Preclinical Rodent Models of Arthritis and Acute Inflammation Indicate Immunomodulatory and Anti-Inflammatory Properties of Juglans regia Extracts.

Juglans regia has been used to treat inflammatory and arthritic disorders in traditional medicine. The present study aimed to investigate the antiarthritic and anti-inflammatory potential of ethanolic leaves extract of J. regia . Arthritis was induced in rodents with Freund's complete adjuvant. J. regia treatment was started on 8 th day of arthritis induction and sustained for 20 days. Acute inflammatory models were developed using carrageenan, histamine, serotonin, and dextran. Qualitative and GC-MS analyses were also performed. Arthritis was determined using an arthritis scoring index and histopathological examination of ankle joints. RT-PCR was performed to determine the expression of pro-inflammatory markers (TNF- α , NF- κ B, IL-6, IL-1 β , and COX-2) and anti-inflammatory IL-4. PGE2 levels were evaluated using an ELISA. Blood and biochemical parameters were also determined. Paw edema was measured using a digital plethysmometer. Treatment with extracts inhibited arthritic development and attenuated paw edema along with all histopathological parameters. The expression levels of pro-inflammatory cytokines and COX-2 were downregulated, while IL-4 was upregulated. PGE2 levels were also reduced in extract-treated groups. Blood and biochemical parameters were nearly normalized in the treatment groups. Both extracts significantly inhibited carrageenan, histamine, serotonin, and dextran-induced paw edema. Qualitative phytochemical screening and GC-MS analysis confirmed that extracts possessed potential medicinal compounds. In conclusion, ethanol and n-hexane extracts of J. regia leaves have immunomodulatory and anti-inflammatory effects that ameliorate experimentally induced arthritis and edema. The inhibition of autacoids may also be one of the mechanisms inducing the immunomodulatory effect.