Anti-inflammatory activities of mogrosides from Momordica grosvenori in murine macrophages and a murine ear edema model

Momordica grosvenori (Luo Han Guo), grown primarily in Guangxi province in China, has been traditionally used for thousands of years by the Chinese to make hot drinks for the treatment of sore throat and the removal of phlegm. The natural noncaloric sweetening triterpenoid glycosides (mogrosides) contained in the M. grosvenori fruits are also antioxidative, anticarcinogenic, and helpful in preventing diabetic complications. The aim of this study was to assess the anti-inflammatory properties of mogrosides in both murine macrophage RAW 264.7 cells and a murine ear edema model. The results indicate that mogrosides can inhibit inflammation induced by lipopolysaccharides (LPS) in RAW 264.7 cells by down-regulating the expression of key inflammatory genes iNOS, COX-2, and IL-6 and up-regulating some inflammation protective genes such as PARP1, BCL2l1, TRP53, and MAPK9. Similarly, in the murine ear edema model, 12-O-tetradecanoylphorbol-13-acetate-induced inflammation was inhibited by mogrosides by down-regulating COX-2 and IL-6 and up-regulating PARP1, BCL2l1, TRP53, MAPK9, and PPARδ gene expression. This study shows that the anticancer and antidiabetic effects of M. grosvenori may result in part from its anti-inflammatory activity.     

Isolation and characterization of two flavonoids, engeletin and astilbin, from the leaves of Engelhardia roxburghiana and their potential anti-inflammatory properties

Engeletin, a flavonoid compound, was isolated from the leaves of Engelhardia roxburghiana for the first time, along with astilbin, another flavonoid. The chemical structures of engeletin and astilbin were confirmed by (1)H and (13)C nuclear magnetic resonance (NMR) and mass spectrometry (MS) spectra, and their anti-inflammatory activities were studied in lipopolysaccharide (LPS)-stimulated mouse J774A.1 macrophage cells. LPS induced the inflammatory state in macrophage cells and increased mRNA expressions of pro-inflammatory cytokines. Engeletin and astilbin exhibited remarkable inhibitory effects on interleukin (IL)-1β and IL-6 mRNA expression. Significant inhibition of LPS-mediated mRNA expressions were also seen in LPS binding toll-like receptor (TLR)-4, pro-inflammatory cytokine tumor necrosis factor (TNF)-α, IL-10, chemoattractant monocyte chemotactic protein (MCP)-1, and cyclooxygenase (COX)-2 genes. The reduced expression of these cytokines may alleviate immune response and reduce inflammatory activation, indicating that engeletin and astilbin may serve as potential anti-inflammatory agents.     

Cinnamon polyphenol extract regulates tristetraprolin and related gene expression in mouse adipocytes

Cinnamon (Cinnamomum verum) has been widely used in spices, flavoring agents, and preservatives. Cinnamon polyphenol extract (CPE) may be important in the alleviation of chronic diseases, but the molecular evidence is not substantial. Tristetraprolin (TTP) family proteins have anti-inflammatory effects through the destabilization of pro-inflammatory mRNAs. TTP expression is reduced in fats of obese people with metabolic syndrome and brains of suicide victims. This study used quantitative real-time PCR to explore the effects of CPE on the regulation of TTP, VEGF, and related gene expression in mouse 3T3-L1 adipocytes. CPE (100 μg/mL) increased TTP mRNA levels by up to 10-fold, and this stimulation was sustained over 16 h. The levels of VEGF mRNA, a putative target of TTP, were decreased 40-50% by CPE. It also affected the expression of other genes coding for ZFP36L1 and ZFP36L3 (TTP homologues), GM-CSF, COX2, IL6, APP, G-CSF, and PAI1. This study demonstrated that CPE rapidly induces TTP mRNA and reduces VEGF mRNA and affects the expression of a number of other genes in the cultured adipocytes.     

