Nephroprotective activity of Aframomum melegueta seeds extract against diclofenac-induced acute kidney injury: A mechanistic study

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Abdou R.M.; El-Maadawy W.H.; Hassan M.; El-Dine R.S.; Aboushousha T.; El-Tanbouly N.D.; El-Sayed A.M.

Journal: Journal of Ethnopharmacology

Publisher: Elsevier Ireland Ltd

Publication Date: June 2021

Volume / Issue: Volume 273

Article No.: 113939

ISSN: 3788741

DOI: 10.1016/j.jep.2021.113939

Scopus: View on Scopus

PubMed: 33610709

Document Type: Article

Authors and Affiliations

Abdou R.M., Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt; El-Maadawy W.H., Department of Pharmacology, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza, 12411, Egypt; Hassan M., Department of Immunology, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza, 12411, Egypt; El-Dine R.S., Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt; Aboushousha T., Department of Pathology, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza, 12411, Egypt; El-Tanbouly N.D., Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt; El-Sayed A.M., Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt

Abstract

Ethnopharmacological relevance: In Africa, Aframomum species have been traditionally used to treat illnesses such as inflammation, hypertension, diarrhea, stomachache and fever. Moreover, Aframomum melegueta seed extracts (AMSE) are used in traditional medicine to relieve stomachaches and inflammatory diseases. Aim: Chronic administration of diclofenac (DIC) has been reported to cause acute kidney injury (AKI), which is a serious health condition. The nephroprotective effect of AMSE is yet to be elucidated. Accordingly, this study aims to investigate the phytoconstituents of standardized AMSE, evaluate its nephroprotective effects against DIC-induced AKI in rats, and elaborate its underlying molecular mechanisms. Materials and methods: The quantitative estimation of major AMSE constituents and profiling of its secondary metabolites were conducted via RP-HPLC and LC-ESI/Triple TOF/MS, respectively. Next, DIC (50 mg/kg)-induced AKI was achieved in Sprague-Dawley rats and DIC-challenged rats were administered AMSE (100 and 200 mg/kg) orally. All treatments were administered for five consecutive days. Blood samples were collected and the sera were used for estimating creatinine, urea and, kidney injury molecule (KIM)-1 levels. Kidney specimens were histopathologically assessed and immunohistochemically examined for c-Myc expression. A portion of the kidney tissue was homogenized and examined for levels of oxidative stress markers (MDA and GSH). Heme oxygenase (HO)-1, TNF-α, IL-6, Bax, Bcl2 and caspase-3 renal levels were quantified by ELISA. Moreover, the protein expression levels of NF-ҡB p65 was quantified using Western blot analysis, whereas mRNA expression levels of AMPK, SIRT-1, nuclear factor erythroid-2-related factor (Nrf2) and STAT3 were detected using qRT-PCR in the remaining kidney tissues. Results: Standardized AMSE was shown to primarily contain 6-gingerol, 6-shogaol and 6-paradol among the 73 compounds that were detected via LC-ESI/Triple TOF/MS including phenolic acids, hydroxyphenylalkanes, diarylheptanoids and fatty acids. Relative to DIC-intoxicated rats, AMSE modulated serum creatinine, urea, KIM-1, renal MDA, TNF-α, IL-6, Bax, and caspase-3 levels. AMSE has also improved renal tissue architecture, enhanced GSH and HO-1 levels, and upregulated renal Nrf2, AMPK, and SIRT-1 mRNA expression levels. Furthermore, AMSE suppressed NF–ҡB p65 protein and STAT3 mRNA expression, and further reduced c-Myc immunohistochemical expression in renal tissues. Overall, our findings revealed that AMSE counteracted DIC-induced AKI via its antioxidant, anti-inflammatory, and antiapoptotic activities. Moreover, AMSE activated Nrf2/HO1 and AMPK/SIRT1, and inhibited NF-ҡB/STAT3 signaling pathways. Therefore, AMSE is a promising agent for inhibiting DIC-induced nephrotoxicity. © 2021

Keywords

Acute kidney injury; Aframomum melegueta seeds extract; AMPK pathway; Diclofenac; Nrf2 pathway; STAT3; Adenylate Kinase; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Cytokines; Disease Models, Animal; Inflammation; Male; NF-E2-Related Factor 2; Oxidative Stress; Plant Extracts; Protective Agents; Rats, Sprague-Dawley; Seeds; Sirtuin 1; STAT3 Transcription Factor; Zingiberaceae; (6) gingerol; 6 paradol; 6 shogaol; Aframomum melegueta extract; alkane derivative; antioxidant; caspase 3; creatinine; fatty acid; fatty acid derivative; heme oxygenase 1; hepatitis A virus cellular receptor 1; heptane derivative; hydroxymethylglutaryl coenzyme A reductase kinase; interleukin 6; messenger RNA; Myc protein; phenol derivative; plant extract; protein Bax; shogaol; STAT3 protein; transcription factor NF E2; transcription factor Nrf2; tumor necrosis factor; unclassified drug; urea; antiinflammatory agent; cytokine; Nfe2l2 protein, rat; protective agent; Sirt1 protein, rat; Stat3 protein, rat; acute kidney failure; Aframomum melegueta; animal experiment; animal model; animal tissue; antiapoptotic activity; Article; controlled study; creatinine blood level; enzyme linked immunosorbent assay; histopathology; immunohistochemistry; kidney tissue; medicinal plant; mRNA expression level; nephrotoxicity; nonhuman; oncogene c myc; plant seed; polymerase chain reaction; protein expression level; protein fingerprinting; quantitative analysis; rat; renal protection; reversed phase high performance liquid chromatography; signal transduction; time of flight mass spectrometry; Western blotting; animal; chemistry; disease model; drug effect; genetics; metabolism; pathology; Sprague Dawley rat

Citation Information

Scopus Citations: 39

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