OBJECTIVETo study the effect of oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) on adjusting angiogeneic/inflammatory mediators and ameliorating the pathology of bones in rats with collagen-induced arthritis (CIA).

METHODSWistar rat model of CIA was set up using bovine collagen type II. Fifty rats were divided into five groups randomly: normal, CIA model, DDB treatment, methotrexate (MTX) treatment, and combined DDB+MTX treatment. Ankle joints of rats were imaged with digital X-ray machine to show the destruction of joints. Fore and hind paw and knee joints were removed above the ankle joint then processed for haematoxylin and eosin staining. Plasma levels of vascular endothelial growth factor (VEGF), platelet derived growth factor, interleukin-8 (IL-8), IL-4, tumor necrosis factor α (TNF-α), and cyclooxygenase-2 (COX-2) were quantified by enzyme-linked immunosorbent assay. Nitric oxide levels were detected by Griess reagent.

RESULTSCompared with the CIA model group, a remarkable reduction in various angiogenic (VEGF and IL-8) and inflammatory mediators (TNF-α, IL-4 and COX-2) after treatment with DDB either alone or combined with MTX P<0.05 or P<0.01). Histopathological and X-ray findings were confirmatory to the observed DDB anti-arthritic effect. The DDB-treated group showed amelioration in signs of arthritis which appeared essentially similar to normal.

CONCLUSIONOur data shed light on the therapeutic efficacy of DDB in experimental rheumatoid arthritis (RA) compared with a choice drug (MTX) and it may be offered as a second-line drug in the treatment of RA.

Animals ; Arthritis, Experimental ; chemically induced ; diagnostic imaging ; drug therapy ; pathology ; Arthritis, Rheumatoid ; diagnostic imaging ; drug therapy ; pathology ; Collagen ; Cyclooxygenase 2 ; blood ; Dioxoles ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Female ; Interleukin-4 ; blood ; Interleukin-8 ; blood ; Methotrexate ; therapeutic use ; Nitric Oxide ; biosynthesis ; Platelet-Derived Growth Factor ; analysis ; Radiography ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; blood ; Vascular Endothelial Growth Factor A ; blood

In this study, we aimed to determine the antinociceptive and/or anti-inflammatory effect of Bang-Poong (BP, Radix Ledebouriellae) on Freund's adjuvant-induced arthritis in rats. Traditionally, BP has been used to treat several inflammatory diseases such as arthritis. Whole BP is extracted into two fractions that were ethylacetate and hexane-soluble fractions. Adult Sprague-Dawley rats (n=30, 130-150 g) were subcutaneously administered by the Freund's complete adjuvant (FCA) into the plantar surface of right hindpaw. Twelve days after the injection of FCA, the rats initially showed typical inflammatory edema and arthritis-related symptoms on the contralateral side (i.e. left hindpaw). Both antinociceptive (evaluation of mechanical, thermal pain threshold and analysis of spinal Fos expression) and anti- inflammatory (evaluation of paw edema, serum interleukin-6 level and x-ray analysis) effect of BP extracts were examined. The ethylacetate fraction of BP (BPE) significantly suppressed the FCA-induced paw edema as well as the serum level of interleukin-6 and it alleviated the radiological changes. Moreover, both mechanical and thermal hyperalgesia were attenuated by the treatment of BPE. In addition, spinal Fos expression that was increased by FCA- injection was suppressed in BPE group. Therefore, this study showed that BPE produced significant both antinociceptive and anti-inflammatory effects on FCA- induced arthritis in rats, while hexane fraction of BP did not show these effects. In conclusion, it is suggested that the ethylacetate fraction of BP is recommended to alleviate the arthritis-related symptoms in human according to the results of this study.
Analgesics/*pharmacology ; Animals ; Anti-Inflammatory Agents/*pharmacology ; Arthritis, Experimental/*drug therapy/radiography ; Drugs, Chinese Herbal/*pharmacology ; Edema/veterinary ; Hindlimb/radiography ; Hyperalgesia/veterinary ; Interleukin-6/blood ; Male ; Pain Measurement/veterinary ; *Phytotherapy ; Plant Extracts/pharmacology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord/metabolism