Encapsulation of the ethylene inhibitor 1-Methylcyclopropene by cucurbit[6]uril

1-Methylcyclopropene (1-MCP) is an excellent safe and commercially available ethylene antagonist for the preservation of horticultural products. However 1-MCP has to be stored in absorbents due to its gaseous and unstable characteristics. In this paper cucurbit[6]uril (CB[6]) was used as the absorbent to encapsulate 1-MCP, and the resultant inclusion complex was characterized by IR, powder X-ray diffraction, thermal analysis, and fluorescent spectra. The effects of encapsulation conditions on the formation of inclusion complex were also investigated. The amount of 1-MCP encapsulated by CB[6] was about 4.5% by weight when the initial concentration of 1-MCP, encapsulation temperature, CB[6] concentration, and encapsulation time were set at 75 mL/L, 20 °C, 30 mM, and 8 h, respectively. Furthermore, the release of 1-MCP from the complex can be realized with different solutions such as sodium bicarbonate, benzoic acid, and distilled water. CB[6] can be used as an excellent absorbent for encapsulation of 1-MCP.     

Licochalcone a inhibits lipopolysaccharide-induced inflammatory response in vitro and in vivo

Licochalcone A (Lico A), a flavonoid found in licorice root (Glycyrrhiza glabra), is known for its antimicrobial activity and its reported ability to inhibit cancer cell proliferation. In the present study, we found that Lico A exerted potent anti-inflammatory effects in in vitro and in vivo models induced by lipopolysaccharide (LPS). The concentrations of TNF-α, interleukin (IL)-6, and IL-1β in the culture supernatants of RAW 264.7 cells were determined at different time points following LPS administration. LPS (0.5 mg/kg) was instilled intranasally (i.n.) in phosphate-buffered saline to induce acute lung injury, and 24 h after LPS was given, bronchoalveolar lavage fluid was obtained to measure pro-inflammatory mediator and total cell counts. The phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) p65 protein was analyzed by Western blotting. Our results showed that Lico A significantly reduced the amount of inflammatory cells, the lung wet-to-dry weight (W/D) ratio, protein leakage, and myeloperoxidase activity and enhances oxidase dimutase activity in mice with LPS-induced acute lung injury (ALI). Enzyme-linked immunosorbent assay results indicated that Lico A can significantly down-regulate TNF-α, IL-6, and IL-1β levels in vitro and in vivo, and treatment with Lico A significantly attenuated alveolar wall thickening, alveolar hemorrhage, interstitial edema, and inflammatory cells infiltration in mice with ALI. In addition, we further demonstrated that Lico A exerts an anti-inflammation effect in an in vivo model of acute lung injury through suppression of NF-κB activation and p38/ERK MAPK signaling in a dose-dependent manner.     

外源一氧化氮协同1-甲基环丙烯处理对水蜜桃常温贮藏品质及活性氧代谢的影响研究

为探讨外源一氧化氮(NO)协同1-甲基环丙烯(1-MCP)处理对水蜜桃常温贮藏品质、活性氧代谢及其对货架期的影响,本研究以湖景蜜露水蜜桃为试材,采用0.5 μL·L-1 1-MCP、25 μmol·L-1硝普钠水溶液浸泡(NO)、1-MCP协同NO(NO+1-MCP)共3种处理方式,将其置于28±2℃室温中贮藏7 d....     

Andrographolide inhibits ICAM-1 expression and NF-κB activation in TNF-α-treated EA.hy926 cells

Several lines of evidence indicate that inflammation and endothelial cell dysfunction are important initiating events in atherosclerosis. Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, induces the expression of cell adhesion molecules and results in monocyte adherence and atheromatous plaque formation. Andrographolide (AP) is a major bioactive diterpene lactone in Andrographis paniculata that has anti-inflammatory activity. A previous study demonstrated the role of heme oxygenase 1 (HO-1) in the inhibition of TNF-α-induced ICAM-1 expression by AP. The present study investigated the effect of AP on the IKK/NF-κB signaling pathway, which mediates TNF-α-induced ICAM-1 expression in EA.hy926 cells. Similar to the previous study, AP inhibited TNF-α-induced ICAM-1 mRNA and protein levels, its expression on the cell surface, and subsequent adhesion of HL-60 cells to EA.hy926 cells. AP inhibited TNF-α-induced κB inhibitor (IκB) kinase (IKK) and IκBα activation, p65 nuclear translocation, NF-κB and DNA binding activity, and promoter activity of ICAM-1. Although AP increased the intracellular cAMP concentration and induced the phosphorylation of cAMP response element-binding protein (CREB), knocking down CREB protein expression by transfecting the cells with CREB-specific small interfering RNA did not relieve the inhibition of ICAM-1 expression by AP. Taken together, these results suggest that AP down-regulates TNF-α-induced ICAM-1 expression at least in part via attenuation of activation of NF-κB in EA.hy926 cells rather than through activation of CREB. The results suggest that AP may have potential as a cardiovascular-protective agent.     

