<i>In vitro</i> Anti‐Inflammatory Potency of Sanguinarine and Chelerythrine via Interaction with Glucocorticoid Receptor

Zhang, Jie; Liang, Yuan; Li, Ren; Zhang, Tiehua

doi:10.2991/efood.k.210118.001

Cited by 18 publications

(5 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FP results stated that both compounds could bind well to the glucocorticoid receptors (GR) receptors with potent affinities, while LR results showed that chelerythrine did not stimulate GR transcription in HeLa cells, nor did sanguinarine. In the same study, both chelerythrine and sanguinarine showed comparable TNF-α inhibitory activity to dexamethasone as a standard drug in RAW 264.7 cells, indicating their remarkable anti-inflammatory effects [ 18 ]. In another study, Xiao-Feng Niu et al, evaluated the anti-inflammatory activities and mechanisms of action of this alkaloid in vivo and in vitro .…”

Section: Chelerythrine Has Anti-inflammatory Effectsmentioning

confidence: 99%

Therapeutic potential of chelerythrine as a multi-purpose adjuvant for the treatment of COVID-19

et al. 2021

View full text Add to dashboard Cite

Multifunctional nature of phytochemicals and their chemical diversity has attracted attention to develop leads originated from nature to fight COVID-19. Pharmacological activities of chelerythrine and its congeners have been studied and reported in the literature. This compound simultaneously has two key therapeutic effects for the treatment of COVID-19, antiviral and anti-inflammatory activities. Chelerythrine can prevent hyper-inflammatory immune response through regulating critical signaling pathways involved in SARS-CoV-2 infection, such as alteration in Nrf2, NF-κB, and p38 MAPK activities. In addition, chelerythrine has a strong protein kinase C-α/-β inhibitory activity suitable for cerebral vasospasm prevention and eryptosis reduction, as well as beneficial effects in suppressing pulmonary inflammation and fibrosis. In terms of antiviral activity, chelerythrine can fight with SARS-CoV-2 through various mechanisms, such as direct-acting mechanism, viral RNA-intercalation, and regulation of host-based antiviral targets. Although chelerythrine is toxic in vitro, the in vivo toxicity is significantly reduced due to its structural conversion to alkanolamine. Its multifunctional action makes chelerythrine a prominent compound for the treatment of COVID-19. Considering precautions related to the toxicity at higher doses, it is expected that this compound is useful in combination with proper antivirals to reduce the severity of COVID-19 symptoms.

show abstract

Section: Chelerythrine Has Anti-inflammatory Effectsmentioning

confidence: 99%

Therapeutic potential of chelerythrine as a multi-purpose adjuvant for the treatment of COVID-19

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Chelerythrine is a widely dispersed plant benzo[c]phenanthridine alkaloid (Table 1), with a range of biological activities including anti-inflammatory and anti-proliferative (anticancer) effects [71,72]. Chelerythrine is a promising dual cholinesterase inhibitor (IC 50 s of 1.54 µM and 10.34 µM for human AChE and BuChE, respectively) that is also able to inhibit Aβ aggregation [37].…”

Section: Discussionmentioning

confidence: 99%

In Silico Design of Dual-Binding Site Anti-Cholinesterase Phytochemical Heterodimers as Treatment Options for Alzheimer’s Disease

Amat-ur-Rasool

Ahmed

Hasnain

et al. 2021

CIMB

View full text Add to dashboard Cite

The number of patients with neurodegenerative diseases, particularly Alzheimer’s disease (AD), continues to grow yearly. Cholinesterase inhibitors (ChEIs) represent the first-line symptomatic drug treatment for mild-to-moderate AD; however, there is an unmet need to produce ChEIs with improved efficacy and reduced side effects. Herein, phytochemicals with reported anti-acetylcholinesterase (AChE) activity were ranked in silico for their anti-AChE potential. Ligands with a similar or higher binding affinity to AChE than galantamine were then selected for the design of novel dual-binding site heterodimeric drugs. In silico molecular docking of heterodimers with the target enzymes, AChE and butyrylcholinesterase (BuChE), were performed, and anti-cholinesterase binding affinities were compared with donepezil. Drug-likeliness properties and toxicity of the heterodimers were assessed using the SwissADME and ProTox-II webservers. Nine phytochemicals displayed similar or higher binding affinities to AChE than galantamine: sanguinarine > huperzine A > chelerythrine > yohimbine > berberine > berberastine > naringenin > akuammicine > carvone. Eleven heterodimeric ligands were designed with phytochemicals separated by four- or five-carbon alkyl-linkers. All heterodimers were theoretically potent AChE and BuChE dual-binding site inhibitors, with the highest affinity achieved with huperzine-4C-naringenin, which displayed 34% and 26% improved affinity to AChE and BuChE, respectively, then the potent ChEI drug, donepezil. Computational pharmacokinetic and pharmacodynamic screening suggested that phytochemical heterodimers would display useful gastrointestinal absorption and with relatively low predicted toxicity. Collectively, the present study suggests that phytochemicals could be garnered for the provision of novel ChEIs with enhanced drug efficacy and low toxicity.

show abstract

“…Based on the optimal conformation of 20( S )-Rh2 obtained from molecular docking, a 20 ns molecular dynamics simulation was performed using GROMACS 2019 [ 24 ]. The topologies of EGFR and 20( S )-Rh2 were developed using CHARMM36 all-atom force field and CGenFF server, respectively [ 25 , 26 ].…”

Section: Methodsmentioning

confidence: 99%

Identification of 20(S)-Ginsenoside Rh2 as a Potential EGFR Tyrosine Kinase Inhibitor

Liang

Zhao

Zou

et al. 2022

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

As the main active ingredients of Panax ginseng, ginsenosides possess numerous bioactivities. Epidermal growth factor receptor (EGFR) was widely used as a valid target in anticancer therapy. Herein, the EGFR targeting activities of 20(S)-ginsenoside Rh2 (20(S)-Rh2) and the relationship of their structure-activity were investigated. Homogeneous time-resolved fluorescence assay showed that 20(S)-Rh2 significantly inhibited the activity against EGFR kinase. 20(S)-Rh2 was confirmed to effectively inhibited cell proliferation in a dose-dependent manner by MTT assay. Furthermore, quantitative real-time PCR and western blotting analysis revealed that 20(S)-Rh2 inhibited A549 cells growth via the EGFR-MAPK pathway. Meanwhile, 20(S)-Rh2 could promote cell apoptosis, block cell cycle, and reduce cell migration of A549 cells, respectively. In silico, the result suggested that both hydrophobic interactions and hydrogen-bonding interactions could contribute to stabilize their binding. Molecular dynamics simulation showed that the side chain sugar moiety of 20(S)-Rh2 was too flexible to be fixed at the active site of EGFR. Collectively, these findings suggested that 20(S)-Rh2 might serve as a potential EGFR tyrosine kinase inhibitor.

show abstract

In vitro Anti‐Inflammatory Potency of Sanguinarine and Chelerythrine via Interaction with Glucocorticoid Receptor

Cited by 18 publications

References 31 publications

Therapeutic potential of chelerythrine as a multi-purpose adjuvant for the treatment of COVID-19

Therapeutic potential of chelerythrine as a multi-purpose adjuvant for the treatment of COVID-19

In Silico Design of Dual-Binding Site Anti-Cholinesterase Phytochemical Heterodimers as Treatment Options for Alzheimer’s Disease

Identification of 20(S)-Ginsenoside Rh2 as a Potential EGFR Tyrosine Kinase Inhibitor

Contact Info

Product

Resources

About