Inhibitory effect of Antrodia camphorata constituents on the Helicobacter pylori-associated gastric inflammation

Helicobacter pylori infection plays a crucial role in the pathogenesis of peptic ulcer, and gastric cancer. Among the 13 chemical constituents isolated from fruiting bodies of Antrodia camphorata, methyl antcinate B (4), antcins K (10) and A (12) displayed potential anti-H. pylori activity with inhibition zones of 13, 12 and 10 mm, respectively, at a concentration of 0.2 mM. The isolates 4 and 10 exhibited a dose response inhibition of H. pylori adhesion and invasion to AGS cells in a range of concentrations between 0.005 and 0.02 mM, while 12 has moderate effect at relatively higher concentration. Furthermore, at these concentrations (0.005–0.02 mM) the isolates 4 and 10 also inhibited the H. pylori-induced nuclear factor (NF)-кB activation, and the subsequent release of interleukin (IL)-8 in AGS cells. These results open the possibility of considering A. camphorata a chemopreventive agent for peptic ulcer or gastric cancer, but this bioactivity should be confirmed in vivo in the future.     

Methyl Brevifolincarboxylate Attenuates Free Fatty Acid-Induced Lipid Metabolism and Inflammation in Hepatocytes through AMPK/NF-κB Signaling Pathway

The prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases worldwide. This study examined the potential protective effects of a naturally occurring polyphenolic compound, methyl brevifolincarboxylate (MBC) on fatty liver injury in vitro. The results showed that MBC at its non-cytotoxic concentrations, reduced lipid droplet accumulation and triglyceride (TG) levels in the oleic acid (OA)-treated human hepatocarcinoma cell line, SK-HEP-1 and murine primary hepatocytes. In OA-treated SK-HEP-1 cells and primary murine hepatocytes, MBC attenuated the mRNA expression levels of the de novo lipogenesis molecules, acetyl-coenzyme A carboxylase (Acc1), fatty acid synthase (Fasn) and sterol regulatory element binding protein 1c (Srebp1c). MBC promoted the lipid oxidation factor peroxisome proliferator activated receptor-α (Pparα), and its target genes, carnitine palmitoyl transferase 1 (Cpt1) and acyl-coenzyme A oxidase 1 (Acox1) in both the SK-HEP-1 cells and primary murine hepatocytes. The mRNA results were further supported by the attenuated protein expression of lipogenesis and lipid oxidation molecules in OA-treated SK-HEP-1 cells. The MBC increased the expression of AMP activated protein kinase (AMPK) phosphorylation. On the other hand, MBC treatment dampened the inflammatory mediator’s, tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), IL-8, and IL-1β secretion, and nuclear factor (NF)-κB expression (mRNA and protein) through reduced reactive oxygen species production in OA-treated SK-HEP-1 cells. Taken together, our results demonstrated that MBC possessed potential protective effects against NAFLD in vitro by amelioration of lipid metabolism and inflammatory markers through the AMPK/NF-κB signaling pathway.     

cAMP inhibits linoleic acid-induced growth by antagonizing p27(kip1) depletion, but not interfering with the extracellular signal-regulated kinase or AP-1 activities

To understand the underlying signaling events of polyunsaturated fatty acid-induced growth, we studied the effect of cAMP on early and delayed growth response events induced by linoleic acid in smooth muscle cells (SMC). cAMP significantly inhibited both basal and linoleic acid-induced DNA synthesis. Linoleic acid-induced early growth response events, such as activation of ERKs, induction of expression of c-fos and jun-B and stimulation of AP-1 activity, however, were not affected by cAMP. In contrast, linoleic acid-induced c-jun expression was blocked by cAMP. cAMP alone stimulated ERKs activation, c-fos and jun-B expression and increased AP-1 activity. Linoleic acid induced depletion of p27kip1 and increased CDK2 activity, events required for G1/S transition. In contrast to early growth response events, linoleic acid-induced G1/S transition signals were significantly inhibited by cAMP. These findings suggest that in addition to inducing immediate early growth response events, linoleic acid mimics growth factors in activating cell cycle events that are associated with G1/S transition in SMC and the negative regulation of linoleic acid-induced growth by cAMP is apparently due to its antagonism with linoleic acid-induced p27kip1 depletion and CDK2 activation.