Inhibition of inducible nitric oxide synthase expression by an acetonic extract from Feijoa sellowiana Berg. fruits

Feijoa sellowiana Berg. fruits and especially the acetonic extract have been shown to possess biological activities, although the responsible compounds have never been identified. The present study was designed to evaluate the anti-inflammatory activity of an acetonic extract from F. sellowiana Berg. fruits on the nitric oxide (NO) pathway, which plays an important role in inflammation. To this aim the J774 cell line, which expresses inducible nitric oxide synthase (iNOS) following stimulation with lipopolysaccharide (LPS), has been utilized, and the effects of this extract and its fractions on NO production, iNOS protein expression, and signal pathways involved in its regulation have been evaluated. This study demonstrates that at least some part of the anti-inflammatory activity of the acetonic extract is due to the suppression of NO production by flavone and stearic acid. The mechanism of this inhibition seems to be related to an action on the expression of the enzyme iNOS through the attenuation of nuclear factor kappaB (NF-kappaB) and/or mitogen-activated protein kinase (MAPK) activation.     

Five bitter compounds display different anti-inflammatory effects through modulating cytokine secretion using mouse primary splenocytes in vitro

Bitter foods are generally recognized as anti-inflammatory agents in traditional Chinese medicine. To verify the anti-inflammatory effects of some bitter compounds in foods or plants, five bitter compounds, aloperine, amygdalin, berberine, crotaline, and naringenin, were selected and added to primary mouse splenocytes in the absence or presence of lipopolysaccharide (LPS) under four different in vitro experimental models. Anti-inflammatory cytokine secretions such as interleukin (IL)-10 and pro-inflammatory cytokines such as IL-6 as well as tumor necrosis factor (TNF)-α were determined using enzyme-linked immunosorbent assay (ELISA). The results showed that all selected bitter compounds except amygdalin exhibited apparent cytotoxic effects. On the basis of changes in the secretion profiles between anti- and pro-inflammatory cytokines, the five selected bitter compounds demonstrated anti-inflammatory activities via modulating either IL-6/IL-10 or TNF-α/IL-10 ratios at noncytotoxic doses. Berberine and naringenin treatments showed the strongest potential for anti-inflammation among the five selected bitter compounds. Berberine especially displayed strong anti-inflammatory activity in both preventive and repair manners.     

Tangeretin reduces ultraviolet B (UVB)-induced cyclooxygenase-2 expression in mouse epidermal cells by blocking mitogen-activated protein kinase (MAPK) activation and reactive oxygen species (ROS) generation

The present study examined the effects of tangeretin, a polymethoxylated flavonone present in citrus fruits, on ultraviolet B (UVB)-induced cyclooxygenase-2 (COX-2) expression in JB6 P+ mouse skin epidermal cells. Tangeretin suppressed UVB-induced COX-2 expression and transactivation of nuclear factor-κB and activator protein-1 in JB6 P+ cells. Moreover, tangeretin blocked UVB-induced phosphorylation of Akt and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase, c-Jun N-terminal kinase, and p38, and attenuated the phosphorylation of MAPK kinases 1/2, 3/6, and 4. Tangeretin also limited the endogenous generation of reactive oxygen species (ROS), thereby protecting the cells against oxidative stress. However, tangeretin did not scavenge the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and influence the nicotinamide adenine dinucleotide phosphate oxidase activity. These results suggest that the anti-inflammatory effects of tangeretin stem from its modulation of cell signaling and suppression of intracellular ROS generation. Tangeretin may have a potent chemopreventive effect in skin cancer.     

