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Background: Annona muricata L. (Annonaceae) (AM)'s remarkable anti-inflammatory and anti-cancer activities make it a targeted plant to be explored for its immunomodulatory properties. Traditional practitioners have employed various components of AM to cure a variety of ailments, including cancer, diabetes, and inflammation. Objective: The present study evaluated the immunosuppressive effects of 80% ethanol extract of of AM leaves in male Wistar rats on different parameters of humoral and cellular immune responses. Methods: AM leaf extract (AMLE) was analyzed using UHPLC-MS/MS to profile its secondary metabolites. AMLE was rich in polyphenols which include (epi)catechin-(epi)catechin-(epi) catechin, caffeic acid, coumaroylquinic acid, hyperin, kaempferol, quinic acid and rutin. The rats were administered 100, 200 and 400 mg/kg bw of the extract daily for 14 days. The effects of AMLE on innate immune responses were determined by evaluating phagocytosis, neutrophils migration, reactive oxygen species (ROS) release, CD11b/CD18 integrin expression, and ceruloplasmin, lysozyme and myeloperoxidase (MPO) levels. The adaptive immune parameters were evaluated by immunizing the rats with sheep red blood cells (sRBC) on day 0 and administered orally with AMLE for 14 days. Results: AMLE established significant immunosuppressive effects on the innate immune parameters by inhibiting the neutrophil migration, ROS production, phagocytic activity and expression of CD11b/CD18 integrin in a dose-dependent pattern. AMLE also suppressed ceruloplasmin, MPO and lysozyme expressions in the rat plasma dose-dependently. AMLE dose-dependently inhibited T and B lymphocytes proliferation, Th1 and Th2 cytokine production, CD4+ and CD8+ co-expression in splenocytes, immunoglobulins (IgM and IgG) expression and the sRBC-induced swelling rate of rat paw in delayed-type hypersensitivity (DTH). Conclusion: The strong inhibitory effects on the different parameters of humoral and cellular responses indicate that AMLE has potential to be an important source of effective immunosuppressive agents.

Leukaemia is a heterogeneous hematologic malignancy characterized by unregulated proliferation of the early blood-forming cells which starts in bone marrow. The basic strategy of leukaemia therapy involves the induction of leukemic cells apoptosis. Research on natural products have shown that some plant derivatives have anticancer properties by inducing apoptosis of leukemic cells. Plants such as Camellia sinensis and Phyllanthus amarus are those that had gained a wide interest due to their anti-cancer effect. The aim of this study was to investigate the anti-cancer effects of C. sinensis and P. amarus extracts on human leukemic cell lines by analysing the cell cycle and determining the apoptotic state. The cell lines were treated with ethanolic plant extracts at the concentrations of 31.25 - 500 µg/mL for 24 h followed by MTT assay to determine the IC50. The IC50 of C. sinensis and P. amarus on the U937 cells were 170±10.39 and 210±6.78 µg/mL, respectively. Flow cytometric analysis of apoptosis using Annexin V/propidium iodide (PI) staining was also performed. C. sinensis extract at 170 µg/mL significantly increase apoptosis in U-937 (p

Purpose: To investigate the blood pressure-lowering effect of green tea (GT) extract alone and in combination with an angiotensin converting enzyme (ACE) inhibitor, perindopril, on rats. Methods: The study consisted of four groups of five spontaneously hypertensive rats (SHR): negative control (2 % tragacanth mucilage), positive control group (perindopril, 0.36 mg/kg/day) and two treatment groups (green tea, 25 mg/kg/day; and combined green tea/perindopril). The treatments were given orally for 14 days. Systolic blood pressure was measured before and after treatment using the tail cuff technique. Angiotensin converting enzyme activity in the lung homogenate of the hypertensive rats was determined spectrophotometrically. Results: Green tea extract significantly reduced the rats’ systolic blood pressure (p < 0.05) but did not inhibit the angiotensin-converting enzyme. The combination of green tea extract with perindopril also caused a significant decline in blood pressure (p < 0.001). However, the green tea extract attenuated the inhibition of the angiotensin-converting enzyme activity by perindopril. Conclusion: Green tea extract produces anti-hypertensive activity in rats, but its mechanism of action is not via inhibition of angiotensin-converting enzyme. The interaction of GT extract with perindopril results in a reduction of ACE inhibitory activity.

Purpose: To investigate the inhibitory effects of a chalcone derivative on lipopolysaccharide (LPS)- induced interleukin (IL)-6 and IL-8 secretions and on LPS-induced mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB) activation in human U937 macrophage-like cell line. Methods: The effects of chalcone derivative on LPS-induced secretion of IL-6 and IL-8 in endothelial cells were determined by enzyme-linked immunosorbent assay while the effects of chalcone on the activation of MAPK and NF-kB pathway were determined by Western blotting. Results: The results showed that 3-(5-methyl-furan-2-yl)-naphthalen-1-yl-propenone (compound 1) significantly inhibited the secretion of LPS-induced IL-6 and IL-8 in U937 macrophages. This compound also demonstrated significant suppression of c-Jun N-terminal kinases (JNK) and extracellular signalregulated kinases (ERK) phosphorylation. However, the compound did not reverse the degradation of inhibitor kappa B alpha (IκBα) and did not inhibit the phosphorylation of NF-κB subunit and P-38 MAPK. Conclusion: Compound 1 inhibits the secretion of cytokines via the inhibition of ERK and JNK pathways. These results suggest that chalcone derivative could act as an antiinflammatory agent by altering cytokine secretion and inflammatory pathways.

Long-term nicotine intake is associated with an increased risk of myocardial damage and dysfunction. However, it remains unclear whether targeting mitochondrial reactive oxygen species (ROS) prevents nicotine-induced cardiac remodeling and dysfunction. This study investigated the effects of mitoTEMPO (a mitochondria-targeted antioxidant), and resveratrol (a sirtuin activator) , on nicotine-induced cardiac remodeling and dysfunction. Sprague–Dawley rats were administered 0.6 mg/kg nicotine daily with 0.7 mg/kg mitoTEMPO, 8 mg/kg resveratrol, or vehicle alone for 28 days. At the end of the study, rat hearts were collected to analyze the cardiac structure, mitochondrial ROS level, oxidative stress, and inflammation markers. A subset of rat hearts was perfused ex vivo to determine the cardiac function and myocardial susceptibility to ischemia–reperfusion injury. Nicotine administration significantly augmented mitochondrial ROS level, cardiomyocyte hypertrophy, fibrosis, and inflammation in rat hearts. Nicotine administration also induced left ventricular dysfunction, which was worsened by ischemia–reperfusion in isolated rat hearts. MitoTEMPO and resveratrol both significantly attenuated the adverse cardiac remodeling induced by nicotine, as well as the aggravation of postischemic ventricular dysfunction. Findings from this study show that targeting mitochondrial ROS with mitoTEMPO or resveratrol partially attenuates nicotine-induced cardiac remodeling and dysfunction.

Nitric oxide (NO) overproduction by inducible nitric oxide synthase (iNOS) may be associated with acute and chronic inflammations. Macrophages as important cells in the innate immune system are able to be stimulated and can lead to iNOS activation and excessive NO production. Gynura procumbens is a medicinal plant traditionally used in treating various ailments including inflammation but the mechanism of anti-inflammatory activity of this plant is still elusive. This study was carried out to investigate the anti-inflammatory therapeutic effects of Gynura procumbens ethanolic extract on NO production and iNOS protein expression in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). Cell viability of RAW 264.7 macrophages treated with Gynura procumbens ethanolic extract was determined by MTT assay. NO production was determined by Griess assay following Gynura procumbens ethanolic extract treatment alone or in combination with LPS stimulation. Protein expression of iNOS was determined by western blot. RAW 264.7 macrophages viability of more than 90% was observed after 24 h treatment with Gynura procumbens ethanolic extract concentration range of 3.9 μg/mL to 500 μg/mL. Significant inhibition of NO production level has been identified in LPS-stimulated RAW 264.7 cells pre-treated with 250 μg/mL Gynura procumbens ethanolic extract (p

