Identification of Rubisco anxiolytic-like peptides (rALPs) by comprehensive analysis of spinach green leaf protein digest

Kimura, Saeko; Uchida, Tomoki; Tokuyama, Yuki; Hosokawa, Mayumi; Nakato, Junya; Kurabayashi, Atsushi; Satô, Masaru; Suzuki, Hideyuki; Kanamoto, Ryuhei; Ohinata, Kousaku

doi:10.1016/j.bbrc.2018.09.195

Cited by 21 publications

(16 citation statements)

References 19 publications

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“…In the present study, we demonstrated a novel intervention to mitigate obesogenic conditions. Our ex vivo experiments revealed a previously unidentified nutritional link between plant-derived peptides and neuronal leptin signaling; YHIEPV, also named rALP-2 16 , derived from the protease digestion of the major green leaf protein Rubisco in the gastrointestinal tract, mimicking postprandial digestion, increased leptin sensitivity. These results were supported by those obtained in in vivo experiments.…”

Section: Discussionmentioning

confidence: 79%

“…The digestion of proteins in the gastrointestinal tract induces the release of numerous peptides, some of which have multiple physiological functions, such as improvements in glucose homeostasis, appetite regulation, cholesterol-lowering, anti-depressive-like, and anti-anxiety-like effects, improvements in cognitive function, and memory-enhancing activities 14 , 41 , 42 . Some bioactive peptides are also effective when orally administered in vivo 14 , 16 , 43 – 47 . Therefore, dietary proteins are recognized as a source of biologically active peptides, which have potential as orally active compounds to improve leptin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

“…Control (saline) or YHIEPV (0.3 mg/kg/day) was orally administered once a day. The dosage of YHIEPV was selected based on a previous study 16 . The administration of peptide solution was performed by oral gavage.…”

Section: Methodsmentioning

confidence: 99%

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An orally active plant Rubisco-derived peptide increases neuronal leptin responsiveness

Kikuchi

Takekuma

Goto

et al. 2022

Sci Rep

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Nutrient excess, such as the intake of a high-fat diet, reduces hypothalamic responses to exogenously administered leptin and induces dietary obesity; however, orally active components that attenuate neural leptin dysregulation have yet to be identified. We herein demonstrated that YHIEPV, derived from the pepsin-pancreatin digestion of the green leaf protein Rubisco, increased the leptin-induced phosphorylation of STAT3 in ex vivo hypothalamic slice cultures. We also showed that YHIEPV mitigated palmitic acid-induced decreases in leptin responsiveness. Furthermore, orally administered YHIEPV promoted leptin-induced reductions in body weight and food intake in obese mice. In addition, dietary-induced body weight gain was significantly less in mice orally or centrally administered YHIEPV daily than in saline-control mice. Cellular leptin sensitivity and the levels of proinflammatory-related factors, such as IL1β and Socs-3, in the hypothalamus of obese mice were also restored by YHIEPV. YHIEPV blocked cellular leptin resistance induced by forskolin, which activates Epac-Rap1 signaling, and reduced the level of the GTP-bound active form of Rap1 in the brains of obese mice. Collectively, the present results demonstrated that the orally active peptide YHIEPV derived from a major green leaf protein increased neural leptin responsiveness and reduced body weight gain in mice with dietary obesity.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

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An orally active plant Rubisco-derived peptide increases neuronal leptin responsiveness

Kikuchi

Takekuma

Goto

et al. 2022

Sci Rep

Self Cite

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“…As Veyssiere et al (Veyssiere et al, 2015) have shown, a peptide named spadin, consisting of 17 amino acids, works faster than classical antidepressants and does not induce side effects. Kimura et al (Kimura et al, 2018) identi ed that the three peptides obtained from the hydrolysis of spinach green leaf protein showed strong antianxiety effects after oral administration. As a new therapeutic tool, food-derived peptides have shown outstanding advantages in nding new safe and effective antidepressants.…”

Section: Super High a Nity Oligopeptidesmentioning

confidence: 99%

Screening of Monoamine Oxidase A Inhibitory Peptides from Proteins of Edible Fungi

Zhou

Liu

et al. 2022

Preprint

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In this paper, the binding relationship between oligopeptides of edible fungi and monoamine oxidase A (MAO-A) was explored by computer simulation. The frequency of high affinity oligopeptides (F value) was calculated, and the MAO-A inhibitory peptide was screened. By simulating the hydrolysis of 27 proteins from 8 common edible fungi in China, the oligopeptides obtained by hydrolysis were docked with MAO-A to screen high affinity oligopeptides (docking fraction ≤ -120) and ultra-high affinity oligopeptides (docking fraction ≤ -160). At the same time, the F value was calculated to predict the inhibitory effect of edible fungi protein on MAO-A. A total of 430 high-affinity oligopeptides and 32 ultra-high-affinity oligopeptides were obtained by molecular docking after 27 proteins were simulated hydrolysis. Among them, the three oligopeptides with the highest docking were PQSTW (-195.952), PTSGW (-187.942) and QCQW (-180.007). In addition, the simulated hydrolyzed edible fungi all contained oligopeptides with strong inhibitory effect on MAO-A. In summary, this paper aims to screen MAO-A inhibitory peptides, provide new possibilities for high-speed screening of MAO-A inhibitory peptides, and provide a theoretical basis for exploring the potential value of edible fungi.

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“…Opioid peptides act in conjunction with opioid receptors, the activation of which can inhibit P38 phosphorylation via PCK and MAPK activation, prevent cell apoptosis, and scavenge free radicals to protect nerve cells (Staples et al, 2013). In addition, scientists have recently extracted Rubisco peptides from spinach leaves that have been shown to have significant anti-anxiety effects (Kimura et al, 2018).…”

Section: Active Peptidesmentioning

confidence: 99%

Plant-Derived Antioxidants Protect the Nervous System From Aging by Inhibiting Oxidative Stress

Cui

Lin

Liang

2020

Front. Aging Neurosci.

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Alzheimer's disease (AD) has become a major disease contributing to human death and is thought to be closely related to the aging process. The rich antioxidant substances in plants have been shown to play a role in delaying aging, and in recent years, significant research has focused on also examining their potential role in AD onset and progression. Many plant-derived antioxidant research studies have provided insights for the future treatment and prevention of AD. This article reviews various types of plant-derived antioxidants with anti-aging effects on neurons. Also it distinguishes the different types of active substances that exhibit different degrees of protection for the nervous system and summarizes the mechanism thereof. Plant-derived antioxidants with neuroprotective functions can protect various components of the nervous system in a variety of ways and can have a positive impact on interventions to prevent and alleviate AD. Furthermore, when considering neuroprotective agents, glial cells also contribute to the defense of the nervous system and should not be ignored.

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Identification of Rubisco anxiolytic-like peptides (rALPs) by comprehensive analysis of spinach green leaf protein digest

Cited by 21 publications

References 19 publications

An orally active plant Rubisco-derived peptide increases neuronal leptin responsiveness

An orally active plant Rubisco-derived peptide increases neuronal leptin responsiveness

Screening of Monoamine Oxidase A Inhibitory Peptides from Proteins of Edible Fungi

Plant-Derived Antioxidants Protect the Nervous System From Aging by Inhibiting Oxidative Stress

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