Comprehensive analysis of the compound profiles of Folium Camelliae Nitidissimae extract by ultrafast liquid chromatography with quadrupole–time-of-flight mass spectrometry and hepatoprotective effect against CCl4-induced liver injury in mice

Folium Camelliae Nitidissimae (jinhuacha in Chinese, JHC) is a kind of caffeine-less tea with antioxidant, antitumor and antibacterial effects. Studies on the chemical profiles and hepatoprotective effects of JHC extracts have not been systematically conducted so far. This study comprehensively investigated the compound profiles of JHC extract by ultrafast liquid chromatography with quadrupole time-of-flight tandem mass spectrometry. We also determined JHC's hepatoprotective effects against CCl₄-induced liver injury in mice. A JHC extract was administered orally to mice at 1.95 and 7.80 g/kg body weight once daily for 14 consecutive days prior to CCl₄ treatment. Eighty-four compounds including flavonoids, organic acids, catechins, coumarins, phenylpropanol, amino acids, anthraquinones, saponins and nucleosides in JHC extract were authentically identified or tentatively identified by comparing MS information and retention times with those of authentic standards or available references. JHC administration significantly decreased elevated levels of aspartate aminotransferase and alanine aminotransferase in mouse serum, inhibited hepatic malondialdehyde formation and enhanced glutathione and superoxide dismutase activities in the liver of CCl₄-treated mice. The histological observations also further supported the results. These results demonstrate that JHC contains various chemical compounds and its hepatoprotective effects against CCl₄-induced liver injury correlated with decreasing lipid oxidation are significant.     

Isofuranodiene is the main volatile constituent of Smyrnium perfoliatum L. subsp. perfoliatum growing in central Italy

The essential oil hydrodistilled from the aerial parts of Smyrnium perfoliatum subsp. perfoliatum growing in central Italy was analysed by GC-MS. The main peak in the gas chromatogram was given by the furanosesquiterpene curzerene which is the Cope rearrangement product of isofuranodiene formed into injector and column during the gas chromatographic run. A truthful quantification of these compounds was achieved by HPLC-DAD analysis which showed that isofuranodiene is the main volatile component (180.0 mg/g eo) of S. perfoliatum subsp. perfoliatum, while curzerene occurs in small amounts (18.1 mg/g eo).     

SPA0355 attenuates ischemia/reperfusion-induced liver injury in mice

Hepatic ischemia/reperfusion (I/R) injury leads to oxidative stress and acute inflammatory responses that cause liver damage and have a considerable impact on the postoperative outcome. Much research has been performed to develop possible protective techniques. We aimed to investigate the efficacy of SPA0355, a synthetic thiourea analog, in an animal model of hepatic I/R injury. Male C57BL/6 mice underwent normothermic partial liver ischemia for 45 min followed by varying periods of reperfusion. The animals were divided into three groups: sham operated, I/R and SPA0355 pretreated. Pretreatment with SPA0355 protected against hepatic I/R injury, as indicated by the decreased levels of serum aminotransferase and reduced parenchymal necrosis and apoptosis. Liver synthetic function was also restored by SPA0355 as reflected by the prolonged prothrombin time. To gain insight into the mechanism involved in this protection, we measured the activity of nuclear factor-κB (NF-κB), which revealed that SPA0355 suppressed the nuclear translocation and DNA binding of NF-κB subunits. Concomitantly, the expression of NF-κB target genes such as IL-1β, IL-6, TNF-α and iNOS was significantly downregulated. Lastly, the liver antioxidant enzymes superoxide dismutase, catalase and glutathione were upregulated by SPA0355 treatment, which correlated with the reduction in serum malondialdehyde. Our results suggest that SPA0355 pretreatment prior to I/R injury could be an effective method to reduce liver damage.     

Anti-inflammatory bibenzyls from the stems of Dendrobium huoshanense via bioassay guided isolation

Abstract

The stems of Dendrobium huoshanense have long been used to prevent various diseases, including inflammatory diseases. This study was aimed to explain the anti-inflammatory effect of D. huoshanense stems in LPS-induced RAW 264.7 macrophages and to discover potential anti-inflammatory compounds. Results exhibited that D. huoshanense stems ethanol extract could significantly inhibit LPS-induced production of NO, TNF-α and IL-1β. Based on bioassay guided strategy, four bibenzyls (1–4) were isolated from D. huoshanense stems for the first time. Anti-inflammatory assay showed 1–4 could remarkably inhibit the production of NO in LPS-induced macrophages. Moreover, quantitative RT-PCR analysis displayed that the mRNA levels of iNOs, TNF-α and IL-1β could also be significantly reduced by 1–4. These results suggested that D. huoshanense stems ethanol extract and bibenzyls 1–4 might be well developed as therapeutic agent to prevent inflammatory diseases.     

Hepatoprotective Effect of β-Chitosan from Gladius of Sepioteuthis lessoniana Against Carbon Tetrachloride-Induced Oxidative Stress in Wistar Rats

Chitosan has attracted much attention as a biomedical material, owing to its unique biological activities. In this study, hepatoprotective effect of β-chitosan obtained from the gladius of squid Sepioteuthis lessoniana was studied against carbon tetrachloride (CCl₄)-induced oxidative stress and liver injury in rats. The rats that received β-chitosan along with the administration of CCl₄ showed significantly decreased plasma and tissue alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and total cholesterol, triglyceride (TG) and free fatty acid (FFA) contents, whereas the treatment with β-chitosan alone markedly increased rat hepatic and circulatory superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) and reduced glutathione (GSH) levels and decreased the malondialdehyde level. Histopathological observations recommended the marked hepatoprotective effect of β-chitosan. The CCl₄-induced alterations on circulatory and hepatic antioxidant defence system were normalised by β-chitosan, and it could be concluded that the hepatoprotective effect of chitosan may be due to its antioxidant and antilipidemic property. Therefore, β-chitosan could be considered as antihepatotoxic agent.     

The Ameliorative Effects of Fucoidan in Thioacetaide-Induced Liver Injury in Mice

Liver disorders have been recognized as one major health concern. Fucoidan, a sulfated polysaccharide extracted from the brown seaweed Fucus serratus, has previously been reported as an anti-inflammatory and antioxidant. However, the discovery and validation of its hepatoprotective properties and elucidation of its mechanisms of action are still unknown. The objective of the current study was to investigate the effect and possible modes of action of a treatment of fucoidan against thioacetamide (TAA)-induced liver injury in male C57BL/6 mice by serum biochemical and histological analyses. The mouse model for liver damage was developed by the administration of TAA thrice a week for six weeks. The mice with TAA-induced liver injury were orally administered fucoidan once a day for 42 days. The treated mice showed significantly higher body weights; food intakes; hepatic antioxidative enzymes (catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD)); and a lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and C-reactive protein (CRP) levels. Additionally, a reduced hepatic IL-6 level and a decreased expression of inflammatory-related genes, such as cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA was observed. These results demonstrated that fucoidan had a hepatoprotective effect on liver injury through the suppression of the inflammatory responses and acting as an antioxidant. In addition, here, we validated the use of fucoidan against liver disorders with supporting molecular data.     

Monascin and Ankaflavin of Monascus purpureus Prevent Alcoholic Liver Disease through Regulating AMPK-Mediated Lipid Metabolism and Enhancing Both Anti-Inflammatory and Anti-Oxidative Systems

Alcohol metabolism causes an excessive accumulation of liver lipids and inflammation, resulting in liver damage. The yellow pigments monascin (MS) and ankaflavin (AK) of Monascus purpureus-fermented rice were proven to regulate ethanol-induced damage in HepG2 cells, but the complete anti-inflammatory and anti-fatty liver mechanisms in the animal model are still unclear. This study explored the roles of MS and AK in improving alcoholic liver injury. MS and AK were simultaneously fed to evaluate their effects and mechanisms in C57BL/6J mice fed the Lieber–DeCarli liquid alcohol diet for 6 weeks. The results indicated that MS and AK significantly reduced the serum aspartate aminotransferase and alanine aminotransferase activity, as well as the total liver cholesterol and triglyceride levels. The histopathological results indicated that MS and AK prevented lipid accumulation in the liver. MS and AK effectively enhanced the activity of antioxidant enzymes and reduced the degree of lipid peroxidation; AK was particularly effective and exhibited a superior preventive effect against alcoholic liver injury and fatty liver. In addition to inhibiting the phosphorylation of the MAPK family, MS and AK directly reduced TNF-α, IL-6, and IL-1β levels, thereby reducing NF-κB and its downstream iNOS and COX-2 expressions, as well as increasing PPAR-γ, Nrf-2, and HO-1 expressions to prevent liver damage. MS and AK also directly reduced TNF-α, IL-6, and IL-1β expression, thereby reducing the production of NF-κB and its downstream iNOS and COX-2, and increasing PPAR-γ, Nrf-2, and HO-1 expressions, preventing alcohol damage to the liver.     

