Crocin attenuates cisplatin-induced hepatotoxicity via TLR4/NF-κBp50 signaling and BAMBI modulation of TGF-β activity: Involvement of miRNA-9 and miRNA-29

Khedr, Lobna H.; Rahmo, Rania M.; Farag, Doaa Boshra; Schaalan, Mona F.; Magdoub, Hekmat M. El

doi:10.1016/j.fct.2020.111307

Cited by 22 publications

(10 citation statements)

References 37 publications

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“…Another adverse effect of CP is hepatoxicity, and in order to ameliorate this complication, some phytochemicals have been investigated. For instance, crocin administration significantly decreased CP-mediated hepatotoxicity via down-regulating NF-κB and TGF-β signaling pathways (Khedr, Rahmo, Farag, Schaalan, & El Magdoub, 2020). It has been suggested that reducing apoptosis and oxidative stress can also effectively ameliorate CP-mediated hepatotoxicity (Man et al, 2020).…”

Section: Hepatotoxicitymentioning

confidence: 99%

Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects

Abadi

Mirzaei

Mahabady

et al. 2021

Phytotherapy Research

111

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Section: Hepatotoxicitymentioning

confidence: 99%

Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects

Abadi

Mirzaei

Mahabady

et al. 2021

Phytotherapy Research

111

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“…Pretreatment with oral crocin improved renal histopathology, enhanced antioxidant defenses, and reduced oxidative stress via down‐regulation of TLR4 and IL6 expression (Abou‐Hany, Atef, Said, Elkashef, & Salem, 2018b). The hepatoprotective effect of crocin against cisplatin hepatotoxicity could be related to TLR4 antagonistic activity (Khedr et al, 2020). Downregulation in TLR4 expression as an effective mechanism for the antiinflammatory activity of crocin may be helpful in bleomycin‐induced pulmonary fibrosis treatment (Zaghloul, Said, Suddek, & Salem, 2019).…”

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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“…The compound T0873 exerts coccidiostatic activity against Eimeria tenella and Eimeria necatrix by arresting the asexual developmental stages of the parasite life-cycle [ 38 ]. Similarly, T2823 has been investigated in the treatment of cisplatin-induced hepatotoxicity via TLR4/NF-κBp50 signalling and BAMBI modulation of TGF-β activity [ 39 ]. T2801 plays multiple role as a nephrotoxin, a carcinogenic agent, a mutagen, a toxin and a metabolite too [ 40 , 41 , 42 , 43 , 44 ] (available experimental data regarding the other biological activities of the compounds and the activity profile is shown in Table S3 ).…”

Section: Resultsmentioning

confidence: 99%

Computational Design of Novel Allosteric Inhibitors for Plasmodium falciparum DegP

et al. 2021

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The serine protease, DegP exhibits proteolytic and chaperone activities, essential for cellular protein quality control and normal cell development in eukaryotes. The P. falciparum DegP is essential for the parasite survival and required to combat the oscillating thermal stress conditions during the infection, protein quality checks and protein homeostasis in the extra-cytoplasmic compartments, thereby establishing it as a potential target for drug development against malaria. Previous studies have shown that diisopropyl fluorophosphate (DFP) and the peptide SPMFKGV inhibit E. coli DegP protease activity. To identify novel potential inhibitors specific to PfDegP allosteric and the catalytic binding sites, we performed a high throughput in silico screening using Malaria Box, Pathogen Box, Maybridge library, ChEMBL library and the library of FDA approved compounds. The screening helped identify five best binders that showed high affinity to PfDegP allosteric (T0873, T2823, T2801, RJC02337, CD00811) and the catalytic binding site (T0078L, T1524, T2328, BTB11534 and 552691). Further, molecular dynamics simulation analysis revealed RJC02337, BTB11534 as the best hits forming a stable complex. WaterMap and electrostatic complementarity were used to evaluate the novel bio-isosteric chemotypes of RJC02337, that led to the identification of 231 chemotypes that exhibited better binding affinity. Further analysis of the top 5 chemotypes, based on better binding affinity, revealed that the addition of electron donors like nitrogen and sulphur to the side chains of butanoate group are more favoured than the backbone of butanoate group. In a nutshell, the present study helps identify novel, potent and Plasmodium specific inhibitors, using high throughput in silico screening and bio-isosteric replacement, which may be experimentally validated.

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Crocin attenuates cisplatin-induced hepatotoxicity via TLR4/NF-κBp50 signaling and BAMBI modulation of TGF-β activity: Involvement of miRNA-9 and miRNA-29

Cited by 22 publications

References 37 publications

Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects

Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects

Crocin molecular signaling pathways at a glance: A comprehensive review

Computational Design of Novel Allosteric Inhibitors for Plasmodium falciparum DegP

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