Design, synthesis and evaluation of ursodeoxycholic acid-cinnamic acid hybrids as potential anti-inflammatory agents by inhibiting Akt/NF-κB and MAPK signaling pathways.

A series of ursodeoxycholic acid (UDCA)-cinnamic acid hybrids were designed and synthesized. The anti-inflammatory activity of these derivatives was screened through evaluating their inhibitory effects of LPS-induced nitric oxide production in RAW264.7 macrophages. The preliminary structure-activity relationship was concluded. Among them, 2m showed the best inhibitory activity against NO (IC50 = 7.70 µM) with no significant toxicity. Further study revealed that 2m significantly decreased the levels of TNF-α, IL-1ß, IL-6 and PGE2, down-regulated the expression of iNOS and COX-2. Preliminary mechanism study indicated that the anti-inflammatory activity of 2m was related to the inhibition of the Akt/NF-κB and MAPK signaling pathway. Furthermore, 2m reduced inflammation by a mouse model of LPS-induced inflammatory disease in vivo. In brief, our findings indicated that 2m might serve as a new lead compound for further development of anti-inflammatory agents.

Gradually Increasing the Temperature Reduces the Diapause Termination Time of Trichogramma dendrolimi While Increasing Parasitoid Performance.

Trichogramma dendrolimi Matsumura is widely used as a biological control agent of many lepidopteran pests. Diapause has been used as an effective method to preserve the Trichogramma products during mass rearing production. However, it currently takes at least 70 days to break diapause, and we tested whether gradually increasing the temperature instead of using constant temperature could reduce the time of diapause termination and offer a higher flexibility to Trichogramma producers. The diapause termination rates of individuals kept at different conditions were measured, and five groups for which diapause termination rate reached the 95% were selected to test five biological parameters, including the number of eggs parasitized, the parasitism and emergence rates, the female sex ratio, the wing deformation rate, and the parasitoid longevity. Compared to the currently used procedure (70 days at 3 °C), treatments with at least two different temperatures resulted in higher parasitism and emergence rates while keeping the other parameters constant. The treatment that consisted of at least two different temperatures preceded by only 55 days of induction period had the highest population trend index, meaning that the population under these conditions grows more rapidly. Our results demonstrate that gradually increasing temperature allows T. dendrolimi to complete diapause earlier than at present while increasing its potential pest control capacity and providing additional flexibility in mass production of T. dendrolimi.

1H-NMR-guided isolation of enantiomeric coumarin-monoterpenes with anti-inflammatory activity from Gerbera piloselloides.

1H-NMR guided fractionation led to the isolation of twenty-two coumarin monoterpenes from the whole plant of Gerbera piloselloides, among which fourteen were undescribed. All coumarin monoterpenes were initially found to be racemates without optical activity. Subsequently, eleven pairs of optically pure enantiomers were successfully separated by chiral phase HPLC. Their structures and absolute configurations were unambiguously determined based on their spectroscopic data, calculated/experimental electronic circular dichroism (ECD) data, and X-ray diffraction analysis. Bioassays in LPS-treated RAW 264.7 cells revealed that the four compounds possessed moderate anti-inflammatory activity. In addition, the correlations between the cotton effect (CE) from δ-lactone at approximately 210-220 nm in CD spectra and γ-C or the ring fused at γ-C of the skeleton were reported for the first time.