Mulberry leaves attenuate D-galactose-induced aging in vivo and in vitro. (15th July 2023) - Zhu, Yan
Abstract: Ethnopharmacological relevance: 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. Aim of the study: The objective of this study was to investigate the antioxidant and anti-aging effects of mulberry leaf extract (MLE) in vivo and in vitro . Materials and methods: 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. Results: 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 . Conclusion: 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. Graphical abstract: Image 1