Cepharanthine and Piperine ameliorate diabetic nephropathy in rats: role of NF-κB and NLRP3 inflammasome.
OBJECTIVE
Hyperglycemia leads to elevation of oxidative stress and proinflammatory cytokines which are the main causes of diabetic nephropathy (DN). NLRP3 inflammasome and thioredoxin-interacting protein (TXNIP) are recently assumed to participate in the development of DN. We aimed to investigate the effects of Cepharanthine (CEP), Piperine (Pip) and their combination in streptozotocin (STZ)-induced DN focusing on their role to modulate NLRP3 and TXNIP induced inflammation.


METHODS
Diabetic rats were treated with intraperitoneal (i.p.) injection of CEP (10mg/kg/day), Pip (30mg/kg/day) or their combination for 8weeks. Nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) were assessed by ELISA technique. TXNIP and NLRP3 genes expressions were evaluated by real time-PCR.


RESULTS
Diabetic rats showed significant increase in renal TXNIP and NLRP3 expression. CEP, Pip or their combination significantly decreased TXNIP and NLRP3 expression in diabetic kidneys. Hyperglycemia induced NF-κB activation leading to increased IL-1β and TNF-α levels. CEP, Pip or their combination showed significant inhibition of NF-κB together with decreased IL-1β and TNF-α levels in diabetic rats. Also, diabetic rats showed significant decrease in creatinine clearance and increase in blood glucose, serum creatinine, blood urea nitrogen, malondialdehyde, proteinuria, and kidney weight to body Weight ratio. All of these changes were reversed by CEP, Pip or their combination.


CONCLUSIONS
The antioxidant and anti-inflammatory effects of CEP and Pip which were accompanied by inhibition of NF-κB and NLRP3 activation might be helpful mechanisms to halt the progression of DN.
Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: Yaraadel1290@yahoo.com.
Yara A
YA
Samra
Department of Microbiology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Heba S
HS
Said
Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Nehal M
NM
Elsherbiny
Department of Ophthalmology, Augusta University, Augusta, GA 30912, USA.
Gregory I
GI
Liou
Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Mamdouh M
MM
El-Shishtawy
Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: lailaeissa2002@yahoo.com.
Laila A
LA
Eissa
D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D052117:Benzodioxoles / Q000627:therapeutic use*; D044182:Benzylisoquinolines / Q000627:therapeutic use*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000517:prevention & control*; D058847:Inflammasomes / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D010880:Piperidines / Q000627:therapeutic use*; D053284:Polyunsaturated Alkamides / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000470:Alkaloids; D052117:Benzodioxoles; D044182:Benzylisoquinolines; D058847:Inflammasomes; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D010880:Piperidines; D053284:Polyunsaturated Alkamides; C006947:cepharanthine; C008922:piperine
Cepharanthine; Diabetes; NF-κB; NLRP3; Piperine; Renal injury; TXNIP