, Volume 21, Issue 5, pp 365-375
Date: 11 Dec 2012

Modulation of Th1 cytokines and inflammatory mediators by Euphorbia hirta in animal model of adjuvant-induced arthritis

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Abstract

Euphorbia hirta L. (Euphorbiaceae) (E. hirta) is a tree locally used as a traditional medicine in Africa and Australia to treat numerous diseases such as hypertension, respiratory ailments, tumors, antipyretic, anti-inflammatory activities. In the present study, we investigated the anti-arthritic activity of fresh leaves of E. hirta ethanol extract that was found to inhibit the production of inflammatory mediators and cytokines of adjuvant arthritis in rats. Adjuvant arthritis was induced in rats (Wistar) by the subplantar injection of 0.05 ml freshly prepared suspension (5.0 mg/ml) of steam killed Mycobacterium tuberculli in liquid paraffin. Animals were treated with graded doses of 25, 50, 100 and 200 mg/kg of E. hirta ethanol extract, p.o. E. hirta significantly inhibited the swelling of the adjuvant-induced arthritis. Moreover, E. hirta at higher dose (200 mg/kg) showed 40.54 ± 1.09 % of CD3+, 15.1 ± 0.76 % of CD4+, 12.2 ± 1.18 % of CD8+ T cell receptor and 17.6 ± 1.11 % gated of CD19+ B cell receptor revealing a down regulation of adjuvant-induced arthritis as compared to the corresponding valves of the arthritic control rats. According to the results shown in Tables 1, 2, the production of IL-1β, TNF-α, IL-2 and IFN-γ were increased in splenocytes of arthritic rats and this increased level was reduced by E. hirta. Also, E. hirta significantly down regulated lipopolysaccharide (LPS)-induced production of nitric oxide production in peritoneal macrophages. These results suggest that E. hirta exhibits an improvement in adjuvant-induced arthritis through down regulation of activated macrophages and T lymphocytes functions. Such unique effects of E. hirta shown on adjuvant arthritis rat model may be advantageous to the long-term treatment of clinical rheumatoid arthritis.

Each value indicates the mean ± SEM of six animals
AC arthritic control, NC normal control; E. hirta (25, 50, 100 and 200 mg/kg) and prednisolone (5 mg/kg) were given p.o. from day 0 to day 21 after Mycobacterium tuberculli injection, respectively
p < 0.05; ** p < 0.01; *** p < 0.001, compared to arthritic control
Table 1
Effect of E. hirta and prednisolone (Pred) on LPS-induced IL-1β and TNF-α productions from splenocytes in Mycobacterium tuberculli-induced inflammatory arthritic rats
Treatment
Dose (mg/kg)
IL-1β (pg/ml)
TNF-α (pg/ml)
Arthritic control (AC)
323.56 ± 31.65
180.91 ± 24.12
E. hirta
25
311.19 ± 29.08*
171.43 ± 22.54*
E. hirta
50
287.12 ± 26.98*
164.54 ± 21.76**
E. hirta
100
243.12 ± 19.21***
157.30 ± 18.54***
E. hirta
200
215.21 ± 16.05***
138.43 ± 17.98***
Prednisolone (Pred)
5
187.18 ± 15.21***
123.77 ± 15.12***
Normal control (NC)
54.12 ± 12.54
71.94 ± 12.12
Each value indicates the mean ± SEM of six animals
AC arthritic control, NC normal control; E. hirta (25, 50, 100 and 200 mg/kg) and prednisolone (5 mg/kg) were given p.o. from day 0 to day 21 after Mycobacterium tuberculli injection, respectively
p < 0.05; ** p < 0.01; *** p < 0.001, compared to arthritic control
Table 2
Effect of E. hirta and Prednisolone (Pred) on Con A-induced IL-2 and IFN-γ productions from splenocytes in Mycobacterium tuberculli-induced inflammatory arthritic rats
Treatment
Dose (mg/kg)
IL-2 (pg/ml)
IFN-γ (pg/ml)
Arthritic control (AC)
235.98 ± 15.23
165.95 ± 13.87
E. hirta
25
225.12 ± 14.76**
154.76 ± 11.07**
E. hirta
50
207.76 ± 13.87**
134.76 ± 11.01**
E. hirta
100
189.98 ± 12.65 ***
110.64 ± 10.98***
E. hirta
200
157.84 ± 14.32 ***
98.54 ± 10.76***
Prednisolone (Pred)
5
131.08 ± 13.31***
87.65 ± 10.61***
Normal control (NC)
78.12 ± 12.04
31.87 ± 10.12