Protective Effect of Foxtail Millet Protein Hydrolysate on Ethanol and Pyloric Ligation-Induced Gastric Ulcers in Mice

Foxtail millet has been traditionally considered to possess gastroprotective effects, but studies evaluating its use as a treatment for gastric ulcers are lacking. Here, we assessed the antiulcer effects of foxtail millet protein hydrolysate (FPH) and explored its mechanism by using blocking agents....

Full description

Bibliographic Details
Main Authors: Bowei Zhang, Xiaoxiao Rao, Yunhui Zhang, Weijia Dai, Yingchuan Xu, Congying Zhao, Zhenjia Chen, Jin Wang, Dancai Fan, Xiaowen Wang, Shuo Wang
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/11/12/2459
_version_ 1797461701155618816
author Bowei Zhang
Xiaoxiao Rao
Yunhui Zhang
Weijia Dai
Yingchuan Xu
Congying Zhao
Zhenjia Chen
Jin Wang
Dancai Fan
Xiaowen Wang
Shuo Wang
author_facet Bowei Zhang
Xiaoxiao Rao
Yunhui Zhang
Weijia Dai
Yingchuan Xu
Congying Zhao
Zhenjia Chen
Jin Wang
Dancai Fan
Xiaowen Wang
Shuo Wang
author_sort Bowei Zhang
collection DOAJ
description Foxtail millet has been traditionally considered to possess gastroprotective effects, but studies evaluating its use as a treatment for gastric ulcers are lacking. Here, we assessed the antiulcer effects of foxtail millet protein hydrolysate (FPH) and explored its mechanism by using blocking agents. In a mouse model of ethanol-induced gastric ulcers, pretreatment with FPH reduced the ulcerative lesion index, downregulated the expression of inflammatory cytokines in the gastric tissue, increased the activity of antioxidant enzymes, and improved the oxidative status. FPH increased constitutive the activity of nitric oxide synthase (cNOS), NO levels, and mucin expression in gastric mucosa, and inhibited the activation of the ET-1/PI3K/Akt pathway. In a mouse model of pyloric ligation-induced gastric ulcers, FPH inhibited gastric acid secretion and decreased the activity of gastric protease. Pretreatment of mice with the sulfhydryl blocker NEM and the NO synthesis inhibitor L-NAME abolished the gastroprotective effect of FPH, but not the KATP channel blocker glibenclamide and the PGE2 synthesis blocker indomethacin. Among the peptides identified in FPH, 10 peptides were predicted to have regulatory effects on the gastric mucosa, and the key sequences were GP and PG. The results confirmed the gastroprotective effect of FPH and revealed that its mechanism was through the regulation of gastric mucosal mucus and NO synthesis. This study supports the health effects of a millet-enriched diet and provides a basis for millet protein as a functional food to improve gastric ulcers and its related oxidative stress.
first_indexed 2024-03-09T17:23:07Z
format Article
id doaj.art-7e397e74ea9f46989d0c6a5687134a01
institution Directory Open Access Journal
issn 2076-3921
language English
last_indexed 2024-03-09T17:23:07Z
publishDate 2022-12-01
publisher MDPI AG
record_format Article
series Antioxidants
spelling doaj.art-7e397e74ea9f46989d0c6a5687134a012023-11-24T12:58:26ZengMDPI AGAntioxidants2076-39212022-12-011112245910.3390/antiox11122459Protective Effect of Foxtail Millet Protein Hydrolysate on Ethanol and Pyloric Ligation-Induced Gastric Ulcers in MiceBowei Zhang0Xiaoxiao Rao1Yunhui Zhang2Weijia Dai3Yingchuan Xu4Congying Zhao5Zhenjia Chen6Jin Wang7Dancai Fan8Xiaowen Wang9Shuo Wang10Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, ChinaTianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, ChinaTianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, ChinaTianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, ChinaTianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, ChinaTianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, ChinaCollege of Food Science and Engineering, Shanxi Agricultural University, Taiyuan 030801, ChinaTianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, ChinaTianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, ChinaCollege of Food Science and Engineering, Shanxi Agricultural University, Taiyuan 030801, ChinaTianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, ChinaFoxtail millet has been traditionally considered to possess gastroprotective effects, but studies evaluating its use as a treatment