Research Paper Volume 13, Issue 5 pp 7096—7119

Berberine-induced TFEB deacetylation by SIRT1 promotes autophagy in peritoneal macrophages

Yinghong Zheng1, , Jiayuan Kou1, , Pengyu Wang1, , Ting Ye1, , Zitong Wang1, , Ziyu Gao1, , Lin Cong1, , Manman Li1, , Bowen Dong1, , Wei Yang1, , Quanfeng Li1, , Hong Li1, , Rui Wang2, , Liming Yang3, ,

  • 1 Department of Pathophysiology, Key Laboratory of Cardiovascular Pathophysiology, Harbin Medical University, Harbin 150081, China
  • 2 Yangpu Hospital, Tongji University, Shanghai 200090, China
  • 3 Department of Pathophysiology, Harbin Medical University (Daqing), Daqing 163319, China

Received: June 4, 2020       Accepted: January 13, 2021       Published: February 26, 2021
How to Cite

Copyright: © 2021 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Atherosclerosis is a chronic inflammatory disease that commonly affects the elderly and is characterized by vascular damage, macrophage infiltration, and plaque formation. Moreover, it increases the risk of cardiovascular disease. The pathogenesis of atherosclerosis involves an interplay between macrophage autophagy and apoptosis. A recently discovered transcription factor, transcription factor EB (TFEB) is known to activate autophagy in macrophages. Sirtuin deacetylase 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase, activates several transcription factors, including TFEB. We studied the effects of berberine on the NAD+ synthesis pathway and interactions between SIRT1 and TFEB. We also studied the effects of berberine-induced TFEB activation via SIRT1 on autophagy and apoptosis of peritoneal macrophages. We found that berberine promoted autophagy of peritoneal macrophages by activating SIRT1 via the NAD+ synthesis pathway and, in turn, promoting TFEB nuclear translocation and deacetylation. The functional regulation of SIRT1 and TFEB by berberine could be exploited as a potential therapeutic strategy for atherosclerosis.


AS: atherosclerosis; SIRT1: sirtuin1; NAD+: nicotinamide adenine dinucleotide; TFEB: transcription factor EB; HAT: histone acetyl transferase; HDAC: histone deacetylase; IDO1: indole-2, 3-dioxygenase 1; QPRT: quinolinate phosphoribosyl transferase; NAMPT: nicotinamide phosphoribosyltransferase; NMNAT: nicotinamide/nicotinic acid mononucleotide adenylyltransferase; CVD: cardiovascular disease; NAM: nicotinamide; TSA: trichostatin A; 1MT: 1-methyl-L-tryptophan; PA: phthalic acid; IGF-1: insulin-like growth factor-1; Rapa: rapamycin; RT-qPCR: quantitative reverse transcription PCR; siRNA: small interfering RNA; 3-MA: 3-methyladenine; TEM: transmission electron microscopy; AO: acridine orange; AVOs: acidic vesicle organelles; MDC: monodansylcadaverine; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end-labeling; LC3β: microtubule-associated protein 1 light chain 3-β.