Berberine Improves the Protective Effects of Metformin on Diabetic Nephropathy in db/db Mice through Trib1-dependent Inhibiting Inflammation.

Abstract

PURPOSE:

Diabetic nephropathy (DN), one of severe diabetic complications in the diabetes, is the main cause of end stage renal disease (ESRD). Notably, the currently available medications used to treat DN remain limited. Here, we determined whether berberine (BBR) could enhance the anti-diabetic nephropathy activities of metformin (Met) and explored its possible mechanisms.

METHOD:

The anti-diabetic nephropathy properties were systematically analyzed in the diabetic db/db mice treated with Met, BBR or with combination of Met and BBR.

RESULTS:

We found that both single Met and BBR treatments, and combination therapy could lower blood glucose, and ameliorate insulin resistance. The improvement of lipids metabolism by co-administration was more evident, as indicated by reduced serum cholesterol and less fat accumulation in the liver. Further, it was found that Met and BBR treatments, and co-administration could attenuate the progression of DN. However, anti-diabetic nephropathy activities of Met were enhanced when combined with BBR, as evidenced by improved renal function and histological abnormalities of diabetic kidney. Mechanistically, BBR enhanced renal-protective effects of Met primarily through potently promoting expression of Trib1, which subsequently downregulated the increased protein levels of CCAAT/enhancer binding protein α (C/EBPα), and eventually inhibited fatty synthesis proteins and nuclear factor kappa-B (NF-κB) signaling.

CONCLUSION:

Our data provide novel insight that co-administration of BBR and Met exerts a preferable activity of anti-diabetic nephropathy via collectively enhancing lipolysis and inhibiting inflammation. Combination therapy with these two drugs may provide an effective therapeutic strategy for the medical treatment of diabetic nephropathy.

• Authors: Bin Zhang, Xuelian Zhang, Chenyang Zhang, Guibo Sun, Xiaobo Sun
• Journal: Pharmaceutical research (Pharm Res) Vol. 38 Issue 11 Pg. 1807-1820 (Nov 2021) ISSN: 1573-904X [Electronic] United States
• PMID: 34773184 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Intracellular Signaling Peptides and Proteins
• Trib1 protein, mouse
• Berberine
• Metformin
• Protein Serine-Threonine Kinases

Topics

• Animals
• Berberine (pharmacology, therapeutic use)
• Diabetic Nephropathies (drug therapy, genetics, immunology)
• Disease Models, Animal
• Disease Progression
• Drug Synergism
• Drug Therapy, Combination (methods)
• Humans
• Intracellular Signaling Peptides and Proteins (agonists, metabolism)
• Kidney (drug effects, immunology, pathology)
• Male
• Metformin (pharmacology, therapeutic use)
• Mice
• Nephritis (drug therapy, genetics, immunology, pathology)
• Protein Serine-Threonine Kinases (antagonists & inhibitors, metabolism)