for gastric ulcers are lacking. Here, we assessed the antiulcer effects of foxtail millet protein hydrolysate (FPH) and explored its mechanism by using blocking agents. In a mouse model of ethanol-induced gastric ulcers, pretreatment with FPH reduced the ulcerative lesion index, downregulated the expression of inflammatory cytokines in the gastric tissue, increased the activity of antioxidant enzymes, and improved the oxidative status. FPH increased constitutive the activity of nitric oxide synthase (cNOS), NO levels, and mucin expression in gastric mucosa, and inhibited the activation of the ET-1/PI3K/Akt pathway. In a mouse model of pyloric ligation-induced gastric ulcers, FPH inhibited gastric acid secretion and decreased the activity of gastric protease. Pretreatment of mice with the sulfhydryl blocker NEM and the NO synthesis inhibitor L-NAME abolished the gastroprotective effect of FPH, but not the KATP channel blocker glibenclamide and the PGE2 synthesis blocker indomethacin. Among the peptides identified in FPH, 10 peptides were predicted to have regulatory effects on the gastric mucosa, and the key sequences were GP and PG. The results confirmed the gastroprotective effect of FPH and revealed that its mechanism was through the regulation of gastric mucosal mucus and NO synthesis. This study supports the health effects of a millet-enriched diet and provides a basis for millet protein as a functional food to improve gastric ulcers and its related oxidative stress.https://www.mdpi.com/2076-3921/11/12/2459foxtail millet protein hydrolysatesgastric ulcernitric oxide (NO)peptidesgastric mucosal mucus
spellingShingle Bowei Zhang
Xiaoxiao Rao
Yunhui Zhang
Weijia Dai
Yingchuan Xu
Congying Zhao
Zhenjia Chen
Jin Wang
Dancai Fan
Xiaowen Wang
Shuo Wang
Protective Effect of Foxtail Millet Protein Hydrolysate on Ethanol and Pyloric Ligation-Induced Gastric Ulcers in Mice
Antioxidants
foxtail millet protein hydrolysates
gastric ulcer
nitric oxide (NO)
peptides
gastric mucosal mucus
title Protective Effect of Foxtail Millet Protein Hydrolysate on Ethanol and Pyloric Ligation-Induced Gastric Ulcers in Mice
title_full Protective Effect of Foxtail Millet Protein Hydrolysate on Ethanol and Pyloric Ligation-Induced Gastric Ulcers in Mice
title_fullStr Protective Effect of Foxtail Millet Protein Hydrolysate on Ethanol and Pyloric Ligation-Induced Gastric Ulcers in Mice
title_full_unstemmed Protective Effect of Foxtail Millet Protein Hydrolysate on Ethanol and Pyloric Ligation-Induced Gastric Ulcers in Mice
title_short Protective Effect of Foxtail Millet Protein Hydrolysate on Ethanol and Pyloric Ligation-Induced Gastric Ulcers in Mice
title_sort protective effect of foxtail millet protein hydrolysate on ethanol and pyloric ligation induced gastric ulcers in mice
topic foxtail millet protein hydrolysates
gastric ulcer
nitric oxide (NO)
peptides
gastric mucosal mucus
url https://www.mdpi.com/2076-3921/11/12/2459
work_keys_str_mv AT boweizhang protectiveeffectoffoxtailmilletproteinhydrolysateonethanolandpyloricligationinducedgastriculcersinmice
AT xiaoxiaorao protectiveeffectoffoxtailmilletproteinhydrolysateonethanolandpyloricligationinducedgastriculcersinmice
AT yunhuizhang protectiveeffectoffoxtailmilletproteinhydrolysateonethanolandpyloricligationinducedgastriculcersinmice
AT weijiadai protectiveeffectoffoxtailmilletproteinhydrolysateonethanolandpyloricligationinducedgastriculcersinmice
AT yingchuanxu protectiveeffectoffoxtailmilletproteinhydrolysateonethanolandpyloricligationinducedgastriculcersinmice
AT congyingzhao protectiveeffectoffoxtailmilletproteinhydrolysateonethanolandpyloricligationinducedgastriculcersinmice
AT zhenjiachen protectiveeffectoffoxtailmilletproteinhydrolysateonethanolandpyloricligationinducedgastriculcersinmice
AT jinwang protectiveeffectoffoxtailmilletproteinhydrolysateonethanolandpyloricligationinducedgastriculcersinmice
AT dancaifan protectiveeffectoffoxtailmilletproteinhydrolysateonethanolandpyloricligationinducedgastriculcersinmice
AT xiaowenwang protectiveeffectoffoxtailmilletproteinhydrolysateonethanolandpyloricligationinducedgastriculcersinmice
AT shuowang protectiveeffectoffoxtailmilletproteinhydrolysateonethanolandpyloricligationinducedgastriculcersinmice