Triterpenoids From Kadsura coccinea With Their Anti-inflammatory and Inhibited Proliferation of Rheumatoid Arthritis-Fibroblastoid Synovial Cells Activities.

One new 3,4-seco-17,13-friedo-lanostane triterpenoid heilaohuacid A (1), one new 3,4-seco-17,14-friedo-lanostane triterpenoid heilaohuacid B (2), five new 3,4-seco-lanostane triterpenoids heilaohuacids C-D (3-4) and heilaohumethylesters A-C (7-9), one new 3,4-seco-cycloartane triterpenoid heilaohuacid E (5), and one new intact-lanostane triterpenoid heilaohuacid F (6), together with twenty-two known analogues (10-31), were isolated from heilaohu. Their structures were determined using HR-ESI-MS data, 1D and 2D NMR spectra, 13C NMR calculations, and electronic circular dichroism (ECD) calculations. Heilaohuacids A and B (1 and 2) contain a 3,4-seco ring A and unprecedented migration of Me-18 from C-13 to C-17 or C-14 to C-18. This type of lanostane triterpenoid derivatives was rarely reported so far. More importantly, all compounds against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were evaluated, and compounds 4 and 31 significantly inhibited the release level of IL-6 with IC50 values of 8.15 and 9.86 µM, respectively. Meanwhile, compounds 17, 18, and 31 significantly inhibited proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells in vitro with IC50 values of 7.52, 8.85, and 7.97 µM, respectively.

Triterpenoids from stems of Kadsura heteroclita.

In the present work, we reported the triterpenoids isolated from n-butanol fraction of Kadsura heteroclita which is a Tujia ethnomedicine with trivial name "Xuetong". This effort resulted in the isolation of six unpresented triterpenoids xuetongsu A-F (1-6), along with five known triterpenoids (7-11). The structures of the reported compounds were established on the 1D, and 2D NMR and HRESIMS spectra, along with CD spectroscopic analysis. Moreover, the absolute stereochemistry of compound 7 was determined by X-ray diffraction analysis. Antioxidant and cytotoxic activities were evaluated for all isolated compounds, compound 7 shown weak cytotoxic activity against HL-60 with IC50 value of 50.0 µM.

Identification of potential diagnostic biomarkers of cerebral infarction using gas chromatography-mass spectrometry and chemometrics.

Cerebral infarction (CI) is one of the most common cerebrovascular diseases and remains a major health problem worldwide. In this study, we evaluated the potential diagnostic biomarkers and important relevant metabolic pathways associated with CI. Metabolomics based on gas chromatography-mass spectrometry coupled with the multivariate pattern recognition technique were used to characterize the potential serum metabolic profiles of CI. Forty healthy controls and thirty-three cerebral infarction patients were recruited for the nontargeted global metabolites' study and subsequent targeted fatty acid analysis. Overall, thirty-four endogenous metabolites were found in serum from the untargeted global study, four of which were detected to be significantly different between the CI group and healthy controls, including l-lysine, octadecanoic acid (fatty acid), l-tyrosine and lactic acid. Additionally, fourteen free fatty acids were identified by the subsequent targeted fatty acid analysis, and seven of them were detected to be significantly different between the CI group and healthy controls, which were mainly associated with arachidonic acid metabolism and fatty acid metabolism. Our results suggest several potential diagnostic biomarkers, and serum metabolism research is demonstrated as a powerful tool to explore the pathogenesis of CI.

Induction of GADD45α protects M17 neuroblastoma cells against MPP*.

Growth arrest and DNA-damage-inducible protein 45α (GADD45α) is an important member of the family of growth arrest and DNA damage-inducible (GADD) proteins. The expression patterns and possible roles of GADD45α in Parkinson's disease (PD) are so far less understood. In this study, we found that 1-methyl-4-phenylpyridinium (MPP+) treatment up-regulates the expression of GADD45α in both a time-dependent manner and a dose-dependent manner in human dopamine neuroblastoma M17 cells. The up-regulation of GADD45α was abolished by pretreatment with the c-Jun N-terminal kinases (JNK) inhibitor SP600125 but not the p38 specific inhibitor SB203580. Further study revealed that c-Jun silencing abolished the effects of MPP+ on the expression of GADD45α. Important, ChIP studies verified the ability of c-Jun to bind to the GADD45 promoter. In addition, we found that inhibition of GADD45α by small RNA interference exacerbates the impaired cell viability, LDH release, and apoptosis induced by MPP+. Correspondingly, silence of GADD45 exacerbated Caspase-3 activation induced by MPP+. These data suggested a neuroprotective effect of GADD45α against MPP+ neurotoxicity.

Augmented B lymphocyte response to antigen in the absence of antigen-induced B lymphocyte signaling in an IgG-transgenic mouse line.

IgG-containing B cell antigen receptor (IgG-BCR), the BCR mostly expressed on memory B cells, contains a distinct signaling function from IgM-BCR or IgD-BCR expressed on naïve B cells. Because naïve B cells transgenic for IgG exhibit augmented response to antigens similar to memory B cells, the distinct signaling function of IgG-BCR appears to play a role in augmented antibody responses of memory B cells. However, how IgG-BCR signaling augments B cell responses is not yet well understood. Here we demonstrate that B cells from IgG-transgenic mice are anergic with defect in generation of BCR signaling upon BCR ligation. However, these IgG-transgenic B cells generate markedly augmented antibody response to a T cell-dependent antigen, probably due to hyper-responsiveness to a T cell-derived signal through CD40. Both BCR signaling defect and augmented response to CD40 ligation are partially restored in xid IgG-transgenic mice in which BCR signaling is down-modulated due to a loss-of-function mutation in the tyrosine kinase Btk crucial for BCR signaling. Thus, IgG-BCR induces augmented B cell responses in the absence of antigen-induced BCR signaling probably through high ligand-independent BCR signaling that may "idle" B cells to make them ready to respond to T cell help. This finding strongly suggests a crucial role of ligand-independent signaling in receptor function.