Affiliation:
1. College of Pharmacy Guangxi University of Chinese Medicine Nanning Guangxi 530000 China
2. National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine Jiangxi University of Chinese Medicine Nanchang Jiangxi 330006 China
3. School of Traditional Chinese Medicine and School of Pharmaceutical Sciences Southern Medical University Guangzhou Guangdong 510515 China
4. 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 Guangdong 518020 China
5. 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
6. State Key Laboratory of Antiviral Drugs School of Pharmacy Henan University Kaifeng Henan 475004 China
Abstract
AbstractIn diabetic kidney disease (DKD), inflammation exacerbated by oxidative stress (ROS) is pivotal. This study investigates the impact of Anemoside B4 (B4), an anti‐inflammatory drug, on kidney cell populations in DKD mice using single‐cell RNA sequencing (scRNA‐seq) and mass spectrometry‐based proteomics, focusing on its hypoglycemic, anti‐inflammatory, and anti‐fibrotic properties. Compared to the DKD group, B4 treatment reduces blood lipid metabolism levels, renal inflammation, and fibrosis in mice. Through scRNA‐seq, 14 distinct renal cell clusters are identified, primarily proximal tubular (PT) cells. In DKD mice, PT subtype cells exhibited elevated SPP1 expression, promoting macrophage M1 polarization, inflammatory cell infiltration, and renal fibrosis—all reversed by B4. Macrophage analysis revealed enrichment of the marker gene interlukin‐1β (IL‐1β) in renal macrophage polarization during diabetic nephropathy. B4 effectively mitigated macrophage polarization, alleviating inflammation and fibrosis, confirmed by Western blot. Fibroblast analysis demonstrated reduced fibrosis with B4 treatment, consistent with hematoxylin and eosin staining and Immunofluorescence findings. Notably, oxidative stress contributed to these changes. In conclusion, B4 alleviated kidney inflammation and fibrosis in DKD mice by mitigating macrophage polarization and addressing oxidative stress, providing valuable insights into its multifaceted therapeutic potential.
Funder
National Key Research and Development Program of China