Antioxidant and antiinflammatory activity of pine pollen extract in vitro

To determine the medicinal properties of pine pollen, the antioxidant and antiinflammatory activities of the ethanol extract of pine pollen extract (PPE) were investigated. PPE displayed a strong free radical scavenger activity on 1,1‐diphenyl‐2‐picrylhydrazyl radical and hydrogen peroxide. It was observed also that the antioxidant activity, measured by the ferric thiocyanate method, increased with the addition of PPE to the linoleic acid emulsion system. PPE was also found to inhibit significantly the amount of malondialdehyde and protein carbonyls formed from liver homogenate. Like the antioxidant activity, the reducing power of PPE was excellent. Thereafter, the study investigated the effects of PPE in modulating the production of pro‐inflammatory mediators in lipopolysaccharide (LPS)‐activated RAW 264.7 macrophages, and the effect of PPE on interleukin (IL)‐1β‐induced matrix metalloproteinases (MMPs) production and mitogen‐activated protein kinases (MAPKs) activation in the human synovial sarcoma cell line, SW982. PPE was found to inhibit the production of nitric oxide, tumor necrosis factor‐α, IL‐1 and IL‐6 in LPS‐activated macrophages. Treatment with PPE at 10 µg/mL significantly (p < 0.05) inhibited IL‐1β‐induced MMPs (MMP‐1 and ‐3) production in SW982 cells. IL‐1β‐induced JNK activation was inhibited by PPE (10 µg/mL), whereas p38 and ERK1/2 were not affected. These findings suggest that pine pollen is a potential antioxidant and beneficial for inflammatory conditions through down‐regulation of JNK and MMPs. Copyright © 2008 John Wiley & Sons, Ltd.     

Nimbolide Inhibits Nuclear Factor‐КB Pathway in Intestinal Epithelial Cells and Macrophages and Alleviates Experimental Colitis in Mice

Nimbolide is a limonoid extracted from neem tree (Azadirachta indica) that has antiinflammatory properties. The effect of nimbolide on the nuclear factor‐kappa B (NF‐κB) pathway in intestinal epithelial cells (IECs), macrophages and in murine colitis models was investigated. The IEC COLO 205, the murine macrophage cell line RAW 264.7, and peritoneal macrophages from interleukin‐10‐deficient (IL‐10^?/?) mice were preconditioned with nimbolide and then stimulated with tumor necrosis factor‐α (TNF‐α) or lipopolysaccharide. Dextran sulfate sodium‐induced acute colitis model and chronic colitis model in IL‐10^?/? mice were used for in vivo experiments. Nimbolide significantly suppressed the expression of inflammatory cytokines (IL‐6, IL‐8, IL‐12, and TNF‐α) and inhibited the phosphorylation of IκBα and the DNA‐binding affinity of NF‐κB in IECs and macrophages. Nimbolide ameliorated weight loss, colon shortening, disease activity index score, and histologic scores in dextran sulfate sodium colitis. It also improved histopathologic scores in the chronic colitis of IL‐10^?/? mice. Staining for phosphorylated IκBα was significantly decreased in the colon tissue after treatment with nimbolide in both models. Nimbolide inhibits NF‐κB signaling in IECs and macrophages and ameliorates experimental colitis in mice. These results suggest nimbolide could be a potentially new treatment for inflammatory bowel disease. Copyright © 2016 John Wiley & Sons, Ltd.     

Antioxidant capacity of Melampyrum barbatum – weed and medicinal plant

This study was designed to examine antioxidant and free radical scavenging activities of red and yellow forms of Melampyrum barbatum L. In this study, we report the results concerning flower and leaf antioxidant enzyme activities (superoxide dismutase, catalase, guaiacol peroxidase and glutathione peroxidase), reduced glutathione quantity, flavonoids, photosynthetic pigments and soluble protein contents and quantities of malonyldialdehyde, ^?OH and O₂^?? radicals; total antioxidant capacity was determined by FRAP (Ferric Reducing Antioxidant Power) method and scavenger activity by DPPH (1,1‐diphenyl‐2‐pycril‐hydrasil radical) method. Lipofuscin ‘plant age pigments’ were also determined. According to our results, flowers of the red form of M. barbatum exhibited the highest antioxidant capacity. Copyright © 2009 John Wiley & Sons, Ltd.     

Myrislignan Attenuates Lipopolysaccharide‐induced Inflammation Reaction in Murine Macrophage Cells Through Inhibition of NF‐κB Signalling Pathway Activation

Myrislignan is a new kind of lignan isolated from Myristica fragrans Houtt. Its antiinflammatory effects have not yet been reported. In the present study, the antiinflammatory effects and the underlying mechanisms of myrislignan in lipopolysaccharide (LPS)‐induced inflammation in murine RAW 264.7 macrophage cells were investigated. Myrislignan significantly inhibited LPS‐induced production of nitric oxide (NO) in a dose‐dependent manner. It inhibited mRNA expression and release of interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α). This compound significantly inhibited mRNA and protein expressions of inducible NO synthase (iNOS) and cyclooxygenase‐2 (COX‐2) dose‐dependently in LPS‐stimulated macrophage cells. Further study showed that myrislignan decreased the cytoplasmic loss of inhibitor κB‐α (IκB‐α) protein and the translocation of NF‐κB from cytoplasm to the nucleus. Our results suggest that myrislignan may exert its antiinflammatory effects in LPS‐stimulated macrophages cells by inhibiting the NF‐κB signalling pathway activation. Copyright © 2012 John Wiley & Sons, Ltd.     

Ethanol extract of Prunella vulgaris var. lilacina inhibits HMGB1 release by induction of heme oxygenase-1 in LPS-activated RAW 264.7 cells and CLP-induced septic mice

The ethanol extract of the flower of P. vulgaris var. lilacina (EEPV) has been used traditionally as an antiinflammatory agent in many countries. Inducers of heme oxygenase‐1 (HO‐1) reduce high mobility group box 1 (HMGB1), a late phase cytokine, in sepsis. Although EEPV has been used as an antiinflammatory agent, no report is available as to whether it modifies HMGB1 in sepsis due to HO‐1 induction. It was found that EEPV increased HO‐1 protein expression in RAW 264.7 cells, which was significantly inhibited by LY294002, but not PD98059, SB203580 or SP600125. In addition, EEPV activated NF‐E2‐related factor (Nrf2) to move from the cytosol to the nucleus, and EEPV‐induced HO‐1 and activation of ARE‐luciferase activity were significantly reduced by siNrf2 transfection and LY294002 but not SB203508. EEPV also significantly inhibited NF‐κB luciferase activity, and decreased both iNOS/NO and COX‐2/PGE₂ production in lipopolysaccharide (LPS)‐stimulated macrophages which was reversed by siHO‐1 RNA transfection. Importantly, EEPV inhibited HMGB1 release in LPS‐activated macrophages in a PI3K‐sensitive manner and reduced serum HMGB1 level and lung HMGB1 expression in cecal ligation and puncture (CLP)‐induced septic mice. It is concluded that EEPV induces HO‐1 expression through PI3K/Nrf2 signal pathways, which may be beneficial for the treatment of sepsis due to a reduction of HMGB1 release. Copyright © 2011 John Wiley & Sons, Ltd.     

Antioxidant activity of yellow dock (Rumex crispus L., Polygonaceae) fruit extract

The methanol extract of ripe Rumex crispus L. fruits was evaluated for its antioxidant potential by assays for ferric‐reducing antioxidant power (FRAP), DPPH‐free radical scavenging activity (DPPH) and the influence on lipid peroxidation in liposomes (LP). Considerable activity was observed in all test systems (FRAP: 9.9 mmol Fe²⁺/g; DPPH IC₅₀: 3.7 μg/mL; LP IC₅₀: 4.9 μg/mL), comparable to that of BHT (FRAP: 8.0 μg/mL; DPPH IC₅₀: 19.4 μg/mL; LP IC₅₀: 3.5 μg/mL), but lower than the activity of ascorbic acid, rutin and quercetin, used as positive control substances. The in vivo effects were evaluated in several hepatic antioxidant systems (activities of LPx, GSH‐Px, Px, CAT and XOD, as well as GSH content), after treatment with the studied yellow dock extract in different doses, or in combination with carbon tetrachloride (CCl₄). Pretreatment with the R. crispus extract inhibited CCl₄‐induced oxidative stress by decreasing LPx and increasing GSH content in a dose dependent manner, bringing the levels of antioxidant enzymes to near control values. Copyright © 2010 John Wiley & Sons, Ltd.     

