Trilobatin Possesses Protective Potentials on H2O2-Induced HepG2 Cells by Suppressing Oxidative Stress: Involvement of Nrf2/Keap1 Signal Pathway DOI Open Access

Yuhan Zhai,

Yu‐Qing Zhang, Yaping Li

et al.

American journal of biochemistry & biotechnology/American journal of biochemistry and biotechnology, Journal Year: 2023, Volume and Issue: 19(4), P. 336 - 346

Published: April 1, 2023

Trilobatin, a natural dihydrochalcone compound, possesses various biological activities. However, few investigations have been carried out on the mechanisms of trilobatin against oxidative stress. To comprehend effects and mechanism stress after hepatic injury, H2O2-induced HepG2 cells were used in this research. The results indicated that enhanced viability improved apoptosis morphology induced by H2O2. decrease Mitochondrial Membrane Potential (MMP) increase antioxidant-related enzymes involving Superoxide Dismutase (SOD), Glutathione Peroxidase (GSH-Px), Catalase (CAT), as well reduced levels alanine Aminotransferase (ALT) aspartate (AST), could be responsible for protective effect cells. Furthermore, Nuclear erythroid-2 Related Factor 2 (Nrf2)/Kelch-like ECH Associated Protein-1 (Keap-1) pathway was activated These has strong capacity inhibiting via Nrf2/Keap1 signaling pathway. This research implies might useful antioxidant to prevent liver diseases caused

Language: Английский

Modulation of the crosstalk between Keap1/Nrf2/HO-1 and NF-κB signaling pathways by Tomatidine protects against inflammation/oxidative stress-driven fulminant hepatic failure in mice DOI
Wesam H. Abdulaal, Ulfat M. Omar, Mustafa Zeyadi

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 130, P. 111732 - 111732

Published: Feb. 24, 2024

Language: Английский

Citations

7
Trilobatin suppresses aging-induced cognitive impairment by targeting SIRT2: Involvement of remodeling gut microbiota to mediate the brain-gut axis DOI
Dianyou Xie, Lin Mu,

Yun-mei Luo

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 130, P. 155744 - 155744

Published: May 15, 2024

Language: Английский

Citations

6
Targeting FDX1 by trilobatin to inhibit cuproptosis in doxorubicin‐induced cardiotoxicity DOI Open Access
Jiajia Wei,

Gongchun Lan,

Wenfang Zhang

et al.

British Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Abstract Background and Purpose Doxorubicin (DOX), an anthracycline chemotherapeutic agent, whose use is limited owing to its dose‐dependent cardiotoxicity. Mitochondrial oxidative stress plays a crucial role in the pathogenesis of DOX‐induced cardiotoxicity (DIC). Trilobatin (TLB), naturally occurring food additive, exhibits strong antioxidant properties, but cardioprotective effects DIC unclear. This study investigates effect TLB on DIC. Experimental Approach DOX was used generate vivo vitro model Echocardiography, enzyme‐linked immunosorbent assay (ELISA) haematoxylin eosin (H&E) staining were evaluate cardiac function these models. To identify targets TLB, RNA‐sequence analysis, molecular dynamics simulations, surface plasmon resonance binding assays protein immunoblotting techniques used. Transmission electron microscopy, along with dihydroethidium Mito‐SOX staining, conducted examine impact trilobatin mitochondrial stress. SiRNA transfection performed confirm ferredoxin 1 (FDX1) development. Key Results In mice, improved manner inhibited myocardial fibrosis mice. also attenuated dysfunction reduced found directly bind FDX1 suppresses cuproptosis after treatment, causing significant inhibition cuproptosis‐related proteins. Conclusions Implications first show that strongly inhibits by reducing controlling DOX‐mediated targeting FDX1. Therefore, as potential phytochemical candidate for ameliorating

Language: Английский

Citations

0
Trilobatin, a Naturally Occurring GPR158 Ligand, Alleviates Depressive-like Behavior by Promoting Mitophagy DOI Creative Commons
Lin Mu, Dianyou Xie,

Yunmei Luo

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: 73(9), P. 5163 - 5179

Published: Feb. 18, 2025

The G-protein-coupled receptor (GPR158), an orphan receptor, is highly expressed in the medial prefrontal cortex (mPFC) and identified as a novel therapeutic target for depression. Trilobatin naturally occurring food additive with potent neuroprotective properties. However, its pharmacological effects molecular mechanisms against depression remain unknown. Therefore, we explored whether trilobatin alleviates by targeting GPR158. Our results indicated that alleviated chronic unpredictable mild stress (CUMS)-induced depressive-like behavior mice. Mitophagy contributed to antidepressant-like effect of trilobatin, evidenced qRT-PCR array. Furthermore, up-regulated autophagy-associated protein expression, restored mitochondrial dynamic balance, inhibited oxidative mPFC mice after CUMS insult corticosterone-induced primary neuron injury. Intriguingly, directly bound GPR158 decreased level expression. deficiency attenuated through promoting mitophagy, while antidepressant was strengthened GPR158-deficient findings highlight GPR158-mediated mitophagy acts crucial reveal new-found property trilobatin: serving ligand safeguard from mitophagy.

Language: Английский

Citations

0
Biosynthesis and metabolic engineering of natural sweeteners DOI Creative Commons

Baochen Fan,

Xiqin Liang,

Yingxia Li

et al.

AMB Express, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 18, 2025

Natural sweeteners have attracted widespread attention because they are eco-friendly, healthy, low in calories, and tasty. The demand for natural is increasing together with the popularity of green, low-carbon, sustainable development. With development synthetic biology, microbial cell factories emerged as an effective method to produce large amounts sweeteners. This technology has significantly progressed recent years. review summarizes pathways enzymes related biosynthesis sweeteners, such mogrosides, steviol glycosides, glycyrrhizin, glycyrrhetinic acid, phlorizin, trilobatin, erythritol, sorbitol, mannitol, thaumatin, monellin, brazzein. Moreover, it focuses on research about production these using biology methods, aiming provide a reference future

Language: Английский

Citations

0
IL-33 facilitates endoplasmic reticulum stress and pyroptosis in LPS-stimulated ARDS model in vitro DOI Creative Commons

Pei-Long Li,

Hong-Min Fu,

Kai Liu

et al.

Molecular Immunology, Journal Year: 2025, Volume and Issue: 181, P. 102 - 112

Published: March 21, 2025

Inflammatory activation of pulmonary microvascular endothelial cells (PMVECs) initiated by endoplasmic reticulum stress (ERS) contributes to acute respiratory distress syndrome (ARDS). Interleukin 33 (IL-33) has pro-inflammatory and transcriptional regulatory effects. Therefore, this study intends investigate the effect IL-33 on ERS pyroptosis in hPMVEC. The hPMVEC-associated ARDS cell model was induced with lipopolysaccharide (LPS) treated 4-PBA (ERS inhibitor), thapsigargin activator), or neutralizing antibody. Western blot IF staining were performed analyze expression cell-cell junction-associated (Cx37, Cx40, Cx43, Occludin, Zo-1), ERS-associated (ATF6, IRE1a, p-Erk), pyroptosis-associated (NLRP3, IL-1β, IL-18) proteins. Bioinformatics identified differential ARDS-related datasets targets thapsigargin. highly expressed serum patients cohorts from multiple GEO (GSE237260, GSE216635, GSE89953, GSE263867, GSE5883), significantly correlated clinical features. decreased permeability levels, increased Cx37, Cx40 Cx43 levels model. antibody effectively augmented Zo-1, diminished ATF6, p-Erk, NLRP3, IL-18, ROS, Ca2 +. therapeutic antibodies reverted Moreover, Swiss Target Prediction Super-PRED databases obtained 140 122 targets, which had 14 intersections. These intersections associated immunity, inflammation, apoptosis, pyroptosis, Ca2+ homeostasis. Notably, CASP8 PTGS2 interacted these promotes thereby contributing barrier damage models. is a promising target for ARDS.

