Ginkgo biloba extract ameliorates atherosclerosis via rebalancing gut flora and microbial metabolism

Abstract

The Ginkgo biloba leave extract (GbE) is widely applied in the prevention and treatment of atherosclerotic cardiovascular diseases in clinical practice. However, its mechanism of actions has not been totally elucidated. In this study, we confirmed the beneficial effects of GbE in alleviating hypercholesterolemia, inflammation and atherosclerosis in Ldlr À/À mice, which were fed 12 weeks of Western diet (WD). Moreover, 16S rRNA sequencing revealed that GbE treatment reshaped the WDperturbed intestinal microbiota, particularly decreased the Firmicutes/Bacteroidetes ratio and elevated the abundance of Akkermansia, Alloprevotella, Alistipes, and Parabacteroides. Furthermore, GbE treatment downregulated the intestinal transcriptional levels of proinflammatory cytokines and enhanced the expression of tight junction proteins, exerting the roles of attenuating the intestinal inflammation as well as repairing the gut barrier. Meanwhile, the targeted metabolomic analysis displayed that GbE treatment significantly reversed the dysfunction of the microbial metabolic phenotypes, including promoting the production of short chain fatty acids, indole-3-acetate and secondary bile acids, which were correlated with the atherosclerotic plaque areas. Finally, we confirmed GbE-altered gut microbiota was sufficient to alleviate atherosclerosis by fecal microbiota transplantation. In summary, our findings provide important insights into the pharmacological mechanism underlying the antiatherogenic efficacy of GbE.

Ginkgo biloba Extract Drives Gut Flora and Microbial Metabolism Variation in a Mouse Model of Alzheimer’s Disease

“…Currently, targeting of the intestinal microbiota has been proposed as a prospective therapeutic strategy to ameliorate the pathology of AD [ 31 ]. Ginkgo biloba extract (EGb) has been shown to alleviate neurodegenerative diseases, depression [ 32 ], and atherosclerosis [ 33 ] and restore intestinal integrity through the brain–gut axis [ 34 ]. However, its precise mechanism of action has not yet been elucidated.…”

Potential efficacy and mechanism of eight mild-natured and bitter-flavored TCMs based on gut microbiota: A review

“…The extract of Ginkgo Folium is an extensively used medicine and dietary supplement in clinical to prevent and treat cardiovascular disease. In Ldlr − / − mice, one atherosclerosis animal model, Wang et al found Ginkgo Folium leads to the decreasing of the Firmicutes/Bacteroidetes ratio and the elevating of Akkermansia , Alistipes , Alloprevotella , and Parabacteroides , further promotes the generation of gut microbial metabolites, such as short chain fatty acids (SCFAs), indole-3-acetate and secondary bile acids (BAs), which dramatically associate with the atherosclerotic plaque areas ( Wang et al, 2022 ). Ginkgolide B, an active component of Ginkgo Folium , could also decrease the levels of trimethylamine (TMA) and trimetlylamine oxide (TMAO) in a gut microbiota-depended manner, which is mainly embodied by the enhancement of Bacteroides and the decline of Helicobacter and Roseburia ( Lv et al, 2021 ).…”

The Potential of Ginkgo biloba as a Source of Biologically Active Compounds—A Review of the Recent Literature and Patents

“…In these studies, inhibition of the activity of selected bacterial taxa was demonstrated, and the results became the basis for further research on anti-bacterial activity. In recent years, ginkgetin [ 129 , 133 ], amentofavone [ 132 ], ginkgolic acid C15:1 monomer [ 134 ] and polyprenol [ 135 ] and the effectiveness of leaf extracts obtained with the use of various solvents (water, ethanol, chloroform and methanol) [ 136 , 137 , 138 , 139 ]. The group of microorganisms has been significantly expanded, including taxa of gram-positive and gram-negative bacteria [ 125 , 126 , 134 , 136 , 138 , 140 , 141 ], intestinal microflora typical of the tested mammalian organisms [ 137 , 139 ], as well as human pathogenic fungi (e.g., Candida albicans used in the study by) [ 141 ].…”

“…In recent years, ginkgetin [ 129 , 133 ], amentofavone [ 132 ], ginkgolic acid C15:1 monomer [ 134 ] and polyprenol [ 135 ] and the effectiveness of leaf extracts obtained with the use of various solvents (water, ethanol, chloroform and methanol) [ 136 , 137 , 138 , 139 ]. The group of microorganisms has been significantly expanded, including taxa of gram-positive and gram-negative bacteria [ 125 , 126 , 134 , 136 , 138 , 140 , 141 ], intestinal microflora typical of the tested mammalian organisms [ 137 , 139 ], as well as human pathogenic fungi (e.g., Candida albicans used in the study by) [ 141 ]. In all the studies carried out, different effects on the activity of microorganisms were shown, and the strength of the effect depends on the tested pathogen and the dose/amount of the substance used.…”

“…During the research, a positive, antiatherogenic, anti-obesity and anti-diabetic effect of ginkgo on the metabolism of mammalian organisms was observed. The effects of both leaf extracts [ 130 , 139 , 162 , 163 , 164 ] and seeds [ 165 ], vinegar obtained from fermenting seeds [ 166 ], leaves [ 148 , 167 ], well as ginkgolide B [ 123 , 168 ] and ginkgolide C [ 169 ] were investigated. During the research, positive changes in body weight (decrease) were observed [ 163 , 164 , 170 ], and a reduction in adipose tissue mass [ 167 , 168 , 169 ] was caused by the reduction of fat cells (adipocytes) [ 169 , 170 ].…”