A new coumarin isolated from Sarcandra glabra as potential anti-inflammatory agent

One new coumarin, 3,5-dihydroxy-7-O-α-L-rhamno pyranosyl-2H-chromen-2-one (1), was isolated from the whole plant of Sarcandra glabra. The structure was elucidated by spectroscopic methods. Our results indicated that 1 significantly inhibit nitric oxide (NO) production in LPS-induced RAW264.7 macrophages. RT-PCR analysis indicated it inhibited iNOS mRNA expression. In addition, Western blot analysis showed that 1 attenuated LPS-induced synthesis of iNOS protein in the macrophages. These results suggest that 1 could be potential anti-inflammatory agent by down-regulating iNOS expression.     

Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages,HCl/EtOH-induced Gastritis,and LPS-induced Lung Injury via Attenuation of Src and TAK1

Several Cissus species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of Cissus subtetragona have not been described. In this study, we examined the potential anti-inflammatory effects of C. subtetragona ethanol extract (Cs-EE) in vitro and in vivo, and investigated its molecular mechanism as well as its flavonoid content. Lipopolysaccharide (LPS)-induced macrophage-like RAW264.7 cells and primary macrophages as well as LPS-induced acute lung injury (ALI) and HCl/EtOH-induced acute gastritis mouse models were utilized. Luciferase assays, immunoblotting analyses, overexpression strategies, and cellular thermal shift assay (CETSA) were performed to identify the molecular mechanisms and targets of Cs-EE. Cs-EE concentration-dependently reduced the secretion of NO and PGE₂, inhibited the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells, and decreased NF-κB- and AP-1-luciferase activity. Subsequently, we determined that Cs-EE decreased the phosphorylation events of NF-κB and AP-1 pathways. Cs-EE treatment also significantly ameliorated the inflammatory symptoms of HCl/EtOH-induced acute gastritis and LPS-induced ALI mouse models. Overexpression of HA-Src and HA-TAK1 along with CETSA experiments validated that inhibited inflammatory responses are the outcome of attenuation of Src and TAK1 activation. Taken together, these findings suggest that Cs-EE could be utilized as an anti-inflammatory remedy especially targeting against gastritis and acute lung injury by attenuating the activities of Src and TAK1.     

In vitro anti-inflammatory activities of naucleoffieine H as a natural alkaloid from Nauclea officinalis Pierrc ex Pitard,through inhibition of the iNOS pathway in LPS-activated RAW 264.7 macrophages

Abstract

Naucleoffieine H, a natural indole alkaloid, was isolated and identified from Nauclea officinalis Pierrc ex Pitard which is a traditional Chinese medicine used for the treatment of various diseases, such as cold, fever, bronchitis, pneumonia, acute tonsillitis, etc. In the present study, the effect of naucleoffieine H on the anti-inflammatory activities was investigated in LPS-induced RAW 264.7 macrophages. The results showed that naucleoffieine H significantly inhibited the release of nitric oxide (the level of nitrite as a stable biomarker of NO production) and tumor necrosis factor-α (TNF-α). Interesting, naucleoffieine H down-regulated the overexpression of inflammatory protein induced nitric oxide synthase (iNOS), but no effect on the expression cyclooxygenase-2 (COX-2) protein. In addition, this bioactive alkaloid suppressed enzymatic activity of iNOS activated by LPS. The above results indicated that naucleoffieine H suppress NO and TNF-α overproduction via block the iNOS pathway in LPS-induced RAW 264.7 macrophages.     