Down‐regulatory effect of usnic acid on nuclear factor‐κB‐dependent tumor necrosis factor‐α and inducible nitric oxide synthase expression in lipopolysaccharide‐stimulated macrophages RAW 264.7

The purpose of this study was to investigate the molecular mechanisms that are responsible for the antiinflammatory effect of usnic acid (UA). UA is one of the most common and abundant lichen metabolites. The present study examined the effects of UA on the tumor necrosis factor‐α (TNF‐α) and nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages and the underlying molecular mechanisms. UA decreased the TNF‐α level in LPS‐stimulated RAW264.7 macrophages in dose‐dependent manner, the IC₅₀ value was 12.8 µM. RT‐PCR analysis indicated that it inhibited TNF‐α mRNA expression. Furthermore, it inhibited NO production in LPS‐activated RAW264.7 macrophages, the IC₅₀ value was 4.7 µM. Western blot analysis showed that UA attenuated LPS‐induced synthesis of iNOS protein and nuclear translocation of NF‐κB p65 in the macrophages, in parallel. UA also inhibited LPS‐mediated I‐κBα degradation. Taken together, this suggests that UA has an antiinflammatory effect by inhibiting TNF‐α and iNOS expression, possibly through suppression of nuclear translocation of NF‐κB p65 and I‐κBα degradation. Copyright © 2008 John Wiley & Sons, Ltd.     

Safranal of Crocus sativus L. Inhibits Inducible Nitric Oxide Synthase and Attenuates Asthma in a Mouse Model of Asthma

The present study involves evaluation of antioxidant potential of Crocus sativus and its main constituents, safranal (SFN) and crocin (CRO), in bronchial epithelial cells, followed antiinflammatory potential of the active constituent safranal, in a murine model of asthma. To investigate the antioxidizing potential of Crocus sativus and its main constituents in bronchial epithelial cells, the stress was induced in these cells by a combination of different cytokines that resulted in an increase in nitric oxide production (NO), induced nitric oxide synthase (iNOS) levels, peroxynitrite ion generation, and cytochrome c release. Treatment with saffron and its constituents safranal and crocin resulted in a decrease of NO, iNOS levels, peroxynitrite ion generation, and prevented cytochrome c release. However, safranal significantly reduced oxidative stress in bronchial epithelial cells via iNOS reduction besides preventing apoptosis in these cells. In the murine model of asthma study, antiinflammatory role of safranal was characterized by increased airway hyper‐responsiveness, airway cellular infiltration, and epithelial cell injury. Safranal pretreatment to these allergically inflamed mice lead to a significant decrease in airway hyper‐responsiveness and airway cellular infiltration to the lungs. It also reduced iNOS production, bronchial epithelial cell apoptosis, and Th2 type cytokine production in the lungs. Copyright © 2015 John Wiley & Sons, Ltd.     

Effect of Trimeric Myricetin Rhamnoside (TMR) in Carrageenan‐induced Inflammation and Caecal Ligation and Puncture‐induced Lung Oxidative Stress in Mice

