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

Abstract

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 β-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 β-arrestin 1 and β-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 β-arrestin 1 and β-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 β-arrestin expression, as well as ICAM-1 and VCAM-1 levels in the rat kidney.

Renoprotective effects of emodin against diabetic nephropathy in rat models are mediated via PI3K/Akt/GSK‑3β and Bax/caspase‑3 signaling pathways

“…A continuously increased expression of ICAM-1 can cause serious damage to the structure and function of tissues and organs (24). Furthermore, ICAM-1 molecules are widely present in the body and are expressed in a variety of hematopoietic and non-hematopoietic cells, which are distributed mainly in various epithelial and endothelial cells, fibroblasts, reticular cells, monocytes, macrophages and lymphocytes (25). In the present study, it was revealed that emodin significantly suppressed ICAM-1 expression in DN model rats.…”

Berberine for prevention of dementia associated with diabetes and its comorbidities: A systematic review

“…As shown in Table 6, berberine ameliorated renal inflammation and injury in diabetic models [79,83,85,86,90,96]. Underlying mechanisms include inhibition of kidney fibrosis via tumor growth factor (TGF)- signaling suppression and Nrf2 activity enhancement [76,77,80,82,86,91,93,144], suppression of HG-induced mesangial cell proliferation and hypertrophy via suppression of NF-B and AP-1 [81,84,90], and attenuation of ECM accumulation [87], possibly by restoring β-arrestin [88] and E prostanoid receptor 4 (EP4)-Gαs-cAMP signaling pathway [83,85]. In addition, berberine directly protected podocytes from HG-induced injury in vitro [23,94], possibly by inhibiting podocyte apoptosis via AMPK-dependent autophagy induction [92].…”

Essential Oil from Fructus Alpiniae Zerumbet Protects Human Umbilical Vein Endothelial Cells In Vitro from Injury Induced by High Glucose Levels by Suppressing Nuclear Transcription Factor-Kappa B Signaling

“…The cell adhesion molecules, ICAM-1and VCAM-1, mediate leukocyte and vascular endothelial cell adhesion, as well as leukocyte activation, thereby triggering a proinflammatory response [27]. Previous studies have shown that ICAM-1 and VCAM-1 expression is closely related to the development of diabetic vascular disease [28]. Also, NF-κB signaling manifests as a deep involvement in the inflammatory process, particularly regarding the regulation of ICAM-1and VCAM-1 expression [29].…”