Isolation and Characterization of Three Antihypertension Peptides from the Mycelia of Ganoderma Lucidum (Agaricomycetes)

Qiang Wu; Yong Li; Kuan Peng; Xiao Ling Wang; Zhongyang Ding; Liming Liu; Peng Xu; Gao Qiang Liu

doi:10.1021/acs.jafc.9b02276

Isolation and Characterization of Three Antihypertension Peptides from the Mycelia of Ganoderma Lucidum (Agaricomycetes)

Qiang Wu, Yong Li, Kuan Peng, Xiao Ling Wang^*, Zhongyang Ding, Liming Liu, Peng Xu, Gao Qiang Liu

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

Abstract

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 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 G. lucidum mycelia, paving the way for the possible application of these peptides as potent drug candidates for treating hypertension.

Original language	English
Pages (from-to)	8149-8159
Number of pages	11
Journal	Journal of Agricultural and Food Chemistry
Volume	67
Issue number	29
DOIs	https://doi.org/10.1021/acs.jafc.9b02276
State	Published - 27 Jun 2019
Externally published	Yes

Keywords

ACE inhibitory peptide
Ganoderma lucidum
antihypertension
molecular dynamics simulation
submerged fermentation

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10.1021/acs.jafc.9b02276

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title = "Isolation and Characterization of Three Antihypertension Peptides from the Mycelia of Ganoderma Lucidum (Agaricomycetes)",

abstract = "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 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 G. lucidum mycelia, paving the way for the possible application of these peptides as potent drug candidates for treating hypertension.",

keywords = "ACE inhibitory peptide, Ganoderma lucidum, antihypertension, molecular dynamics simulation, submerged fermentation",

author = "Qiang Wu and Yong Li and Kuan Peng and Wang, {Xiao Ling} and Zhongyang Ding and Liming Liu and Peng Xu and Liu, {Gao Qiang}",

note = "Publisher Copyright: {\textcopyright} 2019 American Chemical Society.",

year = "2019",

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T1 - Isolation and Characterization of Three Antihypertension Peptides from the Mycelia of Ganoderma Lucidum (Agaricomycetes)

AU - Wu, Qiang

AU - Li, Yong

AU - Peng, Kuan

AU - Wang, Xiao Ling

AU - Ding, Zhongyang

AU - Liu, Liming

AU - Xu, Peng

AU - Liu, Gao Qiang

PY - 2019/6/27

Y1 - 2019/6/27

N2 - 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 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 G. lucidum mycelia, paving the way for the possible application of these peptides as potent drug candidates for treating hypertension.

AB - 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 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 G. lucidum mycelia, paving the way for the possible application of these peptides as potent drug candidates for treating hypertension.

KW - ACE inhibitory peptide

KW - Ganoderma lucidum

KW - antihypertension

KW - molecular dynamics simulation

KW - submerged fermentation

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ER -

Isolation and Characterization of Three Antihypertension Peptides from the Mycelia of Ganoderma Lucidum (Agaricomycetes)

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