The Eugenia jambolana is used in folklore medicine. Leaves of E. jambolana contain flavonoids as their active constituents which possess in vitro antiinflammatory, antioxidant and the antimicrobial activity. The aim of the present study was to investigate the antiinflammatory and antioxidant effects of a flavonoid glucoside, trimeric myricetin rhamnoside (TMR) isolated from leaves of E. jambolana. TMR was studied for antiinflammatory activity in carrageenan‐induced hind paw oedema and antioxidant activity in lung by caecal ligation and puncture (CLP)‐induced sepsis in mice. Results of the present study indicated that TMR significantly attenuated the oedema, myeloperoxidase (MPO), cytokines and prostaglandin levels in the paw after 5 h of carrageenan injection as compared to vehicle control. It also reduced the lung MPO, lipid peroxides, and serum nitrite plus nitrate levels and increased lung reduced glutathione levels 20 h of CLP as compared to vehicle control. Thus the results of this study concluded that the TMR appears to have potential benefits in diseases that are mediated by both inflammation and oxidative stress and support the pharmacological basis of use of E. jambolana plant as traditional herbal medicine for the treatment of inflammatory diseases. Copyright © 2015 John Wiley & Sons, Ltd.     

Analgesic and antiinflammatory activity of kaur-16-en-19-oic acid from Annona reticulata L. bark

Kaur‐16‐en‐19‐oic acid was isolated from the bark of Annona reticulata and studied for its analgesic and antiinflammatory activity. Analgesic activity was assessed using the hot plate test and acetic acid‐induced writhing, and the antiinflammatory activity using the carrageenan induced rat paw oedema method. Kaur‐16‐en‐19‐oic acid, at doses of 10 and 20 mg/kg, exhibited significant (p < 0.05) analgesic and antiinflammatory activity. These activities were comparable to the standard drugs used, and furthermore the analgesic effect of kaur‐16‐en‐19‐oic acid was blocked by naloxone (2 mg/kg) in both analgesic models. Copyright © 2011 John Wiley & Sons, Ltd.     

Antiinflammatory effects of Epimedium brevicornum water extract on lipopolysaccharide‐activated RAW264.7 macrophages

Epimedium brevicornum Maxim (Berberidaceae) possesses estrogenic properties. It is one of the most widespread herbal remedies used in Oriental medicine. The present study investigated the effects of Epimedium brevicornum water extract (EB) on proinflammatory mediators secreted from lipopolysaccharide (LPS)‐induced RAW264.7 macrophages. EB significantly inhibited the production of nitric oxide (NO), interleukin (IL)‐3, IL‐10, IL‐12p40, interferon‐inducible protein‐10, keratinocyte‐derived chemokine, vascular endothelial growth factor, monocyte chemotactic protein‐1 and granulocyte macrophage‐colony stimulating factor in LPS‐induced RAW264.7 cells at concentrations of 25, 50, 100 and 200 μg/mL (p < 0.05). These results suggest that EB has antiinflammatory activity related to its inhibition of NO, cytokine, chemokine and growth factor production in macrophages. Copyright © 2010 John Wiley & Sons, Ltd.     

Nephroprotective Effects of Anthocyanin from the Fruits of Panax ginseng (GFA) on Cisplatin‐Induced Acute Kidney Injury in Mice

Cisplatin is an effective anticancer chemotherapeutic agent, but the use of cisplatin in the clinic is severely limited by side effects. Nephrotoxicity is a major factor that contributes to the side effects of cisplatin chemotherapy. The aim of this research was to survey the nephroprotective effects of anthocyanin from the fruits of Panax ginseng (GFA) in a murine model of cisplatin‐induced acute kidney injury. We observed that pretreatment with GFA attenuated cisplatin‐induced elevations in blood urea nitrogen and creatinine levels and histopathological injury induced by cisplatin. The formation of kidney malondialdehyde, heme oxygenase‐1, cytochrome P450 E1 and 4‐hydroxynonenal with a concomitant reduction in reduced glutathione was also inhibited by GFA, while the activities of kidney superoxide dismutase and catalase were all increased. GFA also inhibited the increase in serum tumour necrosis factor‐α and interleukin‐1β induced by cisplatin. In addition, the levels of induced nitric oxide synthase and cyclooxygenase‐2 were suppressed by GFA. Furthermore, GFA supplementation inhibited the activation of apoptotic pathways by increasing B cell lymphoma 2 and decreasing Bcl2‐associated X protein expression. In conclusion, the findings from the present investigation demonstrate that GFA pre‐administration can significantly prevent cisplatin‐induced nephrotoxicity, which may be related to its antioxidant, anti‐apoptotic and antiinflammatory effects. Copyright © 2017 John Wiley & Sons, Ltd.     

