Ellagic acid attenuates testicular disruption in rheumatoid arthritis via targeting inflammatory signals, oxidative perturbations and apoptosis

Arab, Hany H.; Gad, Amany M.; Fikry, Ebtehal Mohammad; Eid, Ahmed M.

doi:10.1016/j.lfs.2019.117012

Cited by 35 publications

(19 citation statements)

References 36 publications

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“…Studies have also demonstrated the protective effect of quercetin on the reproductive system, and in vivo administration of quercetin could help to preserve sperm morphology and testicular functions (Nna et al, 2017;Yelumalai et al, 2019). Other bioactive compounds, such as ellagic acid, can also attenuate testicular disruption and sperm damage, which might be associated with targeting inflammatory signals, oxidative stress, and apoptosis (Türk et al, 2010;Arab et al, 2019). Guan et al study showed that Cuscutae Semen and Lycii Fructus out of WZYZP could improve testicular cell proliferation and inhibits apoptosis in rats with spermatogenic dysfunction FIGURE 6 | Effect of the WZYZP on the expression levels of Bcl-XL and Bax in testes tissues.…”

Section: Discussionmentioning

confidence: 99%

Wuzi Yanzong Pill—Based on Network Pharmacology and In Vivo Evidence—Protects Against Spermatogenesis Disorder via the Regulation of the Apoptosis Pathway

Chen

Ding

et al. 2020

Front. Pharmacol.

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The crisis of male infertility is an issue of human reproductive health worldwide. The Wuzi Yanzong pill (WZYZP) is a traditional Chinese medicine prescription that shows efficacy in kidney reinforcement and essence benefit to ameliorate male reproductive dysfunctions. However, the pharmacological mechanisms of the WZYZP on male infertility have not been investigated and clarified clearly. This study was designed to investigate the effects of the WZYZP on spermatogenesis disorder and explore its underlying pharmacological mechanisms. First, based on a network pharmacology study, 39 bioactive compounds and 40 targets of the WZYZP associated with spermatogenesis disorder were obtained, forming a tight compound-target network. Molecular docking tests showed tight docking of these compounds with predicted targeted proteins. The protein–protein interaction (PPI) network identified TP53, TNF, AKT1, Bcl-XL, Bcl-2, and IκBA as hub targets. The Kyoto Encyclopedia of Genes and Genomes pathway network and pathway-target-compound network revealed that the apoptosis pathway was enriched by multiple signaling pathways and multiple targets, including the hub targets. Subsequently, the chemical characterization of WZYZP was analyzed using liquid chromatography to quadrupole/time-of-flight mass spectrometry, and 40 compounds in positive ion mode and 41 compounds in negative ion mode in the WZYZP were identified. Furthermore, based on the prediction of a network pharmacology study, a rat model of spermatogenesis disorder was established to evaluate the curative role and underlying mechanisms of the WZYZP. The results showed that WZYZP treatment improved rat sperm quality and attenuated serum hormone levels, reversed histopathological damage of the testis, reduced cell apoptosis in testis tissues, and ameliorated the expression of the predicted hub targets (TP53, TNF-α, AKT1, NFκB, and IκBA) and the apoptosis related proteins (Bcl-XL, Bcl-2, Bax, Caspase 3, and Caspase 9). These results indicated that the WZYZP has a protective effect on spermatogenesis disorder, suggesting that it could be an alternative choice for male infertility therapy.

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Section: Discussionmentioning

confidence: 99%

Wuzi Yanzong Pill—Based on Network Pharmacology and In Vivo Evidence—Protects Against Spermatogenesis Disorder via the Regulation of the Apoptosis Pathway

Chen

Ding

et al. 2020

Front. Pharmacol.

