Phage-display library biopanning and bioinformatic analysis yielded a high-affinity peptide to inflamed vascular endothelium both in vitro and in vivo.

Vascular inflammation is considered the primary pathological condition occurring in many chronic diseases. To detect the inflamed endothelium via imaging analysis or guide the drug to target lesions is therefore important for early diagnosis and treatment of vascular inflammatory diseases. In this study, we obtained a novel peptide NTTTH through high throughout biopanning and bioinformatic analysis. In vitro studies indicated that NTTTH homologs could especially target inflamed vascular endothelial cells, as imaging quantitative analysis indicated that the mean of integrated optical density (MIOD) and mean of stained area (MSA) were significantly higher versus control (P<0.05). In vivo studies showed that, after intravenous injection of enhanced green fluorescent protein (EGFP)-labeled NTTTH homologs into the lipopolysaccharide (LPS)-inflamed mice for 30min, NTTTH homologs were distributed in highly vascularized and inflamed organs like liver and kidney. As a control, little fluorescence could be detected in mice injected with EGFP alone. Cryosection showed that NTTTH homologs especially targeted inflamed vasculatures but not normal ones. We did not detect fluorescence signal in either normal or inflamed mice which were injected with EGFP alone. The results suggested the role of NTTTH homologs in guiding the targeted binding of EGFP to inflamed vasculature and the potential usage for imaging detection and drug delivery.

Anti-inflammatory effect of Sanshuibaihu decoction may be associated with nuclear factor-kappa B and p38 MAPK alpha in collagen-induced arthritis in rat.

Sanshuibaihu decoction (SSBH) is an anti-arthritic Chinese herbal formula which has been used in the treatment of rheumatoid arthritis (RA) for many years. We herein aimed to confirm its anti-arthritic effect and explore the potential mechanism of action on collagen-induced arthritis (CIA) in rats. CIA was induced by immunizing 50 female Wistar rats with bovine type II collagen. 13 days following the immunization rats with CIA were treated with SSBH (50mg/kg), leflunomide (LEF) (10mg/kg) and physiological saline for 30 days, and rats without CIA were left untreated. After the treatment, paw edema was obviously improved in SSBH-treated rats, with the significant difference of arthritis score (F=6.032, P=0.006) observed between the three treated groups. In pathological observation, SSBH-treated rats showed a significant improvement of inflammatory infiltration, synovial hyperplasia, cartilage and bone destruction and joint fusion. After the treatment of SSBH, radiological score of knee (t=11.504, P=0.000) and ankle joints (t=9.250, P=0.000) was decreased significantly. In situ hybridization on joint tissue section indicated only slight synovial hyperblastosis and expression of NF-kappaB in SSBH-treated rats. Image analysis indicated a significant difference of means of integrated optical density (MIOD) (F=3.956, P=0.040) and means of stained area (MSA) (F=3.867, P=0.032) of NF-kappaB between the three treated groups. MIOD and MSA of SSBH-treated group were significantly lower vs control. Enzyme linked immunosorbent assay (ELISA) showed a significant difference (F=10.167, P=0.000) of the amount of p-p38 MAPKalpha in the three treated groups. The detected amount of p-p38 MAPKalpha in SSBH-treated group was significantly lower vs control. These results show SSBH has an inhibiting effect on CIA, which may be associated with NF-kappaB and p38 MAPKalpha.