Gynura procumbens (Lour.) Merr. (GP) is a herbaceous plant that grows in Malaysia and other parts of Southeast Asia. The herb is consumed as a remedy for various inflammatory-associated diseases, such as cancer, rheumatism, hypertension, diabetes mellitus and hyperlipidemia. Scientific studies demonstrate that GP extract possesses cardioprotective and anti-inflammatory effects. Cardiovascular disease is mainly caused by atherosclerosis, and inflammation plays a major role in all phases of atherosclerosis. The early inflammatory events in atherogenesis are the activation of endothelial cells and the recruitment of monocytes.This study aimed to evaluate the inhibitory effect of 80% ethanol extract of GP leaves (GPE) on the adherence of monocytes to the activated human endothelial cells and its underlying mechanism.Qualitative and quantitative analyses of the extract were carried out by using a validated HPLC and UHPLC-MS/MS methods. The MTT test was used to select the range of concentration of extract for this study. The effect of GPE on TNF-α-induced monocyte-endothelial interaction was determined by the in vitro adhesion assay. Expression of cell surface proteins (ICAM-1, VCAM-1) and phosphorylation of nuclear factor kappa B (NF-κB) were determined by western blot, while expression of a chemokine (MCP-1) was identified by an enzyme-linked immunosorbent assay.HPLC and UHPLC-MS/MS analyses indicated that GPE contained chlorogenic acid, nicotiflorin and astragalin as the major compounds. GPE at 20, 40 and 60 μg/mL concentrations showed a significant reduction in monocyte adherence to endothelial cells and expression of ICAM-1 and MCP-1. However, only GPE at concentrations of 40 and 60 μg/mL was able to reduce VCAM-1 expression. Furthermore, GPE significantly inhibited IKKα/β, IκBα, NF-κB phosphorylation and NF-κB translocation.In conclusion, GPE may inhibit monocyte adherence to the activated endothelial cells and expression of ICAM-1, VCAM-1 and MCP-1, which are important proteins for monocyte-endothelial interaction, by suppressing the NF-κB signaling pathway. The results of this study support the traditional use of GPE to counteract inflammation-associated diseases and suggest that GP can be a potential source for bioactive compounds for the development of anti-inflammatory agents to prevent atherosclerosis.

Diabetes mellitus is often associated with cardiac functional and structural alteration, an initial event leading to cardiovascular complications. Roselle (Hibiscus sabdariffa) has been widely proven as an antioxidant and recently has incited research interest for its potential in treating cardiovascular disease. Therefore, this study aimed to determine the cardioprotective effects of H. sabdariffa (roselle) polyphenol-rich extract (HPE) in type-1-induced diabetic rats. Twenty-four male Sprague–Dawley rats were randomized into 4 groups (n = 6/group): nondiabetic, diabetic alone (DM), diabetic supplemented with HPE (DM+HPE), and diabetic supplemented with metformin. Type-1 diabetes was induced with streptozotocin (55 mg/kg intraperitoneally). Rats were forced-fed with HPE (100 mg/kg) and metformin (150 mg/kg) daily for 8 weeks. Results showed that HPE supplementation improved hyperglycemia and dyslipidemia significantly (p < 0.05) in the DM+HPE compared with the DM group. HPE supplementation attenuated cardiac oxidative damage in the DM group, indicated by low malondialdehyde and advanced oxidation protein product. As for the antioxidant status, HPE significantly (p < 0.05) increased glutathione level, as well as catalase and superoxide dismutase 1 and 2 activities. These findings correlate with cardiac function, whereby left ventricle developed pressure in DM+HPE (79.13 ± 3.08 mm Hg) was higher significantly compared with DM (45.84 ± 1.65 mm Hg). Coronary flow of DM+HPE (17.43 ± 0.62 mL/min) was also greater compared with DM (13.02 ± 0.6 mL/min), showing that HPE supplementation improved cardiac contractility and relaxation rate significantly (p < 0.05). Histological analysis showed a marked decrease in cardiomyocyte hypertrophy and fibrosis in DM+HPE compared with the DM group. Ultrastructural changes and impairment of mitochondria induced by diabetes were minimized by HPE supplementation. Collectively, these findings suggest that HPE is a potential cardioprotective agent in a diabetic setting through its hypoglycemic, anti-hyperlipidemia, and antioxidant properties.

