Jinzhen Oral Liquid alleviates lipopolysaccharide-induced acute lung injury through modulating TLR4/MyD88/NF-κB pathway.

BACKGROUND: Acute lung injury (ALI) has the attribution of excessive inflammation of the lung. Jinzhen oral liquid (JO), a famous Chinese recipe used to treat ALI, has a favorable therapeutic effect on ALI. However, its anti-inflammatory mechanism has not been extensively studied. PURPOSE: This study was to elucidate the effects of JO on lipopolysaccharide (LPS)-induced ALI and its molecular mechanism. METHODS: An ALI model was established by intratracheal instillation of LPS (2 mg/50 µl). The open field experiment was carried out to explore the spontaneous movement and exploratory behavior of ALI mice. Cytokines levels concentrations (IL-6, IL-10 and TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). Network pharmacology was used to predict the mechanism of JO against ALI. Immunofluorescence, co-immunoprecipitation, fluorescence resonance energy transfer (FRET), Western blot and RT-PCR were used to verify the molecular mechanisms of JO. RESULTS: The in vivo results suggested that JO (1, 2, 4 g/kg) dose-dependently improved the exercise performance of mice and reduced the lung W/D weight ratio as well as the production of IL-6 and TNF-α, but increased the release of IL-10 in the ALI group. The network pharmacological analysis demonstrated that the Toll-like receptor (TLR) pathway might be the fundamental action mechanisms of JO against ALI. Immunofluorescence staining and co-immunoprecipitation analysis showed that JO decreased the expression levels of TLR4 and MyD88 and reduced their interaction in the lung tissue of ALI mice. Meanwhile, JO decreased nuclear translocation and phosphorylation of NF-κB P65. The results from cellular experiments were in line with those in vivo. The FRET experiment also confirmed that JO disturbed the interaction of TLR4 and MyD88. Subsequently, we also found that the six indicative components of JO have the similar therapeutic effect as JO. CONCLUSIONS: In summary, we suggested that JO suppressed the TLR4/MyD88/NF-κB signaling pathway, thus inhibiting LPS-induced ALI in vitro and in vivo. The clarified mechanism provided an important theoretical basis and a novel treatment strategy for the ALI treatment of JO.

Diverse sesquiterpenoids from Litsea lancilimba Merr. with potential neuroprotective effects against H2O2-induced SH-SY5Y cell injury.

Five undescribed sesquiterpenoids (1-5), and nine known sesquiterpenoids (6-14) were obtained from the fruits of Litsea lancilimba Merr. by LC-MS/MS molecular networking strategies. Litsemene A (1) possessed a unique 8-member ring through unexpected cyclization of the methyl group on C-10 of guaiane. Their structures were elucidated by spectroscopic techniques including IR, UV, NMR, HR-ESI-MS, and their absolute configurations were assigned by ECD calculations. All isolated sesquiterpenoids were analyzed by bioinformatics and evaluated for their neuroprotective effects against H2O2-induced injury in human neuroblastoma SH-SY5Y cells.

Lignans with neuroprotective activity from the fruits of Crataegus pinnatifida.

Seven lignans (1a/1b-2a/2b and 3-5), including six new compounds (1b, 2a/2b, 3-5), were isolated from the fruits of Crataegus pinnatifida. Their structures were elucidated by comprehensive spectroscopic analyses. Compounds 1b/1b-2a/2b were two pairs of enantiomers and the absolute configurations were determined by comparison of their experimental and calculated ECD spectra. Moreover, bioinformatics analysis suggested that more than a third of diseases were related to the nervous system. Therefore, all compounds were evaluated for neuroprotective effects toward human neuroblastoma SH-SY5Y cells injury induced by H2O2. Among them, compound 1a exhibited moderate protective effect.

UV-guided isolation of enantiomeric polyacetylenes from Bupleurum scorzonerifolium Willd. with inhibitory effects against LPS-induced NO release in BV-2 microglial cells.

UV-guided fractionation led to the isolation of thirteen new polyacetylenes (1-13) from the roots of Bupleurum scorzonerifolium Willd. All polyacetylenes were analyzed as racemates since the lack of optical activity and Cotton effects in the ECD spectra. The sequent chiral-phase HPLC resolution successfully gave twelve pairs of enantiomers 1a/1b and 3a/3b-13a/13b. Their structures were elucidated based on the HRESIMS and NMR data analyses. The absolute configurations were determined by the combination of Snatzke's method, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Using Griess methods and MTT assays, polyacetylenes 1a, 3a, 4a/4b-12a/12b, and 13a displayed inhibitory activities against LPS-induced NO release in BV-2 microglial cells.