Fufang Zhenzhu Tiaozhi capsule ameliorates hyperuricemic nephropathy by inhibition of PI3K/AKT/NF-κB pathway.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Excessive serum uric acid (SUA) causes hyperuricemic nephropathy (HN), characterized by inflammatory infiltration and tubulointerstitial fibrosis. Most recently, we demonstrated that Fufang Zhenzhu Tiaozhi (FTZ) capsule attenuated diabetic nephropathy through inhibition of renal inflammation and fibrosis. However, whether FTZ ameliorates HN is still unclear.

AIM OF THE STUDY:

To determine the protective roles and mechanism of FTZ in mouse renal injury and fibrosis under hyperuricemic condition.

MATERIALS AND METHODS:

HN mice, induced by potassium oxonate and hypoxanthine, were administrated with 600 and 1200 mg/kg FTZ (intragastrically) daily for three weeks. SUA levels, renal functions and histological changes were analyzed. Western blotting, quantitative real-time PCR (q-PCR) and RNA sequencing were used to identify the roles and underlying mechanism of FTZ in HN mice.

RESULTS:

We demonstrated that FTZ treatment mitigated renal injury in mice, as evidenced by the decrease in SUA, serum creatinine (SCr) and cystatin C (Cys C) levels, as well as improved renal histology. FTZ markedly attenuates inflammasome activation, collagen deposition and the imbalance of uric acid transporters. RNA-sequencing revealed a key mechanism involved in the protective effects on HN mice was related to PI3K/AKT/NF-κB pathway. Western blot also confirmed that FTZ diminished the phosphorylation of AKT and p65 in HN mice.

CONCLUSIONS:

FTZ prevents renal injury, inflammation and fibrosis in HN mice via promoting uric acid excretion and inhibiting PI3K/AKT/NF-κB signaling pathway.

• Authors: Ming-Hui Li, Jin Guan, Zhe Chen, Ju-Xian Mo, Kai-Reng Wu, Xu-Guang Hu, Tian Lan, Jiao Guo
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 298 Pg. 115644 (Nov 15 2022) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 35987412 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• NF-kappa B
• Uric Acid
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Fibrosis
• Hyperuricemia
• Inflammation (drug therapy)
• Kidney
• Mice
• NF-kappa B (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Uric Acid