Anti-inflammatory activity of Euphorbia aegyptiaca extract in rats

Introduction

Euphorbia aegyptiaca belongs to the family: Euphoriaceae. Arabic synonyms are Um Malbeina, Um Lebein and Um Leban. In Sudan, Euphorbia aegyptiaca is distributed in the central region especially along the Nile banks in the Gezira and Rahad. Because of the medicinal interest in Euphoriaceae, these herbs have been examined by several investigators. [1, 2] Euphorbia species contain several important phytochemical constituents like triterpenoids, flavonoids, lignans, coumarins, and alkaloids, [3, 4] which reflect their therapeutic potentials. Recent studies demonstrated anthelmintic and antimicrobial activity of Euphorbia helioscopia extracts, ⁽⁵⁾ anti-retroviral effect of ingenol derived from Euphorbia tirucalli [2] and anti-hepatitis B virus of flavone glucosides isolated from Euphorbia humifusa. [6] Anticancer activities of Euphorbia tirucalli were demonstrated in a wide variety of cancers including breast [7] and gastric [8] carcinomas. Euphorbia hirta attracted the attention of many investigators because of its unique chemical structure, antioxidant contents, potent anti-inflammatory as well as anticancer activities. [9]

Interestingly most of Euphorbia species were proved to have anti-inflammatory effects including Euphorbia hirta, [1, 10] Euphorbia fischeriana, [11] Euphorbia lacteal [12] and Euphorbia neriifolia. [13] In Sudan, Euphorbia aegyptiaca is used by traditional herbalists for the treatment of some inflammatory conditions like rheumatoid arthritis, dermatitis and conjunctivitis; however, phytochemical screening and medicinal effect of this herb, to the best of our knowledge, was not investigated before. The aim of the present study is to determine the phytochemical constituents and the anti-inflammatory activity of Euphorbia aegyptiaca in rats.

Experimental

Phytochemical screening

Results

The phytochemical screening of the plant revealed the presence of saponins, cumarins, flavonoids, tannins, sterols, triterpenes, and absence of alkaloids, anthraquinones glycosides, and cyanogenic glycosides (Table 1).

The highest EI%s were achieved in all groups four hours post oral administration of indomethacin or Euphorbia aegyptiaca extracts. The mean of EI% of rats treated with indomethacin at a dose of 5 mg/kg over different time intervals (64.0%) was significantly lower compared to those treated with Euphorbia aegyptiaca at a dose of 800 mg/kg (75.0%, P < 0.001), but higher when compared to rats treated at a dose of 400 mg/kg (57.4%, P < 0.001) (table 2). In contrast, MPT of rats treated with indomethacin at a dose of 5 mg/kg (6.5±1.1 mm) was significantly higher compared to those treated with Euphorbia aegyptiaca at a dose of 800 mg/kg (6.1±.7 mm, P< 0.001) as well as 400 mg/kg (5.9±.5, P< 0.001) (figure 1 and table 1).

Table 1. Phytochemical screening results of Euphorbia aegyptiaca

Table 2. Effects of ethanolic extracts of Euphorbia aegyptiaca and indomethacin on rat’s EI% and MPT at different time intervals

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Figure 1.

Effects of ethanolic extracts of Euphorbia eagyptiaca seeds and indomethacin on rat’s MPT at different time intervals

