Genetic hyperactivation of Nrf2 causes larval lethality in Keap1a and Keap1b-double-knockout zebrafish

Bian, Lixuan; Nguyen, Vu Tuan; Tamaoki, Junya; Endo, Yuka; Dong, Guilin; Sato, Ayaka

doi:10.1016/j.redox.2023.102673

Cited by 5 publications

(1 citation statement)

References 29 publications

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“…However, Keap1 knockout is lethal in zebrafish, due to the hyperactivation of Nrf2, which increases the expression of Nrf2-target genes and decreases the expression of visual cycle genes. TRG could partially rescue Keap1-knockout larvae from death [ 111 ].…”

Section: Other Protective Effects Of Trgmentioning

confidence: 99%

Pharmacological Activities, Therapeutic Effects, and Mechanistic Actions of Trigonelline

Nguyen,

Taine,

Meng

et al. 2024

IJMS

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Trigonelline (TRG) is a natural polar hydrophilic alkaloid that is found in many plants such as green coffee beans and fenugreek seeds. TRG potentially acts on multiple molecular targets, including nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor γ, glycogen synthase kinase, tyrosinase, nerve growth factor, estrogen receptor, amyloid-β peptide, and several neurotransmitter receptors. In this review, we systematically summarize the pharmacological activities, medicinal properties, and mechanistic actions of TRG as a potential therapeutic agent. Mechanistically, TRG can facilitate the maintenance and restoration of the metabolic homeostasis of glucose and lipids. It can counteract inflammatory constituents at multiple levels by hampering pro-inflammatory factor release, alleviating inflammatory propagation, and attenuating tissue injury. It concurrently modulates oxidative stress by the blockage of the detrimental Nrf2 pathway when autophagy is impaired. Therefore, it exerts diverse therapeutic effects on a variety of pathological conditions associated with chronic metabolic diseases and age-related disorders. It shows multidimensional effects, including neuroprotection from neurodegenerative disorders and diabetic peripheral neuropathy, neuromodulation, mitigation of cardiovascular disorders, skin diseases, diabetic mellitus, liver and kidney injuries, and anti-pathogen and anti-tumor activities. Further validations are required to define its specific targeting molecules, dissect the underlying mechanistic networks, and corroborate its efficacy in clinical trials.

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Section: Other Protective Effects Of Trgmentioning

confidence: 99%