Integrated Strategy of Network Pharmacological Prediction and Experimental Validation Elucidate Possible Mechanism of Bu-Yang Herbs in Treating Postmenopausal Osteoporosis via ESR1

Xia, Hanting; Liu, Jiangyuan; Yang, Wenlong; Liu, Min; Luo, Yunfeng; Yang, Zhijun; Xie, Jingbo; Zeng, Huiliang; Xu, Rui; Ling, Houfu; Zeng, Qinghe; Xu, Huihui; Liang, Fang; Wang, Hongyu; Tong, Peijian; Jin, Hongting; Yang, Fusheng

doi:10.3389/fphar.2021.654714

Cited by 18 publications

(13 citation statements)

References 66 publications

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“…Based on network pharmacology analysis, the core compounds of TCM have made great contributions to the therapeutic effect of treating diseases (42). In the present study, we firstly discovered that the top active compounds in ZGBSF consist of quercetin, luteolin, kaempferol, baicalein, etc.…”

Section: Discussionmentioning

confidence: 81%

Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis

et al. 2022

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Osteoporosis (OP) is a common skeletal disease, characterized by decreased bone formation and increased bone resorption. As a novel Chinese medicine formula, Zhuanggu Busui formula (ZGBSF) has been proved to be an effective prescription for treating OP in clinic, however, the pharmacological mechanisms underlying the beneficial effects remain obscure. In this study, we explored the pharmacological mechanisms of ZGBSF against OP via network pharmacology analysis coupled with in vivo experimental validation. The results of the network pharmacology analysis showed that a total of 86 active ingredients and 164 targets of ZGBSF associated with OP were retrieved from the corresponding databases, forming an ingredient-target-disease network. The protein-protein interaction (PPI) network manifested that 22 core targets, including Caspase-3, BCL2L1, TP53, Akt1, etc, were hub targets. Moreover, functional enrichment analyses revealed that PI3K-Akt and apoptosis signalings were significantly enriched by multiple targets and served as the targets for in vivo experimental study validation. The results of animal experiments revealed that ZGBSF not only reversed the high expression of Caspase-3, Bax, Prap, and low expression of Bcl-2 in osteoblasts of the OP mouse model but also contributed to the phosphorylation of Akt1 and expression of PI3K, thereby promoting osteogenesis and ameliorating the progression of OP. In conclusion, this study systematically and intuitively illustrated that the possible pharmacological mechanisms of ZGBSF against OP through multiple ingredients, targets, and signalings, and especially the inhibition of the apoptosis and the activation of PI3K-Akt signaling.

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Section: Discussionmentioning

confidence: 81%

Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis

et al. 2022

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“…In the current study, the network pharmacology analysis method refers to the previous study. We followed the methods of [ 5 ]. The chemical components of TCM herbs of Radix Rehmanniae Preparata and liquorice were searched on TCMSP and SYMMAP databases [ 16 , 17 ].…”

Section: Methodsmentioning

confidence: 99%

“…OP is characterized by bone mineral density (BMD) loss, bone microarchitecture degenerated, and risk of fracture upregulated [ 3 ]. It is well accepted that OP is led by an imbalance between bone formation and bone resorption [ 4 , 5 ]. First-line clinical therapies mainly focused on inhibition of excessive bone resorption activity and few drugs focusing on enhancing attenuated bone formation were developed.…”

Section: Introductionmentioning

confidence: 99%

Shu-Di-Huang and Gan-Cao Herb Pair Restored the Differentiation Potentials of Mesenchymal Stem Progenitors in Treating Osteoporosis via Downregulation of NF-κB Signaling Pathway

