Liquiritigenin Confers Liver Protection by Enhancing NRF2 Signaling through Both Canonical and Non-canonical Signaling Pathways

Shi, Mei; Zhang, Jian; Li, Miaomiao; Zhao, Ying‐Zheng; Guo, Ying; Xu, Jiayi; Liu, Rongrong; Li, Zongfang; Ren, Dongmei; Liu, Pengfei

doi:10.1021/acs.jmedchem.3c00815

Cited by 6 publications

(4 citation statements)

References 51 publications

(96 reference statements)

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“…, quercetin and its derivatives, catechin, and epigallocatechin 3-glucuronide) and phenols ( e.g. , gingerol) have shown anti-inflammation properties. , Liquiritigenin, a natural flavonoid, has been reported to protect against oxidative hepatotoxicity . While this exploratory network pharmacology analysis did not allow for precise identification of target pathways, the disease–gene–metabolite interaction network revealed that fermentation-enhanced metabolites possess potential therapeutic effects in mitigating colitis via regulating inflammation, oxidative stress, and lipopolysaccharide response pathways.…”

Section: Discussionmentioning

confidence: 97%

Characterization of Eurotium cristatum Fermented Thinned Young Apple and Mechanisms Underlying Its Alleviating Impacts on Experimental Colitis

Song,

Zhou,

Liu

et al. 2024

J. Agric. Food Chem.

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A hundred million tons of young apples are thinned and discarded in the orchard per year, aiming to increase the yield and quality of apples. We fermented thinned young apples using a potential probiotic fungus, Eurotium cristatum, which notably disrupted the microstructure of raw samples, as characterized by the scanning electron microscope. Fermentation substantially altered the metabolite profiles of samples, which are predicted to alleviate colitis via regulating inflammatory response and response to lipopolysaccharide by using network pharmacology analysis. In vivo, oral gavage of water extracts of E. cristatum fermented young apples (E.YAP) effectively alleviated DSS-induced colitis, restored the histopathology damage, reduced the levels of inflammatory cytokines, and promoted colonic expressions of tight junction proteins. Moreover, E.YAP ameliorated gut dysbacteriosis by increasing abundances of Lactobacillus,Blautia, Muribaculaceae, and Prevotellaceae_UCG-001 while inhibiting Turicibacter, Alistipes, and Desulfovibrio. Importantly, E.YAP increased colonic bile acids, such as CA, TCA, DCA, TUDCA, and LCA, thereby alleviating colitis via PXR/NF-κB signaling. Furthermore, a synbiotic combination with Limosilactobacillus reuteri WX-94, a probiotic strain isolated from feces of healthy individuals with anti-inflammatory properties, augmented anticolitis capacities of E.YAP. Our findings demonstrate that E.YAP could be a novel, potent, food-based anti-inflammatory prebiotic for relieving inflammatory injuries.

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Section: Discussionmentioning

confidence: 97%

Characterization of Eurotium cristatum Fermented Thinned Young Apple and Mechanisms Underlying Its Alleviating Impacts on Experimental Colitis

Song,

Zhou,

Liu

et al. 2024

J. Agric. Food Chem.

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“…The nuclear factor erythroid 2-related factor 2 (Nrf2) functions as a critical regulator of intracellular antioxidant mechanisms and forms an association with the antioxidant response element (ARE), prompting the upregulation of antioxidant genes that include NAD(P)H quinone oxidoreductase 1 (NQO1) and (HO-1) [54]. Nrf2 is activated mainly by entering the cell nucleus, and the translocation of Nrf2 is regulated by two main pathways, the canonical and non-canonical mechanisms [55]. In the canonical pathway, the Keap1-Nedd8-Cul3-Rbx1 complex sequesters the Nrf2 protein and facilitates the transfer of ubiquitin (Ub) proteins to the Neh2 domain in Nrf2.…”

Section: Discussionmentioning

confidence: 99%

Verapamil Attenuates the Severity of Tendinopathy by Mitigating Mitochondrial Dysfunction through the Activation of the Nrf2/HO-1 Pathway

