Zhu Yan, Han Yaping, Wang Wuyang, Liang Guangming, Qi Jin
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China.
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China.
J Ethnopharmacol. 2023 Jul 15;311:116286. doi: 10.1016/j.jep.2023.116286. Epub 2023 Mar 23.
Mulberry leaves contain many bioactive compounds and have been widely used in traditional medicines and functional foods for prevention and treatment of age-related diseases, such as diabetes, cognitive impairment and obesity-mediated liver cancer. Aging has an irreversible negative impact on human health for many years, even decades, before death, which is a social and economic burden on society.
The objective of this study was to investigate the antioxidant and anti-aging effects of mulberry leaf extract (MLE) in vivo and in vitro.
The Caenorhabditis elegans (C. elegans) was used as a model organism to observe the effects of different concentrations of MLE (1, 2, 4, 8 mg/mL) on nematodes' healthy lifespan, reproductive capacity, locomotion, stress resistance, and antioxidation. In addition, D-galactose (D-gal) induced liver aging in mice and L-02 cells were established. The antioxidant and anti-aging effects of MLE were evaluated by body weight, organ indexes, malondialdehyde (MDA), total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), aspartate and alanine aminotransferases (AST and ALT), reactive oxygen species (ROS), mitochondrial membrane potential (MMP), hematoxylin and eosin (H&E), senescence-associated β-galactosidase (SA-β-Gal). Besides, the expressions of AMPK/SIRT1/PGC-1α and Nrf2-Keap1 were detected by Western blotting.
MLE could significantly prolonged nematodes' average life span and improved most physiological indicators related to aging of C. elegans. Moreover, Treatment with MLE ameliorated the decreased body weight and organ index (weight of organ/body weight) in model mice, and protected against oxidative stress in mice and liver cells, in a dose-dependent manner, up-regulating T-SOD and T-AOC, while reducing ROS and MDA levels. MLE decreased both liver and cell levels of AST and ALT, and enhanced the mitochondrial membrane potential. MLE activated the AMPK/SIRT1/PGC-1α pathways, participated in mitochondrial biosynthesis and oxidative metabolism and delayed D-gal-induced aging. MLE promoted the accumulation of Nrf2 in the nucleus, indicating that the improved oxidative stress response was mediated by the Nrf2-Keap1 pathway in vivo and in vitro.
MLE appeared to have great potential for stimulating the oxidative stress response and attenuating the aging process of in vivo and in vitro, and provide a novel health-promoting resource against aging and aging-related diseases.
桑叶含有多种生物活性化合物，已广泛用于传统药物和功能性食品中，用于预防和治疗与年龄相关的疾病，如糖尿病、认知障碍和肥胖介导的肝癌。衰老在死亡前的许多年甚至几十年里，都会对人类健康产生不可逆转的负面影响，这对社会来说是一种社会和经济负担。
本研究的目的是在体内和体外研究桑叶提取物（MLE）的抗氧化和抗衰老作用。
以秀丽隐杆线虫为模式生物，观察不同浓度（1、2、4、8mg/mL）的MLE对线虫健康寿命、繁殖能力、运动能力、抗应激能力和抗氧化能力的影响。此外，建立D-半乳糖（D-gal）诱导的小鼠肝脏衰老模型和L-02细胞衰老模型。通过体重、器官指数、丙二醛（MDA）、总超氧化物歧化酶（T-SOD）、总抗氧化能力（T-AOC）、天冬氨酸氨基转移酶和丙氨酸氨基转移酶（AST和ALT）、活性氧（ROS）、线粒体膜电位（MMP）、苏木精和伊红（H&E）、衰老相关β-半乳糖苷酶（SA-β-Gal）来评估MLE的抗氧化和抗衰老作用。此外，通过蛋白质免疫印迹法检测AMPK/SIRT1/PGC-1α和Nrf2-Keap1的表达。
MLE可显著延长线虫的平均寿命，并改善大多数与秀丽隐杆线虫衰老相关的生理指标。此外，MLE处理可改善模型小鼠体重和器官指数（器官重量/体重）的下降，并以剂量依赖的方式保护小鼠和肝细胞免受氧化应激，上调T-SOD和T-AOC，同时降低ROS和MDA水平。MLE降低了肝脏和细胞中AST和ALT的水平，并增强了线粒体膜电位。MLE激活了AMPK/SIRT1/PGC-1α通路，参与线粒体生物合成和氧化代谢，延缓D-gal诱导的衰老。MLE促进了Nrf2在细胞核中的积累，表明体内和体外氧化应激反应的改善是由Nrf2-Keap1通路介导的。
MLE在体内和体外似乎具有极大的潜力来刺激氧化应激反应并减轻衰老过程，为对抗衰老及衰老相关疾病提供了一种新型的促进健康的资源。
