Ginkgo Biloba Extract Reduces Cardiac and Brain Inflammation in Rats Fed a HFD and Exposed to Chronic Mental Stress through NF-κB Inhibition

Abstract

Background. Cardiac and brain inflammation can lead to a host of deleterious health effects. Our formal experimental research showed that Ginkgo Biloba Extract (GBE) contributed to the reduction of inflammation in mice with myocardial infarction along with depression. This study is aimed at expanding on these findings via analysis of the cardiac and brain inflammation, which was prevented by GBE in rats suffering with a high-fat diet (HFD) combined with unpredictable chronic mild stress (UCMS). Methods. Fifty male Wistar rats were randomly divided into 5 groups treated with normal diet, UCMS, HFD, HFD+UCMS, or HFD+UCMS+GBE respectively. Rats treated with HFD were fed a high-fat diet for 10 or 13 weeks. Rats treated with UCMS were exposed to 8 types of chronic physical and psychological stressors for 10 or 13 weeks. The HFD+UCMS+GBE group was given GBE via intragastric gavage for 8 consecutive weeks. Sucrose preference was established for the assessment of depressive behaviors. The heart function was evaluated by echocardiography. The rats were terminated at the end of the 10th or 13th week. The blood was used for detecting low-density lipoprotein cholesterol (LDL-c) and total cholesterol (TCHO) by the kit instructions; Helper T Lymphocytes (TH cells, CD3+CD4+) by flow cytometry; and Interleukin- (IL-) 1β, IL-37, IL-38, NT-proBNP, hs-cTNI, and Ischemia-modified albumin (IMA) by enzyme-linked immunosorbent assay (ELISA). The cardiac tissues were used for detecting IL-1β, nuclear factor kappa B (NF-κB), inhibitor molecule protein (IκB), and IL-1 receptor (IL-1R) by ELISA and P65, P-P65, IκB, and phosphorylated inhibitor molecule protein α (P-IκBα) for western blotting. Cortex tissues were used for detecting 8-iso-prostaglandinF2α (8-iso-PGF2α) by ELISA. Oil Red staining was carried out to evaluate the lipid deposits in the rats’ aortic arteries. Sirius Red staining was performed to display collagen fibers in the arteries. Hematoxylin and Eosin (HE) staining was applied to reveal pathological changes to arteries and cardiac tissue. Immunohistochemical staining was employed to assess the distribution of inflammatory cytokine IL-1β in arteries and cardiac tissues. Transmission Electron Microscopy (TEM) was performed to observe the ultrastructure of hippocampal cornu ammonis (CA)1 (CA1) neurons. Results. In the rats with HFD+UCMS+GBE, over 13 weeks, GBE exerted a protective role of both the heart and brain, by attenuating cardiac inflammation and brain oxidative stress. Levels of Helper T lymphocytes and serum anti-inflammatory cytokines involving IL-37 and IL-38 were all elevated, and the depressive behaviors of HFD+UCMS rats were attenuated by GBE. This protective role was accomplished via inhibition of the canonical NF-κB signaling pathway, through downregulation of the expressions of P-P65 and P-IκB-α in the heart, hippocampus, cortex, and hypothalamus. Conclusions. This study suggests that GBE poses a protective role from the various pathologies associated with high-fat diets, unpredictable chronic mild stress, and depression, possibly via improving peripheral immunity and reducing cardiac and brain inflammation.

A mixture of extracts from natural ingredients reduces the neurotoxic polarization of microglia via modulating NF‐κB/NF‐E2‐related factor 2 activation

“…In comparison to propolis alone, the mixture had greater suppression effects on the AL‐upregulated TNF‐α and IL‐1β, demonstrating that the mixture synergistically reduced the neurotoxic polarization of microglia in the environment of the AD brain. The synergistic effects of the mixture on neurotoxic responses in microglia may be dependent on the comprehensive effects of individual ingredients because the production of IL‐1β and TNF‐α was inhibited by CA, GK, PS, GB, and CL (De Simone et al., 2003 ; Delerue et al., 2021 ; Huynh et al., 2002 ; Shi et al., 2015 ; Sowndhararajan et al., 2018 ; Wu, Sun, et al., 2013 ; Wu, Zhu, et al., 2013 ; Zhang et al., 2022 ). The reduction of TNF‐α and IL‐1β in microglia is extremely important for delaying the pathological process of AD because microglia‐produced IL‐1β promotes Aβ aggregation and microglia‐produced TNF‐α promotes tau phosphorylation in neurons (Jiang et al., 2021 ; Wu et al., 2017 ).…”

“…Curcuma longa (CL), a component in curry spices, is known to reduce proinflammatory mediator production by cells, including microglia (Shi et al, 2015;Sowndhararajan et al, 2018;Zhang et al, 2022).…”

“…Phosphatidylserine (PS), a component in soybeans (Richter et al., 2013 ), has been shown to attenuate neuroinflammation (De Simone et al., 2003 ; Huynh et al., 2002 ). Curcuma longa (CL), a component in curry spices, is known to reduce proinflammatory mediator production by cells, including microglia (Shi et al., 2015 ; Sowndhararajan et al., 2018 ; Zhang et al., 2022 ). PS, Ginkgo biloba (GB), and Gotu kola (GK) have been reported to improve the memory functions in individuals (Kandiah et al., 2021 ; Ma et al., 2022 ; McDaniel et al., 2003 ; Puttarak et al., 2017 ), in addition to their effects of reducing the production of proinflammatory effectors by cells, including microglia (Shi et al., 2015 ; Sowndhararajan et al., 2018 ; Zhang et al., 2022 ), Furthermore, propolis, a resinous mixture that honeybees produce by mixing saliva and beeswax, has been determined to prevent memory decline in humans by its anti‐inflammatory and neuroprotective effects (Ni et al., 2017 ; Wu, Sun, et al., 2013 ; Wu, Zhu, et al., 2013 ; Zhu et al., 2018 ).…”

The infiltration of monocytes aggravates liver fibrosis in mice infected with Echinococcus granulosus

“…12 Sirius Red staining the samples were immersed by soaking in decreasing graded alcohol (100%, 96%, 80%, and 70%), then stained with Sirius Red solution for 8 min and quickly dehydrated with 100% alcohol. Finally, the samples were dehydrated with xylene for 5 min and sealed with neutral gum [13].…”

Estudo do efeito de extratos do Ginkgo biloba e da quercetina no ducto deferente de camundongo

“…No trabalho de Nunez e colaboradores (1986) foi testado os efeitos do GBE na agregação de plaquetas humanas, induzida pelo fator de ativação plaquetária e demonstrado que o GBE inibe competitivamente a agregação plaquetária de maneira dependente da concentração. Também foi descrito que o GBE exerceu um papel protetor no coração e no cérebro, diminuindo a inflamação cardíaca e o estresse oxidativo cerebral em ratos (Zhang et al, 2022). Os principais componentes do GB são os flavonoides e as lactonas terpênicas (Amin et al, 2012).…”