Mitochondrial fusion/fission process involved in the improvement of catalpol on high glucose-induced hepatic mitochondrial dysfunction

Abstract

Catalpol, an iridoid glycoside, has been shown to exert hypoglycemic effect by rescuing mitochondrial function, but the detailed mechanism remains unclear yet. In this study, the effect and mechanism of catalpol on the hepatic mitochondria under diabetic conditions were further examined. Oral administration of catalpol significantly reduced the blood glucose, triglyceride, and cholesterol levels in high-fat diet-and streptozotocin-induced diabetic mice. Additionally, catalpol attenuated the decrease in liver mitochondrial ATP content resulting from diabetes. Furthermore, the number of mitochondria possessing a long size was increased in catalpol-treated mice. Interestingly, the catalpol-induced recovery of mitochondrial function was associated with decreased fission protein 1 and dynamin-related protein 1 expression as well as increased mitofusin 1 expression in the liver. In HepG2 cells, catalpol alleviated the decrease of ATP content and mitochondrial membrane potential, and the increase of reactive oxygen species formation induced by high glucose. MitoTracker Green stain shows that the tubular feature of mitochondria was maintained when cells were treated with catalpol. Catalpol also decreased fission protein 1 and dynamin-related protein 1 expression and increased mitofusin 1 expression in HepG2 cells. The present results suggest that catalpol can ameliorate hepatic mitochondrial dysfunction under a diabetic state, and this may be related to its regulation of mitochondrial fusion and fission events.

SIRT1 activation inhibits hyperglycemia-induced apoptosis by reducing oxidative stress and mitochondrial dysfunction in human endothelial cells

“…DM-associated mitochondrial dysfunction has been demonstrated to be markedly upregulated by hyperglycemia in hepatocytes (28,29), skeletal muscle cells (30), cardiomyocytes (31,32), retinal cells (33) and in renal proximal tubular cells (34). Dysfunctional mitochondria are one of the two major sources of increased ROS production under hyperglycemic conditions (8)(9)(10).…”

Screening and identification of potential hypoglycemic components in Zeng Ye Tang by high‐performance liquid chromatography coupled with tandem quadrupole time‐of‐flight mass spectrometry

“…The first six compounds are derived from Xuanshen and the last two homoisoflavonoids are derived from Maidong. It has previously been reported that homoisoflavonoids, which are antioxidants from Maidong, increase glucose uptake in 3T3‐L1 adipocytes and that catalpol has antihyperglycemic activity and improves glucose tolerance and lipid levels . Recent studies have also indicated that trans‐cinnamic acid increases adiponectin levels and phosphorylation of adenosine monophosphate‐activated protein kinase through G‐protein‐coupled receptors in 3T3‐L1 adipocytes and that angoroside C has antioxidant and anti‐inflammatory effects.…”

Catalpol prevents alteration of cholesterol homeostasis in non-alcoholic fatty liver disease via attenuating endoplasmic reticulum stress and NOX4 over-expression

“…Catalpol is a natural product present in the roots of Rehmannia glutinosa with multiple pharmacological effects, 35,36 and recent studies indicated that catalpol might inuence lipid metabolism in the liver. 39 In our study, we rstly attempted to demonstrate that (1) catalpol confers the prevention against hepatic lipid accumulation, ER stress, NOX4mediated oxidative stress and alteration of cholesterol homeostasis in HFD-and PA-induced NAFLD; (2) ER stress and NOX4 over-expression regulate each other in PA-induced NAFLD; and (3) catalpol prevents against PA induced hepatic lipid accumulation and alteration of cholesterol homeostasis by attenuating ER stress and NOX4 over-expression in HepG2 cells.…”

“…Catalpol, an iridoid glucoside isolated from the root of Radix Rehmanniae, has been found to possess multiple pharmacological properties, including antioxidant, anti-inammation, anti-apoptosis, anti-diabetic and neuroprotective properties in previous studies. 35,36 Notably, catalpol might inuence lipid metabolism in the liver, [37][38][39] yet the role of catalpol in NAFLD is still unknown until now. Therefore, the purposes of the present study were to explore the therapeutic effects of catalpol on lipid accumulation, ER stress, NOX4-mediated oxidative stress and alteration of cholesterol homeostasis in NAFLD, and the possible molecular mechanism underlying the effects of catalpol protecting against lipid accumulation and alteration of cholesterol homeostasis in NAFLD.…”