Therapeutic potential of Ganoderma lucidum polysaccharide peptide in Doxorubicin-induced nephropathy: modulation of renin-angiotensin system and proteinuria

Hui Fang; Dongmei Lin; Xinxuan Li; Lianfu Wang; Teng Yang

doi:10.3389/fphar.2023.1287908

Therapeutic potential of Ganoderma lucidum polysaccharide peptide in Doxorubicin-induced nephropathy: modulation of renin-angiotensin system and proteinuria

Front Pharmacol. 2023 Sep 29:14:1287908. doi: 10.3389/fphar.2023.1287908. eCollection 2023.

Authors

Hui Fang¹, Dongmei Lin², Xinxuan Li¹, Lianfu Wang², Teng Yang¹

Affiliations

¹ Key Laboratory of Applied Pharmacology in Universities of Shandong, Department of Pharmacology, School of Pharmacy, Weifang Medical University, Weifang, Shandong, China.
² National Engineering Research Center of JUNCAO Technology, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China.

Abstract

Introduction: In the Doxorubicin (DOX)-induced nephropathy model, proteinuria is a manifestation of progressive kidney injury. The pathophysiology of renal illness is heavily influenced by the renin-angiotensin system (RAS). To reduce renal RAS activation and proteinuria caused by DOX, this study evaluated the effectiveness of Ganoderma lucidum polysaccharide peptide (GL-PP), a new glycopeptide produced from Ganoderma lucidum grown on grass. Methods: Three groups of BALB/c male mice were created: control, DOX, and DOX + GL-PP. GL-PP (100 mg/kg) was administered to mice by intraperitoneal injection for 4 weeks following a single intravenous injection of DOX (10 mg/kg via the tail vein). Results: After 4 weeks, full-length and soluble pro(renin) receptor (fPRR/sPRR) overexpression in DOX mouse kidneys, which is crucial for the RAS pathway, was dramatically inhibited by GL-PP therapy. Additionally, GL-PP successfully reduced elevation of urinary renin activity and angiotensin II levels, supporting the idea that GL-PP inhibits RAS activation. Moreover, GL-PP showed a considerable downregulation of nicotinamide adenine nucleotide phosphate oxidase 4 (NOX4) expression and a decrease in hydrogen peroxide (H₂O₂) levels. GL-PP treatment effectively reduced glomerular and tubular injury induced by DOX, as evidenced by decreased proteinuria, podocyte damage, inflammation, oxidative stress, apoptosis, and fibrosis. Discussion: GL-PP inhibits intrarenal PRR/sPRR-RAS activation and upregulation of NOX4 and H₂O₂, suggesting potential therapeutic approaches against DOX-induced nephropathy.

Keywords: Doxorubicin; Ganoderma lucidum polysaccharide peptide; pro(renin) receptor; proteinuria; renin-angiotensin system.

Grants and funding

The authors declare that financial support was received for the research, authorship, and/or publication of this article. This study received financial support from various sources, including the central government guides local science and technology development projects (No. 2021L3008), the National Natural Science Foundation of China Grants (No. 82000400), and the Weifang Science and Technology Development Plan (No. 2021YX043). The funding provided by these organizations helped to support the research conducted in this study.