Cepharanthine and Piperine ameliorate diabetic nephropathy in rats

role of NF-κB and NLRP3 inflammasome

Yara A. Samra, Heba S. Said, Nehal M. Elsherbiny, Gregory I Liou, Mamdouh M. El-Shishtawy, Laila A. Eissa

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Aims 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. Main methods Diabetic rats were treated with intraperitoneal (i.p.) injection of CEP (10 mg/kg/day), Pip (30 mg/kg/day) or their combination for 8 weeks. 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. Key findings 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. Significance 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.

Original languageEnglish (US)
Pages (from-to)187-199
Number of pages13
JournalLife sciences
Volume157
DOIs
StatePublished - Jul 15 2016

Fingerprint

piperine
Inflammasomes
NF-kappa B
Diabetic Nephropathies
Thioredoxins
Rats
Interleukin-1
Proteins
Kidney
Hyperglycemia
Creatinine
Chemical activation
Oxidative stress
Blood Urea Nitrogen
Streptozocin
Intraperitoneal Injections
Malondialdehyde
Proteinuria
Gene expression
Blood Glucose

Keywords

  • Cepharanthine
  • Diabetes
  • NF-κB
  • NLRP3
  • Piperine
  • Renal injury
  • TXNIP

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Samra, Y. A., Said, H. S., Elsherbiny, N. M., Liou, G. I., El-Shishtawy, M. M., & Eissa, L. A. (2016). Cepharanthine and Piperine ameliorate diabetic nephropathy in rats: role of NF-κB and NLRP3 inflammasome. Life sciences, 157, 187-199. https://doi.org/10.1016/j.lfs.2016.06.002

Cepharanthine and Piperine ameliorate diabetic nephropathy in rats : role of NF-κB and NLRP3 inflammasome. / Samra, Yara A.; Said, Heba S.; Elsherbiny, Nehal M.; Liou, Gregory I; El-Shishtawy, Mamdouh M.; Eissa, Laila A.

In: Life sciences, Vol. 157, 15.07.2016, p. 187-199.

Research output: Contribution to journalArticle

Samra, YA, Said, HS, Elsherbiny, NM, Liou, GI, El-Shishtawy, MM & Eissa, LA 2016, 'Cepharanthine and Piperine ameliorate diabetic nephropathy in rats: role of NF-κB and NLRP3 inflammasome', Life sciences, vol. 157, pp. 187-199. https://doi.org/10.1016/j.lfs.2016.06.002
Samra, Yara A. ; Said, Heba S. ; Elsherbiny, Nehal M. ; Liou, Gregory I ; El-Shishtawy, Mamdouh M. ; Eissa, Laila A. / Cepharanthine and Piperine ameliorate diabetic nephropathy in rats : role of NF-κB and NLRP3 inflammasome. In: Life sciences. 2016 ; Vol. 157. pp. 187-199.
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abstract = "Aims 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. Main methods Diabetic rats were treated with intraperitoneal (i.p.) injection of CEP (10 mg/kg/day), Pip (30 mg/kg/day) or their combination for 8 weeks. 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. Key findings 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. Significance 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.",
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AU - El-Shishtawy, Mamdouh M.

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AB - Aims 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. Main methods Diabetic rats were treated with intraperitoneal (i.p.) injection of CEP (10 mg/kg/day), Pip (30 mg/kg/day) or their combination for 8 weeks. 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. Key findings 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. Significance 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.

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