Inhibitory effect of Triperygium wilfordii polyglucoside on dipeptidyl peptidase I in vivo and in vitro

Abstract

BackgroudDipeptidyl peptidase I (DPPI), a lysosomal cysteine protease is derived from granule immune cells including mast cell, neutrophils, and toxicity T cells. DPPI can activate serine proteases by removal of dipeptides from N-termini of the pro-proteases, resulting in granule immune cells activation which involved in physiological or pathological responses. Triperygium Wilfordii Polyglucoside (TWP) is one of the traditional Chinese medicines, and commonly used in rheumatoid arthritis (RA) treatment. The present study intended to evaluate the effects of TWP on DPPI activity. MethodsIn vivo and in vitro studies were carried out to investigate the functions of TWP or triptolide (TP) on DPPI activities in serum, tissues of CIA rats. Rats were divided into five groups randomly: normal group, untreated CIA rat group, TWP treatment CIA groups (the low dose 2.5mg/100g body-weight and high dose 5mg/100g body-weight), and TP treatment CIA group (4μg/100g body-weight). Arthritis development was monitored visually, and joint pathology was examined radiologically. Total protein concentrations in synovial fluids (SFs) were determined by BCA method. Serums and tissue homogenates from CIA rats were collected and DPPI activities were detected using fluorescence substrate GF-AFC. The in vitro interactions between DPPI in serums or in tissue homogenates and TWP or TP were assessed. ResultsTWP-treated CIA rats showed a significant improvement in bone erosion. TWP significantly suppressed paw swelling and total protein concentration in the SFs of CIA rats compared with untreated CIA rats. The elevated activities of DPPI in serums or tissues of CIA rats were significantly inhibited by TWP, but not by TP in vivo. The inhibitory effects of TWP on DPPI activities were also confirm by in vitro study. ConclusionOne of the therapeutic functions of TWP in RA treatment could be inhibiting DPPI activity in serums and synovial tissue produced during RA development, and then reducing inflammatory serine proteases activities and further recovering CIA rats from RA symptoms.