Context Gynura procumbens (Lour.) Merr. (Asteraceae) has been reported to have various pharmacological activities including anti-inflammatory effects. Objective This study sought to determine whether Gynura procumbens (GP) could improve vascular reactivity by suppressing inflammation in postmenopausal rats fed with five-times heated palm oil (5HPO) diet. Materials and methods Forty-eight female Sprague-Dawley rats were randomly divided into sham [non-ovariectomized; grouped as control, GP extracts (250 and 500 mg/kg), atorvastatin (ATV, 10 mg/kg)] and postmenopausal (PM) groups [ovariectomized rats fed with 5HPO; grouped as PM, GP extracts (250 and 500 mg/kg) and ATV (10 mg/kg)]. Each group (n = 6) was either supplemented with GP extract or ATV orally once daily for 6 months. Results In comparison with the untreated PM group, 250 and 500 mg/kg GP supplementation to PM groups reduced the systolic blood pressure (103 ± 2.7, 86 ± 2.4 vs. 156 ± 7.83 mmHg, p

Increased exposure to nicotine contributes to the development of cardiac dysfunction by promoting oxidative stress, fibrosis, and inflammation. These deleterious events altogether render cardiac myocytes more susceptible to acute cardiac insults such as ischemia-reperfusion (I/R) injury. This study sought to elucidate the role of angiotensin II type I (AT1) receptors in cardiac injury resulting from prolonged nicotine administration in a rat model. Male Sprague-Dawley rats were given nicotine (0.6 mg/kg ip) for 28 days to induce cardiac dysfunction, alone or in combination with the AT1 receptor antagonist, irbesartan (10 mg/kg, po). Vehicle-treated rats were used as controls. Rat hearts isolated from each experimental group at study endpoint were examined for changes in function, histology, gene expression, and susceptibility against acute I/R injury determined ex vivo. Rats administered nicotine alone exhibited significantly increased cardiac expression of angiotensin II and angiotensin-converting enzyme (ACE) in addition to elevated systolic blood pressure (SBP) and heart rate. Furthermore, nicotine administration markedly reduced left ventricular (LV) performance with concomitant increases in myocardial oxidative stress, fibrosis, and inflammation. Concomitant treatment with irbesartan attenuated these effects, lowering blood pressure, heart rate, oxidative stress, and expression of fibrotic and inflammatory genes. Importantly, the irbesartan-treated group also manifested reduced susceptibility to I/R injury ex vivo. These findings suggest that AT1 receptors play an important role in nicotine-induced cardiac dysfunction, and pharmacological approaches targeting cardiac AT1 receptors may thus benefit patients with sustained exposure to nicotine.

Background: Gynura species have been used traditionally to treat various ailments, such as fever, pain, and to control blood glucose level. This systematic review critically discusses studies regarding Gynura species that exhibited antioxidant and anti-inflammatory effects, thus providing perspectives and instructions for future research of the plants as a potential source of new dietary supplements or medicinal agents. Methods: A literature search from internet databases of PubMed, Scopus, Science Direct, e-theses Online Service, and ProQuest was carried out using a combination of keywords such as “Gynura,” “antioxidant,” “anti-inflammatory,” or other related words. Research articles were included in this study if they were experimental (in vitro and in vivo) or clinical studies on the antioxidant or anti-inflammatory effects of Gynura species and if they were articles published in English. Results: Altogether, 27 studies on antioxidant and anti-inflammatory effects of Gynura species were selected. The antioxidant effects of Gynura species were manifested by inhibition of reactive oxygen species production and lipid peroxidation, modulation of glutathione-related parameters, and enzymatic antioxidant production or activities. The anti-inflammatory effects of Gynura species were through the modulation of inflammatory cytokine production, inhibition of prostaglandin E2 and nitric oxide production, cellular inflammatory-related parameters, and inflammation in animal models. The potential anti-inflammatory signaling pathways modulated by Gynura species are glycogen synthase kinase-3, nuclear factor erythroid 2-related factor 2, PPARγ, MAPK, NF-κB, and PI3K/Akt. However, most reports on antioxidant and anti-inflammatory effects of the plants were on crude extracts, and the chemical constituents contributing to bioactivities were not clearly understood. There is a variation in quality of studies in terms of design, conduct, and interpretation, and in-depth studies on the underlying mechanisms involved in antioxidant and anti-inflammatory effects of the plants are in demand. Moreover, there is limited clinical study on antioxidant and anti-inflammatory effects of Gynura species. Conclusion: This review highlighted antioxidant and anti-inflammatory effects of genus Gynura and supported their traditional uses to treat oxidative stress and inflammatory-related diseases. This review is expected to catalyze further studies on genus Gynura. However, extensive preclinical data need to be generated from toxicity and pharmacokinetic studies before clinical studies can be pursued for their development into clinical medicines to treat oxidative stress and inflammatory conditions.

