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人参皂苷 Rb1 通过调节细胞周期、凋亡途径和衰老小鼠的代谢来延缓衰老过程。

Ginsenoside Rb1 retards aging process by regulating cell cycle, apoptotic pathway and metabolism of aging mice.

机构信息

The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, China.

Hubei University of Chinese Medicine, Wuhan, Hubei, 430065, China.

出版信息

J Ethnopharmacol. 2020 Jun 12;255:112746. doi: 10.1016/j.jep.2020.112746. Epub 2020 Mar 9.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Ginsenoside Rb1 (GRb1), an active ingredient of traditional Chinese medicine Panax ginseng C. A. Meyer, has displayed various activities such as antioxidative stress, autophagic regulation and apoptotic inhibition. However, the role of GRb1 in natural aging process remains unclear.

AIM OF THE STUDY

In this study, we investigated the anti-aging effect and underlying molecular mechanisms of ginsenoside Rb1 in natural aging process.

MATERIALS AND METHODS

We treated the natural aging C57BL/6J mice by intragastrical administration of GRb1 (100 mg/kg·BW) every other day for 10 months and investigated the effect of GRb1 on aging symptoms. By RT-qPCR and WB analysis, we examined the expression levels of senescence-associated biomarkers and aging-related pathways, including cell cycle, apoptosis and inflammation in aging process. Further, metabolomics analysis was conducted to investigate the changes of aging-related metabolites after GRb1 treatment.

RESULTS

Treatment with GRb1 significantly attenuated the aging-induced physiological changes, including slowed reduction of body weight, suppression of hair loss, decrease of arterial wall thickness and heart weight. We found that GRb1 treatment remarkably reversed the changed expression of p53-p21-Cdk2 axis in heart tissues of aging mice, which was responsible for the cell cycle repression. And the activations of apoptosis-associated factors (Bax and Caspase-3) were also inhibited by GRb1 treatment. Further, based on the serum metabolomics analysis using HPLC-MS/MS analysis, several metabolites were identified as potential biomarkers related to the anti-aging effect of GRb1, including glycerophospholipids, carboxylic acids and fatty acyls. Especially, the change of glycerophospholipid metabolism pathway was found to be the mostly changed.

CONCLUSION

Our studies suggest that GRb1 retards the aging process in mice by regulating cell cycle and apoptotic pathway, which were associated with the alleviation of metabolic disorders.

摘要

民族药理学相关性

人参皂苷 Rb1(GRb1)是传统中药人参 Panax ginseng C. A. Meyer 的一种有效成分,具有抗氧化应激、自噬调节和凋亡抑制等多种活性。然而,GRb1 在自然衰老过程中的作用尚不清楚。

研究目的

本研究旨在探讨人参皂苷 Rb1 在自然衰老过程中的抗衰老作用及其潜在的分子机制。

材料与方法

我们通过灌胃给予自然衰老 C57BL/6J 小鼠 GRb1(100mg/kg·BW),每隔一天一次,连续 10 个月,观察 GRb1 对衰老症状的影响。通过 RT-qPCR 和 WB 分析,检测衰老过程中衰老相关生物标志物和衰老相关通路(包括细胞周期、凋亡和炎症)的表达水平。进一步进行代谢组学分析,探讨 GRb1 处理后与衰老相关的代谢物变化。

结果

GRb1 治疗显著减轻了衰老引起的生理变化,包括体重减轻速度减慢、脱发抑制、动脉壁厚度和心脏重量降低。我们发现,GRb1 治疗显著逆转了衰老小鼠心脏组织中 p53-p21-Cdk2 轴的改变表达,这是细胞周期抑制的原因。GRb1 治疗还抑制了凋亡相关因子(Bax 和 Caspase-3)的激活。此外,基于 HPLC-MS/MS 分析的血清代谢组学分析,鉴定出几种与 GRb1 抗衰老作用相关的潜在生物标志物,包括甘油磷脂、羧酸和脂肪酸酰基。特别是,甘油磷脂代谢途径的变化被发现是变化最大的。

结论

我们的研究表明,GRb1 通过调节细胞周期和凋亡途径延缓了小鼠的衰老过程,这与代谢紊乱的缓解有关。

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