Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation

Junhui Chen; Qian Zhang; Jinan Guo; Di Gu; Jing Liu; Piao Luo; Yunmeng Bai; Jiayun Chen; Xinzhou Zhang; Sheng Nie; Chunbo Chen; Yulin Feng; Jigang Wang

doi:10.1016/j.apsb.2024.01.003

Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation

Acta Pharm Sin B. 2024 Apr;14(4):1661-1676. doi: 10.1016/j.apsb.2024.01.003. Epub 2024 Jan 11.

Authors

Junhui Chen^{1

2}, Qian Zhang^{2

3}, Jinan Guo⁴, Di Gu⁵, Jing Liu², Piao Luo^{2

3}, Yunmeng Bai², Jiayun Chen^{2

3}, Xinzhou Zhang⁶, Sheng Nie⁷, Chunbo Chen⁸, Yulin Feng¹, Jigang Wang^{1

2

3

9

10}

Affiliations

¹ National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine, Jiangxi University of Chinese Medicine, Nanchang 330006, China.
² Department of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen 518020, China.
³ School of Traditional Chinese Medicine and School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
⁴ Department of Urology, and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, the First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, China.
⁵ Department of Urology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, China.
⁶ Department of Nephrology, Shenzhen Key Laboratory of Kidney Diseases, and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, the First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, China.
⁷ Department of Nephrology, Nanfang Hospital, the First Affiliated Hospital of Southern Medical University, Guangzhou 510515, China.
⁸ Department of Critical Care Medicine, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China.
⁹ State Key Laboratory for Quality Esurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
¹⁰ Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.

Abstract

Diabetic nephropathy (DN) is a severe complication of diabetes, characterized by changes in kidney structure and function. The natural product rosmarinic acid (RA) has demonstrated therapeutic effects, including anti-inflammation and anti-oxidative-stress, in renal damage or dysfunction. In this study, we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell levels. Our results demonstrated that RA significantly alleviated renal tubular epithelial injury, particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes, while attenuating the inflammatory response of macrophages, oxidative stress, and cytotoxicity of natural killer cells. These findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage, oxidative stress, and inflammation, offering valuable guidance for the clinical application of RA in the treatment of DN.

Keywords: Diabetic nephropathy; Inflammation; Injury; Oxidative stress; Proteomics; Rosmarinic acid; scRNA sequencing.