Therapeutic Effects And Mechanism Of Pterocephalus Hookeri Extract On Rheumatoid Arthritis

Objective:In present study, the effective part extract of a commonly used Tibetan herb Pterocephalus hookeri (C.B. Clarke) Hoeck, named Pterocephalus hookeri extract (PE), was selected as the research object; and then we evaluated the anti-arthritic, anti-inflammation, analgesic and immunoregulatory effects as well as anti-rheumatoid arthritic mechanism of PE.Method:Firstly, the anti-inflammatory activities of PE were observed by utilizing the following models:carrageenin-induced paw edema in rats, xylene-induced ear edema, acetic acid-induced peritoneal capillary permeability and agar-induced granuloma formation in mice.Secondly, the analgesic effects of PE were evaluated by hot-plate test and acetic acid-induced writhing response in mice as well as chronic pain model in adjuvant-induced arthritic rats.Thirdly, carbon clearance test, serum hemolysis test and 2,4-dinitrochlorobenzene (DNCB)-induced delayed type hypersensitivity (DTH) reaction in normal mice were used to investigate the immunoregulatory effects of PE.Finally, the adjuvant-induced arthritic (AA) rat models were established to evaluate the anti-arthritic effects of PE. We determined the change of primary paw swelling, secondary paw swelling, the arthritis scores and histological assessment of ankle articular synovium of all AA rats. The levels of serum TNF-α, IL-1βand PGE2 were measured by ELISA. Then the levels of serum MDA and NO as well as activity of SOD were measured by chemical colorimetric analysis. Furthermore, the NF-κB expression of synovial tissues were examined by immunohistological staining.Results:Firstly, PE could significantly inhibite the increase in paw edema induced by carrageenin, ear edema induced by xylene, vascular permeability induced by acetic acid and granuloma induced by agar.Secondly, PE obviously prolonged the writhing latent period and reduced writhing times in acetic acid-induced mice. Moreover, PE also increased the paw withdrawal threshold in AA rats. However, the effect of PE on hot-plate pain threshold was not obvious.Thirdly, the suppression on DNCB-induced DTH reaction was observed in PE treated mice, but the effects of PE on carbon clearance ability and serum hemolysis generation were not observed in PE treated mice.Finally, PE could remarkably inhibite the primary and secondary paw swelling, reduce the arthritis scores. And PE also significantly regulated inflammatory signal transduction networks and related factors, which manifested as reducing levels of serum TNF-a, IL-1βand PGE2 as well as the NF-κB expression. Meanwhile, PE also could elevate the serum SOD activity, reduce the levels of serum NO and MDA. Furthermore, the pathological examination demonstrated that synovial hyperplasia and inflammatory cells infiltration in AA rats were suppressed by PE.Conclusion:All the data indicate that PE has an effective therapeutical action on RA, which may be related to two aspects as following:firstly, adjusting the NF-κB inflammatory signal transduction networks and related factors, reducing the release of proinflammatory and algogenic factors, inhibiting oxidative stress, then improving synovial inflammation;secondly, increasing pain threshold, relieving chronic pain. Based on these results, we believe that Pterocephalus hookeri extract may be used as a potential anti-rheumatoid arthritis candidate drug.