Protective Effect of the Fruit Hull of Gleditsia sinensis on LPS-Induced Acute Lung Injury Is Associated with Nrf2 Activation

The fruit hull of Gleditsia sinensis (FGS) has been prescribed as a traditional eastern Asian medicinal remedy for the treatment of various respiratory diseases, but the efficacy and underlying mechanisms remain poorly characterized. Here, we explored a potential usage of FGS for the treatment of acute lung injury (ALI), a highly fatal inflammatory lung disease that urgently needs effective therapeutics, and investigated a mechanism for the anti-inflammatory activity of FGS. Pretreatment of C57BL/6 mice with FGS significantly attenuated LPS-induced neutrophilic lung inflammation compared to sham-treated, inflamed mice. Reporter assays, semiquantitative RT-PCR, and Western blot analyses show that while not affecting NF-κB, FGS activated Nrf2 and expressed Nrf2-regulated genes including GCLC, NQO-1, and HO-1 in RAW 264.7 cells. Furthermore, pretreatment of mice with FGS enhanced the expression of GCLC and HO-1 but suppressed that of proinflammatory cytokines in including TNF-α and IL-1β in the inflamed lungs. These results suggest that FGS effectively suppresses neutrophilic lung inflammation, which can be associated with, at least in part, FGS-activating anti-inflammatory factor Nrf2. Our results suggest that FGS can be developed as a therapeutic option for the treatment of ALI

4-O-Carboxymethylascochlorin Inhibits Expression Levels of on Inflammation-Related Cytokines and Matrix Metalloproteinase-9 Through NF–κB/MAPK/TLR4 Signaling Pathway in LPS-Activated RAW264.7 Cells

Toll-like receptor 4 (TLR4) and matrix metalloproteinase-9 (MMP-9) are known to play important roles in inflammatory diseases such as arteriosclerosis and plaque instability. The purpose of this study was to perform the effect of 4-O-carboxymethylascochlorin (AS-6) on MMP-9 expression in lipopolysaccharide (LPS)-induced murine macrophages and signaling pathway involved in its anti-inflammatory effect. Effect of AS-6 on MAPK/NF-κB/TLR4 signaling pathway in LPS-activated murine macrophages was examined using ELISA, Western blotting, reverse transcription polymerase chain reaction (RT-PCR) and fluorescence immunoassay. MMP-9 enzyme activity was examined by gelatin zymography. AS-6 significantly suppressed MMP-9 and MAPK/NF-κB expression levels in LPS-stimulated murine macrophages. Expression levels of inducible nitric oxide synthase (iNOS), COX2, MMP-9, JNK, ERK, p38 phosphorylation, and NF-κB stimulated by LPS were also decreased by AS-6. Moreover, AS-6 suppressed TLR4 expression and dysregulated LPS-induced activators of transcription signaling pathway. The results of this study showed that AS-6 can inhibit LPS-stimulated inflammatory response by suppressing TLR4/MAPK/NF-κB signals, suggesting that AS-6 can be used to induce the stability of atherosclerotic plaque and prevent inflammatory diseases in an in vitro model

Antibacterial and synergistic effects of Nardostachytis rhizoma extracts on methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious clinical problem worldwide. Few new drugs are available against MRSA, because it has the ability to acquire resistance to most antibiotics which consequently increases the cost of medication. In the present study, the antibacterial activity of Nardostachytis rhizoma was investigated. The most effective method is to develop antibiotics from the natural products without having any toxic or side effects. Therefore, there is a need to develop alternative antimicrobial drugs for the treatment of infectious diseases. The use of two drugs in combination is a good alternative to slow the process of developing drug resistance and to restore the effectiveness of drugs that are no longer prescribed. Combination therapy is the most commonly recommended empirical treatment for bacterial infections in intensive care units, where monotherapy may not be effective against all potential pathogens, and for preventing the emergence of resistant. Five clinical isolates (MRSA) were obtained from five different patients at Wonkwang University Hospital (Iksan, South Korea). The other two strains were S. aureus ATCC 33591 (methicillin-resistant strain) and S. aureus ATCC 25923 (methicillin-susceptible strain). Antibacterial activity (minimal inhibitory concentrations, MICs) was determined by broth dilution method, disc diffusion method, MTT test and checkerboard dilution test. Antimicrobial activity of n-hexane fraction of N. rhizoma was significant. Against the seven strains, the disc diffusion test was in the range of 14 to 18 mm and had a MICs ranging from 31.25 to 125 ìg/ml. FICI values for n-hexane fraction (HFL) of N. rhizome + ampicillin (AM) and HFL + oxacillin (OX) were 0.1875 and 0.078125-0.09375, showing the increase of synergistic effect. When combined together, these antibiotic effects were dramatically increased. These effective combinations could be new promising agents in the management of MRSA and MSSA.Key words: Nardostachytis rhizoma, synergism, antibacterial, methicillin-resistant Staphylococcus aureus (MRSA)

Reappraisal of Plasmapheresis as a Supportive Measure in a Patient with Hepatic Failure after Major Hepatectomy

Major resection of cirrhotic livers can result in hepatic failure, but no supportive treatment has been found to be generally effective. We successfully treated a 63-year-old woman with post-hepatectomy liver failure with plasmapheresis. Following right hepatectomy, the initial postoperative recovery of liver function was favorable, except for ascites. One month later, however, the amount of drained ascites increased up to 2 l/day. In addition, serum cholesterol concentration gradually decreased to around 30 mg/dl, and serum total bilirubin rose to 11.1 mg/dl. Plasmapheresis was performed, and after just 2 sessions, serum cholesterol level was rapidly corrected and prothrombin time was restored. After 3 sessions of plasmapheresis, the usual rebound rise of serum bilirubin disappeared, and the amount of ascites drained also decreased slowly. The patient underwent a total of 5 sessions of plasmapheresis over 2 weeks, after which liver function improved slowly, and she was finally discharged 72 days after liver resection. Mild ascites requiring diuretic therapy persisted over 3 months. She is doing well to date 10 months after liver resection without tumor recurrence or hepatic decompensation. This limited experience suggests that plasmapheresis can be a useful liver support for post-hepatectomy liver failure