The Role of Estrogens in Rheumatoid Arthritis Physiopathology

Romo-García, Maria Fernanda; Zapata-Zúñiga, Martín; Enciso-Moreno, José Antonio; Castañeda-Delgado, Julio Enrique

doi:10.5772/intechopen.93371

Cited by 8 publications

(7 citation statements)

References 112 publications

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“…Vascular Endothelial Growth Factor (VEGF) signaling pathway: VEGF expression level in RA patients increased significantly, compared with healthy groups; moreover, patients under RA for an extended period exerted higher VEGF expression level in serum [ 32 ]. Estrogen signaling pathway: the estrogen treatment might have an inhibitory effect on RA symptoms or delay in the onset of disease, and estrogen has anti-inflammatory activity in an animal test of RA [ 33 ]. Fc epsilon RI signaling pathway: Fc epsilon RI signaling pathway is associated with inflammatory etiology, antigen-induced autoimmune reaction, and control of lipid metabolic pathway, and damage in human joint [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Uncovering Mechanisms of Zanthoxylum piperitum Fruits for the Alleviation of Rheumatoid Arthritis Based on Network Pharmacology

Adnan

Cho

2021

Biology

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Zanthoxylum piperitum fruits (ZPFs) have been demonstrated favorable clinical efficacy on rheumatoid arthritis (RA), but its compounds and mechanisms against RA have not been elucidated. This study was to investigate the compounds and mechanisms of ZPFs to alleviate RA via network pharmacology. The compounds from ZPFs were detected by gas chromatography–mass spectrometry (GC-MS) and screened to select drug-likeness compounds through SwissADME. Targets associated with bioactive compounds or RA were identified utilizing bioinformatics databases. The signaling pathways related to RA were constructed; interactions among targets; and signaling pathways-targets-compounds (STC) were analyzed by RPackage. Finally, a molecular docking test (MDT) was performed to validate affinity between targets and compounds on key signaling pathway(s). GC-MS detected a total of 85 compounds from ZPFs, and drug-likeness properties accepted all compounds. A total of 216 targets associated with compounds 3377 RA targets and 101 targets between them were finally identified. Then, a bubble chart exhibited that inactivation of MAPK (mitogen-activated protein kinase) and activation of PPAR (peroxisome proliferator-activated receptor) signaling pathway might be key pathways against RA. Overall, this work suggests that seven compounds from ZPFs and eight targets might be multiple targets on RA and provide integrated pharmacological evidence to support the clinical efficacy of ZPFs on RA.

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Section: Discussionmentioning

confidence: 99%

Uncovering Mechanisms of Zanthoxylum piperitum Fruits for the Alleviation of Rheumatoid Arthritis Based on Network Pharmacology

Adnan

Cho

2021

Biology

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“…Among the top positions in the ranking, we find drugs with known effects in rheumatoid arthritis patients or animal models of rheumatoid arthritis, and one of these went into clinical trial stage: rosiglitazone 3 , pioglitazone [Suke et al, 2013], estradiol [Romo-García et al, 2020], captopril [Martin et al, 1984], vitamin c [Carr et al, 2015], baclofen [Huang et al, 2015], deferasirox [Polson et al, 1986], decitabine [Petralia et al, 2019], sirolimus [Wen et al, 2019], hydrocortisone [Boland, 1952], paclitaxel [Kurose et al, 2001], and ethinylestradiol [Subramanian et al, 2005]. Suke et al [Suke et al, 2013] studied the effects of combined pioglitazone and prednisolone on adjuvant-induced arthritis in rats.…”

Section: Drugmerge Results On Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

“…Estradiol is an estrogen steroid female hormone, and estrogens have a direct action upon the immune system. The role of the estrogens in rheumatoid arthritis has been studied here [Romo-García et al, 2020]. Captopril is prescribed for hypertension but it has immunosuppressant activity, as well.…”

Section: Drugmerge Results On Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

Drug Repositioning by Merging Active Subnetworks Validated in Cancer and COVID-19

