Background

Rhododendron nivale Hook. f (R.n), one of the four Manna Stash used in Tibetan medicine to delay aging, possesses anti-aging pharmacological activity. However, which R.n ingredients contain anti-aging properties and the underlying mechanisms involved are unclear.

Hypothesis/Purpose

Based on interactions between gut microbiota and natural medicines and the important role of gut microbiota in anti-aging, the study investigated the hypothesis that R.n possesses anti-aging properties and the interaction of gut microbiota with R.n is responsible for its anti-aging effects.

Study Design

The primary active ingredients of R.n and their target function and pathway enrichment were explored. An aging mouse model was used to clarify the underlying anti-aging mechanisms of R.n.

Methods

Chromatography, spectroscopy, nuclear magnetic technology, and pharmacology were used to reveal the major active ingredients of ethanol extract residues of R.n (RNEA). The target function and pathway enrichment of these active ingredients were explored. Plasma metabolomics coupled with intestinal flora evaluation and bioinformatics analysis was used to clarify the underlying anti-aging mechanisms of RNEA.

Results

Myricetin-3-β-D-xylopyranoside, hyperin, goospetin-8-methyl ether 3-β-D-galactoside, and diplomorphanin B were separated and identified from RNEA. The network pharmacology study revealed that the active ingredients’ target function and pathway enrichment focused mainly on the glutathione antioxidant system. In a D-galactose-induced mouse model of aging, RNEA was shown to possess suitable anti-aging pharmacological activity, as indicated by the amelioration of memory loss and weakened superoxide dismutase and glutathione peroxidase activities. Plasma metabolomics coupled with intestinal flora examination and bioinformatics analysis revealed that RNEA could regulate the expression of glutathione-related enzymes and ameliorate D-galactose-induced imbalances in methionine, glycine, and serine, and betaine and galactose metabolism. The results showed that RNEA reshaped the disordered intestinal flora and mitigated the D-galactose-mediated decline in glutathione oxidase expression, further confirming that the anti-aging effect of RNEA was closely related to regulation of the glutathione antioxidant system.

Conclusion

RNEA, consisting of myricetin-3-β-D-xylopyranoside, hyperin, goospetin-8-methyl ether 3-β-D-galactoside, and diplomorphanin B, possesses anti-aging activity. The anti-aging effect of RNEA might be due to reshaping intestinal flora homeostasis, increasing the expression of glutathione peroxidase 4 in the intestines and liver, enhancing glutathione peroxidase activity, and reinforcing the glutathione antioxidant system.

中文翻译：

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Rhododendron nivale Hook 中的黄酮类化合物。f 通过调节肠道菌群和谷胱甘肽代谢延缓衰老

背景

杜鹃花 nivale 钩。f (Rn)是藏药中用于延缓衰老的四大甘露之一，具有抗衰老药理活性。然而，哪些Rn成分具有抗衰老特性以及所涉及的潜在机制尚不清楚。

假设/目的

基于肠道菌群与天然药物的相互作用以及肠道菌群在抗衰老中的重要作用，该研究探讨了Rn具有抗衰老特性的假设，肠道菌群与Rn的相互作用是其抗衰老作用的原因。

学习规划

探讨了Rn的主要活性成分及其靶功能和通路富集。使用衰老小鼠模型来阐明Rn的潜在抗衰老机制。

方法

色谱、光谱、核磁技术和药理学用于揭示Rn (RNEA) 乙醇提取物残留物的主要活性成分。探索了这些活性成分的靶功能和途径富集。血浆代谢组学结合肠道菌群评估和生物信息学分析用于阐明 RNEA 的潜在抗衰老机制。

结果

从 RNEA 中分离鉴定出杨梅素-3-β-D-xylopyranoside、金丝桃素、goospetin-8-methyl ether 3-β-D-galactoside 和二吗啡肽 B。网络药理学研究表明，活性成分的靶点功能和通路富集主要集中在谷胱甘肽抗氧化系统上。在 D-半乳糖诱导的衰老小鼠模型中，RNEA 被证明具有适当的抗衰老药理活性，如改善记忆丧失和减弱超氧化物歧化酶和谷胱甘肽过氧化物酶活性所示。血浆代谢组学结合肠道菌群检查和生物信息学分析表明，RNEA 可以调节谷胱甘肽相关酶的表达，并改善 D-半乳糖诱导的蛋氨酸、甘氨酸和丝氨酸以及甜菜碱和半乳糖代谢失衡。

结论

RNEA 由 myricetin-3-β-D-xylopyranoside、hyperin、goospetin-8-methyl ether 3-β-D-galactoside 和 dilomorphanin B 组成，具有抗衰老活性。RNEA的抗衰老作用可能是由于重塑肠道菌群稳态，增加肠道和肝脏中谷胱甘肽过氧化物酶4的表达，增强谷胱甘肽过氧化物酶活性，增强谷胱甘肽抗氧化系统。