Comparative effects of two gingerol-containing Zingiber officinale extracts on experimental rheumatoid arthritis

Abstract

Ginger (Zingiber officinale) supplements are being promoted for arthritis treatment in western societies on the basis of ginger's traditional use as an anti-inflammatory in Chinese and Ayurvedic medicine. However, scientific evidence of ginger's antiarthritic effects is sparse, and its bioactive joint-protective components have not been identified. Therefore, the ability of a well-characterized crude ginger extract to inhibit joint swelling in an animal model of rheumatoid arthritis, streptococcal cell wall-induced arthritis, was compared to that of a fraction containing only gingerols and their derivatives. Both extracts were efficacious in preventing joint inflammation. However, the crude dichloromethane extract, which also contained essential oils and more polar compounds, was more efficacious (when normalized to gingerol content) in preventing both joint inflammation and destruction. In conclusion, these data document a very significant joint-protective effect of these ginger samples and suggest that nongingerol components are bioactive and can enhance the antiarthritic effects of the more widely studied gingerols.

Figure 1

Effect of gingerol fraction or DCM extract on joint inflammation. Female Lewis rats were injected on day 0 with SCW (25 μg/g) or vehicle. Joint swelling was assessed by daily calculation of the arthritic index (mean ± SEM) with statistical significance determined by Kruskal-Wallis nonparametric ANOVA with post hoc analysis or Mann Whitney testing as described in the experimental section. (A) Gingerol fraction (26 mg gingerols/kg/day), DCM extract (26 mg gingerols/kg/day) or vehicle alone; i.p. injections were begun 4 days prior to SCW administration (n = 10–11 animals/group) and continued on a daily basis until 14 days after SCW injection at which time treatment frequency decreased to twice weekly. P values (vs. vehicle) are: ^a p < 0.001, DCM extract and p < 0.01, ginger fraction; ^b p < 0.01, DCM extract and p < 0.01, ginger fraction; ^c p < 0.001, DCM extract and p < 0.05, ginger fraction; ^d p < 0.01, DCM extract and p < 0.05, ginger fraction; ^e p < 0.01, DCM extract and ns, ginger fraction. (B) Gingerol fraction (26 mg/kg/day) or vehicle alone i.p. injections were begun 3 days after SCW administration (n = 8 animals/group) and continued daily until 10 days post-SCW at which time treatment frequency decreased to twice weekly. P values (vs. vehicle) are: * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 2

Comparison of gingerol fraction vs. DCM extract on (A) destruction of articular cartilage and (B) hepatic granulomatous inflammatory response. Female Lewis rats were injected on day 0 with SCW (25 μg/g) or vehicle. Botanical extracts or vehicle alone i.p. injections were begun 4 days prior to SCW administration and continued on a daily basis until 14 days after SCW injection at which time treatment frequency decreased to twice weekly. (A) The degree of cartilage destruction in talo-tibial joints was determined histologically as described in methods (mean ± SEM of score range 0–3) (n = 10–11 animals/group) with statistical significance determined by Kruskal-Wallis nonparametric ANOVA with post hoc analysis. *** p < .001. (B) The incidence of granuloma formation (number of animals with hepatic granuloma out of total in group) was assessed histologically as described in methods (n = 10–11 animals/group). Statistical significance of each treatment (vs. vehicle) was determined by Fisher’s Exact Test. ** p < 0.01.