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Eurycoma longifolia alkaloid components ameliorate hyperuricemic nephropathy via regulating serum uric acid level and relieving inflammatory reaction

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Abstract

Hyperuricemia is an independent risk factor for chronic kidney disease. We have previously showed the uric-acid-lowering effect of Eurycoma longifolia Jack, yet the renal protective effect and mechanism of E. longifolia remain obscure. The mouse model of hyperuricemic nephropathy was induced by adenine combined with potassium oxonate in male C57BL/6 J mice. E. Longifolia alkaloid components could reduce the level of serum uric acid by regulating the expression of hepatic phosphoribosyl pyrophosphate synthase (PRPS), hypoxanthine-guanine phosphoribosyl transferase (HPRT), and renal urate transporter organic anion transporter 1 (OAT1) and ATP-binding box subfamily G member 2 (ABCG2) in HN mice. Additionally, E. Longifolia alkaloid components alleviated renal injury and function caused by hyperuricemia, which was characterized by improving renal histopathology, reducing urea nitrogen and creatinine levels. E. Longifolia alkaloid components treatment could reduce the secretion of pro-inflammatory factors by inhibiting the activation of NF-κB and NLRP3 inflammatory signaling pathways, including tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-1 β (IL-1β), and regulated activated normal T cell expression and secretion proteins (RANTES). Meanwhile, E. longifolia alkaloid components improved renal fibrosis, inhibited the transformation of calcium-dependent cell adhesion molecule E (E-cadherin) to α-smooth muscle actin (α-SMA) transformation, and decreased collagen 1 expression in HN mice.

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Abbreviations

ABCG2:

ATP-binding cassette super family G number 2

BUN:

Blood urea nitrogen

cDNA:

Complemental deoxyribonucleic acid

Cur:

Clearance of uric acid

ELISA:

Enzyme-linked immunosorbent assay

E-cadherin:

Calcium-dependent cell adhesion molecule

EMT:

Epithelial-to-mesenchymal transition

ECM:

Extracellular matrix

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GLUT9:

Glucose transporter 9

GMP:

Guanosine monophosphate

H&E:

Hematoxylin–eosin staining

HPRT:

Hypoxanthine-guanine phosphoribosyl transferase

IL-1β:

Interleukin-1β

Masson:

Masson-trichrome staining

MCP-1:

Monocyte chemoattractant protein-1

NF-κB:

Nuclear factor-kappa B

NLRP3:

Nod-like receptor pyrin domain-containing protein 3

OAT1:

Organic anion transporter 1

PAS:

Periodic acid Schiff reaction

PBS:

Phosphate buffered saline

qRT-PCR:

Real-time quantitative polymerase chain reaction

PRPS:

Phosphoribosyl pyrophosphate synthetase

RANTES:

Chemokine (C–C motif) ligand 5

TNF-α:

Tumor necrosis factor-α

UPLC:

Ultra-performance liquid chromatography

URAT1:

Urate-anion transporter

α-SMA:

1α-Smooth muscle actin

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Acknowledgements

The authors thank HY Cao for her help in the experiment in this study.

Funding

This research was funded by Important Drug Development Fund, Ministry of Science and Technology of China (2018ZX09735-002), National Natural Science Foundation of China (81173524; 81673688), and The Scientific Research Project of Tianjin Municipal Education Commission (2019KJ085).

Author information

Author notes

  1. Dan Wang and Lin Liu contributed equally to this work.

Authors and Affiliations

  1. Tianjin University of Traditional Chinese Medicine, 10 Poyang Lake Road, Jinghai District, Tianjin, 301617, China

    Dan Wang, Kaiwen Li, Huiya Cao, Qian Chen, Yuzheng Wu & Tao Wang

  2. State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyang Lake Road, Jinghai District, Tianjin, 301617, China

    Lin Liu, Mengyang Liu & Yi Zhang

  3. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China

    Tao Wang

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  1. Dan Wang
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Contributions

LL, DW, YZ, and TW completed the experimental design. KL, ML, QC, and HC were responsible for conducting experiments and analyzing data. DW and TW were responsible for writing the manuscript. ML, YZ, and TW checked the manuscript. TW and DW provided the funding.

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Correspondence to Yi Zhang or Tao Wang.

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Wang, D., Liu, L., Li, K. et al. Eurycoma longifolia alkaloid components ameliorate hyperuricemic nephropathy via regulating serum uric acid level and relieving inflammatory reaction. J Nat Med 77, 867–879 (2023). https://doi.org/10.1007/s11418-023-01729-3

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