A <i>Lupinus angustifolius</i> protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE<sup>−/−</sup> mice through the modulation of LDLR and PCSK9 pathways

Santos-Sánchez, Guillermo; Cruz‐Chamorro, Ivan; Bollati, Carlotta; Bartolomei, Martina; Pedroche, Justo; Rodríguez, Francisco Millán; Millán-Linares, María del Carmen; Capriotti, Anna Laura; Cerrato, Andrea; Laganà, Aldo; Arnoldi, Anna; Carrillo-Vico, Antonio; Lammi, Carmen

doi:10.1039/d1fo03847h

Cited by 18 publications

(21 citation statements)

References 65 publications

(104 reference statements)

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“…The latter was lyophilized and stored at 20−25 °C. 20 Concentration of proteins, 20 total dietary fiber, 25 oil content, 26 soluble sugars, 27 polyphenols, 28 degree of hydrolysis, 29 molecular weights profile, 20 and peptides identification 22 were measured as previously described (see the Supporting Information for more detail).…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…21 Furthermore, the molecular analysis of the in vivo LPH effects on the cholesterol metabolic pathway of liver showed that LPH regulates the activation of HMGCoAR, the main enzyme responsible for cholesterol synthesis, and the protein levels of LDL-C receptor (LDL-R). 22 In addition, we have reported the beneficial effects of a functional beverage based on LPH on the antioxidant and anti- inflammatory status as well as decreasing of the atherogenic index in healthy subjects. 23 In light of these considerations and because no previous studies have addressed the pleiotropic actions of bioactive peptides from lupin in the key components of the early stages of atherosclerosis (hyperlipidemia, oxidative stress, and inflammation), the main objective of this study was to analyze the effects of LPH on early risk factors for atherosclerosis in a WD-induced hypercholesterolemia model in ApoE −/− mice.…”

Section: ■ Introductionmentioning

confidence: 98%

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Bioactive Peptides from Lupin (Lupinus angustifolius) Prevent the Early Stages of Atherosclerosis in Western Diet-Fed ApoE^–/– Mice

Santos-Sánchez

Cruz‐Chamorro

Álvarez-Ríos

et al. 2022

J. Agric. Food Chem.

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We have previously reported the in vitro hypocholesterolemic, anti-inflammatory, and antioxidant effects of Alcalasegenerated lupin protein hydrolysate (LPH). Given that lipoprotein deposition, oxidative stress, and inflammation are the main components of atherogenesis, we characterized the LPH composition, in silico identified LPH−peptides with activities related to atherosclerosis, and evaluated the in vivo LPH effects on atherosclerosis risk factors in a mouse model of atherosclerosis. After 15 min of Alcalase hydrolysis, peptides smaller than 8 kDa were obtained, and 259 peptides out of 278 peptides found showed biological activities related to atherosclerosis risk factors. Furthermore, LPH administration for 12 weeks reduced the plasma lipids, as well as the cardiovascular and atherogenic risk indexes. LPH also increased the total antioxidant capacity, decreased endothelial permeability, inflammatory response, and atherogenic markers. Therefore, this study describes for the first time that LPH prevents the early stages of atherosclerosis.

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Section: ■ Materials and Methodsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 98%

Bioactive Peptides from Lupin (Lupinus angustifolius) Prevent the Early Stages of Atherosclerosis in Western Diet-Fed ApoE^–/– Mice

Santos-Sánchez

Cruz‐Chamorro

Álvarez-Ríos

et al. 2022

J. Agric. Food Chem.

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“…Moreover, recent studies have shown a strong link between high cholesterol levels and anxiety [ 69 ]. Our group has previously shown that LPH exerts anti-inflammatory, antioxidant, and lipid-lowering effects both in ApoE −/− mice [ 47 , 73 ] and humans [ 45 , 46 ]. Therefore, we suggest that these LPH properties may also be directly or indirectly responsible for the anxiolytic-like effects.…”

Section: Discussionmentioning

confidence: 99%

“…The peptide spectra were obtained using the same parameters described in our previous work [ 73 ]. The protein sequence database of L. angustifolius (31,386 sequences) was downloaded from UnitProt and used for the identification of raw data spectra using Proteome Discoverer v1.3 (Thermo) in combination with the Mascot search engine v2.3.02.…”

Section: Methodsmentioning

confidence: 99%

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A Lupin (Lupinus angustifolius) Protein Hydrolysate Exerts Anxiolytic-Like Effects in Western Diet-Fed ApoE−/− Mice

