morphinans and Autoimmune-Diseases

Rheumatoid arthritis (RA) is an autoimmune disease, which is characterized by inflammatory synovitis, and the subsequent destruction of articular cartilage and bone. Sinomenine is a traditional Chinese medicine, which has been employed as a clinical treatment for RA for several years in China. The present study investigated the anti‑arthritic effects of sinomenine on Sprague‑Dawley rats with collagen‑induced arthritis (CIA). The differentially expressed proteins in serum were measured by proteomic analysis in order to generate a differentially expressed protein network. A total of 320 differentially expressed proteins were detected in the drug‑treated group compared with in the control group. In the sinomenine‑treated group, 79 differentially expressed proteins were detected compared with in the model group, and among these, 46 proteins were upregulated. Gene ontology analysis revealed that five functions were affected by sinomenine treatment of CIA rats compared with in the model group. In addition, Ingenuity® Pathway Analysis was used to measure enriched signaling pathways, which revealed nuclear factor‑κB, histones, heat shock proteins and protein kinase B as core proteins, generating ~60 pair associations in the network. To the best of our knowledge, the present study is the first to perform proteomic analysis in sinomenine‑treated CIA rats, and the results revealed that numerous targets were involved in the process. In addition, the present study provided a novel approach and evidence for exploring the biological effects of sinomenine. Therefore, the findings of the present study may provide a novel insight into the anti‑RA mechanisms of sinomenine, and may justify further exploration into its function in other relevant diseases.

Topics: Animals; Antirheumatic Agents; Arthritis, Experimental; Autoimmune Diseases; Female; Gene Expression Profiling; Gene Expression Regulation; Morphinans; Rats; Rats, Sprague-Dawley

Pruritus is a common, distressing and difficult to manage complication of many autoimmune diseases. A suitable animal model of autoimmune disease associated pruritus would contribute to a better understanding of the pathophysiology of this symptom and lead to the development of safe and effective antipruritic agents. We noticed spontaneous scratching behavior in aged MRL/lpr mice, a model of autoimmune disease. This scratching behavior was observed in a specific pathogen-free environment and was more frequent in female mice. In contrast to animal models of dermatitis; NC/Nga mice, the serum IgE and IgG1 levels in MRL/lpr mice were not elevated. These features indicate that this scratching behavior is similar to human autoimmune disease associated pruritus. The antipruritic effects of an antihistamine (chlorpheniramine), an opioid receptor antagonist (naltrexone), and a novel kappa-opioid receptor agonist (nalfurafine hydrochloride [TRK-820]) were evaluated. The frequency of scratching was not reduced by oral administration of chlorpheniramine, suggesting that the behavior is antihistamine-resistant. The oral administration of nalfurafine and subcutaneously administered naltrexone inhibited the scratching behavior without causing gross behavioral changes. In conclusion, MRL/lpr mice scratching behavior is a suitable model of pruritus that occurs in autoimmune diseases, and nalfurafine was shown to be efficacious against this behavior suggesting that it may be beneficial in patients with autoimmune disease associated pruritus.

Topics: Age Factors; Animals; Antipruritics; Autoimmune Diseases; Behavior, Animal; Chlorpheniramine; Dermis; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Immunoglobulin E; Immunoglobulin G; Male; Mice; Mice, Inbred ICR; Mice, Inbred MRL lpr; Mice, Inbred Strains; Morphinans; Naltrexone; Pruritus; Receptors, Opioid, kappa; Sex Factors; Spiro Compounds