A network pharmacology approach: Inhibition of the NF-κB signaling pathway contributes to the NASH preventative effect of an Oroxylum indicum seed extract in oleic acid-stimulated HepG2 cells and high-fat diet-fed rats

Sun, Wenlong; Li, Panpan; Yang, Bendong; Wang, Meng; Wang, Tianqi; Sun, Wenbo; Wang, Xudong; Zheng, Wei‐Long; Song, Xinhua; Li, Jingda

doi:10.1016/j.phymed.2021.153498

Cited by 18 publications

(6 citation statements)

References 36 publications

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“…A NASH cell model was generated using oleic acid to elucidate the roles of resmetirom, as discussed in a previous publication [ 21 ]. In this study, both human and mouse NAFLD/NASH cell models were established using HepG2 cells and NCTC 1469 cells, respectively.…”

Section: Resultsmentioning

confidence: 99%

Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner

Wang

et al. 2023

IJMS

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Resmetirom, a liver-directed, orally active agonist of THR-β, could play a favorable role in treating NASH, but little is known about the underlying mechanism. A NASH cell model was established to test the preventive effect of resmetirom on this disease in vitro. RNA-seq was used for screening, and rescue experiments were performed to validate the target gene of the drug. A NASH mouse model was used to further elucidate the role and the underlying mechanism of resmetirom. Resmetirom effectively eliminated lipid accumulation and decreased triglyceride (TG) levels. In addition, repressed RGS5 in the NASH model could be recovered by resmetirom treatment. The silencing of RGS5 effectively impaired the role of resmetirom. In the NASH mouse model, obvious gray hepatization, liver fibrosis and inflammation, and increased macrophage infiltration were observed in liver tissues, while resmetirom almost returned them to normal conditions as observed in the control group. Pathological experimental data also confirmed that resmetirom has great potential in NASH treatment. Finally, RGS5 expression was suppressed in the NASH mouse model, but it was upregulated by resmetirom treatment, while the STAT3 and NF-κB signaling pathways were activated in NASH but inhibited by the agent. Resmetirom could improve NASH by recovering RGS5 expression and subsequently inactivating the STAT3 and NF-κB signaling pathways.

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Section: Resultsmentioning

confidence: 99%

Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner

Wang

et al. 2023

IJMS

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“…Network pharmacology is increasingly used in the study of the complex mechanism of drug discovery and prediction of multi-componenttargets. [20] Sun et al [21] used network pharmacology and in vitro model experiments to confirm the therapeutic effect of Oroxylum indicum (Linn.) Kurz seeds extract on nonalcoholic steatohepatitis through NF-кB pathway.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic Effect of the Essential oils from Erigeron Canadensis L. on Human Cervical Cancer HeLa Cells in Vitro

et al. 2022

Chemistry & Biodiversity

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Erigeron Canadensis L. (E. canadensis) is a widely distributed invasive weed species in China. Potentially anticancer qualities may exist in its essential oils (EOs). The purpose of this study was to analyze the components of the EOs of E. canadensis and their effects on the normal liver cell lines L02 and the human cervical cancer cell lines HeLa. The EOs from the upper region of E. canadensis were prepared, its components were identified by GC/MS. Cell viability, cell morphology observation, AO/EB dual fluorescence staining assay, flow cytometry, mitochondrial membrane potential, western blot, caspase inhibitor test, and oxidative stress tests were used to investigate the impact of the EOs on HeLa cells. Network pharmacological analysis was employed to study the potential mechanism of the EOs in the treatment of cervical cancer. According to the findings, the EOs had 21 chemical components, of which limonene made up 65.68 %. After being exposed to the EOs, the cell viability of HeLa and L02 dramatically declined. The inhibition of EOs was more effective than that of limonene when used in an amount equivalent to that in the EOs. L02 cells were less susceptible to the cytotoxicity of EOs than HeLa cells were. Furthermore, EOs altered the cell cycle in HeLa cells and caused oxidative stress and apoptosis. Compared with the control group, the reactive oxygen species (ROS) levels increased in HeLa cells at first and then decreased, total superoxide dismutase (SOD) and catalase (CAT) activities in HeLa cells significantly decreased. G1 phase cells decreased whereas G2/M phase cells increased. The rate of apoptosis rose. Reduced mitochondrial membrane potential and Caspase-3, À 9, and À 12 protein expression were both observed. Nerolidol, dextroparaffinone, and α-pinene were shown to be the primary components for the suppression of HeLa cells, according to the results of the prediction of pharmacologic targets. In conclusion, findings of this study indicated the EOs may have the potential to curb the growth of cervical cancer cells. Further research is needed to explore the in vivo effect of EOs.