Santos-Sánchez

Ponce-España

López-Garcı́a

et al. 2022

IJMS

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Anxiety is the most prevalent psychiatric disorder worldwide, causing a substantial economic burden due to the associated healthcare costs. Given that commercial anxiolytic treatments may cause important side effects and have medical restrictions for prescription and high costs, the search for new natural and safer treatments is gaining attention. Since lupin protein hydrolysate (LPH) has been shown to be safe and exert anti-inflammatory and antioxidant effects, key risk factors for the anxiety process and memory impairment, we evaluated in this study the potential effects of LPH on anxiety and spatial memory in a Western diet (WD)-induced anxiety model in ApoE−/− mice. We showed that 20.86% of the 278 identified LPH peptides have biological activity related to anxiolytic/analgesic effects; the principal motifs found were the following: VPL, PGP, YL, and GQ. Moreover, 14 weeks of intragastrical LPH treatment (100 mg/kg) restored the WD-induced anxiety effects, reestablishing the anxiety levels observed in the standard diet (SD)-fed mice since they spent less time in the anxiety zones of the elevated plus maze (EPM). Furthermore, a significant increase in the number of head dips was recorded in LPH-treated mice, which indicates a greater exploration capacity and less fear due to lower levels of anxiety. Interestingly, the LPH group showed similar thigmotaxis, a well-established indicator of animal anxiety and fear, to the SD group, counteracting the WD effect. This is the first study to show that LPH treatment has anxiolytic effects, pointing to LPH as a potential component of future nutritional therapies in patients with anxiety.

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A lupin protein hydrolysate protects the central nervous system from oxidative stress in WD‐fed ApoE^−/− mice

Santos‐Sánchez,

Ponce‐España,

Álvarez‐López

et al. 2024

Molecular Nutrition Food Res

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Oxidative stress plays a crucial role in neurodegenerative diseases like Parkinson's and Alzheimer's. Studies indicate the relationship between oxidative stress and the brain damage caused by a high‐fat diet. It is previously found that a lupin protein hydrolysate (LPH) has antioxidant effects on human leukocytes, as well as on the plasma and liver of Western diet (WD)‐fed ApoE−/− mice. Additionally, LPH shows anxiolytic effects in these mice. Given the connection between oxidative stress and anxiety, this study aimed to investigate the antioxidant effects of LPH on the brain of WD‐fed ApoE−/− mice. LPH (100 mg kg−1) or a vehicle is administered daily for 12 weeks. Peptide analysis of LPH identified 101 amino acid sequences (36.33%) with antioxidant motifs. Treatment with LPH palliated the decrease in total antioxidant activity caused by WD ingestion and regulated the nitric oxide synthesis pathway in the brain of the animals. Furthermore, LPH increased cerebral glutathione levels and the activity of catalase and glutathione reductase antioxidant enzymes and reduced the 8‐hydroxy‐2’‐deoxyguanosine levels, a DNA damage marker. These findings, for the first time, highlight the antioxidant activity of LPH in the brain. This hydrolysate could potentially be used in future nutraceutical therapies for neurodegenerative diseases.

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A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE^−/− mice through the modulation of LDLR and PCSK9 pathways

Abstract: Lupin protein hydrolysate (LPH) is gaining attention in the food and nutraceutical industries due to several beneficial health effects. Recently, we have shown that LPH treatment reduces liver cholesterol and...

Cited by 18 publications

References 65 publications

Bioactive Peptides from Lupin (Lupinus angustifolius) Prevent the Early Stages of Atherosclerosis in Western Diet-Fed ApoE^–/– Mice

Bioactive Peptides from Lupin (Lupinus angustifolius) Prevent the Early Stages of Atherosclerosis in Western Diet-Fed ApoE^–/– Mice

A Lupin (Lupinus angustifolius) Protein Hydrolysate Exerts Anxiolytic-Like Effects in Western Diet-Fed ApoE−/− Mice

A lupin protein hydrolysate protects the central nervous system from oxidative stress in WD‐fed ApoE^−/− mice

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A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE−/− mice through the modulation of LDLR and PCSK9 pathways

Abstract: Lupin protein hydrolysate (LPH) is gaining attention in the food and nutraceutical industries due to several beneficial health effects. Recently, we have shown that LPH treatment reduces liver cholesterol and...

Cited by 18 publications

References 65 publications

Bioactive Peptides from Lupin (Lupinus angustifolius) Prevent the Early Stages of Atherosclerosis in Western Diet-Fed ApoE–/– Mice

Bioactive Peptides from Lupin (Lupinus angustifolius) Prevent the Early Stages of Atherosclerosis in Western Diet-Fed ApoE–/– Mice

A Lupin (Lupinus angustifolius) Protein Hydrolysate Exerts Anxiolytic-Like Effects in Western Diet-Fed ApoE−/− Mice

A lupin protein hydrolysate protects the central nervous system from oxidative stress in WD‐fed ApoE−/− mice

Contact Info

Product

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A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE^−/− mice through the modulation of LDLR and PCSK9 pathways

Bioactive Peptides from Lupin (Lupinus angustifolius) Prevent the Early Stages of Atherosclerosis in Western Diet-Fed ApoE^–/– Mice

Bioactive Peptides from Lupin (Lupinus angustifolius) Prevent the Early Stages of Atherosclerosis in Western Diet-Fed ApoE^–/– Mice

A lupin protein hydrolysate protects the central nervous system from oxidative stress in WD‐fed ApoE^−/− mice