Trilobatin, an Active Dihydrochalcone from Lithocarpus polystachyus, Prevents Cisplatin-Induced Nephrotoxicity via Mitogen-Activated Protein Kinase Pathway-Mediated Apoptosis in Mice

Yue-Yang Duan; Xiao-Jie Mi; Wen-Ya Su; Shan Tang; Shuang Jiang; Zi Wang; Li-Chun Zhao; Wei Li

doi:10.1021/acsomega.2c04142

Trilobatin, an Active Dihydrochalcone from Lithocarpus polystachyus, Prevents Cisplatin-Induced Nephrotoxicity via Mitogen-Activated Protein Kinase Pathway-Mediated Apoptosis in Mice

ACS Omega. 2022 Oct 13;7(42):37401-37409. doi: 10.1021/acsomega.2c04142. eCollection 2022 Oct 25.

Authors

Yue-Yang Duan^{1

2}, Xiao-Jie Mi^{1

3}, Wen-Ya Su¹, Shan Tang¹, Shuang Jiang¹, Zi Wang¹, Li-Chun Zhao⁴, Wei Li^{1

2}

Affiliations

¹ College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
² National and Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China.
³ Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, Republic of Korea.
⁴ College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530001, China.

Abstract

Although naturally occurring flavonoids have shown beneficial effects on the side effects caused by cisplatin, there are few reports on the protective effect of dihydrochalcone on the cisplatin-induced toxicity. Trilobatin (TLB), as the major sweetener and active ingredient in Lithocarpus polystachyus Rehd, is a dihydrochalcone-like compound that can be present in concentrations of up to 10% or more in tender leaves. Herein, a cisplatin-induced acute kidney injury (AKI) model was established to investigate the protective effect and mechanism of TLB against the cisplatin-induced nephrotoxicity in mice. The results showed that TLB significantly reversed the inhibition of CRE, BUN, and MDA levels compared with the cisplatin group. Furthermore, TLB treatment (50 and 100 mg/kg) for 10 days significantly alleviated cisplatin-induced renal pathological changes. TUNEL staining showed that TLB administration can effectively improve the occurrence of apoptosis of renal tissue cells caused by cisplatin exposure. Importantly, western blot analysis verified that TLB alleviated cisplatin-induced nephrotoxicity by regulating the AKT/MAPK signaling pathway and apoptosis. In summary, our findings showed clearly that TLB has a significant preventive effect on cisplatin-induced AKI.