Anti-inflammatory effect, plasma effective components and therapeutic targets of Huanglian Jiedu Decoction on ulcerative colitis mice / 中国中药杂志

This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1β, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P<0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P<0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1β, IL-6 and TNF-α were increased significantly in the model group(P<0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P<0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1β, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.

Mechanism and clinical significance of anti-apoptotic gene bcl-2 expression in diffuse large B-cell lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the molecular mechanism and prognostication of bcl-2 protein expression in different subgroups of diffuse large B-cell lymphoma(DLBCL) in Guangxi Zhuang Autonomous Region, China.</p><p><b>METHODS</b>Immunohistochemical stains for CD10, bcl-6, MUM-1, bcl-2 and NF-κB were performed in 214 cases of DLBCL. The Hans immunologic classification was applied to classify DLBCL into GCB and non-GCB subgroups. Using a dual-probe fluorescence in-situ hybridization (FISH) assay, IgH/bcl-2 gene translocation and bcl-2 amplification were analyzed.</p><p><b>RESULTS</b>In 214 cases of DLBCL, 30.8% (66/214) of cases were GCB and 69.2% (148/214) were non-GCB. Twenty-seven point three percent (18/66) of GCB subgroups and 59.5% (88/148) of non-GCB subgroups had bcl-2 protein expression, with a significant difference (P < 0.01). IgH/bcl-2 translocation was positive in 3.7% (8/214) of cases, even majority of them (6/8) was found in GCB subgroup, while represented only 9.1% of GCB case. There was a significant difference (P = 0.02) in bcl-2 gene amplification between GCB (27/66, 40.9%) and non-GCB subgroup (86/148, 58.1%). Among non-GCB cases, the expression of bcl-2 was correlated with that of NF-κB expression and bcl-2 gene amplification (r = 0.216 and 0.219, respectively, P < 0.05). No similar correlation was observed in GCB cases. The overall survival time of bcl-2-positive patients (31.4 ± 3.8) months was shorter than that of bcl-2-negative patients (40.2 ± 4.2) months. In conjunction with immunophenotypes and clinical stages, the bcl-2 positive patients had a 1.89 times higher risk than that of the bcl-2 negative patients.</p><p><b>CONCLUSIONS</b>Majority of the cases were prognostically unfavorable non-GCB subgroups among DLBCL, which were characterized by high frequency of bcl-2 gene amplification and low frequency of IgH/bcl-2 translocation. The anti-apoptotic gene bcl-2 was frequently expressed in non-GCB subgroups and closely related to the gene amplification and NF-κB activation. bcl-2 positive patients had more short overall survival times, would face significant higher risk of death, these results suggested that bcl-2 could be a prognostic marker independent to clinical staging and immunophenotyping.</p>