Anti-inflammatory effect of different curcumin preparations on adjuvant-induced arthritis in rats

Abstract

Background: Curcumin, a natural polyphenolic substance, has been known for more than two millennia as having strong anti-inflammatory activity towards multiple ailments, including arthritis. The main drawback of curcumin is its poor solubility in water, which leads to low intestinal absorption and minimal bioavailability. In this study, we aimed to compare the anti-arthritic in vivo effect of different curcumin preparations - basic curcumin extract, micellar curcumin, curcumin mixture with piperine, and microencapsulated curcumin.

Methods: Arthritis was induced in Wistar rats by complete Freund's adjuvant, and the severity of arthritis was evaluated daily using the arthritis score system. Curcumin preparations were given to animals per os daily for 20 consecutive days, starting at 6th day after arthritis induction. To determine the inflammatory background, pro-inflammatory cytokines were determined using the ELISA test. In addition, hematologic test, weight change, and limb swelling were tracked.

Results: Our results indicate that curcumin had a rather weak effect on arthritis progression in the Wistar rat model, microencapsulated curcumin effectively prevented the progression of arthritis - the disease stabilized after 10 days of supplementation. It also reduced the levels of immune cells (neutrophils and leukocytes), as well as pro-inflammatory cytokines - TNFα, IL-1, and IL-6, which levels were close to arthritis-free control. Other formulations of curcumin had lower or no effect on arthritis progression.

Conclusion: Our study shows that the same concentrations of curcumin had a distinctly expressed positive anti-inflammatory effect depending on the form of its delivery. Specifically, we found that microencapsulated curcumin had the most promising effect for treatment.

Keywords: Adjuvant-induced arthritis; Curcumin; Inflammatory cytokines; Microencapsulation.

Fig. 1

Body weight and arthritis score evaluation of Wistar rats after AIA initiation. Data are shown as mean ± SD. a-b Body weight change in rats at 0, 5, 11, 15, 18, and 25 days after CFA injection. *(p < 0.05) - denotes statistically significant differences compared with Control– group, ns - not significant. Detail statistical analysis of the male group (see Additional file 2). Data table presented in Additional file 3. c-f Daily arthritis score measurements of rat paws over 25 days. Comparison of Control+ and Control- groups arthritis score (see Additional file 4). Data table presented in Additional file 5

Fig. 2

Hind paws swelling in Wistar rats at 0, 6, 12, 15, 19, and 25 days after AIA initiation. Data are shown as median with IQR. a-f Hind paws swelling measurements, * denotes statistically significant differences Control– vs group - *(p < 0.05), **(p < 0.01), ***(p < 0.001), while Δ(p < 0.05) denotes statistically significant differences compared to MIC group, and $(p < 0.05) denotes statistically significant differences compared to LIPO group. g Pictures of swelled hind paws 15 and 25 days after CFA injection. All treatment period (see Additional file 6)

Fig. 3

Levels of white blood cells in Wistar rats at 0, 6, 12, 19, and 25 days after AIA initiation. Data are shown as median with IQR. * denotes statistically significant differences Control– vs group - *(p < 0.05), **(p < 0.01), ***(p < 0.001), while Δ(p < 0.05) denotes statistically significant differences compared to MIC group and #(p < 0.05) denotes statistically significant differences compared to Control+ group

Fig. 4

Levels of neutrophils in Wistar rats at 0, 6, 12, 19, and 25 days after AIA initiation. Data are shown as median with IQR. * denotes statistically significant differences Control– vs group - *(p < 0.05), **(p < 0.01), ***(p < 0.001) and Δ(p < 0.05) denotes statistically significant differences compared to MIC group. Comparison of neutrophil levels in separate groups during the experiment (see Additional file 7)

Fig. 5

Levels of red blood cells (a-e) and haemoglobin (f-g) in Wistar rats at 0, 6, 12, 19, and 25 days after AIA initiation. Data are shown as median with IQR. * denotes statistically significant differences Control– vs group - *(p < 0.05), **(p < 0.01), ***(p < 0.001), and Δ(p < 0.05) denotes statistically significant differences compared to MIC group