Antioxidant Polyphenols of Antirhea borbonica Medicinal Plant and Caffeic Acid Reduce Cerebrovascular, Inflammatory and Metabolic Disorders Aggravated by High-Fat Diet-Induced Obesity in a Mouse Model of Stroke

Abstract

Metabolic disorders related to obesity and type 2 diabetes are associated with aggravated cerebrovascular damages during stroke. In particular, hyperglycemia alters redox and inflammatory status, leading to cerebral endothelial cell dysfunction, blood–brain barrier (BBB) disruption and brain homeostasis loss. Polyphenols constitute the most abundant dietary antioxidants and exert anti-inflammatory effects that may improve cerebrovascular complications in stroke. This study evaluated the effects of the characterized polyphenol-rich extract of Antirhea borbonica medicinal plant and its major constituent caffeic acid on a high-fat diet (HFD)-induced obesity mouse model during ischemic stroke, and murine bEnd3 cerebral endothelial cells in high glucose condition. In vivo, polyphenols administered by oral gavage for 12 weeks attenuated insulin resistance, hyperglycemia, hyperinsulinemia and dyslipidemia caused by HFD-induced obesity. Polyphenols limited brain infarct, hemorrhagic transformation and BBB disruption aggravated by obesity during stroke. Polyphenols exhibited anti-inflammatory and antioxidant properties by reducing IL-1β, IL-6, MCP-1, TNF-α and Nrf2 overproduction as well as total SOD activity elevation at the cerebral or peripheral levels in obese mice. In vitro, polyphenols decreased MMP-2 activity that correlated with MCP-1 secretion and ROS intracellular levels in hyperglycemic condition. Protective effects of polyphenols were linked to their bioavailability with evidence for circulating metabolites including caffeic acid, quercetin and hippuric acid. Altogether, these findings show that antioxidant polyphenols reduced cerebrovascular, inflammatory and metabolic disorders aggravated by obesity in a mouse model of stroke. It will be relevant to assess polyphenol-based strategies to improve the clinical consequences of stroke in the context of obesity and diabetes.

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.…”

“…From the C‐T‐P network analysis, it can be seen that among the 19 potential active ingredients that were initially were screened, caffeic acid, protocatechuic acid, gallic acid, bilobalide, ginkgolide A, quercetin‐3‐O‐rutinoside, kaempferol‐3‐O‐rutinoside, kaempferol‐3‐O‐glucoside, isorhamnetin‐3‐O‐rutinoside, and so on are the main active ingredients of GBE that contribute to its anti‐IS effect. 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 anti‐inflammatory 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 37–44 . The ingredients such as caffeic acid, protocatechuic acid, gallic acid, bilobalide, ginkgolide A, quercetin‐3‐O‐rutinoside, kaempferol‐3‐O‐rutinoside, kaempferol‐3‐O‐glucoside, and isorhamnetin‐3‐O‐rutinoside also have anti‐oxidative, free radical‐scavenging, and anti‐apoptotic effects 22–50 . Consequently, it was deduced that anti‐inflammatory, anti‐oxidative, anti‐apoptotic, and other activities are the main anti‐IS effects of GBE.…”

“…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.…”