期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 67, 期 29, 页码 8149-8159出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.9b02276
关键词
Ganoderma lucidum; ACE inhibitory peptide; submerged fermentation; molecular dynamics simulation; antihypertension
资金
- National Natural Scientific Foundation of China [31772374, 21804145]
- Intergovernmental Key Project of the International Science and Technology Cooperation Research of China [2017YFE0108100]
- Foundation of Hunan International Cooperation Base of Scientific and Technological Innovation [2018WK4008]
- Hunan Natural Science Foundation [2017JJ2406]
- Outstanding Youth Project of Hunan Forestry Technology Innovation Plan [XLK201944]
Ganoderma lucidum (G. lucidum) has been widely used in Asia to treat hypertension, but the active substances responsible for its antihypertensive effects remain unclear. Using the well-established angiotensin I-converting enzyme (ACE) as a target, we identified three ACE inhibitory peptides (ACEIPs), Gln-Leu-Val-Pro (QLVP), Gln-Asp-Val-Leu (QDVL), and Gln-Leu-Asp-Leu (QLDL), which account for the antihypertensive activity of G. lucidum. Notably, QLVP worked in a mixed-type manner against ACE with an IC50 value of 127.9 mu mol/L. Molecular dynamics simulation suggested that the potent charge energy of QLVP, which interacted with Gln242 and Lys472 of ACE via a hydrogen bond and a salt bridge, potentially contributed to ACE inhibitory activity. Moreover, QLVP markedly activated angiotensin I-mediated phosphorylation of endothelial nitric oxide synthase in human umbilical vein endothelial cells and partly reduced mRNA and protein expression of the vasoconstrictor factor endothelin-1. This is the first report of the antihypertensive activity of small ACEIPs originating from G. lucidum mycelia, paving the way for the possible application of these peptides as potent drug candidates for treating hypertension.
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