Modulation of Inflammatory Gene Expression by a Bilberry ( Vaccinium myrtillus L.) Extract and Single Anthocyanins Considering Their Limited Stability under Cell Culture Conditions

Studies with nonintestinal models indicate that anthocyanin-rich extracts can modulate inflammatory gene expression and may help prevent development of inflammatory bowel diseases (IBD). This work investigated the influence of a bilberry ( Vaccinium myrtillus L.) extract (BE) and comprising anthocyanins on pro-inflammatory genes in IFN-γ/IL-1β/TNF-α stimulated human colon epithelial cells (T84) by qRT-PCR and cytokine arrays. Moreover, the stability of selected anthocyanins under cell culture conditions was examined to assess their anti-inflammatory properties. BE and single anthocyanins significantly inhibited the expression and secretion of IBD-associated pro-inflammatory mediators (TNF-α, IP-10, I-TAC, sICAM-1, GRO-α) in the stimulated cells. The anti-inflammatory activity thereby strongly depends on the aglycon structure (hydroxylation and methylation pattern) and the sugar moiety. In contrast to anthocyanidins, which were highly unstable in cell culture medium, suggesting that their degradation products might contribute to the inhibitory effects assigned to the parent compounds, anthocyanins have higher stability and may directly contribute to BE's effects.     

Inhibitory effect on activator protein-1, nuclear factor-kappaB, and cell transformation by extracts of strawberries (Fragaria x ananassa Duch.)

The inhibitory effects of strawberry (Fragaria x ananassa Duch.) antioxidant enzymes on tetradecanoylphorbol-13-acetate (TPA) or ultraviolet-B (UVB) induced activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) were studied. The inhibitory effects of strawberry extracts on the proliferation and transformation of human and mouse cancer cells were also evaluated. Strawberries had high activities of glutathione peroxidase, superoxide dismutase, guaiacol peroxidase, ascorbate peroxidase, and glutathione reductase. Strawberry extracts inhibited the proliferation of human lung epithelial cancer cell line A549 and decreased TPA-induced neoplastic transformation of JB6 P+ mouse epidermal cells. Pretreatment of JB6 P+ mouse epidermal cells with strawberry extract resulted in the inhibition of both UVB- and TPA-induced AP-1 and NF-kappaB transactivation. Furthermore, strawberry extract also blocked TPA-induced phosphorylation of extracellular signal-regulated kinases (ERKs) and UVB-induced phosphorylation of ERKs and JNK kinase in JB6 P+ mouse epidermal cell culture. These results suggest that the ability of strawberries to block UVB- and TPA-induced AP-1 and NF-kappaB activation may be due to their antioxidant properties and their ability to reduce oxidative stress. The oxidative events that regulate AP-1 and NF-kappaB transactivation can be important molecular targets for cancer prevention. The strawberries may be highly effective as a chemopreventive agent that acts by targeting the down-regulation of AP-1 and NF-kappaB activities, blocking MAPK signaling, and suppressing cancer cell proliferation and transformation.     

60Co-γ辐照结合1-MCP处理对蓝莓贮藏品质的影响

为研究⁶⁰Co-γ辐照结合1-甲基环丙烯(1-MCP)处理对蓝莓贮藏品质的影响,以粉蓝蓝莓为试验材料,对采后蓝莓生理指标、营养指标及相关酶活性进行测定,研究0±0.5℃条件下6种处理(1.5 kGy辐照处理记为A、2.5 kGy辐照处理记为B、1.5 kGy辐照+1 μL·L^-1 1-MCP 处理记为C、2.5 kGy辐照+1 μL·L^-1 1-MCP处理记为D、1 μL·L^-1 1-MCP处理记为E,不进行任何处理记为F)对蓝莓贮藏品质的影响。结果表明,与对照(F)比较,4种处理(A、C、D、E)均能够抑制果实腐烂率的上升和风味指数的下降,延缓果实的生理代谢,更好地保持果实的营养品质和酶活性,而2.5 kGy辐照处理(B)降低了果实的硬度、L^*值、可溶性固形物含量和花色苷含量,加快了果实多聚半乳糖醛酸酶活性的上升。其中,在贮藏80 d时,A、B、C、D、E、F组蓝莓的腐烂率分别为24.94%、38.36%、13.87%、30.78%、22.96%和48.38%。因此,1.5 kGy ⁶⁰Co-γ辐照结合1 μL·L^-1 1-MCP处理蓝莓对果实的贮藏效果最好。本研究结果为蓝莓的贮藏保鲜提供了新思路。     

