Context: The seed of Litchi chinensis Sonn., a famous traditional Chinese medicine, was recently reported to enhance cognitive function by inhibiting neuronal apoptosis in rats. Objective: We determined whether the seed of Litchi chinensis fraction (SLF) can ameliorate hippocampal neuronal injury via the AKT/GSK-3b pathway. Materials and methods: We established Alzheimer's disease (AD) model by infusing Ab 25-35 into the lateral ventricle of Sprague-Dawley (SD) rats and randomly divided into five groups (n ¼ 10): sham, donepezil and SLF (120, 240 and 480 mg/kg/d). Rats were treated by intragastric administration for 28 consecutive days. Spatial learning and memory were evaluated with Morris water maze, while protein expression of AKT, GSK-3b and tau in the hippocampal neurons was measured by Western blotting and immunohistochemistry. Results: On the fifth day, escape latency of the AD model group was 45.78 ± 2.52 s and that of the sham operative group was 15.98 ± 2.32 s. SLF could improve cognitive functions by increasing the number of rats that crossed the platform (p < 0.01), and their platform quadrant dwell time (p < 0.05). The protein expression level of AKT was upregulated (p < 0.001), while that of GSK-3b and tau (p < 0.01) was remarkably downregulated in the hippocampal CA1 area. Discussion and conclusions: To our knowledge, the present study is the first to show that SLF may exert neuroprotective effect in AD rats via the AKT/GSK-3b signalling pathway, thereby serving as evidence for the potential utility of SLF as an effective drug against AD.

Background:Sanguisorba Officinalis L. (SO) is a well-known traditional Chinese medicine (TCM), commonly applied to treat complex diseases, such as anticancer, antibacterial, antiviral, anti-inflammatory, anti-oxidant and hemostatic effects. Especially, it has been reported to exert anti-tumor effect in various human cancers. However, its effect and pharmacological mechanism on hepatocellular carcinoma (HCC) remains unclear.Methods: In this study, network pharmacology approach was applied to characterize the underlying mechanism of SO on HCC. Active compounds and potential targets of SO, as well as related genes of HCC were obtained from the public databases, the potential targets and signaling pathways were determined by protein-protein interaction (PPI), gene ontology (GO) and pathway enrichment analyses. And the compound-target and target-pathway networks were constructed. Subsequently, in vitro experiments were also performed to further verify the anticancer effects of SO on HCC.Results: By using the comprehensive network pharmacology analysis, 41 ingredients in SO were collected from the corresponding databases, 12 active ingredients screened according to their oral bioavailability and drug-likeness index, and 258 potential targets related to HCC were predicted. Through enrichment analysis, SO was found to show its excellent therapeutic effects on HCC through several pathways, mainly related to proliferation and survival via the EGFR, PI3K/AKT, NFκB and MAPK signaling pathways. Additionally, in vitro, SO was found to inhibit cell proliferation, induce apoptosis and down-regulate cell migration and invasion in various HCC cells. Moreover, western blot analysis showed that SO treatment down-regulated the expression of p-EGFR, p-PI3K, p-AKT, p-NFκB and p-MAPK proteins in HepG2 cells. These results validated that SO exerted its therapeutic effects on HCC mainly by the regulation of cell proliferation and survival via the EGFR/MAPK and EGFR/PI3K/AKT/NFκB signaling pathways.Conclusion: Taken together, this study, revealed the anti-HCC effects of SO and its potential underlying therapeutic mechanisms in a multi-target and multi-pathway manner.

