Integrating transcriptomics, metabolomics, and network pharmacology to investigate multi-target effects of sporoderm-broken spores of Ganoderma lucidum on improving HFD-induced diabetic nephropathy rats
Lidan Hu, Lili Yu, Zhongkai Cao, Yue Wang, Cai-Feng Zhu, Yayu Li, Jiazhen Yin, Zhichao Ma, Xuelin He, Ying Zhang, Wunan Huang, Yuelin Guan, Yue Chen, Xue Li, Xiangjun Chen
Abstract
Diabetes mellitus (DM) is a major metabolic disease endangering global health, with diabetic nephropathy (DN) as a primary complication lacking curative therapy. Sporoderm-broken spores of Ganoderma lucidum (GLP), an herbal medicine, has been used for the treatment of metabolic disorders. In this study, DN was induced in Sprague-Dawley rats using streptozotocin (STZ) and a high-fat diet (HFD), and the protective mechanisms of GLP were investigated through transcriptomic, metabolomic, and network pharmacology (NP) analyses. Our results demonstrated that GLP intervention ameliorated renal damage and inflammation levels in DN rats. Integrative metabolomic and transcriptomic analysis revealed that GLP treatment modulated glucose and cellular energy metabolisms by regulating relevant genes. GLP significantly suppressed the inflammations by impacting glucose and energy metabolism-related gene expression ( Igfbp1 and Angptl4 ) and enhanced metabolic biomarkers of 4-Aminocatechol. In addition, NP analysis further indicated that GLP may efficiently alleviate DN via immune-related pathways. In conclusion, this study provides supportive evidence of the anti-inflammatory effects of GLP supplements, highlighting their potential for promising clinical applications in treating DN. • Revealing an integrated landscape of transcriptomic and metabolomic profiling in diabetic nephropathy. • GLP suppressed the inflammations through downregulating key glucose and energy metabolism-related genes expression ( Igfbp1 and Angptl4 ). • GLP may treat DN efficiently via immune-related signalling pathways from network pharmacology. • Providing a theoretical insight of anti-immunity mechanisms for GLP treatment in future clinical applications.