Yang Yu

, TNF-α, and IL-6 in LPS-stimulated THP-1 macrophages. Furthermore, DC inhibited the macrophage M1 phenotype and the production of reactive oxygen species (ROS) in LPS-activated RAW264.7 cells. Mechanism studies showed that DC mainly activated nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, increased the level of anti-oxidant protein heme oxygenase-1 (HO-1) and thus produced the anti-inflammatory and anti-oxidant effects, which were abolished by Nrf2 siRNA and HO-1 inhibitor. These findings suggested that DC could be a new Nrf2 activator for the treatment and prevention of diseases related to inflammation and oxidative stress.

The recognition of lysine-type peptidoglycans (PG) by the PG recognition complex has been suggested to cause activation of the serine protease cascade leading to the processing of Spätzle and subsequent activation of the Toll signaling pathway. So far, two serine proteases involved in the lysine-type PG Toll signaling pathway have been identified. One is a modular serine protease functioning as an initial enzyme to be recruited into the lysine-type PG recognition complex. The other is the Drosophila Spätzle processing enzyme (SPE), a terminal enzyme that converts Spätzle pro-protein to its processed form capable of binding to the Toll receptor. However, it remains unclear how the initial PG recognition signal is transferred to Spätzle resulting in Toll pathway activation. Also, the biochemical characteristics and mechanism of action of a serine protease linking the modular serine protease and SPE have not been investigated. Here, we purified and cloned a novel upstream serine protease of SPE that we named SAE, SPE-activating enzyme, from the hemolymph of a large beetle, Tenebrio molitor larvae. This enzyme was activated by Tenebrio modular serine protease and in turn activated the Tenebrio SPE. The biochemical ordered functions of these three serine proteases were determined in vitro, suggesting that the activation of a three-step proteolytic cascade is necessary and sufficient for lysine-type PG recognition signaling. The processed Spätzle by this cascade induced antibacterial activity in vivo. These results demonstrate that the three-step proteolytic cascade linking the PG recognition complex and Spätzle processing is essential for the PG-dependent Toll signaling pathway.

Seven new iridoid glucosides, 6''-O-trans-sinapoylgenipin gentiobioside (1), 6''-O-trans-p-coumaroylgenipin gentiobioside (2), 6''-O-trans-cinnamoylgenipin gentiobioside (3), 6'-O-trans-p-coumaroylgeniposide (4), 6'-O-trans-p-coumaroylgeniposidic acid (5), 10-O-succinoylgeniposide (6), and 6'-O-acetylgeniposide (7), two new monoterpenoids, 11-(6-O-trans-sinapoylglucopyranosyl)gardendiol (8) and 10-(6-O-trans-sinapoylglucopyranosyl)gardendiol (9), and three known ones, 6'-O-trans-sinapoylgeniposide (10), geniposide (11), and 10-O-acetylgeniposide (12), were isolated from the fruit of Gardenia jasminoides. The structures of these compounds were elucidated on the basis of 1D and 2D NMR spectra analyses. Furthermore, short-term memory assays on an Abeta transgenic drosophila model showed that compounds 4 and 6-12 can improve the short-term memory capacity to varying degrees, with compounds 4 and 7 being the most active ones, suggesting that these compounds may have a potential antagonism effect against Alzheimer's disease.

Aberrant neural progenitor cell (NPC) proliferation and self-renewal have been linked to age-related neurodegeneration and neurodegenerative disorders including Alzheimer's disease (AD). Rhizoma Acori tatarinowii is a traditional Chinese herbal medicine against cognitive decline. In this study, we found that the extract of Rhizoma Acori tatarinowii (AT) and its active constituents, asarones, promote NPC proliferation. Oral administration of AT enhanced NPC proliferation and neurogenesis in the hippocampi of adult and aged mice as well as that of transgenic AD model mice. AT and its fractions also enhanced the proliferation of NPCs cultured in vitro. Further analysis identified α-asarone and β-asarone as the two active constituents of AT in promoting neurogenesis. Our mechanistic study revealed that AT and asarones activated extracellular signal-regulated kinase (ERK) but not Akt, two critical kinase cascades for neurogenesis. Consistently, the inhibition of ERK activities effectively blocked the enhancement of NPC proliferation by AT or asarones. Our findings suggest that AT and asarones, which can be orally administrated, could serve as preventive and regenerative therapeutic agents to promote neurogenesis against age-related neurodegeneration and neurodegenerative disorders.