The Antioxidant and Anticancer Effects of Wild Carrot Oil Extract

Daucus carota L. ssp. carota (Apiacea) is used in traditional medicine in Lebanon and in different regions throughout the world. The present study investigates the in vitro anticancer activities of Daucus carota oil extract (DCOE) on four human cancer cell lines as well as its in vitro antioxidant activity. DCOE was extracted from the dried umbels with 50:50 acetone‐methanol. The oil extract was analyzed by gas chromatography–mass spectrometry and screened for its antioxidant properties in vitro using 1,1‐diphenyl‐2‐picryl hydrazyl free radical scavenging assay (DPPH), ferrous ion chelating assay (FIC) and the ferric reducing antioxidant power assay (FRAP). The anticancer activity of the oil extract against human colon (HT‐29, Caco‐2) and breast (MCF‐7, MDA‐MB‐231) cancer cell lines was evaluated using the trypan blue exclusion method and the WST‐1 cell proliferation assay. DCOE exhibited antioxidant activity in all assays used. The FRAP value was 164 ± 5.5 µmol FeSO₄/g, and the IC₅₀ values for DPPH and FIC assays were 2.1 ± 0.03 mg/ml and 0.43 ± 0.02 mg/ml, respectively. Also, DCOE demonstrated a significant increase in cell death and decrease in cell proliferation. The effect of DCOE on the cell lines exhibited time and dose‐dependent responses. The present study established that DCOE possesses both antioxidant and promising anticancer activities. Copyright © 2012 John Wiley & Sons, Ltd.     

Antiinflammatory and antinociceptive activities of gossypin and procumbentin – cyclooxygenase‐2 (COX‐2) inhibition studies

In the present study the antiinflammatory and antinociceptive activities of a few selected flavonoids were investigated. Procumbentin, gossypin, chrysin and methylhespiridin were studied for antiinflammatory and antinociceptive activities using in vitro enzymatic assays and in animal models utilizing acetic acid‐induced writhing in mice and hind paw edema in rats. In vitro studies were performed using TMPD (NNN′N′‐tetramethyl‐p‐phenylene diamine) and oxygraphic methods for COX‐1 (cyclooxygenase‐1), COX‐2, 5‐LOX (5‐lipoxygenase) and 15‐LOX. Gossypin and procumbentin showed COX‐2 inhibitory activity and exhibited IC₅₀ (COX‐2/COX‐1) ratios of 0.14 and 0.11, respectively. None of the flavonoids tested in this study showed LOX inhibitory activity. Four groups were studied for each test compound following intraperitoneal (i.p.) administration of doses of 10, 30 and 100 mg/kg. Antiinflammatory activity was measured by the carrageenin‐induced rat hind paw edema model and antinociceptive activity by acetic acid‐induced writhing. Procumbentin and gossypin showed antinociceptive activity at the 100 mg/kg dose. Gossypin showed antiinflammatory activity at doses of 10, 30, 100 mg/kg. Procumbentin and gossypin exhibited COX‐2 inhibitory activity when tested by in vitro methods. Procumbentin and gossypin showed antinociceptive, and gossypin showed antiinflammatory, activities. Copyright © 2008 John Wiley & Sons, Ltd.     

Evaluation of antioxidant,antiinflammatory, and gastroprotective properties of Rubus fruticosus L. fruit juice

