Investigation of the relationship between ergocristinine and vascular receptors DOI Creative Commons
Jensen E. Cherewyk,

Barry Blakley,

Ahmad Al‐Dissi

et al.

Toxicology Reports, Journal Year: 2023, Volume and Issue: 10, P. 604 - 611

Published: Jan. 1, 2023

Ergot alkaloids are secondary metabolites that exist in two configurations, the C-8-R-isomer (R-epimer), and C-8-S-isomer (S-epimer). Toxic effects of ergot, such as vasoconstriction, have been primarily attributed to R-epimer bioactivity, compared S-epimer. Recent studies demonstrated potential bioactivity S-epimers. Therefore, further cost-effective investigations S-epimers needed. The present study investigated S-epimer - vascular receptor binding relationship. An silico molecular docking approach, utilizing AutoDock Vina DockThor, was used determine if (ergocristinine) binds receptors compare affinity interactions corresponding (ergocristine) a structural analogue (lysergic acid amide). energy (kcal/mol) ergocristinine 9.7 or 11.0 serotonin (5-HT) 2 A 8.7 11.4 alpha adrenergic receptor, depending on software used. hydrogen bond formed between amino residues 5-HT sites, with lengths 3.10 Å 3.28 Å, respectively. Binding affinities among ligands each differed. Different may relate differences chemical structures. strong contribute observed physiological manifestations occur after ergot alkaloid exposure. results suggest investigation alkaloids.

Language: Английский

Deciphering Acetaminophen-Induced Hepatotoxicity: The Crucial Role of Transcription Factors like Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) as Genetic Determinants of Susceptibility to Drug-Induced Liver Injury DOI Open Access
Ankit P. Laddha, Hangyu Wu, José E. Manautou

et al.

Drug Metabolism and Disposition, Journal Year: 2024, Volume and Issue: 52(8), P. 740 - 753

Published: June 10, 2024

Acetaminophen (APAP) is the most commonly used over-the-counter medication throughout world. At therapeutic doses, APAP has potent analgesic and antipyretic effects. The efficacy safety of are influenced by multifactorial processes dependent upon dosing, namely frequency total dose. poisoning repeated ingestion supratherapeutic depletes glutathione stores in liver other organs capable metabolic bioactivation, leading to hepatocellular death due exhausted antioxidant defenses. Numerous genes, encompassing transcription factors signaling pathways, have been identified as playing pivotal roles toxicity, with being primary organ studied its central role metabolism injury. Nuclear factor erythroid 2-related 2 (NRF2) array downstream responsive genes crucial counteracting toxicity. NRF2, along negative regulator Kelch-like ECH-associated protein 1, plays a vital regulating intracellular redox homeostasis. This regulation significant modulating oxidative stress, inflammation, induced APAP. In this review, we provide an updated overview mechanisms through which NRF2 activation critically influence threshold for developing We also describe how genetically modified rodent models related underscoring significance response pathway. While focus, article comprehensively explores genetic involved phase I II APAP, pathways that contribute thereby providing holistic understanding landscape influencing susceptibility condition. SIGNIFICANCE STATEMENT: review summarizes elements underlying APAP-induced focusing on protective NRF2. delves into intricacies potential harm. It emphasizes need deeper insight molecular hepatotoxicity, especially interplay pathways.

Language: Английский

Citations

5
Thalidomide interaction with inflammation in idiopathic pulmonary fibrosis DOI Creative Commons

Nikitha Naomi Dsouza,

Varun Alampady,

Krishnaprasad Baby

et al.

