The protective effects of 18β-glycyrrhetinic acid against inflammation microenvironment in gastric tumorigenesis targeting PGE2-EP2 receptor-mediated arachidonic acid pathway

Abstract

Accumulating epidemiological and clinical evidence shows that inflammation is an important risk factor for gastrointestinal diseases. Glycyrrhiza glabra, a traditional Chinese medicine, has been shown to safely suppress gastric cancer; however, the anti-inflammatory mechanisms in gastric tumorigenesis have been poorly investigated. Therefore, this study is committed to demonstrate the in vivo anti-inflammatory effect of 18β-glycyrrhetinic acid (GRA), the main active component of G. glabra. The lymphocytes and macrophages were heavily infiltrated in the transgenic mice that highly expressed cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1; however, a significant reduction was observed after treatment with GRA. In addition, GRA downregulated the protein levels of COX-2, GαS, EP2, and β-catenin, which were involved in the arachidonic acid pathway. In conclusion, our study showed the potential protective effects of GRA against inflammatory environment that might be involved in gastric tumorigenesis in vivo through the PGE2-EP2 receptor-mediated arachidonic acid pathway.

Synthesis and Antiproliferative Activity of Novel A-Ring Cleaved Glycyrrhetinic Acid Derivatives

“…Glycyrrhetinic acid (GA) 1 is the hydrolyzed metabolite of glycyrrhizin, a major pentacyclic triterpenoid saponin obtained from the roots of licorice ( Glycyrrhiza species) in high yields up to 24% [16,17]. This compound has been shown to inhibit tumor initiation [18,19,20,21,22] and proliferation in several cancer cell lines; its antiproliferative activity is mediated by cell cycle arrest [23,24] and induction of apoptosis [21,25,26,27,28]. The antitumor effects of GA 1 were also observed in animal models [20,29,30].…”

Revisiting liquorice (Glycyrrhiza glabra L.) as anti-inflammatory, antivirals and immunomodulators: Potential pharmacological applications with mechanistic insight.

“…Progressively, a similar study on liquorice extract and its phytoconstituents established anti-inflammatory activity by involvement of TNF, PGE2, MMPs and free radicals cascade ( Yang et al, 2017 ). Further, protective effect on gastric tumorigenesis by 18-β-glycyrrhetinic acid was established by anti-inflammatory action through PGE2-EP2 receptor-mediated arachidonic acid pathway ( Cao et al, 2018 ). In another study, two isolates namely isoliquiritigenin and naringenin from liquorice was identified to improve T cells synthesis and regulation involve for anti-inflammatory action ( Tiwari et al, 2018 ).…”