Electrochemical aerobic Wacker-type oxygenation of triaryl substituted alkenes to 1,2,2-triarylethanones.

An effective synthetic approach for various 1,2,2-triarylethanones from triaryl substituted alkenes has been developed via an electrochemical Wacker-type oxygenation with O2 as the sole oxygen source. It presents the first instance of the Wacker-type oxidation expanding its substrate scope to trisubstituted alkenes. The approach is transition-metal-free, compatible with various functional groups, and can be carried out under mild conditions resulting in satisfactory yields. Mechanistic experiments suggest the CO bond formation occurs through reactions between cationic carbon species and the superoxide radical, which involves the 1,2-shift of the electron-rich substituent.

Oxymatrine Alleviates Gentamicin-Induced Renal Injury in Rats.

Gentamicin is an aminoglycoside antibiotic commonly used to treat Gram-negative bacterial infections that possesses considerable nephrotoxicity. Oxymatrine is a phytochemical with the ability to counter gentamicin toxicity. We investigated the effects and protective mechanism of oxymatrine in rats. The experimental groups were as follows: Control, Oxymatrine only group (100 mg/kg/d), Gentamicin only group (100 mg/kg/d), Gentamicin (100 mg/kg/d) plus Oxymatrine (100 mg/kg/d) group (n = 10). All rats were treated for seven continuous days. The results indicated that oxymatrine alleviated gentamicin-induced kidney injury, and decreased rats' kidney indices and NAG (N-acetyl-beta-d-glucosaminidase), BUN (blood urea nitrogen) and CRE (creatine) serum levels. The oxymatrine-treated group sustained less histological damage. Oxymatrine also relived gentamicin-induced oxidative and nitrative stress, indicated by the increased SOD (superoxidase dismutase), GSH (glutathione) and CAT (catalase) activities and decreased MDA (malondialdehyde), iNOS (inducible nitric oxide synthase) and NO (nitric oxide) levels. Caspase-9 and -3 activities were also decreased in the oxymatrine-treated group. Oxymatrine exhibited a potent anti-inflammatory effect on gentamicin-induced kidney injury, down-regulated the Bcl-2ax and NF-κB mRNAs, and upregulated Bcl-2, HO-1 and Nrf2 mRNAs in the kidney tissue. Our investigation revealed the renal protective effect of oxymatrine in gentamicin-induced kidney injury for the first time. The effect was achieved through activation of the Nrf2/HO-1 pathways. The study underlines the potential clinical application of oxymatrine as a renal protectant agent for gentamicin therapy.

Bergenin Monohydrate Attenuates Inflammatory Response via MAPK and NF-κB Pathways Against Klebsiella pneumonia Infection.

Background: Klebsiella pneumonia has emerged as a critical pathogen causing severe clinical problems, such as pneumonia and sepsis. Meanwhile, intensified drug resistance induced by antibiotic therapy necessitates discovering novel and active molecules from Traditional Chinese Medicine (TCM) for treatment. Methods and results: In this study, the isolated Bergenin monohydrate showed an anti-inflammatory effect in Klebsiella-infected mice. We initially investigated the anti-inflammatory effects and cytoprotection against oxidative stress in vitro and in vivo. Interestingly, a specific dose of Bm can effectively ameliorate lung injury and suppress the expression of inflammatory cytokines such as TNF-α, IL-6, IL-1ß and PEG2. Moreover, Bm was also shown to reduced the levels of MPO, MDA and increased SOD and GSH activities. Moreover, we assessed the intracellular signaling molecules including p38, ERK, JNK, IκB, NF-κB-p65 by western blotting and verified through MAPK and NF-κB pathways inhibition experiments. These results reveal that Bm executed its effects via the classical MAPK signaling pathway and NF-κB pathway. Conclusion: Given its underlying anti-inflammatory effect, Bm may be used as a promising therapeutic against Klebsiella-induced infection, thus providing a benefit for the future clinical therapy of pneumonia and medicine design.

Kaempferol-3-O-glucorhamnoside inhibits inflammatory responses via MAPK and NF-κB pathways in vitro and in vivo.

Klebsiella pneumoniae causes severe infections including pneumonia and sepsis and treatments are complicated by increased levels of antibiotic resistance. We have identified a flavonoid kaempferol-3-O-glucorhamnoside derived from the plant Thesium chinense Turcz that possessed potent anti-inflammatory effects in K. pneumoniae infected mice. Administration of kaempferol-3-O-glucorhamnoside before bacterial challenge effectively suppressed expression of the major inflammatory cytokines TNF-α, IL-6, IL-1ß and PGE2 and ameliorated lung edema. In addition, administration of this compound to cultured RAW macrophages or Balb/c mice resulted in the suppression of NFκB and MAP kinase phosphorylation indicating an inhibitory effect on inflammation in vitro and in vivo. Kaempferol-3-O-glucorhamnoside also decreased ROS levels and overall oxidative stress in lungs and in cultured cells generated by K. pneumoniae exposure. Taken together, kaempferol-3-O-glucorhamnoside is a potent anti-inflammatory in vitro and in vivo and is a promising therapeutic agent for treating K. pneumoniae infections in the clinic.