionally, a significant negative correlation was found between the elevated levels of heavy metals and TAC, indicative of the role of metal-induced oxidative stress as a prominent phenomenon associated with the pathophysiology of the underlying PCOS. Data obtained in the study suggest toxic metals as risk factors causing PCOS, and thus protective measures should be considered to minimize exposure to prevent such reproductive anomalies

An Insight into the Impact of Serum Tellurium, Thallium, Osmium and Antimony on the Antioxidant/Redox Status of PCOS Patients: A Comprehensive Study

Humans exploit heavy metals for various industrial and economic reasons. Although some heavy metals are essential for normal physiology, others such as Tellurium (Te), Thallium (TI), antimony (Sb), and Osmium (Os) are highly toxic and can lead to Polycystic Ovarian Syndrome (PCOS), a common female factor of infertility. The current study was undertaken to determine levels of the heavy metals TI, Te, Sb and Os in serum of PCOS females (n = 50) compared to healthy non-PCOS controls (n = 56), and to relate such levels with Total Antioxidant Capacity (TAC), activity of key antioxidant enzymes, oxidative stress marker levels and redox status. PCOS serum samples demonstrated significantly higher levels of TI, Te, Sb and Os and diminished TAC compared to control (p p < 0.001 for all parameters). Additionally, a significant negative correlation was found between the elevated levels of heavy metals and TAC, indicative of the role of metal-induced oxidative stress as a prominent phenomenon associated with the pathophysiology of the underlying PCOS. Data obtained in the study suggest toxic metals as risk factors causing PCOS, and thus protective measures should be considered to minimize exposure to prevent such reproductive anomalies

Brief Report: Reduction in creatine metabolites in macrophages exposed to small molecule analogues of the anti-inflammatory parasitic worm product ES-62

ES-62, a protein secreted by Acanthocheilonema viteae, is anti-inflammatory by virtue of covalently attached phosphorylcholine (PC) residues and thus a library of drug-like small molecule analogues (SMAs) based on its PC moieties has been designed for therapeutic purposes. Two members, SMAs 11a and 12b, were previously found to suppress production of pro-inflammatory cytokines by mouse bone marrow-derived macrophages (BMMs) exposed to cytosine-phosphate-guanosine oligodeoxynucleotides (CpG), agonists for Toll-like receptor 9. In order to explore the mechanism of action underlying such activities, an untargeted mass spectrometry-based metabolomics screen was undertaken. Stimulation of BMMs with CpG produced significant metabolic changes relating to glycolysis and the TCA cycle but the SMAs had little impact on this. Also, the SMAs did not promote alterations in metabolites known to be associated with macrophage M1/M2 polarisation. Rather, BMMs exposed to SMAs 11a or 12b prior to CpG treatment, or even alone, revealed downregulation of metabolites of creatine, a molecule whose major role is in the transport of high energy phosphate from the mitochondria to the cytosol. These data therefore provide insight into a possible mechanism of action of molecules with significant therapeutic potential that has not previously been described for parasitic worm products