Language: Английский

Citations

0
Molecular Mechanisms of Pyroptosis in Non-alcoholic Steatohepatitis and Feasible Diagnosis and Treatment Strategies DOI Creative Commons
Dong Shang,

Wanning Xu,

Qing Zhao

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107754 - 107754

Published: April 1, 2025

Pyroptosis is a distinct form of cell death that plays critical role in intensifying inflammatory responses. It primarily occurs via the classical pathway, non-classical caspase-3/6/7/8/9-mediated pathways, and granzyme-mediated pathways. Key effector proteins involved pyroptosis process include gasdermin family pannexin-1 protein. intricately linked to onset progression non-alcoholic steatohepatitis (NASH). During development NASH, factors such as pyroptosis, innate immunity, lipotoxicity, endoplasmic reticulum stress, gut microbiota imbalance interact interweave, collectively driving disease progression. This review analyzes molecular mechanisms its pathogenesis NASH. Furthermore, it explores potential diagnostic therapeutic strategies targeting offering new avenues for improving diagnosis treatment

Language: Английский

Citations

0
Quercetin attenuates SiO2-induced ZBP-1-mediated PANoptosis in mouse neuronal cells via the ROS/TLR4/NF-κb pathway DOI
Meichen Liu,

Meichen Gao,

Xu Shi

et al.

Journal of Environmental Management, Journal Year: 2024, Volume and Issue: 370, P. 122948 - 122948

Published: Oct. 17, 2024

Language: Английский

Citations

3
Trilobatin, a Novel Naturally Occurring Food Additive, Ameliorates Alcoholic Liver Disease in Mice: Involvement of Microbiota–Gut–Liver Axis and Yap/Nrf2 Signaling Pathway DOI
Yang Yi,

You Yan,

Guiyu Zhan

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(43), P. 23819 - 23831

Published: Aug. 22, 2024

Trilobatin, a novel natural food additive, exerts protective effect on acute liver injury. However, whether Trilobatin can protect against alcoholic disease (ALD) has not been elucidated. This research is intended to ascertain the impact of ALD in mice and decipher potential underlying mechanisms. Lieber–DeCarli liquid alcohol diet was used induce mice, followed by administration (10, 20, 40 mg·kg–1·d–1) for 15 days. The results suggested that significantly alleviated ethanol-induced hepatic injury mice. Furthermore, RNA-Seq analysis revealed yes-associated protein (YAP) downregulation occurred after treatment. Mechanistically, directly bound YAP hindered its nuclear translocation, which activated Nrf2 pathway reduce pro-inflammatory cytokines oxidative stress. Intriguingly, 16S rDNA reshaped gut microbiota, reducing harmful bacteria increasing beneficial bacteria. It also enhanced tight junction proteins, defending damage intestinal barrier. These findings only highlight microbiota–gut–liver axis YAP/Nrf2 as crucial targets treat but reveal effectively protects ALD, at least partly, through modulating pathway.

Language: Английский

Citations

2
A Novel Bifunctional Fusion Protein (Anti-IL-17A-sST2) Protects against Acute Liver Failure, Modulating the TLR4/MyD88 Pathway and NLRP3 Inflammasome Activation DOI Creative Commons
Yu Bai,

Rongrui Zhou,

Xinlei Xie

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(5), P. 1118 - 1118

Published: May 17, 2024

Acute liver failure (ALF) is a serious inflammatory disorder with high mortality rates, which poses significant threat to human health. The IL-33/ST2 signal crucial regulator in inflammation responses associated lipopolysaccharide (LPS)-induced macrophages. IL-17A signaling pathway promotes the release of chemokines and cytokines, recruiting neutrophils T cells under LPS stimulation, thus facilitating responses. Here, potential therapeutic benefits neutralizing modulating ALF were investigated. A novel dual-functional fusion protein, anti-IL-17A-sST2, was constructed, displayed purity biological activities. administration anti-IL-17A-sST2 resulted anti-inflammatory mice, amelioration hepatocyte necrosis interstitial congestion, reduction TNF-α IL-6. Furthermore, injection downregulated expression TLR4 NLRP3 as well important molecules such MyD88, caspase-1, IL-1β. results suggest that reduced secretion factors, attenuated response, protected hepatic function by regulating TLR4/MyD88 inhibiting inflammasome, providing new approach for ALF.

Language: Английский

Citations

1