Isolation and Characterization of Three Antihypertension Peptides from the Mycelia of <i>Ganoderma Lucidum</i> (Agaricomycetes)

Abstract

<i>Ganoderma lucidum</i> (<i>G. lucidum</i>) 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 <i>G. lucidum</i>. Notably, QLVP worked in a mixed-type manner against ACE with an IC₅₀ value of 127.9 μmol/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 <i>G. lucidum</i> mycelia, paving the way for the possible application of these peptides as potent drug candidates for treating hypertension.