Citri Reticulatae Semen Extract Promotes Healthy Aging and Neuroprotection via Autophagy Induction in Caenorhabditis elegans

Abstract

Nutrition intervention has emerged as a potential strategy to delay aging and promote healthy longevity. Citri Reticulatae Semen (CRS) has diverse beneficial effects and has been used for thousands of years to treat pain. However, the health benefits of CRS in prolonging health span and improving aging-related diseases and the exact mechanisms remain poorly characterized. In this study, Caenorhabditis elegans (C. elegans) was used as a model organism to study the antiaging and health span promoting activities of 75% ethanol extract of CRS (CRSE). The results showed that treatment with CRSE at 1 000 μg/mL significantly extended the life span of worms by 18.93% without detriment to health span and fitness, as evidenced by the delayed aging-related phenotypes and increased body length and width, and reproductive output. In addition, CRSE treatment enhanced the ability of resistance to heat, oxidative, and pathogenic bacterial stress. Consistently, heat shock proteins and antioxidant enzyme-related and pathogenesis-related genes were up-regulated by CRSE treatment. Furthermore, CRSE supplementation also improved α-synuclein, 6-OHDA, and polyQ40-induced pathologies in transgenic C. elegans models of Parkinson’s disease and Huntington’s disease. The mechanistic study demonstrated that CRSE induced autophagy in worms, while the RNAi knockdown of 4 key autophagy-related genes, including lgg-1, bec-1, vps-34, and unc-51, remarkably abrogated the beneficial effects of CRSE on the extending of life span and health span and neuroprotection, demonstrating that CRSE exerts beneficial effects via autophagy induction in worms. Together, our current findings provide new insights into the practical application of CRS for the prevention of aging and aging-related diseases.

Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease

“…C. elegans serves as an exceptional model to study stress resistance during aging 33 . In this study, we examined the effect of CFE on the resistance of worms to various stresses, including heat stress, oxidative stress, and pathogenic bacteria.…”

“…Figure 7A shows that CFE significantly prolonged the lifespan of N2 worms, as evidenced by the increased survival rate. The accumulation of lipofuscin is recognized as a marker of aging 33 . With aging, the intensity of blue fluorescence reflecting the content of lipofuscin increases.…”

“…The pharyngeal pumping behavior of N2 worms was assessed by counting the number of contractions made by the pharyngeal muscles within a 20‐second period. 33 The worms were transferred to agarose pads, and their pharyngeal pumping was observed using a stereomicroscope. The contractions were visually counted by an observer blinded to the treatment groups, and the pumping rate was calculated.…”

Ameliorative effect of Luffa cylindrica fruits on Caenorhabditis elegans and cellular models of Alzheimer's disease‐related pathology via autophagy induction

“…The C. elegans strain CL2331, temperature‐sensitively expressing human Aβ (3–42) peptides fused with GFP in body wall muscle cells, was used to assess Aβ aggregation following previous reports (Long, Tang, et al, 2022). Briefly, CL2331 larvae were incubated in a 15°C incubator until they reached the late L4 larval stage.…”

Chiral Separation, Configuration Confirmation and Bioactivity Determination of the Stereoisomers of Hesperidin and Narirutin in Citrus reticulata Blanco

“…As a common medicinal plant, Citrus reticulata Blanco has been proven to possess multiple functions, such as dredging meridian, promoting blood flow, delaying senescence, etc. [ 15 , 16 ]. Depending on the harvesting period, two different herbal medicines, Citri Reticulatae Pericarpium (Chenpi) and Citri Reticulatae Pericarpium Viride (Qingpi), can be obtained.…”