Potent inhibitory effect of silibinin from milk thistle on skin inflammation stimuli by 12-O-tetradecanoylphorbol-13-acetate

Abstract

Silibinin, a major polyphenol in milk thistle, has been reported to have multiple pharmacological activities; therefore, there is an urgent need to well understand how silibinin works on inflammation-associated skin diseases. We herein designed silibinin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated skin inflammation to test its inhibitory effects. It was demonstrated that silibinin, applied topically onto mouse ears following TPA stimulation, effectively down-regulated the expressions of TPA-induced interleukin-1β (IL-1β), interleukin-6 (IL-6), necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) in a dose-dependent manner. Further mechanistic investigations indicated that silibinin suppressed the expression of IκB kinase (IKK) by inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, and thereby suppressing TPA-stimulated nuclear factor-κB (NF-κB) activation. Promisingly, silibinin, used for transdermal application, may be a potent naturally occurring anti-inflammatory agent for the prevention of inflammation-associated skin diseases.

The Biological Evaluation of Fusidic Acid and Its Hydrogenation Derivative as Antimicrobial and Anti-inflammatory Agents

“…The mice were divided into nine groups: each group consisted of six mice, including a blank group, a TPA group, a dexamethasone group, and six groups for WU-FA-00 and WU-FA-01. In the mouse ear edema model, 20 μL of acetone vehicle was topically applied to the right ear, and 20 μL of the treatment compounds at three different concentrations, which were dissolved in acetone, were used 5 min later after 20 μL of TPA (0.125 μg/mL in acetone) was previously applied to induce the inflammation model (33, 34). Dexamethasone at a concentration of 2.5 μg/mL (6.37 μmol/mL) in acetone was used as the positive control.…”

“…Each histologic type of lesion in the TPA-induced ear model was scored independently by two experienced investigators who were not aware of the identity of the specimens (×200) (33, 35). The staining intensity was scored as follows: 0, no staining; 1+, faint; 2+, moderate; and 3+, strong.…”

“…Finally, peroxidase was detected using the 3, 3-diaminobenzidine tetrahydrochloride reaction, which produced a brown label in the epidermal tissue. The cells that stained positive for TNF-α, IL-1β and COX-2 were counted in the section of the mouse ear using the Image-Pro Plus (Version 6.0) software (33). The results were expressed as the number of stained cells.…”

Synthesis and Anti-inflammatory Effects of Oxaprozin-Paeonol Ester

“…The TNF-α, IL-1β, and IL-6 levels were determined as described previously. [47,48] After deparaffinized treatment, the ear slices were incubated in H 2 O 2 (1.2%). Ear slices then were treated with the primary antibody of proliferating cell nuclear antigen (1∶100) overnight at 4 ℃.…”

Evaluation of the anti-inflammatory properties of telmesteine on inflammation-associated skin diseases

“…For TPA-induced mouse ear edema model, 16,17 both mice ears were topical treated with acetone or telmesteine with different concentrations respectively, 30 min prior to TPA (0.008 nM in acetone) treatment. Then the mice were sacriced aer 6 h. Finally, ear punches of 6 mm diameter from mice ears were taken and weighed.…”