The juice of R. fruticosus (RFJ) fruits grown in Sicily was analysed for polyphenol compounds and tested to evaluate in vitro antioxidant and in vivo antiinflammatory and gastroprotective effects. RFJ, containing mainly anthocyanins, such as cyanidin derivatives, significant amounts of phenolic acids, and smaller amounts of flavonoids, showed significant antioxidant activity in DPPH (2,2‐diphenyl‐1‐picrylhydrazyl radical) (4,147.194 ± 17.199 mg trolox equivalent [TE]/100 ml), TE antioxidant capacity (8,312.444 ± 43.055 mg TE/100 ml), ferric reducing antioxidant power (2,177.830 ± 21.015 mg TE/100 ml), oxygen radical absorbance capacity (95,377.674 ± 616.194 μmol TE/100 ml juice), and β‐carotene bleaching (72% ± 4.58) assay. In vivo studies showed that RFJ inhibit significantly the carrageenan‐induced paw oedema (63–71%) in rats and possess antiinflammatory effects particularly significant in association with phenylbutazone (94–96%). In addition, RFJ pretreatment was able to prevent the ethanol‐induced ulcerogenic effect in rats. All in vivo results were corroborated by histopathological observations and are in good agreement with antioxidant activity, confirming the relationships between biological effects observed and radical scavenging properties of RFJ.     

Antiplatelet activity of Phellinus baummii methanol extract is mediated by cyclic AMP elevation and inhibition of collagen-activated integrin-α(IIb) β₃ and MAP kinase

Phellinus baumii is a mushroom that has been used as folk medicine against various diseases and is reported to have antidiabetic, anticancer, antioxidant, antiinflammatory and antihypertensive activities. However, information on the effects of P. baumii extract in platelet function is limited. Therefore, the aim of this study was to examine the impact of a P. baumii methanol extract (PBME) on platelet activation and to investigate the mechanism behind its antiplatelet activity. PBME effects on agonist‐induced platelet aggregation, granule secretion, [Ca²⁺]_i mobilization, α_IIbβ₃ activation, cyclic AMP release and mitogen‐activated protein kinase (MAPK) phosphorylations were studied using rat platelets. PBME dose‐dependently inhibited collagen, thrombin and ADP‐induced platelet aggregation with an IC₅₀ of 51.0 ± 2.4, 54.0 ± 2.1 and 53.0 ± 4.3 μg/mL, respectively. Likewise, thrombin‐induced [Ca²⁺]_i and collagen‐activated ATP secretions were suppressed in PBME treated platelets. Aggregation and ATP secretion were also markedly attenuated by PBME alone or in combination with PP2 (Src inhibitor) and U‐73122 (PLC inhibitor) in collagen‐stimulated platelets. Besides, PBME treatment elevated basal cyclic AMP levels and inhibited collagen‐induced integrin‐α_IIbβ₃ activation. Moreover, PBME attenuated extracellular‐signal‐regulated protein kinase 2 (ERK2) and c‐Jun N‐terminal kinase 1 (JNK1) phosphorylations. Further PD98059 (ERK inhibitor) and SP60025 (JNK inhibitor) reduced collagen‐induced platelet aggregation and ATP secretion. In conclusion, the observed PBME antiplatelet activity may be mediated by activation of cyclic AMP and inhibition of ERK2 and JNK1 phosphorylations. Finally, these data suggest that PBME may have therapeutic potential for the treatment of cardiovascular diseases that involve aberrant platelet function. Copyright © 2011 John Wiley & Sons, Ltd.     

Praeruptorin a inhibits lipopolysaccharide‐induced inflammatory response in murine macrophages through inhibition of NF‐κB pathway activation

Praeruptorin A (PA) is a pyranocoumarin compound isolated from the dried root of Peucedanum praeruptorum Dunn (Umbelliferae). However, the antiinflammatory effect of PA has not been reported. The present study investigated the antiinflammatory effect of PA in lipopolysaccharide (LPS)‐stimulated RAW 264.7 macrophage cells. PA significantly inhibited the LPS‐induced production of nitric oxide (NO), interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α). The mRNA and protein expressions of inducible nitric oxide synthase (iNOS), IL‐1β and TNF‐α were also suppressed by this compound. Further study showed that PA decreased the cytoplasmic loss of inhibitor κB‐α (IκB‐α) protein and inhibited the translocation of NF‐κB from cytoplasm to nucleus. Taken together, the results suggest that PA may exert antiinflammatory effects in vitro in LPS‐stimulated RAW 264.7 macrophages through inhibition of NF‐κB signal pathway activation. Copyright © 2010 John Wiley & Sons, Ltd.