Levan polysaccharide from Erwinia herbicola protects osteoblast cells against lipopolysaccharide-triggered inflammation and oxidative stress through regulation of ChemR23 for prevention of osteoporosis

Osteoblast cell injury is a type of degenerative disorder characterized by osteolysis. Levan polysaccharide is an active component of Erwinia herbicola, which shows potential anti-inflammatory and antioxidant properties. However, the protective effects of levan on lipopolysaccharide (LPS)-induced inflammatory and oxidative stress injury in osteoblast cells as an in vitro model of osteolysis remain largely unknown. The present study aimed to explore the functions of levan in LPS-triggered inflammation and oxidative stress in osteoblast cells (MC3T3-E1). The protective effects of levan on LPS-induced inflammatory and oxidative stress responses in MC3T3-E1 cells were assessed by quantification of superoxide dismutase (SOD) and catalase (CAT) activity as well as enzyme-linked immunosorbent assay (ELISA) for determination of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Also, the key signaling pathway of ChemR23 was determined by qPCR analysis. Results showed that levan significantly alleviated LPS-induced deactivation of SOD and CAT activity. Levan also downregulated the expression of IL-6, TNF-α, and ChemR23 at mRNA level. These findings indicated that levan may protect MC3T3-E1 cells against LPS-triggered oxidative stress, and inflammation via regulation of ChemR23. This data may provide a potential basis for further clinical investigation of levan in the prevention and treatment of LPS-triggered bone resorption and osteolysis.     

Red Quinoa Bran Extract Prevented Alcoholic Fatty Liver Disease via Increasing Antioxidative System and Repressing Fatty Acid Synthesis Factors in Mice Fed Alcohol Liquid Diet

Alcohol is metabolized in liver. Chronic alcohol abuse results in alcohol-induced fatty liver and liver injury. Red quinoa (Chenopodium formosanum) was a traditional staple food for Taiwanese aborigines. Red quinoa bran (RQB) included strong anti-oxidative and anti-inflammatory polyphenolic compounds, but it was usually regarded as the agricultural waste. Therefore, this study is to investigate the effect of water and ethanol extraction products of RQB on the prevention of liquid alcoholic diet-induced acute liver injury in mice. The mice were given whole grain powder of red quinoa (RQ-P), RQB ethanol extract (RQB-E), RQB water extract (RQB-W), and rutin orally for 6 weeks, respectively. The results indicated that RQB-E, RQB-W, and rutin decreased alcoholic diet-induced activities of aspartate aminotransferase and alanine aminotransferase, and the levels of serum triglyceride, total cholesterol, and hepatic triglyceride. Hematoxylin and eosin staining of liver tissues showed that RQB-E and RQB-W reduced lipid droplet accumulation and liver injury. However, ethanol extraction process can gain high rutin and antioxidative agents contents from red quinoa, that showed strong effects in preventing alcoholic fatty liver disease and liver injury via increasing superoxide dismutase/catalase antioxidative system and repressing the expressions of fatty acid synthesis enzyme acetyl-CoA carboxylase.     

Isolation of a new natural kingiside aglucone derivative and other anti-inflammatory constituents from Syringa reticulata

Abstract

A new secoiridoid, (1R,5S,8S,9R)-1-methyl-kingiside aglucone (1), along with nine known compounds (2–10), were isolated from the ethanol extract of the stem bark of Syringa reticulata (Bl.) Hara. The structure of compound 1 was elucidated using HR-ESI-MS, 1D and 2D NMR spectroscopy. Compounds 1–10 were evaluated for their inhibitory activity against NO, TNF-α and IL-6 production. Compounds 1, 3, 5 and 7–10 significantly inhibited the levels of NO, TNF-α and IL-6 in LPS-induced RAW264.7 cells from concentrations of 3 to 30?μM.     

Sesquiterpene lactones from Artemisia austroyunnanensis suppresses ROS production and reduces cytokines,iNOS and COX-2 levels via NF-KB pathway in vitro

Abstract

The inhibitory effects of six sesquiterpene lactones (1–6) isolated from Artemisia austroyunnanensis Ling & Y. R. Ling were studied on the LPS-induced inflammatory mediator production in RAW264.7 cells. The results showed they can decrease the level of ROS in a concentration-dependent response. The compounds down-regulate the expression of iNOS and COX-2 and a series of classical inflammatory factors, including TNF-α, IL-1β, IL-6 and IL-10. These effects can be partially explained by the supression of the phosphorylation of NF-κB. Additionally, the relationship between their structures and inflammatory factors was analyzed and discussed.     

