Trigonelline Extends the Lifespan of C. Elegans and Delays the Progression of Age‐Related Diseases by Activating AMPK, DAF‐16, and HSF‐1

Abstract

Trigonelline is the main alkaloid with bioactivity presented in fenugreek, which was used in traditional medicine in Asian countries for centuries. It is reported that trigonelline has anti-inflammatory, anti-oxidant, and anti-pathogenic effects. We are wondering whether trigonelline have anti-aging effect. We found that 50 μM of trigonelline had the best anti-aging activity and could prolong the lifespan of Caenorhabditis elegans (C. elegans) by about 17.9%. Trigonelline can enhance the oxidative, heat, and pathogenic stress resistance of C. elegans. Trigonelline could also delay the development of neurodegenerative diseases, such as AD, PD, and HD, in models of C. elegans. Trigonelline could not prolong the lifespan of long-lived worms with loss-of-function mutations in genes regulating energy and nutrition, such as clk-1, isp-1, eat-2, and rsks-1. Trigonelline requires daf-16, hsf-1, and aak-2 to extend the lifespan of C. elegans. Trigonelline can also up-regulate the expression of daf-16 and hsf-1 targeted downstream genes, such as sod-3, gst-4, hsp-16.1, and hsp-12.6. Our results can be the basis for developing trigonelline-rich products with health benefits, as well as for further research on the pharmacological usage of trigonelline.

Rose essential oil diminishes dopaminergic neuron degenerations and reduces α‐synuclein aggregation in Caenorhabditis elegans models of Parkinson's disease

“…Superoxide dismutases ( SOD ‐3) encoded by gene sod‐3‐ in CF1553. These SOD ‐3 enzymes play a fundamental role in protecting the cells from oxidative stress and prolonging lifespan (Zeng et al, 2021). Oxidative stress is one of the leading causes of P.D., as we mentioned earlier.…”

Study of TCM Medication Rules against Aging based on Network Pharmacology and Data Mining

“…A previous study has reported that trigonelline at different concentrations could prolong the healthy lifespan, enhance the locomotor ability and reduce the accumulation of lipofuscin in the body in C. elegans. Moreover, trigonelline was also able to delay the progression of age-related diseases in C. elegans models of AD, PD, and HD [36].…”

Update on new trends and progress of natural active ingredients in the intervention of Alzheimer's disease, based on understanding of traditional Chinese and Western relevant theories: A review

“…Meanwhile, trigonelline reduced the loss of neurons by inhibiting oxidative stress, astrocyte activity and inflammation and also protecting mitochondrial integrity (Chowdhury et al, 2018; Fahanik‐Babaei et al, 2019). Zeng et al (Zeng et al, 2021) showed that trigonelline could prolong the life of Caenorhabditis elegans by 17.9%, enhance the antioxidant capacity of elegans, regulate the expression of some genes，and finally delay the development of neurodegenerative diseases.…”