Previous studies have demonstrated that tannin could inhibit the proliferation and angiogenesis of cancer cells. However, the mechanism(s) associated with its antitumor effect remains unclear. Here, we investigated the effects of 3,3',4'-trimethylellagic acid (TMEA), a tannin compound isolated from Sanguisorba officinalis L., on the proliferation, angiogenesis, and apoptosis in cancer cells, as well as the underlying mechanism(s) related to its antitumor activity. TMEA was isolated from Sanguisorba officinalis L. by silica gel column chromatography. Molecular docking was carried out to assess active pocket binding between TMEA and vascular endothelial growth factor receptor 2 (VEGFR2). The antiangiogenic effect of TMEA on the migration and tube formation was detected in HUVECs by wound healing and tube formation assays, respectively. The antitumor effects of TMEA on the cell proliferation were determined in HepG2, A549, and SW620 cells by MTS assay in vitro and on the tumor growth of SW620 xenografts bearing in nude mice in vivo. The mRNA expression of Bcl-2, Bax, caspase-3, VEGF, PI3K, and mTOR were measured by qRT-PCR and protein expression of Bcl-2, Bax, caspase-3, VEGF, PI3K, and mTOR by Western blotting, and the protein expression of Bcl-2, Bax, caspase-3 and CD31 were detected by immunohistochemical analysis in vivo, respectively. The results showed that TMEA combined with VEGFR2 in the functional pockets of Asn223A, Gly922A, and Leu840A and inhibited the proliferation, migration, tube formation, and expression of VEGF and its downstream signaling mediators in HUVECs. TMEA also significantly inhibited the proliferation of HepG2, A549, and SW620 cancer cells in vitro, and suppressed the growth of SW620 tumors in vivo. Moreover, TMEA upregulated the expression of proapoptotic factors Bax and caspase-3 and downregulated the expression of antiapoptotic factors CD31 and Bcl-2 in cancer cells and/or tumor tissues. The data indicate that TMEA executes its anticancer activity by inducing

Blood–brain barrier (BBB) dysfunction has been implicated in Alzheimer's disease (AD) and is closely linked to the release of proinflammatory cytokines in brain capillary endothelial cells. We have previously reported that lychee seed polyphenols (LSP) exerted anti‐neuroinflammatory effect. In this study, we aimed to explore the protective effect of LSP on BBB integrity. The monolayer permeability of bEnd.3 cells, and the mRNA level and protein expression of tight junction proteins (TJs), including Claudin 5, Occludin, and ZO‐1, were examined. In addition, the inhibition of Aβ(25–35)‐induced NLRP3 inflammasome activation, and the autophagy induced by LSP were investigated by detecting the expression of NLRP3, caspase‐1, ASC, LC3, AMPK, mTOR, and ULK1. Furthermore, the cognitive function and the expression of TJs, NLRP3, caspase‐1, IL‐1β, and p62 were determined in APP/PS1 mice. The results showed that LSP significantly decreased the monolayer permeability and inhibited the NLRP3 inflammasome in Aβ(25–35)‐induced bEnd3 cells. In addition, LSP induced autophagy via the AMPK/mTOR/ULK1 pathway in bEnd.3 cells, and improved the spatial learning and memory function, increased the TJs expression, and inhibited the expression of NLRP3, caspase‐1, IL‐1β, and p62 in APP/PS1 mice. Therefore, LSP protects BBB integrity in AD through inhibiting Aβ(25–35)‐induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1‐mediated autophagy.

The pathogenesis of Huntington's disease (HD), an inherited progressive neurodegenerative disease, is highly associated with the cytotoxicity-inducing mutant huntingtin (mHtt) protein. Emerging evidence indicates that autophagy plays a pivotal role in degrading aggregated proteins such as mHtt to enhance neuronal viability. In this study, by employing preparative high-performance liquid chromatography (pre-HPLC), ultra-high performance liquid chromatography diode-array-detector quadrupole time-of-flight mass spectrometry (UHPLC-DAD-Q-TOF-MS) and nuclear magnetic resonance (NMR), three escins, escin IA (EA), escin IB (EB) and isoescin IA (IEA), were isolated and identified from the seed of Aesculus chinensis Bge. (ACB). After EGFP-HTT74-overexpressing HT22 cells were treated with EA, EB and IEA at safe concentrations, the clearance of mHtt and mHtt-induced apoptosis were investigated by Western blot, immunofluorescence microscopy and flow cytometry methods. In addition, the autophagy induced by these escins in HT22 cells was monitored by detecting GFP-LC3 puncta, P62 and LC3 protein expression. The results showed that EA, EB and IEA could significantly decrease mHtt levels and inhibit its induced apoptosis in HT22 cells. In addition, these three saponins induced autophagic flux by increasing the ratio of RFP-LC3 to GFP-LC3, and by decreasing P62 expression. Among the tested escins, EB displayed the best autophagy induction, which was regulated via both the mTOR and ERK signaling pathways. Furthermore, the degradation of mHtt and the commensurate decrease in its cytotoxic effects by EA, EB and IEA were demonstrated to be closely associated with autophagy induction, which depended on ATG7. In conclusion, we are the first to report that the escins, including EA, EB and IEA are novel autophagy inducers that degrade mHtt and inhibit mHtt-induced apoptosis in vitro and in vivo. As a result of these findings, the triterpenoid saponins in ACB might be considered to be promising candidates for the treatment of HD in the future.