Luteolin modulates gene expression related to steroidogenesis, apoptosis, and stress response in rat LC540 tumor Leydig cells

Couture, Roxanne; Mora, Nathalie; Bittar, Sheiraz Al; Najih, Mustapha; Touaibia, Mohamed; Martin, Luc J.

doi:10.1007/s10565-019-09481-9

Cited by 38 publications

(29 citation statements)

References 81 publications

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“…Luteolin 3, a flavone, has been of growing interest in our laboratory for its potential in improving androgen production. Indeed, we have shown that luteolin (3) can increase Leydig cell steroidogenesis by upregulating StAR expression [24,25]. We also reported that luteolin (3) was able to activate Fdx1 (Ferredoxin 1) transcription in MA-10 Leydig cells [24].…”

Section: Flavonesmentioning

confidence: 81%

“…Quercetin (7) also contributes to the improvement of testosterone production in rats exposed to either cadmium chloride or the herbicide atrazine, where the enzyme activities of Hsd3b and Hsd17b3 are recovered [68,69]. Indeed, we have shown that quercetin (7) can activate the expression of Hsd3b in rat LC540 tumor Leydig cells [25]. An acetylated form of quercetin 7 Icariin (11) is a prenylated flavonol glycoside ( Figure 6) derived from kaempferol (10) and isolated from several species of plant belonging to the genus Epimedium, such as the horny goat weed.…”

Section: Flavonolsmentioning

confidence: 87%

“…Overall, apigenin (2) seems to increase steroidogenesis in Leydig cells mainly by increasing PKA-dependent StAR protein expression. However, such effect may not translate into increased testosterone production as we have also reported that apigenin (1) inhibits Cyp11a1 expression in LC540 tumor Leydig cells [25].…”

Section: Flavonesmentioning

confidence: 88%

“…In this cell model, Only luteolin (3) was able to increase the cAMP-dependent accumulation of progesterone from MA-10 Leydig cells, possibly through its positive regulation of StAR expression. Luteolin (3) also activated StAR expression and resulted in increased progesterone and testosterone syntheses in LC540 tumor Leydig cells [25]. Apigenin (2) and chrysin (1) have been shown to increase cAMP-dependent androgen production from testicular Leydig cells by increasing the StAR gene expression [26,27].…”

Section: Flavonesmentioning

confidence: 99%

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Improvement of Testicular Steroidogenesis Using Flavonoids and Isoflavonoids for Prevention of Late-Onset Male Hypogonadism

Martin

Touaibia

2020

Antioxidants

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Androgen production, being important for male fertility, is mainly accomplished by the Leydig cells from the interstitial compartment of the testis. Testosterone plays a critical role in testis development, normal masculinization, and the maintenance of spermatogenesis. Within seminiferous tubules, appropriate Sertoli cell function is highly dependent on testicular androgen levels and is essential to initiate and maintain spermatogenesis. During aging, testosterone production by the testicular Leydig cells declines from the 30s in humans at a rate of 1% per year. This review outlines the recent findings regarding the use of flavonoids and isoflavonoids to improve testosterone production, contributing to normal spermatogenesis and preventing age-related degenerative diseases associated with testosterone deficiency. With the cumulation of information on the actions of different flavonoids and isoflavonoids on steroidogenesis in Leydig cells, we can now draw conclusions regarding the structure-activity relationship on androgen production. Indeed, flavonoids having a 5,7-dihydroxychromen-4-one backbone tend to increase the expression of the steroidogenic acute regulatory protein (StAR), being critical for the entry of cholesterol into the mitochondria, leading to increased testosterone production from testis Leydig cells. Therefore, flavonoids and isoflavonoids such as chrysin, apigenin, luteolin, quercetin, and daidzein may be effective in delaying the initiation of late-onset hypogonadism associated with aging in males.

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Section: Flavonesmentioning

confidence: 81%

Section: Flavonolsmentioning

confidence: 87%

Section: Flavonesmentioning

confidence: 88%

Section: Flavonesmentioning

confidence: 99%

See 2 more Smart Citations

Improvement of Testicular Steroidogenesis Using Flavonoids and Isoflavonoids for Prevention of Late-Onset Male Hypogonadism

Martin

Touaibia

2020

Antioxidants

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“…Quercetin exhibits extremely antiproliferative, proapoptotic, and antimetastatic activities on NSCLC by enhancing cytotoxic efficacy [37], regulating the pathways related to the inhibition of snaildependent Akt activation and Snail-independent ADAM9 expression [38], mediating BCL2/BAX gene [39], and regulating-down IL-6/STAT-3 signals [40]. Similarity, Luteolin possesses a wide spectra of pharmacological actions, including anti-inflammation [41][42] [43], neuroprotective effect [43], protection against nonalcoholic steatohepatitis [44], anti-tumor [45] [46], anti-ischemia/reperfusion injury [47], and anti-diabetic cardiomyopathy [48]. A recent pharmacological study presented that luteolin modulates the expression of genes relevant to steroidogenesis, apoptosis, and stress response, such as Fas, Tp53, and PARP.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Identification of Pharmacological Mechanisms of Inula japonica Thunb. on Non-small Cell Lung Cancer

Qian¹,

Wang²,

Zhang³

et al. 2020

Preprint

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Background Inula japonica Thunb. (IJT) is an extensively applied herbal medicine for treating non-small cell lung cancer (NSCLC) due to its anti-asthma, antitussive, and expectorant properties. However, the mechanism of IJT against NSCLC remains to be elucidated. Methods Network pharmacology analysis was applied to determine the function mechanism of IJT against NSCLC. Databases were used to collect compounds and their related and known therapeutic targets. The compound–target (C–T) and target–target networks were then constructed to screen the kernel compounds and NSCLC-related targets of IJT. Moreover, the NSCLC-related targets of IJT were input in the DAVID Bioinformatics Resources (version 6.8) for Gene Ontology Biological Processes (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, the binding affinity of major compounds with the NSCLC-relevant targets of IJT was further verified by molecular docking. Results Two active compounds (quercetin and luteolin) and six putative targets (RAC-alpha serine/threonine-protein kinase, G1/S-specific cyclin-D1, cyclin-dependent kinase inhibitor 2A, epidermal growth factor receptor, receptor tyrosine-protein kinase erbB-2, and cellular tumor antigen p53) were screened as the effective compounds and NSCLC-related targets of IJT. GOBP and KEGG enrichment analysis indicated that NSCLC was the major pathway of IJT in the treatment of NSCLC and the mediation of apoptosis, cell cycle, tumor progression, and proliferation of biological processes, including the Ras, ERBB, MAPK, PI3K–Akt, calcium, and p53 signaling pathways. The results of molecular docking validated that 10 of the 12 pairs of compound-target had effective binding. Conclusions The mechanisms of IJT against NSCLC through multi-compounds, multi-targets, and multi-pathways were elucidated.

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Exploring the treatment of COVID‐19 with Yinqiao powder based on network pharmacology

Lin

Wang

Liu

et al. 2021

Phytotherapy Research

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Coronavirus disease 2019 (COVID‐19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). In China, Yinqiao powder is widely used to prevent and treat COVID‐19 patients with Weifen syndrome. In this study, the screening and verification of active ingredients, target selection and DisGeNET scoring, drug–ingredient–gene network construction, protein–protein interaction network construction, molecular docking and surface plasmon resonance (SPR) analysis, gene ontology (GO) functional analysis, gene tissue analysis, and kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were used to explore the active ingredients, targets, and potential mechanisms of Yinqiao powder in the treatment of COVID‐19. We also predicted the therapeutic effect of Yinqiao powder using TCM anti‐COVID‐19 (TCMATCOV). Yinqiao powder has a certain therapeutic effect on COVID‐19, with an intervention score of 20.16. Hesperetin, eriodictyol, luteolin, quercetin, and naringenin were the potentially effective active ingredients against COVID‐19. The hub‐proteins were interleukin‐6 (IL‐6), mitogen‐activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and tumor protein P53 (TP53). The potential mechanisms of Yinqiao powder in the treatment of COVID‐19 are the TNF signaling pathway, T‐cell receptor signaling pathway, Toll‐like receptor signaling pathway, and MAPK signaling pathway. This study provides a new perspective for discovering potential drugs and mechanisms of COVID‐19.

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Luteolin modulates gene expression related to steroidogenesis, apoptosis, and stress response in rat LC540 tumor Leydig cells

Cited by 38 publications

References 81 publications

Improvement of Testicular Steroidogenesis Using Flavonoids and Isoflavonoids for Prevention of Late-Onset Male Hypogonadism

Improvement of Testicular Steroidogenesis Using Flavonoids and Isoflavonoids for Prevention of Late-Onset Male Hypogonadism

Network Pharmacology-Based Identification of Pharmacological Mechanisms of Inula japonica Thunb. on Non-small Cell Lung Cancer

Exploring the treatment of COVID‐19 with Yinqiao powder based on network pharmacology

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