NAD+ · research summary

SIRT3-Dependent Actions of Berberine: From Molecular Therapies to Toxicity.

Journal of biochemical and molecular toxicology · 2026. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Systematic review of experimental studies on berberine and SIRT3 modulation
“This review aims to bridge this knowledge gap by providing a SIRT3‐centered synthesis of current evidence, critically evaluating the therapeutic and toxicological implications of berberine‐mediated SIRT3 modulation, and delineating the unresolved translational challenges in this field.”

Subjects

Various disease models including mice, rats, zebrafish, and human cell lines
“The final set comprised 18 studies that met all eligibility criteria.”

Sample size

18 studies included in the review
“The final set comprised 18 studies that met all eligibility criteria.”

Duration

Literature search conducted up to December 2025
“Electronic databases including PubMed, Scopus, and Web of Science were systematically searched for relevant publications up to December 2025.”

Reported findings

Berberine exerts antihyperglycemic effects by inhibiting SIRT3, leading to mitochondrial dysfunction and AMPK activation
“The antihyperglycemic effects of berberine are mediated through SIRT3 inhibition, which promotes hyperacetylation of complex I subunits, degradation of MPC1, an increased AMP/ATP ratio, AMPK activation, and suppression of PEPCK1, collectively resulting in the inhibition of gluconeogenesis.”
Berberine activates SIRT3 to produce hypolipidemic, cardioprotective, and hepatoprotective effects
“In contrast, the hypolipidemic, cardioprotective, and hepatoprotective effects of berberine are associated with SIRT3 activation, which facilitating adipose tissue remodeling, enhancing β‐oxidation in NAFLD, promoting lipophagy in diabetic cardiomyopathy, and mitigates doxorubicin‐induced cardiotoxicity.”
Berberine exhibits context-dependent effects on SIRT3 in cancer and ocular toxicity models
“Furthermore, berberine exhibits antitumor duality, exerting contrasting effects in colorectal cancer and hepatoma models, and demonstrates versatile mitochondrial metabolic reprogramming in polycystic ovarian syndrome.”

Limitations stated by the authors

Lack of direct genetic validation in some models and context-dependent variability of SIRT3 modulation
“However, the existing literature reveals an apparent paradox: berberine appears to upregulate SIRT3 activity in various models of metabolic and cardiovascular injury, while suppressing it in pathways such as hepatic gluconeogenesis.”

Source: PubMed 42859914 · DOI 10.1002/jbt.71126 · all study summaries

Study type

Systematic review of experimental studies on berberine and SIRT3 modulation

“This review aims to bridge this knowledge gap by providing a SIRT3‐centered synthesis of current evidence, critically evaluating the therapeutic and toxicological implications of berberine‐mediated SIRT3 modulation, and delineating the unresolved translational challenges in this field.”

Reported findings

Berberine exerts antihyperglycemic effects by inhibiting SIRT3, leading to mitochondrial dysfunction and AMPK activation

“The antihyperglycemic effects of berberine are mediated through SIRT3 inhibition, which promotes hyperacetylation of complex I subunits, degradation of MPC1, an increased AMP/ATP ratio, AMPK activation, and suppression of PEPCK1, collectively resulting in the inhibition of gluconeogenesis.”

Berberine activates SIRT3 to produce hypolipidemic, cardioprotective, and hepatoprotective effects

“In contrast, the hypolipidemic, cardioprotective, and hepatoprotective effects of berberine are associated with SIRT3 activation, which facilitating adipose tissue remodeling, enhancing β‐oxidation in NAFLD, promoting lipophagy in diabetic cardiomyopathy, and mitigates doxorubicin‐induced cardiotoxicity.”

Berberine exhibits context-dependent effects on SIRT3 in cancer and ocular toxicity models

“Furthermore, berberine exhibits antitumor duality, exerting contrasting effects in colorectal cancer and hepatoma models, and demonstrates versatile mitochondrial metabolic reprogramming in polycystic ovarian syndrome.”

Limitations stated by the authors

Lack of direct genetic validation in some models and context-dependent variability of SIRT3 modulation

“However, the existing literature reveals an apparent paradox: berberine appears to upregulate SIRT3 activity in various models of metabolic and cardiovascular injury, while suppressing it in pathways such as hepatic gluconeogenesis.”