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

文献类型：期刊论文

作者Puopolo, Tess1,2; Chang, Tanran3,4; Liu, Chang1; Li, Huifang1; Liu, Xu5; Wu, Xian6; Ma, Hang1,2; Seeram, Navindra P.1,2
刊名BIOLOGY-BASEL
出版日期2022-10-01
卷号11期号:10页码:15
关键词Cannabis sativa L. cannflavin A kynurenine pathway tryptophan inflammation neurodegeneration binding affinity surface plasmon resonance
DOI10.3390/biology11101416
英文摘要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 mu M, 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 4.1x10(-)(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.
WOS关键词KYNURENINE PATHWAY ; THERAPEUTIC TARGET ; RO 61-8048
资助项目Rhode Island Institutional Development Award (IDeA) Network of Biomedical Research Excellence from the National Institute of General Medical Sciences of the National Institutes of Health[P20GM103430]
WOS研究方向Life Sciences & Biomedicine - Other Topics
语种英语
WOS记录号WOS:000872272200001
出版者MDPI
资助机构Rhode Island Institutional Development Award (IDeA) Network of Biomedical Research Excellence from the National Institute of General Medical Sciences of the National Institutes of Health
源URL[http://ir.ipe.ac.cn/handle/122111/55264]  
专题中国科学院过程工程研究所
通讯作者Ma, Hang; Seeram, Navindra P.
作者单位1.Univ Rhode Isl, Coll Pharm, Dept Biomed & Pharmaceut Sci, Bioact Bot Res Lab, Kingston, RI 02881 USA
2.Univ Rhode Isl, George & Anne Ryan Inst Neurosci, Kingston, RI 02881 USA
3.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Yunnan Hempmon Pharmaceut Co Ltd, Kunming 650032, Yunnan, Peoples R China
6.Miami Univ, Dept Kinesiol Nutr & Hlth, Oxford, OH 45056 USA
推荐引用方式
GB/T 7714		 Puopolo, Tess,Chang, Tanran,Liu, Chang,et al. Gram-Scale Preparation of Cannflavin A from Hemp (Cannabis sativa L.) and Its Inhibitory Effect on Tryptophan Catabolism Enzyme Kynurenine-3-Monooxygenase[J]. BIOLOGY-BASEL,2022,11(10):15.
APA Puopolo, Tess.,Chang, Tanran.,Liu, Chang.,Li, Huifang.,Liu, Xu.,...&Seeram, Navindra P..(2022).Gram-Scale Preparation of Cannflavin A from Hemp (Cannabis sativa L.) and Its Inhibitory Effect on Tryptophan Catabolism Enzyme Kynurenine-3-Monooxygenase.BIOLOGY-BASEL,11(10),15.
MLA Puopolo, Tess,et al."Gram-Scale Preparation of Cannflavin A from Hemp (Cannabis sativa L.) and Its Inhibitory Effect on Tryptophan Catabolism Enzyme Kynurenine-3-Monooxygenase".BIOLOGY-BASEL 11.10(2022):15.

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来源：过程工程研究所

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