Sanguinarine-Chelerythrine Fraction of Coptis chinensis Exerts Anti-inflammatory Activity in Carrageenan Paw Oedema Test in Rats and Reveals Reduced Gastrotoxicity

Abstract

Inflammatory diseases are a common therapeutic problem and nonsteroidal anti-inflammatory drugs are not deprived of side effects, of which ulcerogenic activity is one of the most frequent. The aim of the study was to evaluate the anti-inflammatory activity of the sanguinarine-chelerythrine (SC) fraction of Coptis chinensis and its influence on the integrity of gastric mucosa. The study was conducted on sixty male rats randomly divided into six experimental groups: two control groups (a negative control group CON and a positive control group CAR); three groups receiving an investigational fraction of C. chinensis (1, 5, 10 mg/kg i.g.) named SC₁, SC₅, and SC₁₀, respectively; and a group receiving indomethacin (IND) (10 mg/kg i.g.) as a reference drug. In all animals, the carrageenan-induced paw oedema was measured; PGE₂ release, TNFα production, and MMP-9 concentration in inflamed tissue were determined. Additionally, the macroscopic and microscopic damage of gastric mucosa was evaluated. Administration of SC dose-dependently inhibited the second phase of carrageenan rat paw oedema and PGE₂ release, decreased the production of TNFα, and reduced the concentration of MMP-9, and the efficacy of the highest dose was comparable to the effect of IND. Contrary to IND, no gastrotoxic activity of SC was detected. The investigated sanguinarine-chelerythrine fraction of C. chinensis seems to be a promising candidate for further research on new anti-inflammatory and analgesic drugs characterized with a safer gastric profile compared to existing NSAIDs.

Figure 1

Chemical structures of sanguinarine (a) and chelerythrine (b).

Figure 2

Paw oedema in the experimental groups. CON: negative control group; CAR: positive control group; IND: group receiving indomethacin 10 mg/kg; SC₁, SC₅, and SC₁₀ : groups receiving investigational alkaloid fraction of C. chinensis containing sanguinarine and chelerythrine (1, 5, and 10 mg/kg, respectively). Data are presented as the mean ± SD. ^∗∗∗∗p < 0.0001vs. CON, ^#p < 0.05 and^##p < 0.01vs. CAR.

Figure 3

Paw oedema in the experimental groups. CON: negative control group; CAR: positive control group; IND: group receiving indomethacin 10 mg/kg; SC₁, SC₅, and SC₁₀ : groups receiving investigational alkaloid fraction of C. chinensis containing sanguinarine and chelerythrine (1, 5, and 10 mg/kg, respectively).

Figure 4

Inhibition of the paw oedema with indomethacin and investigational mixture 6 hours after the injection of 1% carrageenan solution. IND: group receiving indomethacin 10 mg/kg; SC₁, SC₅, and SC₁₀: groups receiving an investigational fraction of C. chinensis containing sanguinarine and chelerythrine (1, 5, and 10 mg/kg, respectively). Data are presented as the mean ± SD. ^∗p < 0.05vs. IND.

Figure 5

Macroscopic examination of the gastric mucosa. Experimental groups (n = 10): (a) group receiving investigational alkaloid fraction of C. chinensis containing sanguinarine and chelerythrine 1 mg/kg (SC₁); (b) group receiving investigational alkaloid fraction of C. chinensis containing sanguinarine and chelerythrine 5 mg/kg (SC₅); (c) group receiving investigational alkaloid fraction of C. chinensis containing sanguinarine and chelerythrine 10 mg/kg (SC₁₀); (d) group receiving indomethacin 10 mg/kg (IND); (e) positive control group (CAR); (f) negative control group (CON).

Figure 6

Microscopic examination of the gastric mucosa after hematoxylin-eosin (H&E) staining (×100). Experimental groups (n = 10): (a) group receiving investigational alkaloid fraction of C. chinensis containing sanguinarine and chelerythrine 1 mg/kg (SC₁); (b) group receiving investigational alkaloid fraction of C. chinensis containing sanguinarine and chelerythrine 5 mg/kg (SC₅); (c) group receiving investigational alkaloid fraction of C. chinensis containing sanguinarine and chelerythrine 10 mg/kg (SC₁₀); (d) group receiving indomethacin 10 mg/kg (IND); (e) positive control group (CAR); (f) negative control group (CON). In CAR group (e) and SC₁ group (a) generally normal mucosa showing a mild inflammation was detected. In indomethacin receiving animals (d) moderate inflammation and ulceration in the mucosa was present. In (b), (c), and (f), normal mucosa with no inflammation was observed.

Figure 7

Multicriteria decision analysis (MCDA) of the anti-inflammatory effect of investigational groups. IND: group receiving indomethacin 10 mg/kg; SC₁, SC₅, and SC₁₀ : groups receiving investigational fraction of C. chinensis containing sanguinarine and chelerythrine (1, 5, and 10 mg/kg, respectively). Data are presented as the mean ± SD. ^∗p < 0.05vs. IND.