Paper Title
INTEGRATION OF NETWORK PHARMACOLOGY AND PROTEOMICS TO ELUCIDATE THE MECHANISM AND TARGETS OF TRADITIONAL CHINESE MEDICINE SIMIAO BIEJIA GRANULEAGAINST DIABETES MELLITUS-INDUCED ERECTILE DYSFUNCTION IN THEGK RAT MODEL

Abstract
Abstract - Simiao Biejia granule (SMBJ) is a traditional Chinese medicine that has been used in China to clinically treat patients with Diabetes mellitus-induced erectile dysfunction (DMED). It is often used to regulate bodily functions and considered as adjuvant therapy for nourishing Yin, tonifying Kidney, clearing heat and promoting blood circulationyet, yet its underlying mechanism and targetsare notknown. The study aimed to investigate the potential mechanism of SMBJ improve ED of Goto-Kakizaki Rats (GK) rat model. Integrating network pharmacology and proteomics to investigate possible targets of SMBJ for DMED. The compounds in SMBJ were analyzed using UHPLC-ESI-QE-Orbitrap-MS. The Penile intracavernous pressure (ICP), Immunohisto chemistry (IHC), Masson, Hematoxylin-eosin (HE) staining, Enzyme-linked Immunosorbent Assay (ELISA) and differentially expressed proteins were examined. Proteomics analysis elucidated the potential mechanisms of SMBJ to improve DMED, which was further validated by Western blot (WB) assay. The compounds and potential targets of SMBJ were systematically elucidated by integrating network pharmacology and proteomics analysis to explore the mechanism. The binding affinity between key potential targets and corresponding compounds was then validated using molecular docking. Molecular docking results were verified by a western blotting.SMBJ restores injure of Penile Smooth Muscle Cells (SMCs) and penile vascular endothelial cells (VECs) from Hyperglycemic and Oxidative Stress, meanwhile one of core Components luteolin in SMBJ improves DMED through Inducing Endothelial-Dependent Vasodilation and angiogenesis by AKT1-dependent mechanism. Our results suggest that SMBJ maybe offer a new therapeutic basis for the treatment of DMED via altering the gene expression of involved AKT1 inflammation related pathways. Keywords - Simiao Biejia Granule, Penile Smooth Muscle Cells (SMCS), Penile Vascular Endothelial Cells (VECS), Diabetes Mellitus-Induced Erectile Dysfunction(DMED)