Renoprotective effect of isoliquiritigenin on cisplatin-induced acute kidney injury through inhibition of FPR2 in macrophage

Tan, Ruizhi; Xie, Ke-huan; Yuan, Ling; Lin, Xin; Zhu, Bingwen; Liu, Tongtong; Li, Wang

doi:10.1016/j.jphs.2021.10.001

Cited by 19 publications

(10 citation statements)

References 30 publications

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Section: Original Articlementioning

confidence: 99%

“…Flavonoids are considered to be the main biologically active components of licorice. Studies revealed that flavonoids exert different pharmacological functions, such as antiplatelet, anti-inflammatory, anticancer, antioxidative, antimicrobial, immunomodulatory, and cardioprotective effects ( 14 - 16 ). Ten chemicals have been identified from flavonoids, and one of them, isoliquiritigenin (ILTG), was found to have anti-inflammatory, antioxidative, and anticancer properties ( 17 - 19 ).…”

Section: Introductionmentioning

confidence: 99%

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The inhibitory effect of isoliquiritigenin on human platelets in vitro

Wu¹,

Cheng²,

Wang³

et al. 2023

Ann Transl Med

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Background: Platelets play important roles in several physiological and pathological processes. Multiple antiplatelet drugs have been developed for clinical practice. The active components of traditional Chinese medicine with antithrombotic effects are promising drugs to modulate platelet function. In our study, the antiplatelet effect of isoliquiritigenin (ILTG) and its mechanisms were examined.Methods: Human platelet-rich plasma and a washed platelet suspension were prepared. Platelets were stimulated using collagen, thrombin, or adenosine diphosphate (ADP). The platelet lumi-aggregometer was applied to detect the aggregation of platelets and the release of adenosine triphosphate (ATP). The expression of P-selectin and the activation of integrin αIIbβ3 were detected using flow cytometry. The spreading of platelets on a fibrinogen-coated surface was visualized using immunofluorescent staining. The mechanisms of the antiplatelet effect were investigated using Western blotting.Results: In this study, ILTG inhibited collagen-and thrombin-induced platelet aggregation, the release of dense granules and α-granules, and the activation of integrin αIIbβ3 in a dose-dependent manner. In addition, ILTG suppressed the spreading of platelets on immobilized fibrinogen. In collagen-activated platelets, ILTG markedly inhibited the expression of phosphorylation of phospholipase C gamma-2 (PLCγ2) and protein kinase B (Akt).Conclusions: These results indicated that ILTG could inhibit the collagen-and thrombin-induced platelet aggregation and granule release via the glycoprotein VI-mediated signal pathway in vitro.

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Section: Original Articlementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The inhibitory effect of isoliquiritigenin on human platelets in vitro

Wu¹,

Cheng²,

Wang³

et al. 2023

Ann Transl Med

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“…[41,42] It also inhibits the expression of xanthine oxidase, inducible nitric oxide synthase, cyclooxygenase, lipoxygenase, and prostaglandin E2. [41] Furthermore, IsoLQ has protective effects in in vitro and in vivo models of renal damage [41,[43][44][45][46] and regulates ER stress. [43,47,48] This study aimed to assess whether IsoLQ pretreatment could induce hormesis-mediated ER stress and attenuate oxidative stress and mitochondrial dysregulation in CP-induced nephrotoxicity in adult male rats.…”

Section: Introductionmentioning

confidence: 99%

Isoliquiritigenin pretreatment regulates ER stress and attenuates cisplatin‐induced nephrotoxicity in male Wistar rats

Gómez-Sierra

Ortega-Lozano

Rojas-Morales

et al. 2023

J Biochem & Molecular Tox

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Cisplatin (CP) is a chemotherapeutic drug used to treat solid tumors. However, studies have revealed its nephrotoxic effect. Oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction are involved in CP‐induced renal damage. Thus, preconditioning (hormetic effect) of ER stress is a strategy to prevent CP‐induced renal damage. On the other hand, isoliquiritigenin (IsoLQ) is recognized as a flavonoid with antioxidant properties and an inducer of ER stress. Therefore, we evaluated the ER stress‐inducing capacity of IsoLQ and its possible protective effect against CP‐induced nephrotoxicity in adult male Wistar rats. The findings reflected that IsoLQ pretreatment might decrease renal damage by reducing plasma creatinine and blood urea nitrogen levels in animals with CP‐induced nephrotoxicity. These may be associated with IsoLQ activating ER stress and unfolded protein response (UPR). We found increased messenger RNA levels of the ER stress marker glucose‐related protein 78 kDa (GRP78). In addition, we also found that pretreatment with IsoLQ reduced the levels of CCAAT/enhancer‐binding protein‐homologous protein (CHOP) and X‐box‐binding protein 1 (XBP1) in the renal cortex, reflecting that IsoLQ can regulate the UPR and activation of the apoptotic pathway. Moreover, this preconditioning with IsoLQ of ER stress had oxidative stress‐regulatory effects, as it restored the activity of glutathione peroxidase and glutathione reductase enzymes. Finally, IsoLQ modifies the protein expression of mitofusin 2 (Mfn‐2) and voltage‐dependent anion channel (VDAC). In conclusion, these data suggest that IsoLQ pretreatment has a nephroprotective effect; it could functionally regulate the ER and mitochondria and reduce CP‐induced renal damage by attenuating hormesis‐mediated ER stress.

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“…Isoliquiritigenin (ISL), a flavonoid derived from licorice, exhibits numerous pharmaceutical properties. For instance, ISL has been demonstrated to attenuate adipose tissue inflammation [ 17 ], alleviate diabetic symptoms [ 18 ], protect the kidneys during chemotherapy [ 19 ], and exhibit anticancer activities [ 20 ]. However, mechanisms underlying stemness inhibition and tumor microenvironment regulation in gastric cancer remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Isoliquiritigenin Inhibits Gastric Cancer Stemness, Modulates Tumor Microenvironment, and Suppresses Tumor Growth through Glucose-Regulated Protein 78 Downregulation

et al. 2022

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Chemotherapy is the treatment of choice for gastric cancer; however, the currently available therapeutic drugs for treatment have limited efficacy. Cancer stemness and the tumor microenvironment may play crucial roles in tumor growth and chemoresistance. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum chaperone facilitating protein folding and cell homeostasis during stress and may participate in chemoresistance. Isoliquiritigenin (ISL) is a bioactive flavonoid found in licorice. In this study, we demonstrated the role of GRP78 in gastric cancer stemness and evaluated GRP78-mediated stemness inhibition, tumor microenvironment regulation, and chemosensitivity promotion by ISL. ISL not only suppressed GRP78-mediated gastric cancer stem cell–like characteristics, stemness-related protein expression, and cancer-associated fibroblast activation but also gastric tumor growth in xenograft animal studies. The findings indicated that ISL is a promising candidate for clinical use in combination chemotherapy.

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Renoprotective effect of isoliquiritigenin on cisplatin-induced acute kidney injury through inhibition of FPR2 in macrophage

Cited by 19 publications

References 30 publications

The inhibitory effect of isoliquiritigenin on human platelets in vitro

The inhibitory effect of isoliquiritigenin on human platelets in vitro

Isoliquiritigenin pretreatment regulates ER stress and attenuates cisplatin‐induced nephrotoxicity in male Wistar rats

Isoliquiritigenin Inhibits Gastric Cancer Stemness, Modulates Tumor Microenvironment, and Suppresses Tumor Growth through Glucose-Regulated Protein 78 Downregulation

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