Wang,

Dong,

et al. 2024

Biomedicines

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Tendinopathy is a prevalent condition in orthopedics patients, exerting a profound impact on tendon functionality. However, its underlying mechanism remains elusive and the efficacy of pharmacological interventions continues to be suboptimal. Verapamil is a clinically used medicine with anti-inflammation and antioxidant functions. This investigation aimed to elucidate the impact of verapamil in tendinopathy and the underlying mechanisms through which verapamil ameliorates the severity of tendinopathy. In in vitro experiments, primary tenocytes were exposed to interleukin-1 beta (IL−1β) along with verapamil at a concentration of 5 μM. In addition, an in vivo rat tendinopathy model was induced through the localized injection of collagenase into the Achilles tendons of rats, and verapamil was injected into these tendons at a concentration of 5 μM. The in vitro findings highlighted the remarkable ability of verapamil to attenuate extracellular matrix degradation and apoptosis triggered by inflammation in tenocytes stimulated by IL−1β. Furthermore, verapamil was observed to significantly suppress the inflammation-related MAPK/NFκB pathway. Subsequent investigations revealed that verapamil exerts a remediating effect on mitochondrial dysfunction, which was achieved through activation of the Nrf2/HO-1 pathway. Nevertheless, the protective effect of verapamil was nullified with the utilization of the Nrf2 inhibitor ML385. In summary, the in vivo and in vitro results indicate that the administration of verapamil profoundly mitigates the severity of tendinopathy through suppression of inflammation and activation of the Nrf2/HO-1 pathway. These findings suggest that verapamil is a promising therapeutic agent for the treatment of tendinopathy, deserving further and expanded research.

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“…Studies have shown that Licochalcone A activates the Nrf2/HO-1/NF-κB axis, inhibits pyrodeath and inflammatomes, and relieves osteoarthritis [60]. ISL activates the Nrf2 pathway through both classical and unclassical pathways, enhances antioxidant activity, and protects against liver damage [61]. ISL alleviates liver toxicity caused by rhubarb by activating the Nrf2 pathway and enhancing phase II metabolic enzymes [62].…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Isoliquiritigenin and Licochalcone B on the Immunotoxicity of BDE-47: Antioxidant Effects Based on the Activation of the Nrf2 Pathway and Inhibition of the NF-κB Pathway

Dong,

Yang,

Gao

et al. 2024

Antioxidants

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2,2′,4,4′-Tetrabrominated biphenyl ether (BDE-47) is a polybrominated diphenyl ether (PBDE) homologue that is ubiquitous in biological samples and highly toxic to humans and other organisms. Prior research has confirmed that BDE-47 can induce oxidative damage in RAW264.7 cells, resulting in apoptosis and impaired immune function. The current study mainly focused on how Isoliquiritigenin (ISL) and Licochalcone B (LCB) might protect against BDE-47’s immunotoxic effects on RAW264.7 cells. The results show that ISL and LCB could increase phagocytosis, increase the production of MHC-II, and decrease the production of inflammatory factors (TNF-α, IL-6, and IL-1β) and co-stimulatory factors (CD40, CD80, and CD86), alleviating the immune function impairment caused by BDE-47. Secondly, both ISL and LCB could reduce the expressions of the proteins Bax and Caspase-3, promote the expression of the protein Bcl-2, and reduce the apoptotic rate, alleviating the apoptosis initiated by BDE-47. Additionally, ISL and LCB could increase the levels of antioxidant substances (SOD, CAT, and GSH) and decrease the production of reactive oxygen species (ROS), thereby counteracting the oxidative stress induced by BDE-47. Ultimately, ISL and LCB suppress the NF-κB pathway by down-regulating IKBKB and up-regulating IκB-Alpha in addition to activating the Nrf2 pathway and promoting the production of HO-1 and NQO1. To summarize, BDE-47 causes oxidative damage that can be mitigated by ISL and LCB through the activation of the Nrf2 pathway and inhibition of the NF-κB pathway, which in turn prevents immune function impairment and apoptosis. These findings enrich the current understanding of the toxicological molecular mechanism of BDE-47 and the detoxification mechanism of licorice.

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Liquiritigenin Confers Liver Protection by Enhancing NRF2 Signaling through Both Canonical and Non-canonical Signaling Pathways

Cited by 6 publications

References 51 publications

Characterization of Eurotium cristatum Fermented Thinned Young Apple and Mechanisms Underlying Its Alleviating Impacts on Experimental Colitis

Characterization of Eurotium cristatum Fermented Thinned Young Apple and Mechanisms Underlying Its Alleviating Impacts on Experimental Colitis

Verapamil Attenuates the Severity of Tendinopathy by Mitigating Mitochondrial Dysfunction through the Activation of the Nrf2/HO-1 Pathway

Protective Effects of Isoliquiritigenin and Licochalcone B on the Immunotoxicity of BDE-47: Antioxidant Effects Based on the Activation of the Nrf2 Pathway and Inhibition of the NF-κB Pathway

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