Gallic acid ameliorates dextran sulfate sodium-induced ulcerative colitis in mice via inhibiting NLRP3 inflammasome

Abstract

Background: Ulcerative colitis (UC) is a chronic recurrent inflammatory bowel disease (IBD). The conventional drugs for UC may induce severe side effects. Herbal medicine is considered as a complementary and alternative choice for UC.Purpose: This study aims to estimate the effect of natural polyphenol gallic acid (GA) on the NLRP3 inflammasome with dextran sulfate sodium (DSS)-induced colitis in mice.Study design: The body weights and symptoms of BALB/c mice were recorded. Histological evaluation, ELISA, q-PCR, immunohistochemistry, and western blotting were carried out to observe the morphology, cytokine contents, mRNA expressions, and protein expressions, respectively. Lipopolysaccharide (LPS)-induced RAW264.7 macrophage was used to probe GA’s effect on relative protein expression.Results: GA attenuated weight loss (p < 0.05), relieved symptoms, and ameliorated colonic morphological injury (p < 0.05) in mice with colitis induced by DSS. GA also lowered the contents of TNF-α, IL-1β, IL-18, IL-33, and IFN-γ in the serum and colon of mice, which were elevated by DSS, downregulated protein, and mRNA expressions of the NLRP3 pathway in the colon tissue. Furthermore, GA downregulated the expressions of NLRP3 (p < 0.05), iNOS (p < 0.01), COX2 (p < 0.01), and P-p65 (p < 0.05), and suppressed NO release (p < 0.001) in LPS-induced RAW264.7 cells.Conclusion: GA ameliorated DSS-induced UC in mice via inhibiting the NLRP3 inflammasome. These findings furnish evidence for the anti-inflammatory effect of herbal medicines containing GA on UC.

Study on network pharmacology of Ginkgo biloba extract against ischaemic stroke mechanism and establishment of UPLC‐MS/MS methods for simultaneous determination of 19 main active components

“…The benefits of G. biloba and its preparations in the prevention and treatment of cardiovascular diseases mainly derive from the effective chemical components such as flavonoids and terpenoid lactones. In this study, through data mining and network pharmacology analysis of relevant literature, we found that the organic acid components (protocatechuic acid, caffeic acid, chlorogenic acid, and gallic acid), flavonoid components (quercetin‐3‐O‐glucoside, quercetin‐3‐O‐rutinoside, kaempferol‐3‐O‐rutinoside, kaempferol‐3‐O‐glucoside, isorhamnetin‐3‐O‐rutinoside, isorhamnetin‐3‐O‐glucoside, apigenin‐7‐O‐glucoside, and apigenin), and terpenoid lactones (bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, and ginkgolide J) had different effects such as anti‐inflammatory and anti‐oxidative activities, protecting the nervous system, changing blood rheology, and so on 22–50 . These components may be the potential active substance basis of its anti‐IS effect, so they were included in the scope of analysis and investigation of the active components of GBE against IS.…”

“…Some studies have shown that ingredients such as caffeic acid, protocatechuic acid, gallic acid, bilobalide, and ginkgolide A can inhibit the TLR4/NF-κB signalling pathway, reduce the expression level of MAPK, and achieve anti-inflammatory effects. 23,25,29,31,33 Bilobalide, ginkgolide A, and so on can play an antiinflammatory role by regulating inflammation-related pathways and inhibiting the release of inflammatory factors. Quercetin-3-O-rutinoside, kaempferol-3-O-rutinoside, kaempferol-3-O-glucoside, and isorhamnetin-3-O-rutinoside can inhibit the PI3K-Akt, NF-κB, and other signalling pathways and reduce cardiovascular and cerebrovascular injuries.…”

“…Based on literature data mining, flavonoid‐glycosides and terpenes in G. biloba are the main components of its pharmacological activities such as anti‐inflammatory, antioxidant, blood circulation‐improving, and platelet anti‐aggregatory activities 22–51 . Therefore, the above ingredients were selected for the study of the active ingredients of GBE against IS, as shown in Table 1.…”

Cyclizine‐induced proinflammatory responses through Akt‐NFκB pathway in macrophages

“…19,20 However, macrophage overactivation can also lead to acute and chronic inflammatory diseases, such as neuroinflammation, neurodegenerative disease, inflammatory bowel disease, pneumonia, and pulmonary fibrosis. [21][22][23][24] Cognitive decline, confusion, impaired motor abilities, tremors, sensory changes, ataxia, and seizures are symptoms of neuroinflammatory and neurovegetative diseases such as stroke, Parkinson's disease, Alzheimer's disease, multiple sclerosis, and epilepsy. [25][26][27] The adverse responses to cyclizine are similar to such symptoms, which are induced by macrophage activation.…”

“…Macrophages are a type of leukocyte that play a critical role in homeostasis and disease prevention by defending the body against invading pathogens 19,20 . However, macrophage overactivation can also lead to acute and chronic inflammatory diseases, such as neuroinflammation, neurodegenerative disease, inflammatory bowel disease, pneumonia, and pulmonary fibrosis 21–24 . Cognitive decline, confusion, impaired motor abilities, tremors, sensory changes, ataxia, and seizures are symptoms of neuroinflammatory and neurovegetative diseases such as stroke, Parkinson's disease, Alzheimer's disease, multiple sclerosis, and epilepsy 25–27 .…”