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Discussion

The present results indicate that Euphorbia aegyptiaca possesses significant antiinflammatory activity, which exceeds indomethacin when the first was administered at a dose rate of 800 mg/kg. In all groups, the peak edema inhibition was achieved within four hours after oral dosing regardless of type of drug/extracts or the dose. However, the effect of Euphorbia aegyptiaca extract at a dose rate of 800 mg/kg is more than that of indomethacin at the time intervals of 1, 2, 3, 4 and 24 hours post-treatment. Although Euphorbia aegyptiaca ethanolic extracts at dose rates of 400 and 800 mg/kg achieved comparable EI% and MPT in the first hour following oral administration, these parameters were significantly less thereafter in rats offered the extract at a dose rate of 400 mg/kg. The higher degree of edema inhibition offered by the dose 800 mg/kg suggests a dose-dependent antiinflammatory effect of Euphorbia aegyptiaca. To our best of knowledge the present study is the first to confirm the anti-inflammatory activity of Euphorbia aegyptiaca, and to screen the plant for possible phytoconistituents. The potential anti-inflammatory effects of other species of Euphorbia were documented in the literature especially for Euphorbia hirta. [1, 9] Ahmed and his group investigated the potential anti-arthritic effects of Euphorbia hirta in mouse models of adjuvant induced arthritis. [10] Mice treated by Euphorbia hirta in Ahmed et al study were proved to have substantially lower levels of pro-inflammatory cytokines (interferon-γ (IFN-γ), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and higher concentrations of anti-inflammatory cytokines (IL-4 and IL-5), pointing to the therapeutic antiinflammatory potential of this herb. In a separate study, Euphorbia hirta was proved to inhibit the inflammatory effects of prostaglandin E2 (PGE2) on rabbit synovial fibroblasts. [1] Alternatively, the diterpenoids isolated from the roots of Euphorbia fischeriana were able to inhibit production of inflammatory mediators such as PGE2, nitric oxide (NO), IL-6 and TNF-α. [11] Likewise, local application of tirucallol isolated from Euphorbia lacteal latex was proved to suppress ear edema in a mouse model in a dose-dependent manner, probably by suppressing synthesis of NO in macrophages stimulated by lipopolysaccharide. [12] Llanes-Coronel et al evaluated the activity of fourteen extracts derived from seven Euphorbiaceae herbs on immune cell cultures from healthy individuals.[4] Results showed that 14 Euphorbiaceae’s extracts could at least minimally modulate one of the immunological parameters investigated in that study. Nonetheless, only the latex extracts of Euphorbia cotinifolia and Euphorbia tirucalli strongly enhanced both production and death in mononuclear cells of the peripheral blood.

A Polyamide column chromatography followed by preparative TLC of Euphorbia aegyptiaca resulted in the isolation of three flavonoid compounds, [16] which may explain anti-inflammatory activity of this herb. [14, 15] This is because previous reports demonstrated that flavonoids can suppress both pathways of arachidonic metabolism, namely lioxygenase and cyclooxygenase pathways. [17, 18] In a separate study, Luyen and his colleagues ⁽¹⁹⁾ isolated twenty six compounds from Euphorbia humifusa. [19] Most of these compounds demonstrated anti-inflammatory activities as indicated by their inhibitory effects on soluble epoxide hydrolase, lipopolysaccharide-induced NO and TNF-α production. In a comparable study, thirteen diterpenoids were isolated from the roots of Euphorbia ebracteolata. At least three of the isolated compounds exhibited significant inhibition of NO production in lipopolysaccharide-induced macrophages. [3] Fan et al ⁽²⁰⁾ attributed the anti-inflammatory activity of Terminali acatappa to triterpenic acids. [20] The presence of flavonoids and triterpenes in Euphorbia aegyptiaca may account for the observed anti-inflammatory activity. [15] In a recent study, Abodola et al attributed anti-inflammatory effect of Blumea aurita to presence of triterpenes, flavonoids, saponin, cumarins, and tannins. [14] The present study documents the presence of flavonoids, sterols, triterpenes, saponins, tannins and cumarins in Euphorbia aegyptiaca, which explains anti-inflammatory activity of this herb based on results of previous studies on these phytoconistituents.

Conclusion

The results of the present study demonstrate that Euphorbia aegyptiaca possesses sustained, dose-dependent anti-inflammatory activity. These findings explain the traditional use of this herb in the treatment of rheumatoid arthritis and other inflammatory conditions in Sudan. Further studies are needed to determine the potential toxic effects and the ideal dose of Euphorbia aegyptiaca.