Gynura procumbens (Lour.) Merr. (GP) has been reported in previous studies to possess antihyperlipidaemic, antioxidative, and cardioprotective properties. This study was aimed to determine the effect of standardised 80% ethanol extract of GP on lipid profiles and oxidative status of hypercholesterolemic rats. Postmenopausal (PM) Sprague-Dawley rats were ovariectomised and fed with 2% cholesterol diet fortified with five times heated palm oil to develop hyperlipidaemia status. Two doses of the extract (250 and 500 mg/kg) and atorvastatin (10 mg/kg) were administered once daily via oral gavage for 24 weeks. Systolic blood pressure (SBP) was increased during the first month in the postmenopausal group and decreased with GP supplementation. Lipid droplets accumulation was shown at the tunica media (TM) area of the aorta in the postmenopausal group and reduced with GP supplementation. Total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL), and malondialdehyde (MDA) levels increased (p<0.05) at 3 and 6 months in the postmenopausal group and were reduced with GP supplementation. GP also increased high-density lipoprotein (HDL) level in the postmenopausal group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were reduced in the postmenopausal group compared to control in the sham group but increased (p<0.05) with GP supplementation. The results showed that the higher dose of GP (500 mg/kg) gave better effect. GP has the ability to reduce oxidative stress and prevent membrane cell damage through antioxidant enzyme activity modification and lipid profile changes in postmenopausal rats related to atherosclerosis.

The syntheses and bioactivities of symmetrical curcumin and its analogues have been the subject of interest by many medicinal chemists and pharmacologists over the years. To improve our understanding, we have synthesized a series of unsymmetrical monocarbonyl curcumin analogues and evaluated their effects on prostaglandin E2 production in lipopolysaccharide-induced RAW264.7 and U937 cells. Initially, compounds 8b and 8c exhibited strong inhibition on the production of PGE2 in both LPS-stimulated RAW264.7 (8b, IC50=12.01μM and 8c, IC50=4.86μM) and U937 (8b, IC50=3.44μM and 8c, IC50=1.65μM) cells. Placing vanillin at position Ar2 further improved the potency when both compounds 15a and 15b significantly lowered the PGE2 secretion level (RAW264.7: 15a, IC50=0.78μM and 15b, IC50=1.9μM while U937: 15a, IC50=0.95μM and 15b, IC50=0.92μM). Further experiment showed that compounds 8b, 8c, 15a and 15b did not target the activity of downstream inflammatory COX-2 mediator. Finally, docking simulation on protein targets COX-2, IKK-β, ERK, JNK2, p38α and p38β were performed using the conformation of 15a determined by single-crystal XRD.

Diabetes mellitus complications mainly occur due to the oxidative stress-related condition. Thus, this study aimed to investigate the protective effect of the polyphenol-rich extract of Hibiscus sabdariffa (roselle) (HPE) on the aorta of streptozotocin-induced diabetic rats. Twenty-four male Sprague-Dawley rats were divided into four groups (n=6/group); non-diabetes control (NDM), diabetes (DM), diabetes treated with HPE (DM+HPE) and metformin (DM+MET). HPE and metformin were given orally at the dose of 100mg/kg and 150mg/kg respectively for eight weeks duration. At the end of the experiment period, blood pressure was measured before the rats were sacrificed. Blood was taken for measurement of plasma glucose and lipid levels whilst aorta was excised for oxidative stress and histological evaluation. Results showed that HPE treatment reduced plasma glucose level, blood pressure and improved dyslipidemia significantly (p

Oxidised 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) induces the production of proinflammatory chemokines has been widely studied for its role in vascular inflammation. There is increasing evidence on the role of chalcones as potential anti-inflammatory agents but less is known about its effects on OxPAPC-induced chemokines production and the involvement of unfolded protein response (UPR) signalling, particularly through XBP1 pathway. The present study sought to investigate the inhibitory potential of synthetic chalcone derivatives on the release of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), induced by OxPAPC through XBP1 signalling pathway on differentiated U-937 macrophages. The effects of synthetic chalcone derivatives on the chemokines productions were investigated using enzyme-linked immunosorbent assays, while the inhibitions of XBP1 signalling were detected using western immunoblot. Results show that all the three tested synthetic chalcone derivatives inhibited OxPAPC-induced chemokines production in a concentration-dependent manner. Compound 1.5 exhibited the strongest inhibition of IL-8 and MCP-1 at 61.4 ± 4.23% and 63.8 ± 2.16%, respectively. Compound 1.5 also achieved the lowest IC50 values for both IL-8 (18.33 ± 1.59 μM) and MCP-1 (13.05 ± 1.37 μM) inhibitions. For XBP1 protein expression, both compound 1.4 and 1.5 exhibited significant concentration-dependent suppression of the protein expressions. The results suggest that synthetic chalcone derivatives may serve as potential alternatives for future development of anti-inflammatory agents, particularly in vascular inflammation.

