Ellagic acid (EA) is a kind of polyphenol compound extracted from a variety of herbs, such as paeoniae paeoniae, raspberry, Chebule, walnut kernel, myrrh, loquat leaf, pomegranate bark, quisquite, and fairy herb. It has anti-tumor, anti-oxidation, anti-inflammatory, anti-mutation, anti-bacterial, anti-allergic and multiple pharmacological properties. Studies have shown its anti-tumor effect in gastric cancer, liver cancer, pancreatic cancer, breast cancer, colorectal cancer, lung cancer and other malignant tumors, mainly through inducing tumor cell apoptosis, inhibiting tumor cell proliferation, inhibiting tumor cell metastasis and invasion, inducing autophagy, affecting tumor metabolic reprogramming and other forms of anti-tumor efficacy. Its molecular mechanism is mainly reflected in inhibiting the proliferation of tumor cells through VEGFR-2 signaling pathway, Notch signaling pathway, PKC signaling pathway and COX-2 signaling pathway. PI3K/Akt signaling pathway, JNK (cJun) signaling pathway, mitochondrial pathway, Bcl-2 / Bax signaling pathway, TGF-β/Smad3 signaling pathway induced apoptosis of tumor cells and blocked EMT process and MMP SDF1α/CXCR4 signaling pathway inhibits the metastasis and invasion of tumor cells, induces autophagy and affects tumor metabolic reprogramming to produce anti-tumor effects. At present, the analysis of the anti-tumor mechanism of ellagic acid is slightly lacking, so this study comprehensively searched the literature on the anti-tumor mechanism of ellagic acid in various databases, reviewed the research progress of the anti-tumor effect and mechanism of ellagic acid, in order to provide reference and theoretical basis for the further development and application of ellagic acid.

Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). But little is known about how alanine-serine-cysteine transporter type-2 (ASCT2), a high affinity glutamine transporter, affects HSC senescence and SASP during liver fibrosis. Here, we identified ASCT2 is mainly elevated in aHSCs and positively correlated with liver fibrosis in human and mouse fibrotic livers. We first discovered ASCT2 inhibition induced HSCs to senescence in vitro and in vivo. The proinflammatory SASP were restricted by ASCT2 inhibition at senescence initiation to prevent paracrine migration. Mechanically, ASCT2 was a direct target of glutaminolysis-dependent proinflammatory SASP, interfering IL-1α/NF-κB feedback loop via interacting with precursor IL-1α at Lys82. From a translational perspective, atractylenolide III is identified as ASCT2 inhibitor through directly bound to Asn230 of ASCT2. The presence of –OH group in atractylenolide III is suggested to be favorable for the inhibition of ASCT2. Importantly, atractylenolide III could be utilized to treat liver fibrosis mice. Taken together, ASCT2 controlled HSC senescence while modifying the proinflammatory SASP. Targeting ASCT2 by atractylenolide III could be a therapeutic candidate for liver fibrosis.

Depression is the most frequent psychiatric disorder in the world. Recent evidence has shown that stress‐induced GABAergic dysfunction in the nucleus accumbens (NAc) contributed to the pathophysiology of depression. However, the molecular mechanisms underlying these pathological changes remain unclear. In this study, mice were constantly treated with the chronic unpredictable mild stress (CUMS) till showing depression‐like behaviours expression. GABA synthesis, release and uptake in the NAc tissue were assessed by analysing the expression level of genes and proteins of Gad‐1, VGAT and GAT‐3 by qRT‐PCR and Western blotting. The miRNA/mRNA network regulating GABA was constructed based on the bioinformatics prediction software and further validated by dual‐luciferase reporter assay in vitro and qRT‐PCR in vivo, respectively. Our results showed that the expression level of GAT‐3, Gad‐1 and VGAT mRNA and protein significantly decreased in the NAc tissue from CUMS‐induced depression‐like mice than that of control mice. However, miRNA‐144‐3p, miRNA‐879‐5p, miR‐15b‐5p and miRNA‐582‐5p that directly down‐regulated the expression of Gad‐1, VGAT and GAT‐3 were increased. In the mRNA/miRNA regulatory GABA network, Gad‐1 and VGAT were directly regulated by binding seed sequence of miR‐144‐3p, and miR‐15b‐5p, miR‐879‐5p could be served negative post‐regulators by binding to the different sites of VGAT 3′‐UTR. Chronic stress causes the impaired GABA synthesis, release and uptake by up‐regulating miRNAs and down‐regulating mRNAs and proteins, which may reveal the molecular mechanisms for the decreased GABA concentrations in the NAc tissue of CUMS‐induced depression.

Pulmonary fibrosis induced by silica dust is an irreversible, chronic, and fibroproliferative lung disease with no effective treatment at present. BMSCs-derived exosomes (BMSCs-Exo) possess similar functions to their parent cells. In this study, we investigated the therapeutic potential and underlying molecular mechanism for BMSCs-Exo in the treatment of silica-induced pulmonary fibrosis. The rat model of experimental silicosis pulmonary fibrosis was induced with 1.0 mL of one-off infusing silica suspension using the non-exposed intratracheal instillation (50 mg/mL/rat). In vivo transplantation of BMSCs-Exo effectively alleviated silica-induced pulmonary fibrosis, including a reduction in collagen accumulation, inhibition of TGF-β1, and decreased HYP content. Treatment of BMSCs-Exo increased the expression of epithelial marker proteins including E-cadherin (E-cad) and cytokeratin19 (CK19) and reduced the expression of fibrosis marker proteins including α-Smooth muscle actin (α-SMA) after exposure to silica suspension. Furthermore, we found that BMSCs-Exo inhibited the expression of Wnt/β-catenin pathway components (P-GSK3β, β-catenin, Cyclin D1) in pulmonary fibrosis tissue. BMSCs-Exo is involved in the alleviation of silica-induced pulmonary fibrosis by reducing the level of profibrotic factor TGF-β1 and inhibiting the progression of epithelial-mesenchymal transition (EMT). Additionally, attenuation of the Wnt/β-catenin signaling pathway closely related to EMT may be one of the mechanisms involved in anti-fibrotic effects of exosomes.