Puerarin mitigates oxidative injuries, opening of mitochondrial permeability transition pores and pathological damage associated with liver and kidney in Xanthium strumarium-intoxicated rats

Alkaç, Zeliha Keskin; Korkak, Fatih Ahmet; Dağoğlu, Gürdal; İncili, Canan Akdeniz; Hark, Betül Dağoğlu; Tanyıldızı, Sadettin

doi:10.1016/j.toxicon.2022.04.004

Cited by 6 publications

(8 citation statements)

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“…The model and treatment groups were given 14 ml kg −1 ( Liang et al, 2021 ) 56°liquor by gavage, while the control and puerarin groups were given an equal volume of distilled water. After 30 min, the treatment and puerarin groups were given 200 mg kg −1 ( Keskin Alkaç et al, 2022 ) puerarin by gavage, and the same amount of distilled water was given to both the control and model groups. Afterward, the rats were placed in metabolic cages for observation, and urine was collected within 6 h. After 6 h, the rats were anesthetized with 1% sodium pentobarbital (6 ml kg −1 , ip), and blood was drawn from the inferior vena cava (3% heparin sodium anti-coagulation) before the kidneys and hypothalamus were removed.…”

Section: Methodsmentioning

confidence: 99%

Integrating network pharmacology and experimental verification to explore the mechanism of puerarin against oliguria in acute alcoholism

Wan

Huang

et al. 2022

Front. Pharmacol.

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Purpose: This study was designed to evaluate the pharmacological mechanisms of puerarin against oliguria in acute alcoholism via network pharmacology analysis combined with experimental verification.Methods: First, this study established an acute alcoholism rat model, compared the changes in urine volume in each group, and observed the therapeutic effect of puerarin by H&E staining, biochemical, RT-qPCR, and immunohistochemical analyses. Second, puerarin-related targets were searched in TCMS, PubChem, CNKI, Wanfang, PubMed, and GeenMedical Academic databases. Also, potential disease targets were obtained from the GeneCards, MalaCards, and NCBI-gene databases and genes with puerarin target gene intersections were screened out. The interaction network for co-predicted targets was obtained using the STRING database, and the core targets were imported into Cytoscape for visualization using DAVID Bioinformatics Resources 6.8. The essential genes were subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses to predict related biological processes and significant signaling pathways. Finally, molecular docking was used to examine the interaction of puerarin with key targets, and the core targets were validated further by RT-qPCR and Western blotting.Results: Compared to the model group, the urine volume of the rats was significantly increased after puerarin treatment, and the levels of anti-diuretic hormone (ADH) and aquaporin 2 (AQP2) expression were decreased. Searching the intersection of puerarin and acute alcoholism targets yielded 214 potential targets, 837 biological processes, and 185 signaling pathways involved. The molecular docking results indicated a good affinity between puerarin and key targets (cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element-binding protein (CREB), and c-Fos). RT-qPCR and Western blotting further verified that puerarin could down-regulate the expression of cAMP/PKA/CREB/c-Fos.Conclusion: This study identified the potential targets of puerarin against oliguria in rats with acute alcoholism using network pharmacology and animal experiments. The mechanism may be closely related to the cAMP signaling pathway.

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Section: Methodsmentioning

confidence: 99%

Integrating network pharmacology and experimental verification to explore the mechanism of puerarin against oliguria in acute alcoholism

Wan

Huang

et al. 2022

Front. Pharmacol.

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“… 2022 ; Keskin Alkaç et al. 2022 ). Moreover, mature (May–October) roots, stems, and leaves of common cockleburs lack ATR (Ozturk et al.…”

Section: Toxicity Of Atractyloside- and Carboxyatractyloside-containi...mentioning

confidence: 99%

“…2021 ; Keskin Alkaç et al. 2022 ). This finding is not surprising as the two glycosides are responsible for impairing mitochondrial oxidative phosphorylation (OXPHOS).…”

Section: Basics Of Atractyloside and Carboxyatractyloside Toxicities ...mentioning

confidence: 99%

“…2011 ; Keskin Alkaç et al. 2022 ). These data are consistent with independent studies showing that palmitoyl-coenzyme A (P-CoA), another direct negative regulator of AAC, increases reactive oxygen species (ROS) release (Ciapaite et al.…”

Section: Basics Of Atractyloside and Carboxyatractyloside Toxicities ...mentioning

confidence: 99%

“…In turn, puerarin, an isoflavone glycoside that merges antioxidant and MPT blockade properties, may also provide hope to patients intoxicated by X. strumarium (Keskin Alkaç et al. 2022 ).…”

Section: Basics Of Atractyloside and Carboxyatractyloside Toxicities ...mentioning

confidence: 99%

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Direct and indirect targets of carboxyatractyloside, including overlooked toxicity toward nucleoside diphosphate kinase (NDPK) and mitochondrial H ⁺ leak

Woyda-Płoszczyca

2023

Pharmaceutical Biology

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Context The toxicity of atractyloside/carboxyatractyloside is generally well recognized and commonly ascribed to the inhibition of mitochondrial ADP/ATP carriers, which are pivotal for oxidative phosphorylation. However, these glycosides may 'paralyze' additional target proteins. Objective This review presents many facts about atractyloside/carboxyatractyloside and their plant producers, such as Xanthium spp. (Asteraceae), named cockleburs. Methods Published studies and other information were obtained from databases, such as 'CABI - Invasive Species Compendium', 'PubMed', and 'The World Checklist of Vascular Plants', from 1957 to December 2022. The following major keywords were used: 'carboxyatractyloside', 'cockleburs', 'hepatotoxicity', 'mitochondria', 'nephrotoxicity', and ' Xanthium '. Results In the third decade of the twenty first century, public awareness of the severe toxicity of cockleburs is still limited. Such toxicity is often only perceived by specialists in Europe and other continents. Interestingly, cocklebur is among the most widely distributed invasive plants worldwide, and the recognition of new European stands of Xanthium spp. is provided here. The findings arising from field and laboratory research conducted by the author revealed that (i) some livestock populations may instinctively avoid eating cocklebur while grazing, (ii) carboxyatractyloside inhibits ADP/GDP metabolism, and (iii) the direct/indirect target proteins of carboxyatractyloside are ambiguous. Conclusions Many aspects of the Xanthium genus still require substantial investigation/revision in the future, such as the unification of the Latin nomenclature of currently distinguished species, bur morphology status, true fruit (achene) description and biogeography of cockleburs, and a detailed description of the physiological roles of atractyloside/carboxyatractyloside and the toxicity of these glycosides, mainly toward mammals. Therefore, a more careful interpretation of atractyloside/carboxyatractyloside data, including laboratory tests using Xanthium -derived extracts and purified toxins, is needed.

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Puerarin alleviates chronic renal failure-induced pyroptosis in renal tubular epithelial cells by targeting miR-342-3p/TGF-β/SMAD axis

Yang,

Li,

Wang

et al. 2023

Genes Genom

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Puerarin mitigates oxidative injuries, opening of mitochondrial permeability transition pores and pathological damage associated with liver and kidney in Xanthium strumarium-intoxicated rats

Cited by 6 publications

References 45 publications

Integrating network pharmacology and experimental verification to explore the mechanism of puerarin against oliguria in acute alcoholism

Integrating network pharmacology and experimental verification to explore the mechanism of puerarin against oliguria in acute alcoholism

Direct and indirect targets of carboxyatractyloside, including overlooked toxicity toward nucleoside diphosphate kinase (NDPK) and mitochondrial H ⁺ leak

Puerarin alleviates chronic renal failure-induced pyroptosis in renal tubular epithelial cells by targeting miR-342-3p/TGF-β/SMAD axis

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Puerarin mitigates oxidative injuries, opening of mitochondrial permeability transition pores and pathological damage associated with liver and kidney in Xanthium strumarium-intoxicated rats

Cited by 6 publications

References 45 publications

Integrating network pharmacology and experimental verification to explore the mechanism of puerarin against oliguria in acute alcoholism

Integrating network pharmacology and experimental verification to explore the mechanism of puerarin against oliguria in acute alcoholism

Direct and indirect targets of carboxyatractyloside, including overlooked toxicity toward nucleoside diphosphate kinase (NDPK) and mitochondrial H + leak

Puerarin alleviates chronic renal failure-induced pyroptosis in renal tubular epithelial cells by targeting miR-342-3p/TGF-β/SMAD axis

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Resources

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Direct and indirect targets of carboxyatractyloside, including overlooked toxicity toward nucleoside diphosphate kinase (NDPK) and mitochondrial H ⁺ leak