Abstract：
BACKGROUND: Areca nut polyphenols (AP) that extracted from areca nut, have been demonstrated for their potential of anti-fatigue effects. However, the underlying mechanisms for the anti-fatigue properties of AP has not been fully elucidated to date. Previous studies have predominantly concentrated on single aspects, such as antioxidation and anti-inflammation, yet have lacked comprehensive multi-dimensional analyses.
OBJECTIVE: To explore the underlying mechanism of AP in exerting anti-fatigue effects.
METHODS: In this study, we developed a chronic sleep deprivation-induced fatigue model and used physiological, hematological, and biochemical indicators to evaluate the anti- fatigue efficacy of AP. Additionally, a multi-omics approach was employed to reveal the anti-fatigue mechanisms of AP from the perspective of microbiome, metabolome, and proteome.
RESULTS: The detection of physiology, hematology and biochemistry index indicated that AP markedly alleviate mice fatigue state induced by sleep deprivation. The 16S rRNA sequencing showed the AP promoted the abundance of probiotics (Odoribacter, Dubosiella, Marvinbryantia, and Eubacterium) and suppressed harmful bacteria (Ruminococcus). On the other hand, AP was found to regulate the expression of colonic proteins, such as increases of adenosine triphosphate (ATP) synthesis and mitochondrial function related proteins, including ATP5A1, ATP5O, ATP5L, ATP5H, NDUFA, NDUFB, NDUFS, and NDUFV. Serum metabolomic analysis revealed AP upregulated the levels of anti-fatigue amino acids, such as taurine, leucine, arginine, glutamine, lysine, and l-proline. Hepatic proteins express levels, especially tricarboxylic acid (TCA) cycle (CS, SDHB, MDH2, and DLST) and redox-related proteins (SOD1, SOD2, GPX4, and PRDX3), were significantly recovered by AP administration. Spearman correlation analysis uncovered the strong correlation between microbiome, metabolome and proteome, suggesting the anti-fatigue effects of AP is attribute to the energy homeostasis and redox balance through gut-liver axis.
CONCLUSIONS: AP increased colonic ATP production and improve mitochondrial function by regulating gut microbiota, and further upregulated anti-fatigue amino acid levels in the blood. Based on the gut-liver axis, AP upregulated the hepatic tricarboxylic acid cycle and oxidoreductase-related protein expression, regulating energy homeostasis and redox balance, and ultimately exerting anti-fatigue effects. This study provides insights into the anti-fatigue mechanisms of AP, highlighting its potential as a therapeutic agent.
OBJECTIVE: To explore the underlying mechanism of AP in exerting anti-fatigue effects.
METHODS: In this study, we developed a chronic sleep deprivation-induced fatigue model and used physiological, hematological, and biochemical indicators to evaluate the anti- fatigue efficacy of AP. Additionally, a multi-omics approach was employed to reveal the anti-fatigue mechanisms of AP from the perspective of microbiome, metabolome, and proteome.
RESULTS: The detection of physiology, hematology and biochemistry index indicated that AP markedly alleviate mice fatigue state induced by sleep deprivation. The 16S rRNA sequencing showed the AP promoted the abundance of probiotics (Odoribacter, Dubosiella, Marvinbryantia, and Eubacterium) and suppressed harmful bacteria (Ruminococcus). On the other hand, AP was found to regulate the expression of colonic proteins, such as increases of adenosine triphosphate (ATP) synthesis and mitochondrial function related proteins, including ATP5A1, ATP5O, ATP5L, ATP5H, NDUFA, NDUFB, NDUFS, and NDUFV. Serum metabolomic analysis revealed AP upregulated the levels of anti-fatigue amino acids, such as taurine, leucine, arginine, glutamine, lysine, and l-proline. Hepatic proteins express levels, especially tricarboxylic acid (TCA) cycle (CS, SDHB, MDH2, and DLST) and redox-related proteins (SOD1, SOD2, GPX4, and PRDX3), were significantly recovered by AP administration. Spearman correlation analysis uncovered the strong correlation between microbiome, metabolome and proteome, suggesting the anti-fatigue effects of AP is attribute to the energy homeostasis and redox balance through gut-liver axis.
CONCLUSIONS: AP increased colonic ATP production and improve mitochondrial function by regulating gut microbiota, and further upregulated anti-fatigue amino acid levels in the blood. Based on the gut-liver axis, AP upregulated the hepatic tricarboxylic acid cycle and oxidoreductase-related protein expression, regulating energy homeostasis and redox balance, and ultimately exerting anti-fatigue effects. This study provides insights into the anti-fatigue mechanisms of AP, highlighting its potential as a therapeutic agent.
