Abstract
It has been reported that Celtis sinensis Pers. is employed as a folk medicine for the treatment of inflammatory diseases. But the mechanism supporting its use as anti-inflammatory remains unclear. To investigate the anti-inflammatory of Celtis sinensis Pers. ICR mice were provided Celtis sinensis Pers. leaf extract (CLE) at 100, 200 mg/kg after ginkgolic acids (GA) sensitization. Our data showed that CLE and the main flavonoid isovitexin in CLE could ameliorate GA-induced contact dermatitis in mice. Ear swelling, inflammatory cell infiltration and splenomegaly were inhibited significantly by isovitexin, while the weight loss of mice in the isovitexin-treated group was much better than that in the dexamethasone-treated group (positive control drug). It has been reported in previous research that GA-induced inflammation is closely related to the T cell response. Therefore, T cells were the focus of the anti-inflammatory effect of isovitexin in this paper. The in vivo results showed that isovitexin (10, 20 mg/kg) inhibited the expression of proinflammatory cytokines (TNF-α, IFN-γ, IL-2 and IL-17A) in lymph nodes, inhibited the secretion of cytokines into the serum from mice with contact dermatitis and promoted the expression of apoptosis-related proteins. In vitro, isovitexin also induced apoptosis and inhibited proinflammatory cytokine expression in Con A-activated T cells. Further study showed that the MAPK and STAT signaling pathways and the phosphorylation of SHP2 were inhibited by isovitexin. Both molecular docking and biological experiments indicated that SHP2 may be an anti-inflammatory target of isovitexin in T cells. Taken together, isovitexin can serve as a potential natural agent for the treatment or prevention of GA-induced inflammatory problems.
Highlights
Ginkgo seeds has been used as a nutritious food for thousands of years, and a variety of medicinal effects have been attributed to the ginkgo seeds
Mice that received Celtis sinensis Pers. leaf extract (CLE) exhibited significantly reduced susceptibility to ginkgolic acids (GA)-induced allergic contact dermatitis, as shown by the milder splenomegaly and ear swelling compared with the model group (Figures 1B,C)
Since isovitexin is the predominant flavone of Celtis sinensis (Ota et al, 2017), we further examined the possible role of isovitexin in dermal inflammation
Summary
Ginkgo seeds has been used as a nutritious food for thousands of years, and a variety of medicinal effects have been attributed to the ginkgo seeds. The main active pharmaceutical ingredients in Ginkgo biloba include oxyglycoside flavonoids, terpene trilactones, proanthocyanidins and so on (Zhou et al, 2018; Omidkhoda et al, 2019). Food poisoning by Ginkgo seeds has been reported in Japan and China, which presents as frequent vomiting and generalized convulsions (Miwa et al, 2001). Ginkgolic acids (GA), the alkylphenol constituents in ginkgo seeds, have been considered one of the potential toxic components in Ginkgo biloba. It has been reported that contact allergic dermatitis (ACD) can be induced by ginkgolic acids when people contact ginkgo leaf during the picking of Ginkgo seeds (Hotta et al, 2013; Mei et al, 2017).
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