Spermidine Prevents Ethanol and Lipopolysaccharide-Induced Hepatic Injury in Mice

To date, there is no effective treatment for alcoholic liver disease, despite its prevalence world-wide. Because alcohol consumption is associated with oxidative stress-induced liver injury and pro-inflammatory responses, naturally occurring antioxidants and/or anti-inflammatories may be potential therapeutics. Spermidine is an abundant, ubiquitous polyamine that has been found to display strong antioxidant and anti-inflammatory properties. To further investigate whether spermidine is an effective intervention for alcohol-induced liver disease, we examined its hepatoprotective properties using a two-hit, chronic ethanol and acute lipopolysaccharide (LPS)-induced mouse model of liver injury. We determined that spermidine administration prevented ethanol and LPS-induced increases in liver injury using plasma ALT as a readout. Furthermore, histological analysis of tissue from control and treated animals revealed that the pathology associated with ethanol and LPS treatment was prevented in mice additionally treated with spermidine. As predicted, spermidine also prevented ethanol and LPS-induced oxidative stress by decreasing the levels of both reactive oxygen species (ROS) and lipid peroxidation. We further determined that spermidine treatment prevented the nuclear translocation of nuclear factor κB (NFκB) by blocking the phosphorylation of the inhibitory protein, IκB, thereby preventing expression of pro-inflammatory cytokines. Finally, by measuring expression of known markers of hepatic stellate cell activation and monitoring collagen deposition, we observed that spermidine also prevented alcohol and LPS-induced hepatic fibrosis. Together, our results indicate that spermidine is an antioxidant thereby conferring anti-inflammatory and anti-fibrotic effects associated with alcoholic liver injury.     

Terminalia chebula supplementation attenuates cisplatin-induced nephrotoxicity in Wistar rats through modulation of apoptotic pathway

In the present study, we have evaluated the nephroprotective effect of hydroalcoholic extract of Terminalia chebula in cisplatin-induced nephrotoxicity model. Standardised extract was orally administered to Wistar rats for 10 days at different doses. On day 7, 8 mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. T. chebula, in a dose-dependent manner significantly inhibited the elevation of serum creatinine, blood urea nitrogen and oxidant stress markers. The immunohistochemical analysis revealed the increased levels of apoptotic markers and cytokines in cisplatin group were significantly lowered by T. chebula extract. The cisplatin-treated rats kidney showed diffused tubular necrosis and infilteration of inflammatory cells which was reversed in the treatment group. Chemical characterisation of extract by HPLC revealed the presence of corilagin, chebulinic, chebulagic, chebulic, gallic and ellagic acid. The findings of this study discovered that T. chebula ameliorated oxidative and histological damage caused by cisplatin.     

固本活血壮骨颗粒对实验性肝纤维化大鼠肝细胞的保护作用

为探讨固本活血壮骨颗粒对实验性肝纤维化大鼠肝细胞的保护作用,采用CCl4致大鼠肝纤维化模型,观察固本活血壮骨颗粒对肝功能及肝细胞损伤超微结构的影响。结果表明,固本活血壮骨颗粒明显改善肝细胞变性及炎性细胞浸润等情况,同时明显降低血清转氨酶活性、升高血清白蛋白,降低白蛋白与球蛋白比例并使之接近正常;电镜观察表明固本活血壮骨颗粒对实验性肝纤维化大鼠肝细胞线粒体等细胞器的损伤有保护作用。提示固本活血壮骨颗粒明显减轻四氯化碳所致的肝细胞损伤,保护肝细胞,改善肝功能。     

p-Cymene protects mice against lipopolysaccharide-induced acute lung injury by inhibiting inflammatory cell activation

The objective of this study was to test the hypothesis that p-cymene can attenuate acute lung injury induced by lipopolysaccharide (LPS) in vivo. In the mouse model of LPS-induced acute lung injury, intraperitoneal preconditioning with p-cymene resulted in a significant reduction of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), lung water gain, inflammatory cell infiltration, lung tissue myeloperoxidase activity. In addition, p-cymene blocked the phosphorylation of IκBα protein and mitogen-activated protein kinases (MAPK) signaling pathway activation. Histopathologic examination of lung tissue indicated that p-cymene treatment markedly decreased focal thickening, congestion, pulmonary edema, and inflammatory cells infiltration. The results showed that p-cymene had a protective effect on LPS-induced ALI in mice.