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“…In addition, EA is found in food products conjugated with glycoside moieties [40,41]. Its potent health benefits are diverse, including antiproliferative [42], antioxidative, and anti-inflammatory [22] features, which can be beneficial for treating chronic diseases. However, the effects of EA on the representative chronic skin inflammatory disease AD have not previously been investigated.…”

Section: Discussionmentioning

confidence: 99%

“…EA has strong antioxidant and anticancer properties owing to its antiproliferative and apoptotic effects [17][18][19]. EA has anti-inflammatory effects in acute or chronic models of ulcerative colitis [20], Crohn's disease [21], and rheumatoid arthritis [22]. Recently, an increasing number of studies have investigated EA as a potential protective agent of the liver or skin via cell proliferation, apoptosis, DNA damage, angiogenesis, and inflammatory properties [23].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Effects of Ellagic Acid on Keratinocytes via MAPK and STAT Pathways

Gil

Hong

2021

IJMS

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Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by an impaired skin barrier and intense itchiness, which decreases the individual’s quality of life. No fully effective therapeutic agents have prevailed for AD due to an insufficient grasp of the complex etiology. Ellagic acid (EA), a natural compound, has anti-inflammatory properties in chronic diseases. The effects of EA on AD have not yet been explored. The present study investigated the effects of EA on TNF-α/IFN-γ-stimulated HaCaT keratinocytes and house dust mite-induced AD-like skin lesions in NC/Nga mice. Treatment with EA suppressed inflammatory responses in keratinocytes by regulating critical inflammatory signaling pathways, such as mitogen-activated protein kinases and signal transducers and activators of transcription. In vivo studies using a DfE-induced AD mouse model showed the effects of EA administration through ameliorated skin lesions via decremented histological inflammatory reactions. These results suggest that EA could be a potential therapeutic alternative for the treatment of AD by inhibiting inflammatory signaling pathways.

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“…It can also increase the level of testosterone by upregulating the level of testicular steroidogenic (StAR and 17β‐HSD) proteins. Furthermore, the anti‐apoptotic activity of ellagic acid could be attributed to the suppression of pro‐oxidant/pro‐inflammatory signals and regulation of apoptosis‐related markers (Arab et al., 2019). Moreover, p‐coumaric acid (Nishi et al., 2018) and α‐tocopherol (Elayapillai et al., 2017) can inhibit testicular dysfunction and improve fertility hormones by their antioxidant and anti‐apoptotic activities.…”

Section: Discussionmentioning

confidence: 99%

Ginger reserves testicular spermatogenesis and steroidogenesis in difenoconazole‐intoxicated rats by conducting oxidative stress, apoptosis and proliferation

et al. 2021

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Endocrine-disrupting chemicals (EDCs) can disrupt the endocrine system by interfering with the production, release, transport and metabolism or elimination of natural hormones (Kahn et al., 2020).Consequently, they may induce testicular dysgenesis syndrome by impairing the proliferation and development of testicular cells, which disrupts spermatogenesis (Chang et al., 2015) and steroidogenesis pathways (Sharma et al., 2020).Many classes of pesticides, especially fungicides, act as EDCs, and this behaviour depends on the level and duration of exposure (Mnif et al., 2011). The antifungal activity of triazoles occurs through

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Ellagic acid attenuates testicular disruption in rheumatoid arthritis via targeting inflammatory signals, oxidative perturbations and apoptosis

Cited by 35 publications

References 36 publications

Wuzi Yanzong Pill—Based on Network Pharmacology and In Vivo Evidence—Protects Against Spermatogenesis Disorder via the Regulation of the Apoptosis Pathway

Wuzi Yanzong Pill—Based on Network Pharmacology and In Vivo Evidence—Protects Against Spermatogenesis Disorder via the Regulation of the Apoptosis Pathway

Anti-Inflammatory Effects of Ellagic Acid on Keratinocytes via MAPK and STAT Pathways

Ginger reserves testicular spermatogenesis and steroidogenesis in difenoconazole‐intoxicated rats by conducting oxidative stress, apoptosis and proliferation

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