Ginkgo biloba Extract Attenuates the Disruption of Pro- and Anti-inflammatory Balance of Peripheral Blood in Arsenism Patients by Decreasing Hypermethylation of the Foxp3 Promoter Region

Fang, Xiaolin; Zeng, Qibing; Sun, Baofei; Wei, Shaofeng; Zou, Zhonglan; Xia, Shiqing; Luo, Peng; Zhang, Aihua

doi:10.1007/s12011-022-03101-0

Cited by 11 publications

(4 citation statements)

References 31 publications

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“…25 Our previous studies demonstrated that arsenic exposure could induce FOXP3 hypermethylation, which was involved in arsenic poisoning by triggering inflammation. 21,22 On this basis, this study, using mediation analysis, further revealed that FOXP3 methylation was an epigenetic modification that could both respond to arsenic exposure load and significantly mediate an increased risk of arsenic poisoning. The premise that the epigenetic modifications can be used as biomarkers for the assessment of adverse health risks induced by environmental pollutants is their excellent performance both in response to environmental stimuli and in involvement in environmentally triggered phenotypes and diseases.…”

Section: Discussionmentioning

confidence: 71%

“…[18][19][20] Our previous studies demonstrated that the aberration of FOXP3 methylation could be sustained following continued exposure to arsenic and was involved in arsenic poisoning by triggering inflammation. 21,22 These results suggest that FOXP3 methylation might be an early epigenetic biomarker of arsenic poisoning, but it is unknown whether FOXP3 methylation exhibits accuracy, sensitivity and reliability in prediction of arsenic poisoning risk.…”

Section: Introductionmentioning

confidence: 95%

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The hypermethylation of FOXP3 gene as an epigenetic marker for the identification of arsenic poisoning risk

Fang

Zhang

2022

Hum Exp Toxicol

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Background and Purpose: Arsenic exposure can lead to skin lesions and multiple organ damage, which are not easily reversible and for which there is no effective therapeutics. Identification of reliable epigenetic markers is essential for early recognition of arsenic poisoning risk. Anomalous DNA methylation of immune homeostasis regulator FOXP3 is a critical mechanism for triggering arsenic poisoning. This study aims to explore the value of FOXP3 methylation in the identification of arsenic poisoning risk. Methods: 88 arsenic poisoning subjects and 41 references were recruited. Urinary arsenic contents and FOXP3 methylation in PBLCs was measured by ICP-MS and pyrosequencing, respectively. Results: The results showed that the elevated FOXP3 methylation in PBLCs were associated with the increased levels of urinary arsenic and were positively associated with the increased risk of arsenic poisoning and its progression. The result of mediation analysis revealed that 24.3% of the effect of arsenic exposure on the risk of arsenic poisoning was mediated by increased FOXP3 methylation. Additionally, we constructed a nomogram model with FOXP3 methylation as an epigenetic predictor to assess the probability of individual arsenic poisoning. The model showed a robust ability in the discrimination of arsenic poisoning risk, with an area under receiver operating characteristics curve of 0.897(0.845–0.949) and more than 70% accuracy. The calibration curves and the Harrell concordance index showed that the consistency rate between the probability predicted by the nomogram model and the actual probability is 89.7%. Conclusions: Taken together, we found the great potential of FOXP3 methylation for the identification of arsenic poisoning risk and provided a new approach to the application of epigenetic markers in accurately quantifying the risk of adverse outcomes.

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 95%

The hypermethylation of FOXP3 gene as an epigenetic marker for the identification of arsenic poisoning risk

Fang

Zhang

2022

Hum Exp Toxicol

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“…The results show that arsenic can induce the hypermethylation of 6 sites in the Foxp3 promoter by upregulating the expression of recombinant DNA Methyltransferase 1 (Dnmt1) mRNA, leading to the downregulation of Foxp3 mRNA, Tregs, and interleukin 10 (IL-10, anti-inflammatory cytokine) levels, and increased the levels of interleukin 17 (IL-17, pro-inflammatory cytokine) in the peripheral blood of patients with arsenic poisoning, manifested as the disruption of pro-and anti-inflammatory T cell balance and multiple organ damage. 1 There is a transient platelet increase at the beginning of the onset of both diseases, and then a rapid decrease, and even continuous detection reports the critical value, which may be related to the extensive damage of vascular endothelium caused by the high concentration of hydrogen arsenide in the blood, leading to the massive activation and consumption of platelets, and the formation of extensive platelet thrombosis. 2 In this case, the platelet levels of the two patients gradually returned to normal after the blood arsenic concentration decreased after treatment with platelet infusion and arsenic removal.…”

