Isolation and Identification of Antiarthritic Constituents from Glycine tabacina and Network Pharmacology-Based Prediction of Their Protective Mechanisms against Rheumatoid Arthritis

Longzuan Tongbi Formula (LZTB) is an effective proved prescription in Zhuang medicine for treating active rheumatoid arthritis (RA). However, its active ingredients, underlying targets, and pharmacological mechanism are still not clear in treating RA. We have applied network pharmacology to study LZTB and found that 8 herbs in LZTB and 67 compounds in the 8 herbs are involved in the regulation of RA-related genes; we have conducted pathway analysis of overlapping genes and found that 7 herbs participate in the regulations of 24 pathways associated with RA and that 5 herbs in the 7 herbs and 25 compounds in the 5 herbs participate in the regulation of hsa05323 (rheumatoid arthritis). The results indicated that all herbs in LZTB and some compounds in those herbs participate in the treatment of RA; 25 compounds are main active ingredients and hsa05323 (rheumatoid arthritis) is the major pathway in the treatment of RA. We have also found that three pathways (inflammatory mediator regulation of TRP channels, PPAR signaling pathway, and mTOR signaling pathway) might have some effect on the treatment of RA.

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Herb Network Analysis for a Famous TCM Doctor's Prescriptions on Treatment of Rheumatoid Arthritis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/451319 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Yan Li ◽

Rui Li ◽

Zibo Ouyang ◽

Shao Li

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Practice ◽

Biological Activities ◽

Network Pharmacology ◽

Biological Processes ◽

Hormone Regulation ◽

The Core ◽

Target Disease ◽

Herbal Formulae ◽

Target Sets

Traditional Chinese Medicine (TCM) doctors always prescribe various herbal formulae tailored to individual patients. However, there is still a lack of appropriate methods to study the rule and potential biological basis underlying the numerous prescriptions. Here we developed an Herb-Compound-Target-Disease coherent network approach to analyze 871 herbal prescriptions from a TCM master, Mr. Ji-Ren Li, in his clinical practice on treatment of rheumatoid arthritis (RA). The core herb networks were extracted from Mr. Li’s prescriptions. Then, we predicted target profiles of compounds in core herb networks and calculated potential synergistic activities among them. We further found that the target sets of core herbs overlapped significantly with the RA related biological processes and pathways. Moreover, we detected a possible connection between the prescribed herbs with different properties such as Cold and Hot and the Western drugs with different actions such as immunomodulatory and hormone regulation on treatment of RA. In summary, we explored a new application of TCM network pharmacology on the analysis of TCM prescriptions and detected the networked core herbs, their potential synergistic and biological activities, and possible connections with drugs. This work offers a novel way to understand TCM prescriptions in clinical practice.

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Integrating Network Pharmacology with Molecular Docking to Unravel the Active Compounds and Potential Mechanism of Simiao Pill Treating Rheumatoid Arthritis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/5786053 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Mengshi Tang ◽

Xi Xie ◽

Pengji Yi ◽

Jin Kang ◽

Jiafen Liao ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Molecular Docking ◽

Signaling Pathway ◽

Target Genes ◽

Enrichment Analysis ◽

Binding Activity ◽

New Combination ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Potential Mechanism

Objective. To explore the main components and unravel the potential mechanism of simiao pill (SM) on rheumatoid arthritis (RA) based on network pharmacological analysis and molecular docking. Methods. Related compounds were obtained from TCMSP and BATMAN-TCM database. Oral bioavailability and drug-likeness were then screened by using absorption, distribution, metabolism, and excretion (ADME) criteria. Additionally, target genes related to RA were acquired from GeneCards and OMIM database. Correlations about SM-RA, compounds-targets, and pathways-targets-compounds were visualized through Cytoscape 3.7.1. The protein-protein interaction (PPI) network was constructed by STRING. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed via R packages. Molecular docking analysis was constructed by the Molecular Operating Environment (MOE). Results. A total of 72 potential compounds and 77 associated targets of SM were identified. The compounds-targets network analysis indicated that the 6 compounds, including quercetin, kaempferol, baicalein, wogonin, beta-sitosterol, and eugenol, were linked to ≥10 target genes, and the 10 target genes (PTGS1, ESR1, AR, PGR, CHRM3, PPARG, CHRM2, BCL2, CASP3, and RELA) were core target genes in the network. Enrichment analysis indicated that PI3K-Akt, TNF, and IL-17 signaling pathway may be a critical signaling pathway in the network pharmacology. Molecular docking showed that quercetin, kaempferol, baicalein, and wogonin have good binding activity with IL6, VEGFA, EGFR, and NFKBIA targets. Conclusion. The integrative investigation based on bioinformatics/network topology strategy may elaborate on the multicomponent synergy mechanisms of SM against RA and provide the way out to develop new combination medicines for RA.