Lucchetta

Pellegrini

2021

Preprint

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Computational Drug Repositioning aims at ranking and selecting existing drugs for use in novel diseases or existing diseases for which these drugs were not originally designed. Using vast amounts of available omic data in digital form within an in silico screening has the potential for speeding up considerably the shortlisting of promising candidates in response to outbreaks of diseases such as COVID-19 for which no satisfactory cure has yet been found. We describe DrugMerge as a methodology for preclinical computational drug repositioning based on merging multiple drug rankings obtained with an ensemble of Disease Active Subnetwork construction algorithms. DrugMerge uses differential transcriptomic data from cell lines/tissues of patients affected by the disease and differential transcriptomic data from drug perturbation assays, in the context of a large gene co-expression network. Experiments with four benchmark diseases (Asthma, Rheumatoid Arthritis, Prostate Cancer, and Colorectal Cancer) demonstrate that our method detects in first position drugs in clinical use for the specified disease, in all four cases. Our method is competitive with the state-of-the-art tools such as CMAP (Connectivity Map). Application of DrugMerge to COVID-19 data found rankings with many drugs currently in clinical trials for COVID-19 in top positions, thus showing that DrugMerge is able to mimic human expert judgment

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“…Immuno-enhancing estrogens stimulate the transcription factors (e.g., NF-κB) that are important for producing pro-inflammatory cytokines, i.e., TNF-α, and thus promoting synovitis [42,43].…”

Section: Clinical Course Symptoms and Il-17a And Tnf-α Levels In Serummentioning

confidence: 99%

“…This is positive effect, unlike the one seen in the remission phase of the disease, where the females show a prolongation of the symptoms. It is already known that the activity of several estrogens (E1, E2, E3, and E4) is different and depends not only on the hormone itself but also on the specific disease [43]. Furthermore, estrogens act directly on the immune system through α and β estrogen receptors (ERα and ERβ), which have a distinct affinity to estrogen concentrations and modifications and can affect RA in a dose-dependent manner [44].…”

Section: Clinical Course Symptoms and Il-17a And Tnf-α Levels In Serummentioning

confidence: 99%

Gender-Related Differences in BMP Expression and Adult Hippocampal Neurogenesis within Joint-Hippocampal Axis in a Rat Model of Rheumatoid Arthritis

Omrčen

Cvek

Batičić

et al. 2021

IJMS

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BMPs regulate synovial quiescence and adult neurogenesis in the hippocampus in non-stress conditions. However, changes in BMP expression that are induced by inflammation during rheumatoid arthritis (RA) have not yet been reported. Here, we show that signalling with synovial BMPs (BMP-4 and -7) mediates the effect of systemic inflammation on adult neurogenesis in the hippocampus during pristane-induced arthritis (PIA) in Dark Agouti (DA) rats, an animal model of RA. Moreover, we show gender differences in BMP expressions and their antagonists (Noggin and Gremlin) during PIA and their correlations with the clinical course and IL-17A and TNF-α levels in serum. Our results indicate gender differences in the clinical course, where male rats showed earlier onset and earlier recovery but a worse clinical course in the first two phases of the disease (onset and peak), which correlates with the initial increase of serum IL-17A level. The clinical course of the female rats worsened in remission. Their prolonged symptoms could be a reflection of an increased TNF-α level in serum during remission. Synovial inflammation was greater in females in PIA-remission with greater synovial BMP and antagonist expressions. More significant correlations between serum cytokines (IL-17A and TNF-α), and synovial BMPs and their antagonists were found in females than in males. On the other hand, males showed an increase in hippocampal BMP-4 expression during the acute phase, but both genders showed a decrease in antagonist expressions during PIA in general. Both genders showed a decrease in the number of Ki-67+ and SOX-2+ and DCX+ cells and in the ratio of DCX+ to Ki67+ cells in the dentate gyrus during PIA. However, in PIA remission, females showed a faster increase in the number of Ki67+, SOX-2+, and DCX+ cells and a faster increase in the DCX/Ki67 ratio than males. Both genders showed an increase of hippocampal BMP-7 expression during remission, although males constantly showed greater BMP-7 expression at all time points. Our data show that gender differences exist in the BMP expressions in the periphery–hippocampus axis and in the IL-17A and TNF-α levels in serum, which could imply differences in the mechanisms for the onset and progression of the disease, the clinical course severity, and adult neurogenesis with subsequent neurological complications between genders.

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The Role of Estrogens in Rheumatoid Arthritis Physiopathology

Cited by 8 publications

References 112 publications

Uncovering Mechanisms of Zanthoxylum piperitum Fruits for the Alleviation of Rheumatoid Arthritis Based on Network Pharmacology

Uncovering Mechanisms of Zanthoxylum piperitum Fruits for the Alleviation of Rheumatoid Arthritis Based on Network Pharmacology

Drug Repositioning by Merging Active Subnetworks Validated in Cancer and COVID-19

Gender-Related Differences in BMP Expression and Adult Hippocampal Neurogenesis within Joint-Hippocampal Axis in a Rat Model of Rheumatoid Arthritis

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