Benzo(α)pyrene induces oxidative stress and inflammation in human vascular endothelial cells through AhR and NF-κB pathways

Shi, Hanyu; Liu, Jie; Gao, Haiqing

doi:10.1016/j.mvr.2021.104179

Cited by 22 publications

(3 citation statements)

References 32 publications

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“…Berberrubine Frontiers in Pharmacology frontiersin.org (BRB) is deemed as one of the main metabolites of BBR. Our previous study has indicated that BBR and BRB effectively lowered the sUA levels in PO/HX-induced HUA mice (Lin et al, 2021;Shi et al, 2021). Chelerythrine is a natural benzo [c]phenanthridine alkaloid derived from Chelidonium majus, Macleaya cordata, and Sanguinaria canadensis (Wu et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Integrating network pharmacology and experimental validation to clarify the anti-hyperuricemia mechanism of cortex phellodendri in mice

Cheng

et al. 2022

Front. Pharmacol.

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Hyperuricemia (HUA), a common metabolic disease, is treated as the second-largest metabolic disease after diabetes in China. Cortex Phellodendri (CP) is one of the most frequently used herbal medicines for treating gout or HUA. However, the mechanism underlying the anti-HUA effect of CP is still unrevealed. Hence, this study aimed to explore the pharmacological mechanism of CP against HUA using network pharmacology coupled with in vivo experimental validation. Active compounds and potential targets of CP, as well as the potential targets related to HUA, were retrieved from multiple open-source databases. The drug-disease overlapping targets were obtained by Venn diagram analysis and used to construct the herb-component-target (HCT), protein-protein-interaction (PPI), and component-target-pathway (CTP) networks. The functional enrichment analysis was also performed for further study. Furthermore, a HUA mouse model was induced by a combination of intraperitoneal injection of potassium oxonate (PO, 300 mg/kg) and intragastric administration of hypoxanthine (HX, 300 mg/kg) daily for 10 days. Different dosages of CP (200, 400, and 800 mg/kg) were orally given to mice 1 h after modeling. The results showed that 12 bioactive compounds and 122 drug-disease overlapping targets were obtained by matching 415 CP-related targets and 679 HUA-related targets, and berberine was one of the most important compounds with the highest degree value. The core targets of CP for treating HUA were TP53, MAPK8, MAPK3, IL-6, c-Jun, AKT1, xanthine oxidase (XOD), and ATP-binding cassette subfamily G member 2 (ABCG2). The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results showed that the anti-HUA effect of CP mainly involved the pathways of inflammation and apoptosis, such as PI3K/Akt, TNF, MAPK, TLR, AMPK, NF-κB, and NLRP3 signaling pathways. In vivo animal experiment further confirmed the hypouricemic effect of CP in a HUA mouse model, as evidenced by significantly restored kidney histological deteriorations, and considerably decreased levels of serum uric acid (sUA), creatinine (Cre), blood urea nitrogen (BUN), and hepatic UA. Furthermore, the hypouricemic action of CP in vivo might be attributed to its suppression of XOD activity in the liver, rather than ABCG2 in the kidney. Real-time qPCR (RT-qPCR) and Western blot analysis also confirmed the key roles of the hub genes in CP against HUA. In conclusion, CP exhibited therapeutic effect against HUA via multi-compounds, multi-targets, and multi-pathways. It possessed anti-HUA and nephroprotective effects via suppressing XOD activity, and reversed the progression of renal injury by exerting anti-inflammatory and anti-apoptotic effects.

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Section: Discussionmentioning

confidence: 99%

Integrating network pharmacology and experimental validation to clarify the anti-hyperuricemia mechanism of cortex phellodendri in mice

Cheng

et al. 2022

Front. Pharmacol.

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“…The beneficial properties of polyphenols are often ascribed to their ability to protect against reactive oxygen species (ROS) (Bors et al, 1990, Sandoval-Acuna et al, 2014). Since AhR is involved in oxidative stress-mediated processes (Wang et al, 2019, Kubli et al, 2019, Shi et al, 2021) we wondered whether curcumin may impact animals’ physiology via AhR-regulated antioxidant responses. We observed that ahr-1 mutants produce more mitochondrial(mt)ROS and have a reduced mitochondrial membrane potential ( Fig 4A, B ), two parameters correlating with longevity (Bazopoulou et al, 2019, Lemire et al, 2009).…”

Section: Resultsmentioning

confidence: 99%

Aryl hydrocarbon receptor-dependent and -independent pathways mediate curcumin anti-aging effects

Brinkmann

Romeo

Larigot

et al. 2022

Preprint

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The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor whose activity can be modulated by polyphenols such as curcumin. AhR and curcumin have evolutionarily conserved effects on aging. Here, we investigated whether and how the AhR mediates the anti-aging effects of curcumin across species. Using a combination of in vivo, in vitro, and in silico analyses, we demonstrated that curcumin has AhR-dependent or -independent effects in a context-specific manner. We found that in Caenorhabditis elegans, AhR mediates curcumin-induced lifespan extension, most likely through a ligand-independent inhibitory mechanism related to its antioxidant activity. Curcumin also showed AhR-independent anti-aging activities such as protection against aggregation-prone proteins and oxidative stress in C. elegans and promotion of the migratory capacity of human primary endothelial cells. These AhR-independent effects are largely mediated by the Nrf2/SKN-1 pathway.

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“…Harmful and potentially harmful constituents (HPHCs) ( Food, 2012 ) in CS are considered to cause oxidative stress and inflammatory responses ( Horinouchi, 2020 , Zhou, 2022 , Shi et al, 2021 ). Therefore, reducing exposure to HPHCs is a way to reduce such adverse biological events, could thus potentially contribute to reduce risk of inflammatory diseases including atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

RNA sequencing analysis of early-stage atherosclerosis in vascular-on-a-chip and its application for comparing combustible cigarettes with heated tobacco products

Ohashi,

Hayashida,

Nozawa

et al. 2024

Current Research in Toxicology

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Benzo(α)pyrene induces oxidative stress and inflammation in human vascular endothelial cells through AhR and NF-κB pathways

Cited by 22 publications

References 32 publications

Integrating network pharmacology and experimental validation to clarify the anti-hyperuricemia mechanism of cortex phellodendri in mice

Integrating network pharmacology and experimental validation to clarify the anti-hyperuricemia mechanism of cortex phellodendri in mice

Aryl hydrocarbon receptor-dependent and -independent pathways mediate curcumin anti-aging effects

RNA sequencing analysis of early-stage atherosclerosis in vascular-on-a-chip and its application for comparing combustible cigarettes with heated tobacco products

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