Beijing Institute of Radiation Medicine, Beijing, 100850, China.
School of Basic Medicine, Guizhou Medical University, Guizhou, 550025, China.
Phytochemistry. 2023 Sep;213:113744. doi: 10.1016/j.phytochem.2023.113744. Epub 2023 Jun 8.
The importance of mitochondria in regulation of aging has been extensively recognized and confirmed. Gynostemma pentaphyllum (Thunb.) Makino, a homology of medicine and food, has been widely utilized as dietary supplement. In this study, the transcriptome of normal cells (wild type mouse embryo fibroblasts) regulated by the 30% aqueous EtOH extract of G. pentaphyllum was firstly evaluated by RNA sequencing and the results revealed that the G. pentaphyllum could up-regulate the genes involved in oxidative phosphorylation (OXPHOS) and sirtuin (SIRT) signaling pathways, indicating its effect in promoting cell viability might be attributed to the role of improving mitochondrial functions. To further discover the bioactive compounds, sixteen undescribed dammarane-type saponins along with twenty-eight known analogues were isolated from the active extract of G. pentaphyllum. Their structures were elucidated by means of comprehensive analysis of NMR and HRMS spectroscopic data. All isolates were evaluated for the regulatory effects on SIRT3 and translocase of the outer membrane 20 (TOM20), and thirteen of them exhibited satisfactory agonist activities on both SIRT3 and TOM20 at 5 μM. Furthermore, the preliminary structure-activity relationships analysis demonstrated the additional hydroxymethyl and carbonyl groups or less sugar residues in saponins could contribute positively to the up-regulatory effect on SIRT3 and TOM20. These findings encouraged the potential roles of G. pentaphyllum and its bioactive saponins in the development of natural drugs for the treatment of aging-related diseases.
线粒体在衰老调控中的重要性已得到广泛认可和证实。绞股蓝（Thunb.）Makino 是一种药食同源的植物，已被广泛用作膳食补充剂。在这项研究中，通过 RNA 测序首次评估了绞股蓝 30%水乙醇提取物调节的正常细胞（野生型小鼠胚胎成纤维细胞）的转录组，结果表明绞股蓝能上调与氧化磷酸化（OXPHOS）和沉默调节蛋白（SIRT）信号通路相关的基因，表明其促进细胞活力的作用可能归因于改善线粒体功能的作用。为了进一步发现生物活性化合物，从绞股蓝活性提取物中分离得到了十六个未描述的达玛烷型皂苷和二十八个已知类似物。通过综合分析 NMR 和高分辨质谱（HRMS）光谱数据，阐明了它们的结构。所有分离物均评估了对 SIRT3 和外膜 20 转位酶（TOM20）的调节作用，其中 13 个在 5μM 时对 SIRT3 和 TOM20 均表现出令人满意的激动剂活性。此外，初步的结构-活性关系分析表明，皂苷中额外的羟甲基和羰基基团或较少的糖残基可能对 SIRT3 和 TOM20 的上调作用有积极贡献。这些发现鼓励绞股蓝及其生物活性皂苷在开发用于治疗与衰老相关疾病的天然药物方面发挥潜在作用。
