Gram-Scale Preparation of Cannflavin A from Hemp ( Cannabis sativa L.) and Its Inhibitory Effect on Tryptophan Catabolism Enzyme Kynurenine-3-Monooxygenase

by Selleckchem | Nov 01 2023

Inhibitors targeting kynurenine-3-monooxygenase (KMO), an enzyme in the neurotoxic kynurenine pathway (KP), are potential therapeutics for KP metabolites-mediated neuroinflammatory and neurodegenerative disorders. Although phytochemicals from Cannabis (C. sativa L.) have been reported to show modulating effects on enzymes involved in the KP metabolism, the inhibitory effects of C. sativa compounds, including phytocannabinoids and non-phytocannabinoids (i.e., cannflavin A; CFA), on KMO remain unknown. Herein, CFA (purified from hemp aerial material at a gram-scale) and a series of phytocannabinoids were evaluated for their anti-KMO activity. CFA showed the most active inhibitory effect on KMO, which was comparable to the positive control Ro 61-8048 (IC50 = 29.4 vs. 5.1 μM, respectively). Furthermore, a molecular docking study depicted the molecular interactions between CFA and the KMO protein and a biophysical binding assay with surface plasmon resonance (SPR) technique revealed that CFA bound to the protein with a binding affinity of 4.1×10−5 M. A competitive SPR binding analysis suggested that CFA and Ro 61-8048 bind to the KMO protein in a competitive manner. Our findings show that C. sativa derived phytochemicals, including CFA, are potential KMO inhibitors, which provides insight into the development of therapeutics targeting the KP and its related pathological conditions.

Comments:

The passage you provided highlights a study that investigated the inhibitory effects of compounds from Cannabis sativa, including both phytocannabinoids and non-phytocannabinoids, on kynurenine-3-monooxygenase (KMO), an enzyme involved in the neurotoxic kynurenine pathway (KP). The KP has been implicated in neuroinflammatory and neurodegenerative disorders. The researchers purified cannflavin A (CFA) from hemp aerial material and tested its inhibitory activity against KMO. They compared the inhibitory effect of CFA with a positive control compound called Ro 61-8048. The results showed that CFA exhibited significant inhibitory activity on KMO, similar to Ro 61-8048.

Additionally, the researchers conducted a molecular docking study to understand the interactions between CFA and the KMO protein. They found that CFA formed molecular interactions with the protein, supporting its inhibitory activity. Furthermore, a biophysical binding assay using surface plasmon resonance (SPR) revealed that CFA bound to the KMO protein with a binding affinity of 4.1×10−5 M. A competitive SPR binding analysis suggested that CFA and Ro 61-8048 competed for binding to the KMO protein.

Overall, this study demonstrates that phytochemicals derived from Cannabis sativa, including CFA, have the potential to inhibit KMO. These findings provide valuable insights into the development of therapeutics targeting the KP and associated neuroinflammatory and neurodegenerative disorders.