Diphenylamine metabolism in 'braeburn' apples stored under conditions conducive to the development of internal browning

Diphenylamine metabolism and ethylene action were evaluated as factors influencing the development of 'Braeburn' apple internal browning and cavitation during cold storage. Apples treated with the antioxidant diphenylamine (DPA) and/or the ethylene action inhibitor 1-methylcyclopropene (1-MCP) were held at 1 degrees C for up to 6 months in air or a controlled atmosphere (CA) containing 1 kPa of O2 and 3 kPa of CO2. Cortex tissues from fruit without disorders as well as from symptomatic and asymptomatic areas of fruit with disorders were analyzed for DPA and DPA derivative content. Internal browning and cavities developed in control and 1-MCP-treated fruit stored in CA, whereas air-stored and CA fruit treated with DPA or with DPA and 1-MCP prior to storage did not develop disorders. Depending on the storage regimen and duration, less DPA was detected in 1-MCP-treated fruit. The 4-hydroxydiphenylamine (4OHDPA) content of control fruit decreased during air storage duration but increased between 2 and 4 months in CA storage. 4OHDPA content in 1-MCP-treated fruit increased with storage duration in CA but not air. N-Nitrosodiphenylamine (NODPA) was detected after 2 months in control fruit stored in air or CA and in 1-MCP-treated fruit stored in CA, and NODPA content in control fruit was higher compared to that in 1-MCP-treated fruit. Accumulation of 4-methoxydiphenylamine (4MeODPA) in control fruit stored in air increased with storage duration, but 4MeODPA content did not change in 1-MCP-treated fruit stored in air or CA. 2-Nitrodiphenylamine content was reduced by prestorage treatment with 1-MCP, but storage environment and duration had no effect on its accumulation. The results indicate that CA storage increases the risk of disorder development in 'Braeburn' apples, that DPA can prevent disorder development, and that the content of DPA and DPA derivatives is influenced by storage environment and ethylene action. A clear relationship between DPA derivative formation and storage conditions that promote internal browning was not apparent.     

适宜1-MCP处理保持采后菠萝常温贮藏品质

为了探索1-MCP处理对采后菠萝生理及品质的影响,为菠萝贮藏保鲜措施提供理论依据。以‘巴厘’品种的菠萝果实为试材,采用适宜0.45μL/L体积分数的1-MCP对菠萝进行处理,置于25℃条件下贮藏,采用气相色谱定期测定乙烯释放量,并采用常规理化分析方法测定菠萝品质及相关生理指标。结果表明,1-MCP处理能延缓果实贮藏过程中乙烯的合成速率,与相同贮藏条件下的对照(未处理)果实相比,乙烯释放高峰推迟4 d;1-MCP处理可以延缓果实丙二醛(malondialdehyde,MDA)含量的快速升高,同时对脂氧合酶(lipoxygenase,LOX)酶活性起到抑制作用;与对照相比,1-MCP处理推迟了过氧化物酶(peroxidase,POD)、过氧化氢酶(catalase,CAT)等酶活性高峰的出现,并使POD、CAT、过氧化物歧化酶(superoxide dismutase,SOD)等保持较高的活性,可以有效延缓菠萝在贮藏期间的衰老进程,在贮藏14 d时,分别比对照高出22.30%、32.35%、36.67%,差异显著(P0.05);1-MCP还可减缓果实可滴定酸、维生素C等含量的下降,有助于保持果实的良好品质。1-MCP处理可抑制菠萝贮藏期的果实衰老进程,有利于保持果实品质,提高贮藏效果。研究结果将为菠萝贮藏保鲜措施提供参考。