Aims Obesity increase the risks of hypertension and myocardial infarction (MI) mediated by oxidative stress. This study was undertaken to investigate the actions of roselle aqueous extract (R) on cardiotoxicity in obese (OB) rats and thereon OB rats subjected to MI. Main methods Male Sprague-Dawley rats were fed with either normal diet or high-fat diet for 8 weeks. Firstly, OB rats were divided into (1) OB and (2) OB + R (100 mg/kg, p.o, 28 days). Then, OB rats were subjected to MI (ISO, 85 mg/kg, s.c, 2 days) and divided into three groups: (1) OB + MI, (2) OB + MI + R and (3) OB + MI + enalapril for another 4 weeks. Key findings Roselle ameliorated OB and OB + MI's cardiac systolic dysfunction and reduced cardiac hypertrophy and fibrosis. The increased oxidative markers and decreased antioxidant enzymes in OB and OB + MI groups were all attenuated by roselle. Significance These observations indicate the protective effect of roselle on cardiac dysfunction in OB and OB + MI rats, which suggest its potential to be developed as a nutraceutical product for obese and obese patients with MI in the future.

Lipidome profile of fluids and tissues is a growing field as the role of lipids as signaling molecules is increasingly understood, relying on an effective and representative extraction of the lipids present. A number of solvent systems suitable for lipid extraction are commonly in use, though no comprehensive investigation of their effectiveness across multiple lipid classes has been carried out. To address this, human LDL from normolipidemic volunteers was used to evaluate five different solvent extraction protocols [Folch, Bligh and Dyer, acidified Bligh and Dyer, methanol (MeOH)-tert-butyl methyl ether (TBME), and hexane-isopropanol] and the extracted lipids were analyzed by LC-MS in a high-resolution instrument equipped with polarity switching. Overall, more than 350 different lipid species from 19 lipid subclasses were identified. Solvent composition had a small effect on the extraction of predominant lipid classes (triacylglycerides, cholesterol esters, and phosphatidylcholines). In contrast, extraction of less abundant lipids (phosphatidylinositols, lyso-lipids, ceramides, and cholesterol sulfates) was greatly influenced by the solvent system used. Overall, the Folch method was most effective for the extraction of a broad range of lipid classes in LDL, although the hexane-isopropanol method was best for apolar lipids and the MeOH-TBME method was suitable for lactosyl ceramides.

Oxidized and chlorinated phospholipids are generated under inflammatory conditions and are increasingly understood to play important roles in diseases involving oxidative stress. MS is a sensitive and informative technique for monitoring phospholipid oxidation that can provide structural information and simultaneously detect a wide variety of oxidation products, including chain-shortened and -chlorinated phospholipids. MSn technologies involve fragmentation of the compounds to yield diagnostic fragment ions and thus assist in identification. Advanced methods such as neutral loss and precursor ion scanning can facilitate the analysis of specific oxidation products in complex biological samples. This is essential for determining the contributions of different phospholipid oxidation products in disease. While many pro-inflammatory signalling effects of oxPLs (oxidized phospholipids) have been reported, it has more recently become clear that they can also have anti-inflammatory effects in conditions such as infection and endotoxaemia. In contrast with free radical-generated oxPLs, the signalling effects of chlorinated lipids are much less well understood, but they appear to demonstrate mainly pro-inflammatory effects. Specific analysis of oxidized and chlorinated lipids and the determination of their molecular effects are crucial to understanding their role in disease pathology.