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Dolichosin A, a coumestan isolated from Glycine tabacina, inhibits IL-1β-induced inflammation in SW982 human synovial cells and suppresses RANKL-induced osteoclastogenesis: From network pharmacology to experimental pharmacology

Journal of Ethnopharmacology ◽

10.1016/j.jep.2020.112855 ◽

2020 ◽

Vol 258 ◽

pp. 112855

Author(s):

Yanbei Tu ◽

Kai Wang ◽

Lihua Tan ◽

Bing Han ◽

Yuanjia Hu ◽

...

Keyword(s):

Network Pharmacology ◽

Synovial Cells ◽

Experimental Pharmacology ◽

Glycine Tabacina

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Myrtenal and β-caryophyllene oxide screened from Liquidambaris Fructus suppress NLRP3 inflammasome components in rheumatoid arthritis

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03410-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wen-xuan Li ◽

Ping Qian ◽

Yi-tong Guo ◽

Li Gu ◽

Jessore Jurat ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Molecular Docking ◽

Nlrp3 Inflammasome ◽

Network Pharmacology ◽

Caryophyllene Oxide ◽

Active Ingredients ◽

Caspase 1 ◽

Tnf Α ◽

Cartilage Erosion ◽

And Cartilage

Abstract Background Liquidambaris Fructus (LF) is the infructescence of Liquidambar formosana. In Traditional Chinese Medicine, LF has been used to treat joint pain, a common symptom of arthritis and rheumatism; however, a lack of pharmacological evidence has limited its applications in modern clinics. Therefore, this study aims to explore the protective effect of LF on rheumatoid arthritis (RA) and to identify its active ingredients. Methods Rats with adjuvant-induced arthritis (AIA) were divided into 4 groups and administered petroleum ether extract of LF (PEL), ethyl acetate extract of LF (EEL), water extract of LF (WEL), or piroxicam (PIR) respectively for 3 weeks. Two additional groups were used as normal control (NC) and model control (MC) and administered distilled water as a placebo. The clinical scores for arthritis, bone surface, synovial inflammation and cartilage erosion were used to evaluate the therapeutic efficacy of each treatment. The serum IL-1β and TNF-α level and the expression of NLRP3, IL-1β and caspase-1 p20 in the synovial tissue of AIA rats were evaluated by ELISA and Western blot. The active ingredients of LF were investigated using network pharmacology and molecular docking methods, and their inhibition of NLRP3 inflammasome activation was verified in the human rheumatoid arthritis fibroblast-like synovial cells (RA-FLS) model. Results PEL could alleviate paw swelling, bone and joint destruction, synovial inflammation and cartilage erosion in the AIA rats, with significantly superior efficacy to that of EEL and WEL. PEL reduced IL-1β and TNF-α serum levels, and attenuated the upregulation of NLRP3, IL-1β and caspase-1 p20 expression in the synovial tissue of AIA rats. Network pharmacology and molecular docking results indicated that myrtenal and β-caryophyllene oxide were the main two active ingredients of PEL, and these two compounds showed significant inhibition on TNF-α, NLRP3, IL-1β and caspase-1 p20 expression in RA-FLS. Conclusions Myrtenal and β-caryophyllene oxide screened from PEL could suppress the activation of NLRP3 inflammasome, thereby alleviating RA symptoms.

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Network Pharmacology-Based Analysis on the Curative Effect of Kunxian Capsules against Rheumatoid Arthritis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6812374 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Hong-Xia Yan ◽

Chun-Fang Xu ◽

Hong Yang ◽

Xiao-Ya Wen ◽

Zhi-Peng Wang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Chemical Constituents ◽

Target Prediction ◽

Network Pharmacology ◽

Active Ingredients ◽

Pathway Network ◽

Chemical Profiling ◽

Pharmaceutical Ingredients ◽

Synergistic Mechanism ◽

Chinese Patent

Kunxian capsules (KCs), a Chinese patent medicine, have been clinically proven to be effective in the treatment of rheumatoid arthritis (RA). However, the chemical profile of KC remains to be characterized, and the mechanism underlying the protective effect against RA is yet to be elucidated. Here, a network pharmacology-based approach was adopted, integrated with the chemical profiling of KC by UHPLC-Q-TOF/MS. As a result, a total of 67 compounds have been identified from KC extract, among which 43 were authenticated by comparison to the mass spectrum of standard chemicals. ADME behaviors of the chemical constituents of KC were predicted, resulting in 35 putative active ingredients. Through target prediction of both active ingredients of KC and RA and PPI analysis, core targets were screened out, followed by biological process and related pathway enrichment. Then, a TCM-herb-ingredient-target-pathway network was constructed and a multicomponent, multitarget, and multipathway synergistic mechanism was proposed, providing an information basis for further investigation. The active pharmaceutical ingredients included mainly terpenoids (such as triptolide and celastrol), sesquiterpene pyridines (such as wilforgine and wilforine), and flavonoids (such as icariin, epimedin A, B, and C, and 2″-O-rhamnosylicariside II).

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