Piperine Improves Hyperuricemic Nephropathy by Inhibiting URAT1/GLUT9 and the AKT-mTOR Pathway

Uncontrolled hyperuricemia often leads to the development of hyperuricemic nephropathy (HN), characterized by excessive inflammation and oxidative stress. Piperine, a cinnamic acid alkaloid, possesses various pharmacological activities, such as antioxidant and anti-inflammatory effects. In this study, we intended to investigate the protective effects of piperine on adenine and potassium oxonate-induced HN mice and a uric-acid-induced injury model in renal tubular epithelial cells (mRTECs). We observed that treatment with piperine for 3 weeks significantly reduced serum uric acid levels and reversed kidney function impairment in mice with HN. Piperine (5 μM) alleviated uric acid-induced damage in mRTECs. Moreover, piperine inhibited transporter expression and dose-dependently inhibited the activity of both transporters. The results revealed that piperine regulated the AKT/mTOR signaling pathway both in vivo and in vitro. Overall, piperine inhibits URAT1/GLUT9 and ameliorates HN by inhibiting the AKT/mTOR pathway, making it a promising candidate for patients with HN.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:72

Enthalten in:

Journal of agricultural and food chemistry - 72(2024), 12 vom: 27. März, Seite 6565-6574

Sprache:

Englisch

Beteiligte Personen:

Li, Lu [VerfasserIn]
Zhao, Kunlu [VerfasserIn]
Luo, Jian [VerfasserIn]
Tian, Jinhong [VerfasserIn]
Zheng, Fengxin [VerfasserIn]
Lin, Xueman [VerfasserIn]
Xie, Zijun [VerfasserIn]
Jiang, Heyang [VerfasserIn]
Li, Yongmei [VerfasserIn]
Zhao, Zean [VerfasserIn]
Wu, Ting [VerfasserIn]
Pang, Jianxin [VerfasserIn]

Links:

Volltext

Themen:

268B43MJ25
AKT/mTOR
Alkaloids
Benzodioxoles
EC 2.7.11.1
Glucose transporter 9
Hyperuricemic nephropathy
Journal Article
Membrane Transport Proteins
Piperidines
Piperine
Polyunsaturated Alkamides
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
U71XL721QK
Urate transporter 1
Uric Acid
Uric acid

Anmerkungen:

Date Completed 28.03.2024

Date Revised 28.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1021/acs.jafc.3c07655

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369879996