Preparation of resveratrol dry suspension and its immunomodulatory and anti-inflammatory activity in mice

Abstract

Context: Resveratrol is a natural polyphenol compound. It exhibits antitumor, immunostimulatory, and antiviral activities. However, poor water solubility and structural instability limit its administration and storage.Objective: A resveratrol dry suspension (RDS) was prepared and immunomodulatory effect in immunosuppressive mice induced by cyclophosphamide and anti-inflammatory activities in mice were evaluated.Materials and methods: The preparation of RDS was optimized by the orthogonal design method. To evaluate the immunomodulatory effects, SPF Kunming mice were divided into seven groups comprising of nine males and nine females for each group. The RDS supplemented group was administrated doses of 3.33, 1.67, and 0.83 g/kg/d. Then visceral index, lymphocyte proliferation, the ratio of CD3⁺ CD4⁺/CD3⁺ CD8⁺, and the contents of cytokines in serum were tested. To ameliorate effects of acetic acid induced capillary permeability, xylene-based ear oedema, and cotton pellet granuloma, RDS as anti-inflammatory agent was administered at doses of 1, 0.33, and 0.1 g/kg/d as compared to indomethacin (IM) provided as a positive control at 10 mg/kg.Results: RDS inhibited the degradation of resveratrol and enhanced the CD3⁺ CD4⁺/CD3⁺ CD8⁺ ratio, spleen index, IL-2 level, and splenic lymphocytes in immunosuppressive mice. RDS (0.1 g/kg/d) significantly inhibited the acetic acid-induced capillary permeability, and at doses of 0.33 and 1 g/kg/d repressed the ear swelling and granuloma formation in immunocompromised mice.Discussion and Conclusion: RDS is a stable, cheaper, and suitable preparation with potent immunoregulatory and anti-inflammatory activities. Keeping in view these remarkable properties, RDS could be an appropriate preparation for clinic use of resveratrol.

Keywords: Orthogonal design; granuloma; quality assessment; splenic lymphocytes.

Figure 1.

Concentrations of serum cytokines. (A) Concentration of IL-2; (B) Concentration of IFN-γ. Symbols are represented as means ± SD; n = 6; comparison was made with the model group; one-way ANOVA followed by the Duncan test. The symbols represent statistical significance at *p < 0.05, **p < 0.01.

Figure 2.

Splenic lymphocyte proliferation. (A) Splenic lymphocyte proliferation stimulated by ConA; (B) Splenic lymphocyte proliferation stimulated by LPS. Symbols are represented as means ± SD; n = 6; comparison was made with the model group; one-way ANOVA followed by the Duncan test. The symbols represent statistical significance at *p < 0.05, **p < 0.01.

Figure 3.

The anti-inflammatory activity of resveratrol dry suspension. (A) Coeliac capillary permeability induced by acetic acid; (B) ear swelling induced by xylene; (C) the weight of cotton pellet granuloma. Symbols are represented as means ± SD; n = 8; comparison was made with the normal group; one-way ANOVA followed by the Duncan test. The symbols represent statistical significance at *p < 0.05, **p < 0.01.