Anti-arthritic and disease modifying activity of Terminalia chebula Retz. in experimental models.
OBJECTIVE
This study evaluates the anti-arthritic effect of Terminalia chebula hydroalcoholic extract (TCHE) in experimental models and attempts to correlate the effect of treatment on macrophage-derived pro-inflammatory cytokine expression and extent of disease activity.


METHODS
Arthritis was induced in rats by subplantar administration of either formaldehyde or complete Freund's adjuvant (CFA). Joint size was measured at regular intervals by using a micrometer screw gauge. Serum and ankle joints of rats immunized with CFA were collected and subjected to ELISA for estimation of TNF-α level and immuno-histochemistry for detection of IL-1β, IL-6 and TNF-R1, respectively. An acute and 28-day oral toxicity study was carried out to evaluate the safety of the test drug.


RESULTS
TCHE produced a significant inhibition of joint swelling as compared with control in both formaldehyde-induced and CFA-induced arthritis. TCHE treatment also reduced serum TNF-α level and synovial expression of TNF-R1, IL-6 and IL-1β. Results of acute toxicity study showed that the oral LD50 of TCHE was >2000 mg/kg. Chronic administration also did not produce any significant physiological changes as compared with normal rats.


CONCLUSIONS
Results indicate that the anti-arthritic activity of TCHE was at least in part due to its modulatory effect on pro-inflammatory cytokine expression in the synovium. We believe that TCHE has the potential to be used as a disease-modifying agent in treatment of rheumatoid arthritis.
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Vinod
V
Nair
Surender
S
Singh
Yogendra Kumar
YK
Gupta
D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005638:Fruit; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D007596:Joints / Q000378:metabolism; D007928:Lethal Dose 50; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000378:metabolism; D029766:Terminalia; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018501:Antirheumatic Agents; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha