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

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.

Erxian Decoction, a famous Chinese medicine formula, ameliorate depression-like behavior in perimenopausal mice

Aims: The present study was performed in order to find out the anti-depression effect of Erxian Decoction in perimenopausal mice. Background: Erxian Decoction (EXD) has been used in folk medicine for the treatment of perimenopausal syndrome, but it has not been researched on perimenopausal depression. Objective: The present study aimed to evaluate the effect of extraction of Erxian Decoction on perimenopausal depressive mice. Methods: In this study, female ICR mice were randomly divided into 6 groups: Low, medium and high dose of EXD groups (0.5, 1.5, and 4.5 g/kg), soy isoflavones group (250 mg/kg) and Sham group. The mice in the Sham group received sham surgery (within ovaries), and the others were excised with bilateral ovaries and exerted by 28-day chronic mild unpredictable stimulation for the establishment of a perimenopausal depression model. Results: Behavioral tests showed that EXD could relieve depression symptoms and improve spatial memory in mice. Western blotting showed that EXD significantly up-regulated the expression of brain-derived neurotrophic factor (BDNF) and Bcl-2 in hippocampus and estrogen receptors (ERs) in the uterus and adrenals, protecting hippocampal tissue and antagonizing the symptoms of estrogen deficiency in mice, which was further proved within a uterine morphology test. In addition, EXD reduced the serum levels of follicle-stimulating hormone, luteinizing hormone, and interleukin-6. Conclusion: These results indicated that EXD can regulate hormone secretion and recover hippocampal damage in perimenopausal depressed mice. Besides, it can antagonize the symptoms of ovarian hormone deficiency as well as relieve perimenopausal syndrome.