Background Glycyrrhizinic acid (GA), a major active ingredient enriched in the roots of licorice, possesses well-confirmed anti-inflammatory effects. Objective To evaluate the underlying mechanisms of GA against lipopolysaccharide (LPS)-induced chronic neuroinflammation and memory impairment. Design We explored to investigate the effects of GA on neuroinflammation and memory impairment in an LPS-induced Alzheimer’s mouse model. Results Data of micro-PET/CT imaging and morris water maze test suggested that GA, when administrated orally, could reverse LPS-induced abnormalized glucose intake and metabolism in the brain and alleviate LPS-induced memory loss and cognitive defects in mice. Histological and immunohistochemical staining results revealed that GA treatment suppressed overexpressions of pro-inflammatory cytokines of IL-1 β and TNF-α in the brain of C57 mice by inhibiting toll-like receptor 4 (TLR4) signaling pathway activation. Conclusion Our findings suggest that GA may be a therapeutic agent for the treatment of neuroinflammation and cognitive impairment.

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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.

Glycyrrhizinic acid (GA), a principal component derived from licorice, is attracting considerable attention because of its broad range of bioactivities.

Neuroinflammatory cytokines are promising therapeutic targets for the treatment of Alzheimer's disease. Herein, we described our efforts toward the investigation of cinnamic acid derivatives as antineuroinflammatory agents. Intensive structural modifications led to the identification of compound 4f as the most effective antineuroinflammatory agent in vitro. The oral administration of compound 4f could reverse lipopolysaccharide (LPS)-induced memory disturbance and normalize glucose uptake and metabolism in the brains of mice. Further biological studies in vivo revealed that compound 4f was directly bound to the mitogenactivated protein kinase (MAPK) signaling pathway, resulting in suppression of its downstream signaling pathway by blocking neuroinflammatory progression. Docking studies showed that compound 4f could be inserted into the active pocket of interleukin-1β (IL-1β). Furthermore, it was confirmed that compound 4f formed hydrogen bonds with SER84 to enhance the binding affinity. Taken together, these results are of great importance in the development of cinnamic acid derivatives for the treatment of Alzheimer's disease.