ArticleThe Journal of biological chemistry2015
Inhibition of PCSK9 transcription by berberine involves down-regulation of hepatic HNF1α protein expression through the ubiquitin-proteasome degradation pathway.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- Efficacy of Berberine Alone and in Combination for the Treatment of Hyperlipidemia: A Systematic Review.Journal of evidence-based complementary & alternative medicine · 2017Pooled it
- Identification and evaluation of a lipid-lowering small compound as a PCSK9 inhibitor.Journal of advanced research · 2026Article
- Hypocholesterolemic agents and the gut microbiota: a review of interactions and modulatory activity.Pharmacological reports : PR · 2026Review
- Review: natural compounds as PCSK9 inhibitors for antiviral therapy.Archives of microbiology · 2026Review
- Selected Nutraceuticals in Metabolic Syndrome: Molecular Mechanisms and Clinical Implications.Biomedicines · 2026Review
- PCSK9-Mediated Inflammation in Foam Cell Formation and Exploring the Biologically Active Compounds Derived From Natural Resources.Advances in pharmacological and pharmaceutical sciences · 2026Review
- Berberine's impact on health: Comprehensive biological, pharmacological, and nutritional perspectives.Metabolism open · 2025Review
- Hepatocyte nuclear factor 1 in renal lipid metabolism: molecular mechanisms and therapeutic potentials.Cell biology and toxicology · 2025Review
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach.European journal of medical research · 2025Review
- Anti-atherosclerotic effects of natural compounds targeting lipid metabolism and inflammation: Focus on PPARs, LXRs, and PCSK9.Atherosclerosis plus · 2025Review
- Targeting the gut microbiota and lipid metabolism: potential mechanisms of natural products for the treatment of non-alcoholic fatty liver disease.Frontiers in pharmacology · 2025Review
- Pharmacological properties and therapeutic potential of berberine: a comprehensive review.Frontiers in pharmacology · 2025Review
- Genomic and Transcriptomic Profile of HNF1A-Mutated Liver Adenomas Highlights Molecular Signature and Potential Therapeutic Implications.International journal of molecular sciences · 2024Article
- Tripartite motif 8 promotes the progression of hepatocellular carcinoma via mediating ubiquitination of HNF1α.Cell death & disease · 2024Article
- The Link between miRNAs and PCKS9 in Atherosclerosis.Current medicinal chemistry · 2024Review
- Molecular mechanisms, targets and clinical potential of berberine in regulating metabolism: a review focussing on databases and molecular docking studies.Frontiers in pharmacology · 2024Review
- Association between serum PCSK9 and coronary heart disease in patients with type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2023Article
- Review
- In Vitro and In Vivo SucrosomialNutrients · 2022Article
- The effect of berberine and fenugreek seed co-supplementation on inflammatory factor, lipid and glycemic profile in patients with type 2 diabetes mellitus: a double-blind controlled randomized clinical trial.Diabetology & metabolic syndrome · 2022Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Our previous in vitro studies have identified hepatocyte nuclear factor 1α (HNF1α) as an obligated trans-activator for PCSK9 gene expression and demonstrated its functional involvement in the suppression of PCSK9 expression by berberine (BBR), a natural cholesterol-lowering compound. In this study, we investigated the mechanism underlying the inhibitory effect of BBR on HNF1α-mediated PCSK9 transcription. Administration of BBR to hyperlipidemic mice and hamsters lowered circulating PCSK9 concentrations and hepatic PCSK9 mRNA levels without affecting the gene expression of HNF1α. However, hepatic HNF1α protein levels were markedly reduced in BBR-treated animals as compared with the control. Using HepG2 cells as a model system, we obtained evidence that BBR treatment let to accelerated degradation of HNF1α protein. By applying inhibitors to selectively block the ubiquitin proteasome system (UPS) and autophagy-lysosomal pathway, we show that HNF1α protein content in HepG2 cells was not affected by bafilomycin A1 treatment, but it was dose-dependently increased by UPS inhibitors bortezomib and MG132. Bortezomib treatment elevated HNF1α and PCSK9 cellular levels with concomitant reductions of LDL receptor protein. Moreover, HNF1α protein displayed a multiubiquitination ladder pattern in cells treated with BBR or overexpressing ubiquitin. By expressing GFP-HNF1α fusion protein in cells, we observed that blocking UPS resulted in accumulation of GFP-HNF1α in cytoplasm. Importantly, we show that the BBR reducing effects on HNF1α protein and PCSK9 gene transcription can be eradicated by proteasome inhibitors. Altogether, our studies using BBR as a probe uncovered a new aspect of PCSK9 regulation by ubiquitin-induced proteasomal degradation of HNF1α.
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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.