Inflammopharmacology, Journal Year: 2023, Volume and Issue: 31(3), P. 1167 - 1182

Published: March 25, 2023

Abstract The “Thalidomide tragedy” is a landmark in the history of pharmaceutical industry. Despite limited clinical trials, there continuous effort to investigate thalidomide as drug for cancer and inflammatory diseases such rheumatoid arthritis, lepromatous leprosy, COVID-19. This review focuses on possibilities targeting inflammation by repurposing treatment idiopathic pulmonary fibrosis (IPF). Articles were searched from Scopus database, sorted, selected articles reviewed. content includes proven mechanisms action relevant IPF. Inflammation, oxidative stress, epigenetic are major pathogenic factors Transforming growth factor-β (TGF-β) biomarker Thalidomide an effective anti-inflammatory inhibiting TGF-β, interleukins (IL-6 IL-1β), tumour necrosis factor-α (TNF-α). binds cereblon, process that involved proposed mechanism specific cancers breast cancer, colon multiple myeloma, lung cancer. Cereblon activating AMP-activated protein kinase (AMPK)-TGF-β/Smad signalling, thereby attenuating fibrosis. past few years have witnessed improvement identification biomarkers diagnostic technologies respiratory diseases, partly because COVID-19 pandemic. Hence, investment trials with systematic plan can help repurpose Graphical

Language: Английский

Citations

11
Identification of natural Rutaecarpine as a potent tobacco mosaic virus (TMV) helicase candidate for managing intractable plant viral diseases DOI
Zhenxing Li, Jinhong Hu,

Rong‐Shuang Luo

et al.

Pest Management Science, Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 5, 2023

Abstract BACKGROUND Naturally occurring alkaloids are particularly suitable for use as pesticide precursors and further modifications due to their cost‐effectiveness, unique mechanism of action, tolerable degradation, environmental friendliness. The famous tobacco mosaic virus (TMV) is a persistent plant pathogenic that can parasitize many plants severely reduce crop production. To treat TMV disease, helicase acts crucial target by hydrolyzing adenosine triphosphate (ATP) provide energy double‐stranded RNA unwinding. RESULTS seek novel framework alkaloid leads targeting helicase, this work successfully established an efficient screening platform inhibitors based on natural alkaloids. In vivo activity screening, enzyme detection, binding assays showed Rutaecarpine from Evodia rutaecarpa (Juss.) Benth exhibited excellent inhibitory properties [dissociation constant ( K d ) = 1.1 μ m , half maximal concentration (IC 50 227.24 ] anti‐TMV ability. Molecular docking dynamic simulations depicted could stably bind in active pockets with low (Δ G −17.8 kcal/mol) driven hydrogen bonding hydrophobic interactions. CONCLUSION Given Rutaecarpine's laudable bioactivity structural modifiability, it serve privileged building block discovery.

Language: Английский

Citations

3
Investigation of the relationship between ergocristinine and vascular receptors DOI Creative Commons
Jensen E. Cherewyk,

Barry Blakley,

Ahmad Al‐Dissi

et al.

Toxicology Reports, Journal Year: 2023, Volume and Issue: 10, P. 604 - 611

Published: Jan. 1, 2023

Ergot alkaloids are secondary metabolites that exist in two configurations, the C-8-R-isomer (R-epimer), and C-8-S-isomer (S-epimer). Toxic effects of ergot, such as vasoconstriction, have been primarily attributed to R-epimer bioactivity, compared S-epimer. Recent studies demonstrated potential bioactivity S-epimers. Therefore, further cost-effective investigations S-epimers needed. The present study investigated S-epimer - vascular receptor binding relationship. An silico molecular docking approach, utilizing AutoDock Vina DockThor, was used determine if (ergocristinine) binds receptors compare affinity interactions corresponding (ergocristine) a structural analogue (lysergic acid amide). energy (kcal/mol) ergocristinine 9.7 or 11.0 serotonin (5-HT) 2 A 8.7 11.4 alpha adrenergic receptor, depending on software used. hydrogen bond formed between amino residues 5-HT sites, with lengths 3.10 Å 3.28 Å, respectively. Binding affinities among ligands each differed. Different may relate differences chemical structures. strong contribute observed physiological manifestations occur after ergot alkaloid exposure. results suggest investigation alkaloids.

Language: Английский

Citations

2