Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/ TACE signalling pathway activity in rats

Su Liu, Suliu (2017) Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/ TACE signalling pathway activity in rats. Taylor & Francis Group, 56 (1). pp. 1-786. ISSN 1388-0209

Text Pharmaceutical Biology 2018.pdf Download (160MB)

Abstract

Total flavones extracted from Abelmoschus manihot L. (Malvaceae) medic (TFA) have been proven clinically effective at improving renal inflammation and glomerular injury in chronic kidney disease (CKD). Objective: This study evaluated the function of TFA as an inhibitor of iRhom2/TACE (tumour necrosis factor-a converting enzyme) signalling and investigated its anti-DN (diabetic nephropathy) effects in a DN rat model. Materials and methods: In vitro, cells were treated with 200 lg/mL advanced glycation end products (AGEs), and then co-cultured with 20 lg/mL TFA for 24 h. Real time PCR, western blotting and co-immunoprecipitation assays were performed. In vivo, DN was induced in 8 week old male Sprague-Dawley rats via unilateral nephrectomy and intraperitoneal injection of streptozotocin, then TFA were administered to rats by gavage for 12 weeks at three different doses (300, 135 and 75 mg/kg/d). 4-Phenylbutanoic acid (2.5 mg/kg/d) was used as a positive control. Results: IC50 of TFA is 35.6 lM in HK2 and 39.6 lM in HRMC. TFA treatment (20 lM) inhibited the activation of iRhom2/TACE signalling in cultured cells induced by AGEs. LD50>26 g/kg and ED50¼67 mg/kg of TFA in rat by gavage, TFA dose-dependently downregulated the expression of proinflammatory cytokines and exerted anti-inflammatory effects significantly though inhibiting the activation of iRhom2/TACE signalling. Discussion and conclusions: Our results show that TFA could dose-dependently ameliorate renal inflammation by inhibiting the activation of iRhom2/TACE signalling and attenuating ER stress. These results suggest that TFA has potential therapeutic value for the treatment of DN in humans.

Item Type:	Article
Subjects:	R Medicine > RS Pharmacy and materia medica
Divisions:	Library of Congress Subject Areas > P Language and Literature > Farmasi Library of Congress Subject Areas > P Language and Literature > Fakultas Farmasi > Farmasi Fakultas Farmasi > Farmasi
Depositing User:	Unnamed user with email repo@umsb.ac.id
Date Deposited:	28 Sep 2022 03:09
Last Modified:	28 Sep 2022 03:09
URI:	http://eprints.umsb.ac.id/id/eprint/478

Actions (login required)

View Item