Brazilian propolis mitigates impaired glucose and lipid metabolism in experimental periodontitis in mice

Abstract

BackgroundPeriodontitis has been implicated as a risk factor for metabolic disorders associated with insulin resistance. Recently, we have demonstrated that orally administered Porphyromonas gingivalis, a representative periodontopathic bacterium, induces endotoxemia via reduced gut barrier function coupled with changes in gut microbiota composition, resulting in systemic inflammation and insulin resistance. Propolis, a resinous substance collected by honeybees from leaf buds and cracks in the bark of various plants, can positively affect metabolic disorders in various experimental models. In this study, we thus aimed to clarify the effect of propolis on impaired glucose and lipid metabolism induced by P. gingivalis administration.MethodsEight-week-old male C57BL/6 mice were orally administered P. gingivalis strain W83, propolis ethanol extract powder with P. gingivalis, or vehicle. We then analyzed the expression profile of glucose and lipid metabolism-related genes in the liver and adipose tissues. Serum endotoxin levels were also evaluated by a limulus amebocyte lysate test. In addition, we performed histological analysis of the liver and quantified alveolar bone loss by measuring the root surface area on the lower first molar.ResultsOral administration of P. gingivalis induced downregulation of genes that improve insulin sensitivity in adipose tissue (C1qtnf9, Irs1, and Sirt1), but upregulation of genes associated with lipid droplet formation and gluconeogenesis (Plin2, Acox, and G6pc). However, concomitant administration of propolis abrogated these adverse effects of P. gingivalis. Consistent with gene expression, histological analysis showed that administered propolis suppressed hepatic steatosis induced by P. gingivalis. Furthermore, propolis inhibited the elevation of serum endotoxin levels induced by P. gingivalis administration. Contrary to the systemic effects, propolis had no beneficial effect on alveolar bone loss.ConclusionThese results suggest that administration of propolis may be effective in suppressing periodontopathic bacteria-induced metabolic changes that increase the risk of various systemic diseases.

Porphyromonas gingivalis Promotes 4-Nitroquinoline-1-Oxide-Induced Oral Carcinogenesis With an Alteration of Fatty Acid Metabolism

“…Interestingly, P. gingivalis -treated mice exhibited yellow-white spots on the livers compared with normal appearance of control group ( Figure 4C ). Under the microscopy, the mouse livers in 4NQO + P.g group exhibited severe micro- and macrovesicular steatosis consistent with a previous study ( Nakajima et al, 2016 ). However, 4NQO-treated mice exhibited the characteristics of hepatocyte ballooning and mild microvesicular steatosis ( Figure 4D ).…”

“…Interestingly, P. gingivalis administration increased the levels of FFAs and altered its composition in mice tongue tissues, and further aggravated the changes of FFA metabolism during oral cancer development. In a previous study, Nakajima et al (2016) found that oral administration of P. gingivalis to mice improved insulin sensitivity in adipose tissue and upregulated the genes associated with lipid droplet formation and gluconeogenesis. Furthermore, in our study, the levels and profile of serum FA changed during 4NQO-induced carcinogenesis, which further aggravated by P. gingivalis infection.…”

“…In the present study, the data demonstrated that P. gingivalis infection enhanced tongue carcinogenesis in 4NQO-treated mice. In 2016, Nakajima et al (2016) reported that oral administration of P. gingivalis upregulated the genes associated with lipid droplet formation and gluconeogenesis in the liver, suggesting a link between P. gingivalis and lipid metabolism. Then, we applied GC–MS to examine the effect of P. gingivalis infection on FFA metabolism in 4NQO-treated mice.…”

“…New Zealand White rabbits with periodontitis induced by P. gingivalis had more extensive accumulations of lipids in the aorta than nonperiodontitis animals ( Jain et al, 2003 ). Moreover, the links between P. gingivalis and hepatic steatosis were observed in an experimental periodontitis mice model ( Nakajima et al, 2016 ). Although the effects of P. gingivalis on lipid metabolism were recognized, whether P. gingivalis has similar influences on FA metabolism during oral cancer development remains unclear.…”

Alterations in the Transcriptional Profile of the Liver Tissue and the Therapeutic Effects of Propolis Extracts in Alcohol-induced Steatosis in Rats

“…Propolis is a complex of various phytochemicals, especially rich in phenolic acids and flavonoids, with remarkable pharmacological, therapeutic and biological activities (Oses et al 2016, Wagh 2013, such as anti-microbial, antioxidant, anti-inflammation, and anti-tumor effects. The beneficial roles of propolis, especially the ethanolic extracts of propolis (EEP), on a broad range of hepatic damages have been demonstrated (Andritoiu et al 2014, Babatunde et al 2015, Lin et al 1997, Nakajima et al 2016, Orsolic et al 2012, Wali et al 2015. In recent years, quite a few investigations have reported that plantoriginated polyphenols could attenuate alcoholic liver injury (Liu et al 2014, Park et al 2013, Sun et al 2016.…”