Inflammopharmacology

, Volume 21, Issue 5, pp 365–375

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

  • Sheikh Fayaz Ahmad
  • Phalisteen Sultan
  • Abdelkader E. Ashour
  • Tajdar Husain Khan
  • Sabry M. Attia
  • Saleh A. Bakheet
  • Adel R. A. Abd-Allah
Research Article

DOI: 10.1007/s10787-012-0161-5

Cite this article as:
Fayaz Ahmad, S., Sultan, P., Ashour, A.E. et al. Inflammopharmacol (2013) 21: 365. doi:10.1007/s10787-012-0161-5

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.
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

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

Keywords

Immunomodulatory activity Mycobacterium tuberculli Euphorbia hirta Adjuvant arthritis T lymphocytes Lipopolysaccharide Concanavalin A 

Copyright information

© Springer Basel 2012

Authors and Affiliations

  • Sheikh Fayaz Ahmad
    • 1
  • Phalisteen Sultan
    • 2
  • Abdelkader E. Ashour
    • 1
  • Tajdar Husain Khan
    • 3
  • Sabry M. Attia
    • 1
  • Saleh A. Bakheet
    • 1
  • Adel R. A. Abd-Allah
    • 1
  1. 1.Department of Pharmacology and Toxicology, College of PharmacyKing Saud UniversityRiyadhSaudi Arabia
  2. 2.Indian Institute of Integrative Medicine formerly known as Regional Research Laboratory (CSIR)JammuIndia
  3. 3.Department of Pharmacology, College of PharmacySalman Bin Abdulaziz UniversityAl-KharjSaudi Arabia