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SummaryThe anti-inflammatory effects of (R)-2-(1H-imidazol-1-yl) ethyl-3-(1H-indol-3-yl)-2-(2-p-tolylacetamido)propanamide (RH-1402), a previous designed small molecule Gastrin releasing peptide (GRP) antagonist were evaluated in adjuvant-induced arthritic model of rats, and the inhibitory effect on neutrophil migration induced by GRP was determined by a transwell system experiment in vitro. The arthritis was induced by injection of Complete Freund's Adjuvant (CFA) containing 10 mg/mL of heat killed mycobacterium into the left hind footpad. Experimental rats were randomly divided into 6 groups, including control, placebo, positive control group, RH-1402 of low/middle/high dose group. Disease incidence and severity was evaluated through scoring of the paw edema and histologic features of joint synovial. Blood of all experimental rats was collected for IL-1β and TNF-α cytokine levels. A transwell system was used to investigate whether RH-1402 would inhibit neutrophils migrating up a gradient of GRP in vitro. RH-1402 (5 and 10mg/kg) significantly decreased adjuvant induced increased arthritis index during the administration period (days 14-20). Significant inhibition of joint synovial histological features can be found in the RH-1402 treated group, including alleviated Hyperplasia, Inflammatory of infiltration and activation of pannus formation. It also suppressed TNF-α and IL-1β level. 5mg/kg and 10mg/kg of RH-1402 significantly inhibited the effect of GRP on neutrophil migration with a dose dependent relationship. These findings indicate that RH-1402 have potential protective anti-inflammatory effects on experimental models of arthritis.

Traditional methods for mechanism studies such as immunoassays and immunocytochemical analysis are comparatively expensive and time-consuming and cannot analyze the targets in a living sample directly. In this paper, we developed a new fluorescence-active compound as a tool to directly study the defense signaling pathway of plant activators in plants. At first, with the active and commercial plant activators FBT and BTH as the starting materials, the two new active fluorescence plant activators N-FBT and N-BTH were designed and synthesized; the second, based on a system for the study of protein−protein interactions, a new nucleolus-tethering system (New-NoTS) especially for the study of interaction between small molecules and proteins was developed. With these two new tools, a series of studies for the defense signaling pathway of new plant activators was conducted. The results showed that N-FBT could interact with both SABP2 (SA pathway) and MYC2 (JA pathway) at the same time while N-BTH only interacted with SABP2. This means that FBT can induce the plant immune system by activating both SA and JA signaling pathways, which directly supported the extensive activities of FBT not only for disease but also for insects. On the other hand, with this method, the interactions between fluorescent plant activators and proteins could be studied directly by visualization.

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