Integrating RNA-sequencing and network analysis to explore the mechanism of topical Pien Tze Huang treatment on diabetic wounds

• DOI: 10.3389/fphar.2023.1288406
• Publication Date: 2024-01-16T17:17:23Z
• Authors: Guang-Zhao Cao; Liang-Liang Tian; Jing-Yi Hou; Yi Zhang; He Xu; Hong-Jun Yang; Jing-Jing Zhang
• Keywords: Pharmacology; 0303 health sciences; 03 medical and health sciences; Klrk1, Ifng, Tlr2; Therapeutics. Pharmacology; RM1-950; NF-κB signaling pathway; Pien Tze Huang; diabetic wounds; Nod2

Introduction: Diabetic ulcers have become one of the major complications diabetes mellitus (DM) and are a leading cause death disabling disease. However, current therapies not effective enough to meet clinical needs. A traditional Chinese medicine (TCM) formula, Pien Tze Huang (PZH), is known as that used treat diabetic ulcers. Methods: In this study, PZH (0.05 g/cm 2 0.15 ) positive drug-rhEGF were topically administered in high-fat diet (HFD) streptozotocin (STZ)-induced full-thickness incisional wounds, respectively. Wound healing was assessed by wound closure rate, two-photon microscope (SHG), staining with Hematoxylin eosin (H&E), Masson's trichrome (MTC). Then, RNA sequencing (RNA-seq) analysis, Enzyme-linked immunosorbent assay (ELISA), western blotting, immunofluorescence (IF), network performed. Results discussion: The results showed significantly accelerated healing, well enhanced expression collagen. RNA-seq analysis has functions on various biological processes, key processes inflammatory response. Tlr9, Klrk1, Nod2, Tlr2, Ifng identified vital targets NF-κB signaling pathway pathway. Additionally, profoundly reduced levels Cleaved caspase-3 promoted CD31 TGF-β1. Mechanically, decreased NKG2-D, NOD2, TLR2, further inhibited activation downstream factors (IFN-γ IL-1β). Importantly, we found several active ingredients may play significant role including Notoginsenoside R1, Deoxycorticosterone, Ursolic acid, 4-Methoxyphenol. summary, our study sheds light complicated mechanisms underlying promising anti-diabetic wounds provides discovery agents treating