Analysis of Molecular Mechanism of Erxian Decoction in Treating Osteoporosis Based on Formula Optimization Model.

Lang Yang,Lan Liang,Daogang Guan,Yupeng Chen,Kexin Wang,Liuyi Fan,Peng Cao,Junxiang Peng,Xuemei Qin,Aiping Lu,Bin Yu,Alin Ciobica

doi:10.1155/2021/6641838

Abstract

Osteoporosis (OP) is a highly prevalent orthopedic condition in postmenopausal women and the elderly. Currently, OP treatments mainly include bisphosphonates, receptor activator of nuclear factor kappa-B ligand (RANKL) antibody therapy, selective estrogen receptor modulators, teriparatide (PTH1-34), and menopausal hormone therapy. However, increasing evidence has indicated these treatments may exert serious side effects. In recent years, Traditional Chinese Medicine (TCM) has become popular for treating orthopedic disorders. Erxian Decoction (EXD) is widely used for the clinical treatment of OP, but its underlying molecular mechanisms are unclear thanks to its multiple components and multiple target features. In this research, we designed a network pharmacology method, which used a novel node importance calculation model to identify critical response networks (CRNs) and effective proteins. Based on these proteins, a target coverage contribution (TCC) model was designed to infer a core active component group (CACG). This approach decoded the mechanisms underpinning EXD's role in OP therapy. Our data indicated that the drug response network mediated by the CACG effectively retained information of the component-target (C-T) network of pathogenic genes. Functional pathway enrichment analysis showed that EXD exerted therapeutic effects toward OP by targeting PI3K-Akt signaling (hsa04151), calcium signaling (hsa04020), apoptosis (hsa04210), estrogen signaling (hsa04915), and osteoclast differentiation (hsa04380) via JNK, AKT, and ERK. Our method furnishes a feasible methodological strategy for formula optimization and mechanism analysis and also supplies a reference scheme for the secondary development of the TCM formula.

Highlights

Osteoporosis (OP) is a metabolic bone disorder characterized by bone-mass reduction, bone microstructural degeneration, increased bone fragility, decreased bone strength, and increased fracture risk [1]
We developed a network pharmacology-based strategy to capture core active component group (CACG) and decode underlying Erxian Decoction (EXD) molecular mechanisms for OP therapy (Figure 1)
Mediated targets were enriched in neuroactive ligandreceptor interactions, PI3K-Akt signaling, cAMP signaling, mitogen-activated protein kinase (MAPK) signaling, estrogen signaling, osteoclast differentiation, etc. These results indicated that combining the critical response networks (CRNs) with the target coverage contribution (TCC) model to optimize herbal formulae was reliable, and predicted CACG potentially triggered therapeutic roles by identifying cell proliferationrelated osteoblast and osteoclast pathways

Summary

Introduction

Osteoporosis (OP) is a metabolic bone disorder characterized by bone-mass reduction, bone microstructural degeneration, increased bone fragility, decreased bone strength, and increased fracture risk [1]. Several pharmacological products are available for OP therapy; hormone replacement therapy (HRT) and bisphosphonates are mainly used for bone loss conditions, including OP. Prolonged HRT use may significantly elevate the risks for endometrial and breast cancer, coronary heart. Bisphosphonates may induce necrosis of long bones and the jaw [2]. These serious complications severely limit clinic use of these therapies. It is necessary to find new alternative treatments with less side effects in the treatment of osteoporosis. A recesnt meta-analysis of 644 patients with OP showed that EXD was therapeutically beneficial [12] and its different components elicited curative effects toward OP [5, 13, 14]

Methods

Results

Conclusion