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Forsythiaside attenuates lipopolysaccharide induced inflammatory responses in the bursa of Fabricius of chickens by downregulating the NF κB signaling pathway

Journal name:Experimental and Therapeutic Medicine
Document No.:Pages: 179-184 DOI: 10.3892/etm.2013.1378
Document URL: http://www.spandidos-publications.com/etm/7/1/179
Date publication:October 31, 2013


Glutathione S-transferase (GST) is the key enzyme in multidrug resistance (MDR) of tumour. Inhibition of the expression or activity of GST has emerged as a promising therapeutic strategy for the reversal of MDR. Coniferyl ferulate (CF), isolated from the root of Angelica sinensis (Oliv.) Diels (Radix Angelicae sinensis, RAS), showed strong inhibition of human placental GST. Its 50% inhibition concentration (IC50) was 0.3μM, which was greater than a known GSTP1-1 inhibitor, ethacrynic acid (EA), using the established high-throughput screening model. Kinetic analysis and computational docking were used to examine the mechanism of GST inhibition by CF. Computational docking found that CF could be fully docked into the gorge of GSTP1-1. The further exploration of the mechanisms showed that CF was a reversible noncompetitive inhibitor with respect to GSH and CDNB, and it has much less cytotoxicity. Apoptosis and the expression of P-gp mRNA were evaluated in the MDR positive B-MD-C1 (ADR+/+) cell line to investigate the MDR reversal effect of CF. Moreover, CF showed strong apoptogenic activity and could markedly decrease the overexpressed P-gp. The results demonstrated that CF could inhibit GST activity in a concentration-dependent manner and showed a potential MDR reversal effect for antitumour adjuvant therapy.


Coniferyl ferulate standard (purity ≥ 98%) was purchased for structure identification from Chengdu Herbpurify CO., LTD, Chengdu, China (QC number A-001-120726).

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