薑黃衍生的奈米囊泡透過DAF-16調控體內氧化壓力並延長壽命於秀麗隱桿線蟲模式中

Abstract

老化是所有生物體都會經歷的過程並造成細胞損傷，使體內各種壓力不斷上升，導致疾病和死亡風險的成長。透過健康的生活方式，包括食用健康食品，例如薑黃（Curcuma longa）能夠降低老化相關疾病的發生率。薑黃是一種原產於印度和東南亞的根莖類植物，在先前的研究中已被證明能夠抵抗與老化相關的疾病，近期研究指出從薑黃中提取的奈米囊泡（nanovesicles, NVs）也可以透過調節多種基因來對抗疾病。薑黃衍生的NVs（turmeric-derived nanovesicles, TDNVs）是含有多種潛在有益成分的奈米級小體，包括脂質、蛋白質、多酚和核酸。儘管分別證明薑黃對抗老化進程有效，但分子機制尚未明確。在本研究中，從兩種薑黃中分離出TDNVs，並進行了比較分析。從紅色（RTNV）和黃色（YTNV）薑黃中提取的TDNVs顯示出相似的分佈模式、濃度和平均粒徑分別為131.8 ± 62.1 nm和136.7 ± 74.2 nm。與調控組相比，YTNV提高秀麗隱桿線蟲（Caenorhabditis elegans）在juglone和熱誘導的氧化壓力環境下之存活率分別為29.0%和17.6%，而RTNV沒有表現出任何顯著性差異。儘管與RTNV相比YTNV產生的薑黃素較少，DHE染色實驗結果顯示YTNV可以減少秀麗隱桿線蟲模型中的 ROS 39.6%、老化色素脂核素27.9%，另外，相較於控制組，YTNV具有改善老化行為之功效，包含提高身體擺動率18.6%、咽部收縮率13.4%，最終延長壽命4天。 在DAF-16入核試驗中，相較於控制組，YTNV處理的組別DAF-16入核情形顯著增加68%，而提高DAF-16下游基因hsp-16.2和sod-3表現量，分別為18.37%和21.18%。

Aging is a natural process that happens to all sorts of organisms which phenomenon also translates to the accumulation of molecular and cellular damage over time, increasing a variety of physical stresses on the body, leading to the growing risk of diseases and death. The incidence of aging-related diseases can generally be reduced by living a healthy lifestyle which includes consumption of healthy foods. One such example is turmeric (Curcuma longa), a plant rhizome native to India and Southeast Asia; which have been demonstrated to possess bioactivities against an array of diseases in prior researches, including aging-related ones. Recent studies have indicated that the nanovesicles (NVs) extracted from turmeric may possess the biocapacities to help fight diseases by regulating the expression of a variety of genes involved. Turmeric-Derived NVs (TDNVs) are nanosized bodies containing various, potentially beneficial components including lipids, proteins, polyphenols, and nucleic acids. Although the use of turmeric against aging progression were proven effective, the exact details of the molecular mechanisms are still to be uncovered. In this study, TDNVs were isolated from two variants of turmeric and were analyzed comparatively. TDNVs extracted from both red (RTNV) and yellow (YTNV) turmeric variants showed similar distribution pattern, concentration, and mean particle sizes of 131.8 ± 62.1 nm and 136.7 ± 74.2 nm, respectively. Under juglone and heat stress resistance analyses, YTNV showed a significant increase of 29.0% and 17.6% in bioactivities compared to control group while RTNV did not show any significant increase despite YTNV yielding lower curcuminoids in comparison with RTNV. YTNV was also shown to significantly reduce intracellular superoxide by 39.6%, aging-related behaviors, and aging-related pigment production by 27.9%, as well as increasing lifespan by 36.4% in comparison with control group in C. elegans model. The use of transgenic strains showed a significant increase of 68% of DAF-16 translocation in the group treated with YTNV in comparison with control and juglone-induced group, signifying the ameliorating efficacy through the DAF-16/FoxO signaling pathway, which effects were also accompanied by an upregulation of hsp-16.2 and sod-3 expressions by 18.37% and 21.18%, respectively.