Berberine protects against diabetic kidney disease via promoting PGC‐1α‐regulated mitochondrial energy homeostasis

Abstract

Background and Purpose Disordered lipid metabolism and disturbed mitochondrial bioenergetics play pivotal roles in the initiation and development of diabetic kidney disease (DKD). Berberine is a plant alkaloid, used in Chinese herbal medicine. It has multiple therapeutic actions on diabetes mellitus and its complications, including regulation of glucose and lipid metabolism, improvement of insulin sensitivity, and alleviation of oxidative damage. Here, we investigated the reno‐protective effects of berberine. Experimental Approach We used samples from DKD patients and experiments with models of DKD (db/db mice) and cultured podocytes, to characterize energy metabolism profiles using metabolomics. Molecular targets and mechanisms involved in the regulation of mitochondrial function and bioenergetics by berberine were investigated, along with its effects on metabolic alterations in DKD mice. Key Results Metabolomic analysis suggested altered mitochondrial fuel usage and generalized mitochondrial dysfunction in patients with DKD. In db/db mice, berberine treatment reversed the disordered metabolism, podocyte damage and glomerulosclerosis. Lipid accumulation, excessive generation of mitochondrial ROS, mitochondrial dysfunction, and deficient fatty acid oxidation in DKD mouse models and in cultured podocytes were suppressed by berberine. These protective effects of berberine were accompanied by activation of the peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) signalling pathway, which promoted mitochondrial energy homeostasis and fatty acid oxidation in podocytes. Conclusion and Implications PGC‐1α‐mediated mitochondrial bioenergetics could play a key role in lipid disorder‐induced podocyte damage and development of DKD in mice. Restoration of PGC‐1α activity and the energy homeostasis by berberine might be a potential therapeutic strategy against DKD.

Poor Control of Plasma Triglycerides Is Associated with Early Decline of Estimated Glomerular Filtration Rates in New-Onset Type 2 Diabetes in China: Results from a 3-Year Follow-Up Study

“…Breaking the wretched cycle might have some effect in relieving kidney damage and preserving renal function. Intervention measures, such as liraglutide [ 27 ], disulfide-bond A oxidoreductase-like protein (DsbA-L) [ 28 ], berberine [ 29 ], and resveratrol [ 30 ], whose renal protection effects had been proved to be partly relied on reducing TG contents in the kidney. Here, in our study, we verified the above results and further emphasized the risk of TG for DKD progression and the necessity of controlling TG.…”

Mitochondrial Targeting of Herbal Medicine in Chronic Kidney Disease

“…Qin et al reported that PGC-1α was significantly decreased in db/db mice and palmitic acid-induced podocytes. Berberine increased the expression of PGC-1α and improved mitochondrial function via the AMPK/ PGC-1α pathway both in vivo and in vitro (Qin et al, 2020).…”

“…Qin et al reported that PGC-1α was significantly decreased in db/db mice and palmitic acid-induced podocytes. Berberine increased the expression of PGC-1α and improved mitochondrial function via the AMPK/PGC-1α pathway both in vivo and in vitro ( Qin et al, 2020 ). Hyperoside, also named quercetin 3-o- β - D -galactopyranoside, is a flavonol glycoside extracted from Rhododendron ponticum L that is widely used in Traditional Chinese Medcine ( Li et al, 2013 ; Wang et al, 2018 ).…”

A Song of Ice and Fire: Cold and Hot Properties of Traditional Chinese Medicines

“…In addition to alkaloids, Huanglian also contains chemical components such as organic acids, coumarin, phenylpropanoids, and saccharides ( Meng et al, 2018 ). The wide range of pharmacological effects of the extracts or compounds of Huanglian includes antipyretic, antibacterial, antiviral, antidiabetic, anticancer, anti-inflammatory, and cardiovascular protective effects ( Liu et al, 2011 ; Tan et al, 2016 ; Hung et al, 2018 ; Ishikawa et al, 2018 ; Li et al, 2018 ; Liang et al, 2019 ; Kwon and Chan, 2020 ; Qin et al, 2020 ). In particular, the pharmacological effects of BBR have been extensively studied.…”