Chin J Integr Med. 2026 Apr 27. doi: 10.1007/s11655-026-4037-8. Online ahead of print.
ABSTRACT
OBJECTIVE: To investigate berberine (BBR) promotes mitochondrial biogenesis via the silent mating type information regulation 2 homolog 1/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (SIRT1/PGC-1α) signaling pathway to exert its anti-atherosclerosis effects.
METHODS: A total of 42 8-week-old AopE-/- mice were fed a high-fat diet for 12 weeks, and then randomly divided into 7 groups via a simple randomization method: the model group, the low-, medium- and high-dose BBR groups [BBRL 50 mg/(kg·d), BBRM 100 mg/(kg·d) and BBRH 150 mg/(kg·d), respectively], positive control group [atorvastatin, 3 mg/(kg·d)], BBR combined with nuclear respiratory factor 1 (Nrf1) inhibitor group (BBRH+EX527, 150 mg/kg BBR+10 mg/kg EX527), and Nrf1 inhibitor group [EX527, 10 mg/(kg·d)]. Six C57BL/6J mice fed with a normal diet were served as control. After 4 weeks of intragastric administration, samples were harvested, and serum, aorta, heart, and liver tissues were isolated for subsequent experiments. Biochemical kits were used to detect serum lipid content in mice. Hematoxylin-eosin, Oil Red O and Masson staining were used to assess lesion severity, lipid deposition, and fibrous cap thickness. Transmission electron microscopy and immunofluorescence were used to analyze mitochondrial morphology and function. Real time quantitative PCR assay and Western blot were utilized to measure the expression levels of SIRT1, PGC-1α, Nrf1, and mitochondrial transcription factor A (TFAM) at both the mRNA and protein levels, along with the quantification of mitochondrial DNA (mtDNA) copy-number in mouse aortas.
RESULTS: After BBR intervention, BBRM and BBRH groups significantly reduced blood lipid levels in mice (P<0.01), alleviated aortic plaque deposition, and improved mitochondrial damage (P<0.05 or P<0.01). Additionally, BBR significantly upregulated the mRNA and protein expressions of SIRT1, PGC-1α, Nrf1, and TFAM (P<0.05 or P<0.01). And the relative copy number of mtDNA increased in a dose-dependent manner (P<0.01). In the BBRH+EX527 group, aortic lesions and mitochondrial damage were exacerbated, with concurrent decreases in mRNA and protein expression levels (P<0.05 or P<0.01).
CONCLUSION: BBR promotes mitochondrial biogenesis, maintains mitochondrial function, and inhibits mitochondrial damage through the SIRT1/PGC-1α signaling pathway, thereby improving atherosclerosis.
PMID:42043671 | DOI:10.1007/s11655-026-4037-8