ArticleCell death & disease2019
Ginseng metabolite Protopanaxadiol induces Sestrin2 expression and AMPK activation through GCN2 and PERK.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- A review of pharmacological properties and pharmacokinetic of 20(S)-protopanaxadiol.Journal of ginseng research · 2026Review
- Artemisinin synergizes with CCCP in autophagic cell death induction via ER stress in uveal melanoma.iScience · 2025Article
- Mir-615-3p promotes osteosarcoma progression via the SESN2/AMPK/mTOR pathway.Cancer cell international · 2024Article
- Systemic and molecular analysis dissect the red ginseng induction of apoptosis and autophagy in HCC as mediated with AMPK.Journal of ginseng research · 2023Article
- Solanine Represses Gastric Cancer Growth by Mediating Autophagy Through AAMDC/MYC/ATF4/Sesn2 Signaling Pathway.Drug design, development and therapy · 2023Article
- Sestrin2 in diabetes and diabetic complications.Frontiers in endocrinology · 2023Review
- Genetic and molecular dissection of ginseng (Frontiers in plant science · 2023Article
- Sesn2 Serves as a Regulator between Mitochondrial Unfolded Protein Response and Mitophagy in Intervertebral Disc Degeneration.International journal of biological sciences · 2023Article
- GCN2 inhibition sensitizes arginine-deprived hepatocellular carcinoma cells to senolytic treatment.Cell metabolism · 2022Article
- Eriodictyol ameliorates cognitive dysfunction in APP/PS1 mice by inhibiting ferroptosis via vitamin D receptor-mediated Nrf2 activation.Molecular medicine (Cambridge, Mass.) · 2022Article
- A paradoxical role for sestrin 2 protein in tumor suppression and tumorigenesis.Cancer cell international · 2021Review
- Functional Amino Acids and Autophagy: Diverse Signal Transduction and Application.International journal of molecular sciences · 2021Review
- GCN4 Regulates Secondary Metabolism through Activation of Antioxidant Gene Expression under Nitrogen Limitation Conditions in Ganoderma lucidum.Applied and environmental microbiology · 2021Article
- Duck Hepatitis A Virus Type 1 Induces eIF2α Phosphorylation-Dependent Cellular Translation ShutoffFrontiers in microbiology · 2021Article
- Reciprocal regulation between GCN2 (eIF2AK4) and PERK (eIF2AK3) through the JNK-FOXO3 axis to modulate cancer drug resistance and clonal survival.Molecular and cellular endocrinology · 2020Article
- SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ginseng is one of the most commonly used herbs that is believed to have a variety of biological activities, including reducing blood sugar and cholesterol levels, anti-cancer, and anti-diabetes activities. However, little is known about the molecular mechanisms involved. In this study, we showed that protopanaxadiol (PPD), a metabolite of the protopanaxadiol group ginsenosides that are the major pharmacological constituents of ginsengs, significantly altered the expression of genes involved in metabolism, elevated Sestrin2 (Sesn2) expression, activated AMPK, and induced autophagy. Using CRISPR/CAS9-mediated gene editing and shRNA-mediated gene silencing, we demonstrated that Sesn2 is required for PPD-induced AMPK activation and autophagy. Interestingly, we showed that PPD-induced Sesn2 expression is mediated redundantly by the GCN2/ATF4 amino acid-sensing pathway and the PERK/ATF4 endoplasmic reticulum (ER) stress pathway. Our results suggest that ginseng metabolite PPD modulates the metabolism of amino acids and lipids, leading to the activation of the stress-sensing kinases GCN2 and PERK to induce Sesn2 expression, which promotes AMPK activation, autophagy, and metabolic health.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.