Abstract
Age is the major risk factor for most of the deadliest diseases. Developing small molecule drugs with antiaging effects could improve the health of aged people and retard the onset and progress of aging-associated disorders. Bioactive secondary metabolites from medicinal plants are the main source for development of medication. Orientin is a water-soluble flavonoid monomer compound widely found in many medicinal plants. Orientin inhibits fat production, antioxidation, and anti-inflammatory activities. In this study, we explored whether orientin could affect the aging of C. elegans. We found that orientin improved heat, oxidative, and pathogenic stress resistances through activating stress responses, including HSF-1-mediated heat shock response, SKN-1-mediated xenobiotic and oxidation response, mitochondria unfolded responses, endoplasmic unfolded protein response, and increased autophagy activity. Orientin also could activate key regulators of the nutrient sensing pathway, including AMPK and insulin downstream transcription factor FOXO/DAF-16 to further improve the cellular health status. The above effects of orientin reduced the accumulation of toxic proteins (α-synuclein, β-amyloid, and poly-Q) and delayed the onset of neurodegenerative disorders in AD, PD, and HD models of C. elegans and finally increased the longevity and health span of C. elegans. Our results suggest that orientin has promising antiaging effects and could be a potential natural source for developing novel therapeutic drugs for aging and its related diseases.
Highlights
The longevity of human has improved dramatically during the past century due to improved healthcare and nutrition
We found that orientin increased the longevity of C. elegans in a dosedependent manner and 100 μM of orientin increased the longest longevity of N2 worms by up to 22.2% (p < 0:001) (Figures 1(b) and 1(c), Table S1)
We found that orientin treatment reduced the fluorescence intensity of intestinal lipofuscin in nematodes by 18.7% compared with the control group (p < 0:001) (Figure 1(e), Table S3)
Summary
The longevity of human has improved dramatically during the past century due to improved healthcare and nutrition. Age is the major cause of most life-threatening diseases, including cancer, cardiovascular diseases, neurodegenerative disorder, diabetes, and osteoporosis [1, 2]. The population older than 65 years is increasing fast in over the world [3]. The rise of the population struggling with aging-associated disorders becomes an emerging socioeconomic challenge. Delaying the rate of biological aging would postpone the onset and progression of most age-related disorders. The intervention of aging would be more effective than the treatment of the particular chronic disorders [4]. One of the major strategies is to develop small molecule drugs with antiaging effects.
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