摘要：
背景：从槟榔中提取的槟榔多酚（AP），已经证明了其抗疲劳作用的潜力。然而,迄今为止,AP抗疲劳特性的潜在机制尚未完全阐明.以前的研究主要集中在单一方面，如抗氧化和抗炎，但缺乏全面的多维度分析。
目的：探讨AP抗疲劳作用的潜在机制。
方法：在本研究中，我们开发了一个慢性睡眠剥夺导致的疲劳模型，血液学,生化指标评价AP抗疲劳疗效。此外,采用多组学方法从微生物组的角度揭示了AP的抗疲劳机制，代谢组，和蛋白质组。
结果：生理学的检测，血液学和生化指标表明，AP明显减轻了睡眠剥夺引起的小鼠疲劳状态。16SrRNA测序显示AP促进了益生菌的丰度(Odoribacter，Dubosiella,Marvinbryantia,和Eubacterium）和抑制有害细菌（Ruminococus）。另一方面,发现AP可以调节结肠蛋白的表达，例如三磷酸腺苷（ATP）合成和线粒体功能相关蛋白的增加，包括ATP5A1，ATP5O，ATP5L,ATP5H,NDUFA,NDUFB,NDUFS,和NDUFV。血清代谢组学分析显示，AP上调抗疲劳氨基酸的水平，比如牛磺酸,亮氨酸,精氨酸谷氨酰胺,赖氨酸，还有l-脯氨酸.肝蛋白表达水平，特别是三羧酸(TCA)循环(CS，SDHB,MDH2和DLST）和氧化还原相关蛋白（SOD1，SOD2，GPX4和PRDX3），通过AP管理显着恢复。Spearman相关分析揭示了微生物组之间的强相关性，代谢组和蛋白质组，提示AP的抗疲劳作用归因于通过肠-肝轴的能量稳态和氧化还原平衡。
结论：AP通过调节肠道菌群增加结肠ATP的产生并改善线粒体功能，并进一步上调血液中抗疲劳氨基酸水平。基于肠-肝轴，AP上调肝脏三羧酸循环和氧化还原酶相关蛋白表达,调节能量稳态和氧化还原平衡，并最终发挥抗疲劳作用。这项研究提供了对AP抗疲劳机制的见解，强调其作为治疗剂的潜力。
目的：探讨AP抗疲劳作用的潜在机制。
方法：在本研究中，我们开发了一个慢性睡眠剥夺导致的疲劳模型，血液学,生化指标评价AP抗疲劳疗效。此外,采用多组学方法从微生物组的角度揭示了AP的抗疲劳机制，代谢组，和蛋白质组。
结果：生理学的检测，血液学和生化指标表明，AP明显减轻了睡眠剥夺引起的小鼠疲劳状态。16SrRNA测序显示AP促进了益生菌的丰度(Odoribacter，Dubosiella,Marvinbryantia,和Eubacterium）和抑制有害细菌（Ruminococus）。另一方面,发现AP可以调节结肠蛋白的表达，例如三磷酸腺苷（ATP）合成和线粒体功能相关蛋白的增加，包括ATP5A1，ATP5O，ATP5L,ATP5H,NDUFA,NDUFB,NDUFS,和NDUFV。血清代谢组学分析显示，AP上调抗疲劳氨基酸的水平，比如牛磺酸,亮氨酸,精氨酸谷氨酰胺,赖氨酸，还有l-脯氨酸.肝蛋白表达水平，特别是三羧酸(TCA)循环(CS，SDHB,MDH2和DLST）和氧化还原相关蛋白（SOD1，SOD2，GPX4和PRDX3），通过AP管理显着恢复。Spearman相关分析揭示了微生物组之间的强相关性，代谢组和蛋白质组，提示AP的抗疲劳作用归因于通过肠-肝轴的能量稳态和氧化还原平衡。
结论：AP通过调节肠道菌群增加结肠ATP的产生并改善线粒体功能，并进一步上调血液中抗疲劳氨基酸水平。基于肠-肝轴，AP上调肝脏三羧酸循环和氧化还原酶相关蛋白表达,调节能量稳态和氧化还原平衡，并最终发挥抗疲劳作用。这项研究提供了对AP抗疲劳机制的见解，强调其作为治疗剂的潜力。