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“…Oroxin A or baicalein-7-O-glucoside (PubChem CID: 5320313), a typical avonoid, is the major component of Oroxylum indicum (L.) Kurz (Bignoniaceae). Our previous research in mice showed that oroxin A can decrease blood glucose, increase insulin sensitivity and improve lipid metabolism during the development from prediabetes to diabetes, suggesting that oroxin A might have a therapeutic effect on lipid metabolism disorders under conditions of insulin resistance (Sun et al, 2018(Sun et al, , 2021. However, insulin resistance might induce lipid metabolism, and improving insulin resistance may be an effective way to improve lipid metabolism.…”

Section: Introductionmentioning

confidence: 99%

Oroxin A from Oroxylum indicum improves disordered lipid metabolism by inhibiting SREBPs in oleic acid-induced HepG2 cells and high-fat diet-fed noninsulin-resistant rats

Cai,

Xu,

Dong

et al. 2023

Preprint

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Background Lipid metabolism disorders have become a major global public health issue. Due to the complexity of these diseases, much more research and many more drugs are needed to address them. Oroxin A, the major component of Oroxylum indicum (L.) Kurz (Bignoniaceae), can improve the lipid profiles of diabetic and insulin-resistant (IR) rats. Since insulin resistance is highly correlated with lipid metabolism, improving insulin resistance may also be an effective way to improve lipid metabolism. Thus, more research on the efficacy and mechanism of oroxin A under non-IR conditions is needed. Method In this research, we established lipid metabolism disorder rats by high-fat diet feeding and fatty HepG2 cell lines by oleic acid induction and evaluated the therapeutic effect and mechanism of oroxin A in vitro and in vivo by biochemical indicators, pathological staining, immunoblotting, and immunofluorescence staining. Results Oroxin A improved disordered lipid metabolism under non-IR conditions, improved plasma and hepatic lipid profiles, and enhanced the lipid-lowering action of atorvastatin. Additionally, oroxin A reduced the total triglyceride (TG) level by inhibiting SREBP1 expression and reducing the expression of ACC and FASN in vivo and in vitro. Oroxin A also reduced the total cholesterol (TC) level by inhibiting SREBP2 expression and reducing HMGCR expression in vivo and in vitro. In addition, oroxin A bound LDLR and increased AMPK phosphorylation. Conclusion Our results suggested that oroxin A may modulate the nuclear transcriptional activity of SREBPs by binding to LDLR proteins and increasing AMPK phosphorylation, thereby reducing lipid synthesis for lipid metabolism disorder treatment and prevention.

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A network pharmacology approach: Inhibition of the NF-κB signaling pathway contributes to the NASH preventative effect of an Oroxylum indicum seed extract in oleic acid-stimulated HepG2 cells and high-fat diet-fed rats

Cited by 18 publications

References 36 publications

Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner

Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner

Cytotoxic Effect of the Essential oils from Erigeron Canadensis L. on Human Cervical Cancer HeLa Cells in Vitro

Oroxin A from Oroxylum indicum improves disordered lipid metabolism by inhibiting SREBPs in oleic acid-induced HepG2 cells and high-fat diet-fed noninsulin-resistant rats

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