Dataset Information

Matrine Ameliorates Colorectal Cancer in Rats via Inhibition of HMGB1 Signaling and Downregulation of IL-6, TNF-?, and HMGB1.

ABSTRACT: Matrine may be protective against colorectal cancer (CRC), but how it may work is unclear. Thus, we explored the underlying mechanisms of matrine in CRC. Matrine-related proteins and CRC-related genes and therapeutic targets of matrine in CRC were predicted using a network pharmacology approach. Five targets, including interleukin 6 (IL-6), the 26S proteasome, tumor necrosis factor alpha (TNF-?), transforming growth factor beta 1 (TGF-?1) and p53, and corresponding high-mobility group box 1 (HMGB1) signaling and T helper cell differentiation were thought to be associated with matrine's mechanism. Expression of predicted serum targets were verified in a 1,2-dimethylhydrazine dihydrochloride-induced CRC model rats that were treated with matrine (ip) for 18 weeks. Data show that matrine suppressed CRC growth and decreased previously elevated expression of IL-6, TNF-?, p53, and HMGB1. Matrine may have had a therapeutic effect on CRC via inhibition of HMGB1 signaling, and this occurred through downregulation of IL-6, TNF-?, and HMGB1.

SUBMITTER: Fan H

PROVIDER: S-EPMC5818890 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Matrine Ameliorates Colorectal Cancer in Rats via Inhibition of HMGB1 Signaling and Downregulation of IL-6, TNF-α, and HMGB1.

Fan Huizhen H Jiang Chunyan C Zhong Baoyuan B Sheng Jianwen J Chen Ting T Chen Qingqing Q Li Jingtao J Zhao Hongchuan H

Journal of immunology research 20180110

Matrine may be protective against colorectal cancer (CRC), but how it may work is unclear. Thus, we explored the underlying mechanisms of matrine in CRC. Matrine-related proteins and CRC-related genes and therapeutic targets of matrine in CRC were predicted using a network pharmacology approach. Five targets, including interleukin 6 (IL-6), the 26S proteasome, tumor necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-β1) and p53, and corresponding high-mobi ...[more]

PMID: 29546074

Similar Datasets

Project description:BACKGROUND AND OBJECTIVE:Complement activation as an early and important inflammatory process contributes to multiple organ dysfunction after trauma. We have recently shown that complement inhibition by decay-accelerating factor (DAF) protects brain from blast-overpressure (BOP)-induced damage. This study was conducted to determine the effect of DAF on acute lung injury induced by BOP exposure and to elucidate its possible mechanisms of action. METHODS:Anesthetized adult male Sprague-Daley rats were exposed to BOP (120 kPa) from a compressed air-driven shock tube. Rats were randomly assigned to three experimental groups: 1) Control (no BOP and no DAF treatment), 2) BOP (120 kPa BOP exposure), and 3) BOP followed by treatment with rhDAF (500?g/kg, i.v) at 30 minutes after blast. After a recovery period of 3, 24, or 48 hours, animals were euthanized followed by the collection of blood and tissues at each time point. Samples were subjected to the assessment of cytokines and histopathology as well as for the interaction of high-mobility-group box 1 (HMGB1) protein, NF-?B, receptor for advanced glycation end products (RAGE), C3a, and C3aR. RESULTS:BOP exposure significantly increased in the production of systemic pro- and anti-inflammatory cytokines, and obvious pathological changes as characterized by pulmonary edema, inflammation, endothelial damage and hemorrhage in the lungs. These alterations were ameliorated by early administration of rhDAF. The rhDAF treatment not only significantly reduced the expression levels of HMGB1, RAGE, NF-?B, C3a, and C3aR, but also reversed the interaction of C3a-C3aR and nuclear translocation of HMGB1 in the lungs. CONCLUSIONS:Our findings indicate that early administration of DAF efficiently inhibits systemic and local inflammation, and mitigates blast-induced lung injury. The underlying mechanism might be attributed to its potential modulation of C3a-C3aR-HMGB1-transcriptional factor axis. Therefore, complement and/or HMGB1 may be potential therapeutic targets in amelioration of acute lung injury after blast injury.

Project description:Dao-Chi powder (DCP) has been widely used in the treatment of inflammatory diseases in the clinical practice of traditional Chinese medicine, but has not been used in acute pancreatitis (AP). This study aimed to evaluate the effect of DCP on severe AP (SAP) and SAP-associated intestinal and cardiac injuries. To this end, an SAP animal model was established by retrograde injection of 3.5% taurocholic acid sodium salt into the biliopancreatic ducts of rats. Intragastric DCP (9.6 g/kg.BW) was administered 12 h after modeling. The pancreas, duodenum, colon, heart and blood samples were collected 36 h after the operation for histological and biochemical detection. The tissue distributions of the DCP components were determined and compared between the sham and the SAP groups. Moreover, molecular docking analysis was employed to investigate the interactions between the potential active components of DCP and its targets (Nrf2, HO-1, and HMGB1). Consequently, DCP treatment decreased the serum levels of amylase and the markers of gastrointestinal and cardiac injury, further alleviating the pathological damage in the pancreas, duodenum, colon, and heart of rats with SAP. Mechanistically, DCP rebalanced the pro-/anti-inflammatory cytokines and inhibited MPO activity and MDA levels in these tissues. Furthermore, Western blot and RT-PCR results showed that DCP intervention enhanced the expression of Nrf2 and HO-1 in the duodenum and colon of rats with SAP, while inhibiting the expression of HMGB1 in the duodenum and heart. HPLC-MS/MS analysis revealed that SAP promoted the distribution of ajugol and oleanolic acid to the duodenum, whereas it inhibited the distribution of liquiritigenin to the heart and ajugol to the colon. Molecular docking analysis confirmed that the six screened components of DCP had relatively good binding affinity with Nrf2, HO-1, and HMGB1. Among these, oleanolic acid had the highest affinity for HO-1. Altogether, DCP could alleviated SAP-induced intestinal and cardiac injuries via inhibiting the inflammatory responses and oxidative stress partially through regulating the Nrf2/HO-1/HMGB1 signaling pathway, thereby providing additional supportive evidence for the clinical treatment of SAP.

Dataset Information

Matrine Ameliorates Colorectal Cancer in Rats via Inhibition of HMGB1 Signaling and Downregulation of IL-6, TNF-?, and HMGB1.

Publications

Matrine Ameliorates Colorectal Cancer in Rats via Inhibition of HMGB1 Signaling and Downregulation of IL-6, TNF-<i>α</i>, and HMGB1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets