Chemo-preventive effect of crocin against experimentally-induced hepatocarcinogenesis via regulation of apoptotic and Nrf2 signaling pathways

Elsherbiny, Nehal M.; Eisa, Nada H.; El‐Sherbiny, Mohamed; Said, Eman

doi:10.1016/j.etap.2020.103494

Cited by 17 publications

(6 citation statements)

References 48 publications

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“…Under baseline conditions, the Keap1 repressor protein binds to the inactive NRF-2 factor present in the cytoplasm. In the presence of ROS, Keap1 releases Nrf-2 factor which translocates to the nucleus, and interacts with the ARE, inducing increased expression of various effectors including HO-1, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione (GPx), and superoxide dismutase (SOD), resulting in an antioxidant response [49,50].…”

Section: Discussionmentioning

confidence: 99%

Nanogold Particles Suppresses 5-Flurouracil-Induced Renal Injury: An Insight into the Modulation of Nrf-2 and Its Downstream Targets, HO-1 and γ-GCS

et al. 2021

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The development of the field of nanotechnology has revolutionized various aspects in the fields of modern sciences. Nano-medicine is one of the primary fields for the application of nanotechnology techniques. The current study sheds light on the reno-protective impacts of gold nano-particles; nanoGold (AuNPs) against 5-flurouracil (5-FU)-induced renal toxicity. Indeed, the use of 5-FU has been associated with kidney injury which greatly curbs its therapeutic application. In the current study, 5-FU injection was associated with a significant escalation in the indices of renal injury, i.e., creatinine and urea. Alongside this, histopathological and ultra-histopathological changes confirmed the onset of renal injury. Both gene and/or protein expression of nuclear factor erythroid 2–related factor 2 (Nrf-2) and downstream antioxidant enzymes revealed consistent paralleled anomalies. AuNPs administration induced a significant renal protection on functional, biochemical, and structural levels. Renal expression of the major sensor of the cellular oxidative status Nrf-2 escalated with a paralleled reduction in the renal expression of the other contributor to this axis, known as Kelch-like ECH-associated protein 1 (Keap-1). On the level of the effector downstream targets, heme oxygenase 1 (HO-1) and gamma-glutamylcysteine synthetase (γ-GCS) AuNPs significantly restored their gene and protein expression. Additionally, combination of AuNPs with 5-FU showed better cytotoxic effect on MCF-7 cells compared to monotreatments. Thus, it can be inferred that AuNPs conferred reno-protective impact against 5-FU with an evident modulatory impact on Nrf-2/Keap-1 and its downstream effectors, HO-1 and γ-GCS, suggesting its potential use in 5-FU regimens to improve its therapeutic outcomes and minimize its underlying nephrotoxicity.

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Section: Discussionmentioning

confidence: 99%

Nanogold Particles Suppresses 5-Flurouracil-Induced Renal Injury: An Insight into the Modulation of Nrf-2 and Its Downstream Targets, HO-1 and γ-GCS

et al. 2021

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“…Furthermore, crocin in the in vivo study showed a chemo‐preventive effect against thioacetamide‐induced hepatocarcinogenesis through up‐regulation in the Nrf2 pathway and HO‐1 expression. Crocin administration modulated oxidative/apoptotic biomarkers, including p53 and caspase‐8, Keap‐1, c‐JNK, and TNF‐related apoptosis‐inducing ligand (Elsherbiny, Eisa, El‐Sherbiny, & Said, 2020). In addition, Akbari and coworkers confirmed the hepatoprotection activity of crocin via activation Nrf2 pathway.…”

Section: Introductionmentioning

confidence: 99%

Crocin molecular signaling pathways at a glance: A comprehensive review

Boozari

Rahbardar

2022

Phytotherapy Research

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Crocin is a hydrophilic carotenoid that is synthesized in the flowers of the Crocus genus. Numerous in vitro and in vivo research projects have been published about the biological and pharmacological properties and toxicity of crocin. Crocin acts as a memory enhancer, anxiolytic, aphrodisiac, antidepressant, neuroprotective, and so on. Here, we introduce an updated and comprehensive review of crocin molecular mechanisms based on previously examined and mentioned in the literature. Different studies confirmed the significant effect of crocin to control pathological conditions, including oxidative stress, inflammation, metabolic disorders, neurodegenerative disorders, and cancer. The neuroprotective effect of crocin could be related to the activation of phosphatidylinositol 3‐kinase/protein kinase B (PI3K/AKT)/mammalian target of rapamycin (mTOR), Notch, and cyclic‐AMP response element‐binding protein signaling pathways. The crocin also protects the cardiovascular system through the inhibitory effect on toll‐like receptors. The regulatory effect of crocin on PI3K/AKT/mTOR, AMP‐activated protein kinase, mitogen‐activated protein kinases (MAPK), and peroxisome proliferator‐activated receptor pathways can play an effective role in the treatment of metabolic disorders. The crocin has anticancer activity through the PI3K/AKT/mTOR, MAPK, vascular endothelial growth factor, Wnt/β‐catenin, and Janus kinases‐signal transducer and activator of transcription suppression. Also, the nuclear factor‐erythroid factor 2‐related factor 2 and p53 signaling pathway activation may be effective in the anticancer effect of crocin. Finally, among signaling pathways regulated by crocin, the most important ones seem to be those related to the regulatory effect on the PI3K/AKT/mTOR pathway.

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“…Recently, crocin administration reduced experimentally induced hepatocellular carcinoma by modulating the oxidative/apoptotic pathway. The crocin-induced hepatic expression of Nrf2 promoted downstream modifications in the endogenous KEAP-1 and HO-1 signalling pathway that regulates various apoptotic modulators such as Bcl-2, Bax, caspase-8, TRAIL, p53, and cJNK (Elsherbiny et al, 2020). These results showed that saffron, in combination with other commonly used chemotherapeutic drugs, could be used against liver cancer.…”

Section: Activities Against Cancersmentioning

confidence: 88%

Therapeutic potential of saffron, and its chemical components in the treatment of cancers and cardiovascular disorders – a review

Khan¹,

Muhamad²,

Taha³

et al. 2021

IFRJ

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Crocus sativus L., a medicinally important species of the Iridaceae family which produces the herb saffron, plays an effective role in combating various pathogenic disorders including cancers and cardiovascular diseases. Apart from its conventional colorant and aroma-inducing attributes, various phytochemical compounds associated with saffron are now being intensively studied. More than 300 phytochemical compounds, derived from saffron stigmas alone, belong to various classes of secondary metabolites such as carotenoids, terpenoids, flavonoids, and anthocyanins; and they have immense therapeutic applications. Furthermore, pharmacogenomic studies of saffron extracts have revealed promising biocompatible and anticancer potentials against various drug-resistant cell lines which reduce cellular division and proliferation of malignant cells. Keeping in view with the numerous pharmacological properties associated with saffron, the present review explicitly discusses the role of its elemental contents in the prevention and treatment of various cancers and cardiovascular ailments.

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Chemo-preventive effect of crocin against experimentally-induced hepatocarcinogenesis via regulation of apoptotic and Nrf2 signaling pathways

Cited by 17 publications

References 48 publications

Nanogold Particles Suppresses 5-Flurouracil-Induced Renal Injury: An Insight into the Modulation of Nrf-2 and Its Downstream Targets, HO-1 and γ-GCS

Nanogold Particles Suppresses 5-Flurouracil-Induced Renal Injury: An Insight into the Modulation of Nrf-2 and Its Downstream Targets, HO-1 and γ-GCS

Crocin molecular signaling pathways at a glance: A comprehensive review

Therapeutic potential of saffron, and its chemical components in the treatment of cancers and cardiovascular disorders – a review

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