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

Su Liu, Suliu (2018) Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/ TACE signalling pathway activity in rats. pp. 1-786. ISSN 1388-0209

Text Pharmaceutical Biology 2018.pdf Download (160MB)

Abstract

Context: Total flavones extracted from Abelmoschus manihot L. (Malvaceae) medic (TFA) have been pro�ven 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 fac�tor-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-immuno�precipitation 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 activa�tion 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 inflam�mation 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
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:	27 Sep 2022 07:24
Last Modified:	27 Sep 2022 07:24
URI:	http://eprints.umsb.ac.id/id/eprint/449

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