Screening Anti-Inflammatory Effects of Flavanones Solutions

Abstract

There are a large number of remedies in traditional medicine focused on relieving pain and inflammation. Flavanones have been a potential source in the search for leading compounds and biologically active components, and they have been the focus of much research and development in recent years. Eysenhardtia platycarpa is used in traditional medicine for the treatment of kidney diseases, bladder infections, and diabetes mellitus. Many compounds have been isolated from this plant, such as flavones, flavanones, phenolic compounds, triterpenoid acids, chalcones, sugars, and fatty acids, among others. In this paper, natural flavanone 1 (extracted from Eysenhardtia platycarpa) as lead compound and flavanones 1a-1d as its structural analogues were screened for anti-inflammatory activity using Molinspiration^® and PASS Online in a computational study. The hydro alcoholic solutions (FS) of flavanones 1, 1a-1d (FS1, FS1a-FS1d) were also assayed to investigate their in vivo anti-inflammatory cutaneous effect using two experimental models, a rat ear edema induced by arachidonic acid (AA) and a mouse ear edema induced by 12-O-tetradecanoylphorbol acetate (TPA). Histological studies and analysis of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were also assessed in AA-inflamed rat ear tissue. The results showed that the flavanone hydro alcoholic solutions (FS) caused edema inhibition in both evaluated models. This study suggests that the evaluated flavanones will be effective when used in the future in skin pathologies with inflammation, with the results showing 1b and 1d to be the best.

Keywords: Eysenhardtia platycarpa; cytokines; flavanones; in vivo anti-inflammatory activity.

Figure 1

Natural extracted flavanone 1 and its structural analogues flavanones 1a–d.

Figure 2

(A) Anti-inflammatory activity evaluated after FS treatment in AA-induced edema model showed in the increment or decrement of thickness with respect to initial conditions. (B) Skin hydration results after the application of FS treatments in AA-induced rat ear edema are shown as the difference in hydration compared to initial conditions. Results are expressed as mean ± SD (n = 5). C+ = positive control, RS= reference drug solution, FS = flavanone solution (1, 1a–1d).

Figure 3

Representative micrographs of rat’s ear (x100 magnification). (A): Control −, (B): Control +, (C): reference drug solution (RS), (D): FS1, (E): FS1a, (F): FS1b, (G): FS1c, (H): FS1d. auricular cartilage, dermis, epidermis, stratum corneum. Arrows indicate presence of edema. Scale bar = 200 µm.

Figure 4

Relative expression of cytokines: (A) TNF-α; (B) IL-6; (C) IL-1β. Non-treated rats (Control −), rats treated only with AA (Control +), rats treated with diclofenac sodic solution (reference anti-inflammatory drug) after inducing inflammation (RS), rats treated with flavanone solutions FS1, FS1a- FS1d. Significant difference between Control + (*), Control − (•), RS (‡), FS1 (#), FS1a (▪), FS1b (†), FS1c (◊); (###,•••) p < 0.05; (▪ ▪, ••) p < 0.01; (*, •, ‡, #, ▪, †, ◊) p < 0.001 by non-parametric Tukey’s t-test (n = 5).