The immune system is the defense mechanism in living organisms that protects against the invasion of foreign materials, microorganisms, and pathogens. It involves multiple organs and tissues in human body, such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. However, the execution of immune activities depends on a number of specific cell types, such as B cells, T cells, macrophages, and granulocytes, which provide various immune responses against pathogens. In addition to normal physiological functions, abnormal proliferation, migration, and differentiation of these cells (in response to various chemical stimuli produced by invading pathogens) have been associated with several pathological disorders. The unwanted conditions related to these cells have made them prominent targets in the development of new therapeutic interventions against various pathological implications, such as atherosclerosis and autoimmune diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological activities, such as immunomodulation, as well as anti-inflammatory, anticancer, antiviral, and antimicrobial properties. Many studies have been conducted to determine their inhibitory or stimulatory activities in immune cells, and the findings are of significance to provide a new direction for subsequent research. This review highlights the effects of chalcone derivatives in different types of immune cells.

Lipid peroxidation products like malondialdehyde, 4-hydroxynonenal and F2-isoprostanes are widely used as markers of oxidative stress in vitro and in vivo. This study reports the results of a multi-laboratory validation study by COST Action B35 to assess inter-laboratory and intra-laboratory variation in the measurement of lipid peroxidation. Human plasma samples were exposed to UVA irradiation at different doses (0, 15 J, 20 J), encoded and shipped to 15 laboratories, where analyses of malondialdehyde, 4-hydroxynonenal and isoprostanes were conducted. The results demonstrate a low within-day-variation and a good correlation of results observed on two different days. However, high coefficients of variation were observed between the laboratories. Malondialdehyde determined by HPLC was found to be the most sensitive and reproducible lipid peroxidation product in plasma upon UVA treatment. It is concluded that measurement of malondialdehyde by HPLC has good analytical validity for inter-laboratory studies on lipid peroxidation in human EDTA-plasma samples, although it is acknowledged that this may not translate to biological validity. © 2010 Informa UK, Ltd.

Conclusion: There was an 11.4% trend towards reduced TAR and 21.4% reduction in bilateral radial artery use in patients who underwent radial access angiography. This study was limited by its sample size and ongoing dataset expansion will provide more robust statistical analysis. Given TAR is proposed as having greater long-term graft patency then there may be a need to review current practice. Further studies on graft patency outcomes in patients who have had radial artery grafting after RA will provide important clinical information. Disclosure of Interest: None Declared

More than 25 years ago, it was proposed that the inflammatory disease atherosclerosis arises as a response of vascular wall to endothelial injury and many studies showed that this injury could be due to endothelial apoptosis. As a result of vascular inflammation, oxidized and chlorinated lipids are generated and are thought to be a primary risk factor in the progression of atherosclerosis. There are extensive studies on the biological effects of oxidized phospholipids (oxPAPC) in vascular cells including smooth muscle cells and endothelial cells and more recently, analysis of individual oxidized species, 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC). For instance, oxPAPC has been shown to induce production of IL-8, MCP-1 /MIP-2 and expression of E-selectin in myeloid and endothelial cells (Erridge et al., 2007), whilst POVPC increases monocyte binding to endothelial cells, by inducing the surface expression of connecting segment-1 domain of fibronectin (Leitinger et al., 1999). Oxidized phospholipids can also have anti-inflammatory effects; OxPAPC prevents TLR-2 and 4 activation by lipopolysaccharide and Pam3CSK4 (Erridge et al., 2008). In comparison however, little is known about effects of chlorinated lipids on vascular function. To investigate this, the effect of chlorinated lipids upon NFkB and MAP kinase signaling was studied in HUVECs. Oxidized phospholipids such as oxPAPC, PGPC and POVPC (5–50 μM) and chlorinated lipids including SOPC chlorohydrins and 2-Chlorohexadecanal (5–50 μM) were assessed for IκB-α degradation and phosphorylation of ERK, p38 and JNK, by Western blotting. Results showed that SOPC chlorohydrin and 2-chlorohexadecanal alone did not induce phoshorylation of NFkB and MAPK nor inhibit IκB-α degradation induced by LPS and TNF-α. In contrast, oxidized phospholipids such as oxPAPC inhibited IκB-α degradation induced by LPS but not TNF-α, a result which is in agreement with a previous study (Bochkov et al., 2002). Preliminary studies used microscopy to investigate the effect of oxidized and chlorinated lipids on cellular integrity of endothelial cells. Interestingly, treatment of chlorinated lipids (50–100 μM) induced cell death and this was potentiated in the presence of TNF-α. These results demonstrate that chlorinated lipids may produce pro-atherogenic effects but do not appear to regulate endothelial cell function in the same way as oxidized phospholipids.