探討S-烯丙基半胱胺酸和白皮杉醇的協同作用於秀麗隱桿線蟲之抗老化功效

Abstract

老化是所有生物必經的過程並伴隨氧化壓力堆積與生理功能逐漸下降。 S-烯丙基半胱氨酸（SAC）是一種存在於黑蒜中的有機硫化合物，而白皮杉醇（PIC）則屬於二苯基乙烯類化合物，此兩者先前已被證明具有抗衰老效果。先前的研究觀察到多酚化合物和SAC在抗氧化方面具有協同作用。協同作用是透過將兩種或更多濃度較低的化合物結合在一起，以達到與單獨存在的化合物相同或更強的效果。然而，PIC 和 SAC 作為常見的營養素，其抗衰老的協同效應仍不清楚。本研究旨在以秀麗隱桿線蟲模式探討SAC和PIC是否具有抗氧化及抗老化的協同效應。抗氧化壓力實驗使用250 µM Juglone作為壓力誘導劑並透過DHE染色來探測自由基的多寡。透過比較實驗值 (EV) 和理論值 (TV)，計算了PIC和SAC的協同作用率(SR)。結果顯示，與對照組和單獨介入 SAC 或 PIC相比，SAC + PIC 組別的線蟲於氧化壓力環境下的存活率分別提升 25.5%、9.5% 及9.2%。在 DHE 染色試驗中，與對照組和單獨使用 SAC 或 PIC 的組別相比， SAC + PIC 組別的線蟲體內分別降低了 43%、9% 及24% 的自由基。於線蟲老化試驗中，相較於對照組，SAC+ PIC的組合延長了線蟲的生命週期並顯著改善線蟲老化指標行為，包含身體彎曲和腸道脂褐素。SAC+PIC的組合顯著提升SKN-1於線蟲中體內轉移至細胞核比例達50%，並提高其下游抗氧化基因gcs-1表現量15% 。總結來說，相較於SAC 5 µM 和PIC 50 µM 處理組別，PIC與SAC的樣品比例 (3⁄4 的 5 µM SAC 和 1⁄4 的 50 µM PIC)對於抗氧化與抗老化模式具有顯著的協同效應，其效果更加提升線蟲的抗氧化能力並降低體內ROS累積、延長壽命並改善老化相關指標。因此，SAC + PIC 的組合可透過較低濃度並具達到相同之抗氧化及抗老化的效果有更佳效果之應用，並具有做為營養補充品之潛力。

Aging is a normal process that is inevitable in all living beings and is associated with oxidative stress accumulation, accompanied by a progressive decline of physiological integrity. S-allylcysteine (SAC), an organosulfur compound found in aged black garlic, and Piceatannol (PIC), a stilbene family, have been shown to possess anti-aging properties. Previous research has demonstrated that polyphenol compounds and SAC exhibit synergistic effects in antioxidant activities. Synergism, in this context, refers to the phenomenon where combining two or more compounds in lower concentrations, produces a stronger effect than when each compound is used alone. However, the synergistic effect of PIC and SAC in common daily nutrients remains unclear. To investigate this, an anti-oxidative stress assay was conducted using 250 µM Juglone, as a stress inducer. Free radical levels were measured using dihydroethidium (DHE) staining. The synergistic effect of PIC and SAC was quantified using the Synergistic Rate (SR), by comparing the experimental value (EV) to the theoretical value (TV). The results indicated that the combination group (SAC + PIC) increased survival rates by 25.5%, 9.5%, and 9.2% compared to the control, SAC alone, and PIC alone, respectively. DHE staining showed that this combination (SAC + PIC) reduced ROS levels by 43%, 9%, and 24% compared to the control, SAC alone, and PIC alone, respectively. Additionally, lifespan was prolonged in wild-type C. elegans, and aging behaviors such as body bends and intestinal lipofuscin accumulation were significantly improved. Furthermore, the combination of SAC and PIC activated the SKN-1 pathway by 50% compared to the control and increased the expression of its downstream gene gcs-1 by 15%. Compared to the individual treatments of 5 µM SAC and 50 µM PIC, the combinations of SAC and PIC (3⁄4 of 5 µM SAC and 1⁄4 of 50 µM PIC) showed significant synergistic effects in both antioxidant and anti-aging. In conclusion, the combination of SAC and PIC demonstrated synergistic effects in enhancing the antioxidative capacity of C. elegans, reducing ROS accumulation, extending lifespan, and improving aging-related indicators at lower concentrations. This study suggests a potential model for the future application of nutritional supplements by combining lower concentrations of multiple compounds to achieve better effects.