Renoprotective effects of berberine and its potential effect on the expression of ß-arrestins and intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in streptozocin-diabetic nephropathy rats.

BACKGROUND: Berberine has been shown to exert protective effects against diabetic nephropathy (DN), but the mechanisms involved have not been fully characterized. The aim of the present study was to explore the effects of berberine on the expression of ß-arrestins, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in DN rat kidneys and investigate the underlying molecular mechanisms. METHODS: To create the DN model, rats fed a high-fat and high-glucose diet were injected with a single dose of streptozotocin (35 mg/kg, i.p.). Then, DN rats were either treated or not with berberine (50, 100, 200 mg/kg per day, i.g., 8 weeks). Periodic acid-Schiff staining was used to evaluate renal histopathological changes. Renal tissue levels of ß-arrestin 1 and ß-arrestin 2 were determined by Western blot analysis, whereas immunohistochemistry was used to determine renal ICAM-1 and VCAM-1 levels. RESULTS: Berberine (100, 200 mg/kg) ameliorated the histopathological changes in the diabetic kidney. Western blot analysis revealed significant increases in ICAM-1 and VCAM-1 levels in the kidneys of DN rats, which were reversed by treatment with 100 and 200 mg/kg berberine. In addition, berberine treatment (50, 100, 200 mg/kg) increased diabetic-induced decreases in ß-arrestin 1 and ß-arrestin 2. CONCLUSIONS: Berberine exhibited renoprotective effects in DN rats. The underlying molecular mechanisms may be associated with changes in the levels and regulation of ß-arrestin expression, as well as ICAM-1 and VCAM-1 levels in the rat kidney.

Berberine regulates the expression of E-prostanoid receptors in diabetic rats with nephropathy.

Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients. Effective therapies to prevent the development of this disease and to improve advanced kidney injury are required. Berberine (BBR) has preventive effects on diabetes and its complications. This study is to investigate the effects of BBR on the expression of E-prostanoid receptors (EPs) in rats with high-fat diet and streptozotocin (STZ)-induced DN and underlying molecular mechanisms of BBR on DN rats. DN model was induced in male Sprague-Dawley rats with high-fat diet and low dose of STZ injection. BBR (50, 100, 200 mg/kg/d) were orally administered to rats after STZ injection and conducted for 8 weeks. The levels of interleukin-6 (IL-6) and prostaglandin E2 (PGE2) in renal cortex were measured by enzyme-linked immunosorbent assay. Expression of EPs receptors (EP1-EP4) were determined by western blotting. Remarkable renal damage, hyperglycemia and hyperlipidemia were observed in DN rats. BBR could restore renal functional parameters, suppress alterations in histological and ultrastructural changes in the kidney tissues, improve glucose and lipid metabolism disorders, and increase cAMP levels compared with those of DN model group (Wang et al. in Mol Biol Rep 40:2405-2418, 2013). The level of IL-6 and PGE2 were significantly increased in DN model group compared with normal group, BBR could apparently reduced the level of IL-6 and PGE2. Furthermore, the expression of EP1 and EP3 were both increased and EP4 was lessened in the DN model group compared with normal group, BBR could down-regulate total protein expression of EP1 and EP3 of renal cortex in DN rats and up-regulate the expression of EP4, and there is no significant difference on the expression of EP2 among all groups. These studies demonstrate, for the first time, that BBR exerts renoprotection in high-fat diet and STZ-induced DN rats by modulating the proteins expression of EPs in EP-G protein-cAMP signaling pathway.

Berberine ameliorates renal injury by regulating G proteins-AC- cAMP signaling in diabetic rats with nephropathy.

Diabetic nephropathy (DN) is a progressive kidney disease that is caused by injury to glomerulus and glomerular mesangial cells (MCs) proliferation play a critical role in the pathogenesis of DN. The current studies were undertaken to investigate the protective effects and the possible molecular mechanism of berberine on streptozotocin (STZ)-induced DN rats. Male Wistar rats were randomly assigned to normal control and DN groups of comparable age. Three DN groups received 50, 100 and 200 mg/kg of berberine for 8 weeks via daily intragastrically, respectively. The G proteins-adenylyl cyclase (AC)-cAMP signaling pathway and glomerular MCs proliferation were examined in STZ-induced diabetic rat kidney. Enhanced MCs proliferation and remarkable renal injury were concomitant with activation of Gαi and inhibition of Gαs and cAMP in DN model group. Berberine treatment for 8 weeks abolished the above changes by upregulating the expression of Gαs protein and downregulating the expression of Gαi protein, increasing cAMP level, and inhibiting MCs proliferation compared with model group. Taken together, for the first time, these results demonstrated that berberine can relieve renal injury in DN rats through mediating G proteins-AC-cAMP signaling pathway and inhibiting the abnormal proliferation of MCs by increasing cAMP level, suggesting that berberine could be a potential therapeutic agent for the treatment of DN.

[Effect of compound Rhizoma Coptidis capsule on expression of transforming growth factor-beta1 and type IV collagen proteins in renal tissue of diabetic rats with nephropathy].

OBJECTIVE: To explore the effect and mechanism of compound Rhizoma Coptidis capsule (CRCC) on diabetic nephropathy in experimental rats. METHOD: The rat model of early diabetic nephropathy was induced by injection of streptozotocin (STZ). The rats were divided into 6 groups: normal control group, model group, 3 CRCC treatment groups and XKW treatment group. The fasting blood glucose (FBG), blood urea nitrogen (BUN), creatinine (Cr), insulin (Ins) and urinary protein (Upro) were tested 30 days later. The expression of transforming growth factor-beta1 (TGF-beta1) and type IV collagen (IV-C) proteins and the pathological changes in renal tissue of diabetic rats with nephropathy were observed by optical micrography. RESULT: CRCC could reduce the levels of FBG, BUN, Cr, Upro and the expression of TGF-beta1 and IV-C proteins, and alleviate pathological lesion in renal tissue of diabetic rats with nephropathy. CONCLUSION: CRCC may protect the renal function and slow down the progression of diabetic nephropathy in rats by suppressing the expression of TGF-beta1 and IV-C proteins in renal tissue.