Ling

Wang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Shu-Di-Huang (Radix Rehmanniae Praeparata, RR) and Gan-Cao (liquorice, L) are frequently used traditional Chinese herb pair in treating osteoporosis (OP). However, the exact mechanism of the RR and L herb pair (RR-L) remains unclear. To explore the efficacy and possible mechanisms of RR-L in treating OP, in silico, in vitro, and in vivo experiments were conducted in the current study. Methods. In silico, potential therapeutic target genes and active chemical compounds of RR-L herb pair were predicted and constructed into a network. In vivo, 30 Sprague Dawley rats were divided into 3 groups, including the sham group, the OP model group, and the RR-L-treated OP group. Micro-CT and pathological sections were conducted to validate the therapeutic effects of RR-L in treating OP. MSCs of rats were isolated and cultured in vitro to validate the mesenchymal stem cells (MSCs) related phenotype changes, including Alizarin red staining, Oil red staining, and immunofluorescence. In vitro, cell proliferation analysis, Alizarin red staining, Oil red staining, immunofluorescence of NF-κB, and protein expression of PPARγ, RUNX2, OCN, and p65 were conducted on MSCs to explore the RR-L containing serum in vitro. Also, activator and inhibitor of NF-κB signaling pathway were introduced to determine the possible mechanism of RR-L in the treatment of OP via enhancing MSCs proliferation and differentiation. Results. In silico, 168 chemical compounds with a property of oral bioavailability ≥30% and drug-likeness ≥0.18 were recognized as potentially active compounds in RR-L and 249 genes were found to be the targets of which. Among them, 120 genes were found to be therapeutic genes of RR-L in treating OP and KEGG and GO analysis of which demonstrated that RR-L involves in lipid metabolism and multiple inflammation-related signaling pathways. In vivo, ovariectomy- (OVX-) induced OP phenotypes in Sprague Dawley rats include bone mineral density and microarchitecture damaging, abnormal bone metabolism, upregulation of inflammation markers, and damaged differentiation potential of MSCs. Treatment of RR-L reversed the trend and restored the differentiation potential of MSCs. In vitro, RR-L containing serum promoted the osteogenic differentiation and suppressed adipogenic differentiation of MSCs via downregulation of the NF-κB signaling pathway. Also, RR-L containing serum inhibited the tumor necrosis factor-α (TNF-α) induced activation of the NF-κB signaling pathway. On the opposite, the addition of the NF-κB specific inhibitor significantly reduced the effect of RR-L on MSCs. Conclusions. In the current study, network pharmacology prediction and experimental validation elucidated that the RR-L herb pair restored damaged MSC differentiation potential via the NF-κB signaling pathway; this could be the possible mechanism of RR-L in treating OP. This finding provides an alternative option in OP therapy.

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“… 17 Similarly, with the help of network pharmacology, we predicted and verified the potential pharmacological mechanism of Bu-Yang herbs for postmenopausal osteoporosis via regulating the Wnt/β-catenin signaling pathway. 18 Therefore, all this evidence indicated that network pharmacology analysis may be a good tool for exploring the chemical compositions of LWDHD and its relationships with IVDD.…”

Section: Introductionmentioning

confidence: 94%

Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Liuwei Dihuang Decoction Against Intervertebral Disc Degeneration

Zhang¹,

Yao²,

Zhang³

et al. 2021

DDDT

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To explore the pharmacological mechanisms of Liuwei Dihuang Decoction (LWDHD) against intervertebral disc (IVD) degeneration (IVDD) via network pharmacology analysis combined with experimental validation. Methods: First, active ingredients and related targets of LWDHD, as well as related genes of IVDD, were collected from public databases. The protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed to predict the core targets and pathways of LWDHD against IVDD. Secondly, the IVDD model of mice treated with LWDHD was selected to validate the major targets predicted by network pharmacology. Results: By searching the intersection of the active ingredient targets and IVDD targets, a total of 110 targets matched the related targets of 30 active ingredients in LWDHD and IVDD were retrieved. PPI network analysis indicated that 17 targets, including Caspase-3, IL-1β, P53, etc., were hub targets. GO and KEGG enrichment analyses showed that the apoptosis pathway was enriched by multiple targets and served as the target for in vivo experimental study validation. The results of animal experiments revealed that LWDHD administration not only restored the decrease in disc height and abnormal degradation of matrix metabolism in IVDD mice but also reversed the high expression of Bax, Caspase-3, IL-1β, P53, and low expression of Bcl-2, thereby inhibiting the apoptosis of IVD tissue and ameliorating the progression of IVDD. Conclusion: Using a comprehensive network pharmacology approach, our findings predicted the active ingredients and potential targets of LWDHD intervention for IVDD, and some major target proteins involved in the predictive signaling pathway were validated experimentally, which gave us a new understanding of the pharmacological mechanism of LWDHD in treating IVDD at the comprehensive level.

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Integrated Strategy of Network Pharmacological Prediction and Experimental Validation Elucidate Possible Mechanism of Bu-Yang Herbs in Treating Postmenopausal Osteoporosis via ESR1

Cited by 18 publications

References 66 publications

Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis

Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis

Shu-Di-Huang and Gan-Cao Herb Pair Restored the Differentiation Potentials of Mesenchymal Stem Progenitors in Treating Osteoporosis via Downregulation of NF-κB Signaling Pathway

Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Liuwei Dihuang Decoction Against Intervertebral Disc Degeneration

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