Fuzi (Aconitum carmichaelii Debx) has been traditionally used for the treatment of ulcerative colitis (UC) in China for thousands of years. The total alkaloids of A. carmichaelii (AAC) have been considered as the main medicinal components of fuzi, whereas its underlying anti-UC mechanisms remain elusive. In the present study, the dextran sulfate sodium (DSS)-induced UC mice model, which was consistent with the symptoms and pathological features of human UC, was established to comprehensively evaluate the anti-UC effects of AAC. The results indicated that AAC effectively improved the weight loss, disease activity index (DAI), spleen hyperplasia, and colon shortening, and thus alleviated the symptoms of UC mice. Meanwhile, AAC not only inhibited the MPO enzyme and the abnormal secretion of inflammatory cytokines (TNF-α, IL-1β, IL-6, IFN-γ, and IL-17A) and suppressed the overexpression of inflammatory mediators (TNF-α, IL-1β, and IL-6) of mRNA but also reduced the phosphorylation of p38 MAPK, ERK, and JNK, and the protein expressions of NF-κB, IκB-α, STAT3, and JAK2 in the colon tissue. Furthermore, the LC-MS/MS quantitative determination suggested that the three low toxic monoester alkaloids were higher in both contents and proportion than that of the three high toxic diester alkaloids. Additionally, molecular docking was hired to investigate the interactions between alkaloid-receptor complexes, and it suggested the three monoester alkaloids exhibited higher binding affinities with the key target proteins of MAPK, NF-κB, and STAT3. Our finding showcased the noteworthy anti-UC effects of AAC based on the MAPK/NF-κB/STAT3 signaling pathway, which would provide practical and edge-cutting background information for the development and utilization of A. carmichaelii as a potential natural anti-UC remedy.
A new isocoumarin glycoside, 3R-(+)-5-O-[6'-O-acetyl]-α-D-glucopyranosyl-5-hydroxymellein (1), and a new phenylethanol glycoside, (-)-phenylethyl-8-O-α-L-rhamno-pyranoside (2), were isolated from the ethyl acetate extract of the fungus Xylaria sp. cfcc 87468, together with five known steroids, β-sitosterol (3), stigmast-4-en-3-one (4), ergosterol (5), (22E)-cholesta-4,6,8(14),22-tetraen-3-one (6), and 4α-methyl- ergosta-8(14),24(28)-dien-3β-ol (7). The structures of compounds 1 and 2 were elucidated by MS, extensive 1D and 2D NMR spectroscopy, and the circular dichroism (CD) spectroscopy.
Background: Danshen Baibixiao (DB) is a traditional Chinese medicine formula, which has been used to treat psoriasis for decades. Although DB shows good efficacy in clinical practice, the pharmacological effects and underlying mechanisms of DB remain elusive. This study aimed to evaluate the anti-psoriatic effects of DB and explore its underlying mechanisms in an imiquimod (IMQ)-induced psoriasis-like mouse model. Materials and methods: DB was orally administered on IMQ-induced psoriatic mice. Psoriasis area severity index (PASI) was used to evaluate the severity of the inflammation in skin, and histological changes were evaluated by hematoxylin and eosin (H and E) staining. Levels of inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-17A, IL-23, IL-6, IL-1 β and IL-22 in serum were assessed by enzyme-linked immunosorbent assay (ELISA). mRNA expressions of IL-17A, IL-23, IL-6 and IL-22 were determined by real-time polymerase chain reaction (PCR). Expression levels of proteins related to NF-κB, STAT3 and MAPKs signaling pathways were measured by western blotting (WB). Results: DB significantly ameliorated the psoriatic symptoms in IMQ-induced mice. The serum levels of inflammatory cytokines (TNF-α, IL-17A, IL-23, IL-6, IL-1β and IL-22) were decreased, and mRNA expressions of IL-17A, IL-23, IL-6 and IL-22 in skin tissues were down-regulated. Moreover, WB analysis indicated that DB inhibited the activation of NF-κB, STAT3 and MAPKs signaling pathways. Conclusion: This study confirms the anti-psoriatic activity of DB in IMQ-induced psoriasis-like mice. The possible mechanism may relate to the activities of regulating the IL-23/TH-17 axis and suppressing the activation of NF-κB, STAT3 and MAPKs signaling pathways.
Insufficient trophoblast migration/invasion is associated with the preeclampsia (PE) development. Recently, microRNAs (miRNAs) have been confirmed to be involved in the pathogenesis of PE. The aim of the present study was to evaluate whether miRNAs is involved in the procession of PE by regulating the migration/invasion of trophoblast. First, we compared the expression profiles of miRNAs between normal and preeclamptic placentas using microarray. Validation analysis of miR-20b level in placentas and peripheral blood specimens was performed using quantitative reverse transcription PCR (qRT-PCR). Then, the effects of miR-20b on trophoblast cell migration and invasion were evaluated using wound healing assay and transwell migration assay. Further bioinformatics analysis, luciferase reporter assays and Western blot were performed to identify its target genes. The correlation between miR-20b and matrix metalloproteinase-2 (MMP-2) in placentas was determined by Pearson's correlation coefficient. Finally, HTR8/SVneo cells were co-transfected with miR-20b inhibitor and si-MMP-2 to explore the molecular mechanism by which miR-20b functions in the trophoblast migration/invasion. We found that miR-20b was elevated in placentas and peripheral blood specimens from preeclampsia patients. Further results show that overexpression of miR-20b significantly inhibited the invasiveness of human trophoblast cells, whereas miR-20b knockdown enhanced trophoblast cell invasion. Matrix metalloproteinase-2 (MMP-2), the most common enzymes in remodeling extracellular matrix components for metastasis, was proved to be a direct target of miR-20b. Inhibition of MMP-2 by siRNA could reverse the promoting effect of miR-20b inhibition on the invasion of trophoblast cells. Taken together, our study indicates that miR-20b inhibited trophoblastic invasion by targeting MMP2. The miR-20b/MMP-2 axis may provide novel insights into understanding the molecular pathogenesis of PE and may be a prognostic biomarker and therapeutic target for PE.
To solve the problem that current dynamic intention recognition methods fail to make full use of time domain variation information between multi-temporal group targets, which leads to low accuracy of intention recognition. This paper proposes a bidirectional convolutional long short term memory-attention network for marine formation target intention recognition. The network takes the multi-source trajectory data of the marine ship formation target as the input, extracts and uses the target change rule and time domain characteristics of the Marine formation data, and trains the model to have the ability to independently learn the weight of information in different time periods. The simulation results show that the method has good performance and can meet the needs of practical application.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
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