Section: Discussionmentioning

confidence: 99%

A Report of 2 Cases of Acute Hydrogen Arsenide Poisoning

Wang¹,

Bai²,

Ma³

et al. 2023

IMCRJ

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Arsenic and its compounds are widely found in nature. They are often absorbed into the human body through the respiratory tract, skin and digestive tract, and distributed throughout the body through the blood. It is more common in coal burning arsenic poisoning and drinking water arsenic poisoning. In recent years, arsenic poisoning related to industrial production has also been reported. Two cases of hydrogen arsenide poisoning related to industrial production were reported and analyzed in order to improve the treatment level.

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“…According to our bioinformatics results, Ginkgo biloba may exert anti-arthritic effects by inhibiting inflammatory cytokines such as IL-6 and modulating oxidative stress proteins such as hypoxia-inducible factor 1 subunit alpha (HIF-1α) and nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2). Ginkgo biloba extract maintains the pro-inflammatory and anti-inflammatory balance by inhibiting hypermethylation of the FOXP3 gene to treat the coal-burning type of arsenism [26]. Similarly, Ginkgo biloba-induced anti-inflammatory effects protect hippocampal neurons from trimethyltin-caused Fig.…”

Section: Discussionmentioning

confidence: 99%

Gingko biloba-inspired lactone prevents osteoarthritis by activating the AMPK-SIRT1 signaling pathway

Zhao

Liu

et al. 2022

Arthritis Res Ther

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Background Uncoupled extracellular matrix (ECM) causes cartilage degeneration and osteoarthritis (OA) by suppressing the synthesis and activating the degradation of ECM components. Gingko biloba is a natural Chinese herb with a variety of biological functions; however, the extent to which it can protect against OA and the mechanisms involved are unknown. Methods In our study, using bioinformatics tools, we were able to identify an important lactone, bilobalide (BB), from Gingko biloba. In vitro experiments were performed to evaluate the potential therapeutic effects of BB on ECM homeostasis. In vivo experiments were conducted to assess the protection of systemic administration of BB on cartilage degeneration. Molecular mechanisms underlying BB-regulated anti-arthritic role were further explored. Results In interleukin-1β-incubated human chondrocytes, in vitro treatment with BB increased the expression of cartilage anabolic proteins, while inhibiting the activities of ECM degrading enzymes. In a mice model, systemic administration of BB, in vivo, prevented post-traumatic cartilage erosion and attenuated the formation of abnormal osteophytes in the subchondral bone. Mechanistically, the activation of the adenosine 5′-monophosphate-activated protein kinase (AMPK)-sirtuin 1 (SIRT1) signaling pathway was involved in the anti-arthritic effects of BB. In vitro, blocking BB’s chondroprotection with the AMPK-specific inhibitor Compound C abrogated it. Conclusions These results demonstrated that BB extracted from Gingko biloba regulates ECM balance to prevent OA by activating the AMPK-SIRT1 signaling pathway. This study proposed the monomer BB, a traditional Chinese medicine, as a de novo therapeutic insight for OA. Graphical Abstract Schematic representation of the experimental design. Based on the bioinformatic analysis, bilobalide (BB), a natural herb Gingko biloba-derived ingredient, was identified as a candidate for treating osteoarthritis. In vitro, BB treatment not only facilitates cartilage extracellular matrix synthesis but also inhibits proteolytic enzyme activities. In vivo intraperitoneal injection of BB improves cartilage degeneration and subchondral bone sclerosis. BB, in particular, had anti-arthritic effects by activating the AMPK-SIRT1 signaling pathway.

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Ginkgo biloba Extract Attenuates the Disruption of Pro- and Anti-inflammatory Balance of Peripheral Blood in Arsenism Patients by Decreasing Hypermethylation of the Foxp3 Promoter Region

Cited by 11 publications

References 31 publications

The hypermethylation of FOXP3 gene as an epigenetic marker for the identification of arsenic poisoning risk

The hypermethylation of FOXP3 gene as an epigenetic marker for the identification of arsenic poisoning risk

A Report of 2 Cases of Acute Hydrogen Arsenide Poisoning

Gingko biloba-inspired lactone prevents osteoarthritis by activating the AMPK-SIRT1 signaling pathway

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