The Therapeutic Potential of Bombyx Batryticatus for Chronic Atrophic Gastritis Precancerous Lesions via the PI3K/AKT/mTOR Pathway Based on Network Pharmacology of Blood-Entering Components

<b>Background:</b> Chronic atrophic gastritis precancerous lesions (PL-CAG) are characterized by the atrophy of gastric mucosal glands, often accompanied by intestinal metaplasia or dysplasia. Timely intervention and treatment can effectively reverse its malignant progression and prevent...

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Main Authors: Xiaojie Wang, Miaomiao Chang, Kun Feng, Qingyue Wang, Bowen Li, Weijuan Gao
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/6/791
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author Xiaojie Wang
Miaomiao Chang
Kun Feng
Qingyue Wang
Bowen Li
Weijuan Gao
author_facet Xiaojie Wang
Miaomiao Chang
Kun Feng
Qingyue Wang
Bowen Li
Weijuan Gao
author_sort Xiaojie Wang
collection DOAJ
description <b>Background:</b> Chronic atrophic gastritis precancerous lesions (PL-CAG) are characterized by the atrophy of gastric mucosal glands, often accompanied by intestinal metaplasia or dysplasia. Timely intervention and treatment can effectively reverse its malignant progression and prevent the onset of gastric cancer. Bombyx Batryticatus (BB) exhibits a range of pharmacological effects, including anticoagulation, antiepileptic properties, anticancer activity, and antibacterial effects. However, the pharmacological basis and mechanisms underlying BB’s efficacy in treating PL-CAG remain unclear. <b>Methods:</b> A three-factor modeling approach was implemented to develop a rat PL-CAG model, while the MNNG-induced PLGC (precancerous lesions of gastric cancer) cell model was served as a cell PL-CAG model. UPLC-QE-Orbitrap-MS/MS (Ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry) was utilized to perform an in-depth analysis of the components in the plasma extract of BB. Leveraging network pharmacology, molecular docking analyses, and experimental validation, we initially elucidated the potential mechanisms through which BB mediates its therapeutic effects on PL-CAG at both in vivo and in vitro levels. <b>Results:</b> Prototype compounds of 42 blood-entering components were identified by UPLC-QE-Orbitrap-MS/MS analysis. Network pharmacology analysis and molecular docking studies indicate that the core targets are primarily enriched in the PI3K-Akt signaling pathway, and the key components, including Nepitrin, Quercetin 3-<i>O</i>-neohesperidoside, Rutin, and others, exhibited stable docking conformations with the first eleven pivotal targets. Both in vivo and in vitro experiments validated that BB may effectively treat PL-CAG via modulation of the PI3K-Akt signaling pathway. <b>Conclusions:</b> The therapeutic efficacy of BB in the management of PL-CAG may be achieved through the synergistic interaction of multiple components and targets, which may be more closely related to the inhibition of the PI3K/AKT signaling pathway. This approach will establish a solid experimental foundation and provide essential data for the clinical application of BB in treating PL-CAG, while also facilitating further research initiatives.
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spelling doaj-art-d0985e5d3b0d41af856e44bf250096392025-08-20T03:27:39ZengMDPI AGPharmaceuticals1424-82472025-05-0118679110.3390/ph18060791The Therapeutic Potential of Bombyx Batryticatus for Chronic Atrophic Gastritis Precancerous Lesions via the PI3K/AKT/mTOR Pathway Based on Network Pharmacology of Blood-Entering ComponentsXiaojie Wang0Miaomiao Chang1Kun Feng2Qingyue Wang3Bowen Li4Weijuan Gao5Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Hebei University of Chinese Medicine, Shijiazhuang 050200, ChinaHebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Hebei University of Chinese Medicine, Shijiazhuang 050200, ChinaHebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Hebei University of Chinese Medicine, Shijiazhuang 050200, ChinaHebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Hebei University of Chinese Medicine, Shijiazhuang 050200, ChinaHebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Hebei University of Chinese Medicine, Shijiazhuang 050200, ChinaHebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Hebei University of Chinese Medicine, Shijiazhuang 050200, China<b>Background:</b> Chronic atrophic gastritis precancerous lesions (PL-CAG) are characterized by the atrophy of gastric mucosal glands, often accompanied by intestinal metaplasia or dysplasia. Timely intervention and treatment can effectively reverse its malignant progression and prevent the onset of gastric cancer. Bombyx Batryticatus (BB) exhibits a range of pharmacological effects, including anticoagulation, antiepileptic properties, anticancer activity, and antibacterial effects. However, the pharmacological basis and mechanisms underlying BB’s efficacy in treating PL-CAG remain unclear. <b>Methods:</b> A three-factor modeling approach was implemented to develop a rat PL-CAG model, while the MNNG-induced PLGC (precancerous lesions of gastric cancer) cell model was served as a cell PL-CAG model. UPLC-QE-Orbitrap-MS/MS (Ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry) was utilized to perform an in-depth analysis of the components in the plasma extract of BB. Leveraging network pharmacology, molecular docking analyses, and experimental validation, we initially elucidated the potential mechanisms through which BB mediates its therapeutic effects on PL-CAG at both in vivo and in vitro levels. <b>Results:</b> Prototype compounds of 42 blood-entering components were identified by UPLC-QE-Orbitrap-MS/MS analysis. Network pharmacology analysis and molecular docking studies indicate that the core targets are primarily enriched in the PI3K-Akt signaling pathway, and the key components, including Nepitrin, Quercetin 3-<i>O</i>-neohesperidoside, Rutin, and others, exhibited stable docking conformations with the first eleven pivotal targets. Both in vivo and in vitro experiments validated that BB may effectively treat PL-CAG via modulation of the PI3K-Akt signaling pathway. <b>Conclusions:</b> The therapeutic efficacy of BB in the management of PL-CAG may be achieved through the synergistic interaction of multiple components and targets, which may be more closely related to the inhibition of the PI3K/AKT signaling pathway. This approach will establish a solid experimental foundation and provide essential data for the clinical application of BB in treating PL-CAG, while also facilitating further research initiatives.https://www.mdpi.com/1424-8247/18/6/791chronic atrophic gastritis precancerous lesionsBombyx BatryticatusUPLC-QE-Orbitrap-MS/MSnetwork pharmacologyPI3K/AKT/mTOR pathwayBombyx Batryticatus
spellingShingle Xiaojie Wang
Miaomiao Chang
Kun Feng
Qingyue Wang
Bowen Li
Weijuan Gao
The Therapeutic Potential of Bombyx Batryticatus for Chronic Atrophic Gastritis Precancerous Lesions via the PI3K/AKT/mTOR Pathway Based on Network Pharmacology of Blood-Entering Components
Pharmaceuticals
chronic atrophic gastritis precancerous lesions
Bombyx Batryticatus
UPLC-QE-Orbitrap-MS/MS
network pharmacology
PI3K/AKT/mTOR pathway
Bombyx Batryticatus
title The Therapeutic Potential of Bombyx Batryticatus for Chronic Atrophic Gastritis Precancerous Lesions via the PI3K/AKT/mTOR Pathway Based on Network Pharmacology of Blood-Entering Components
title_full The Therapeutic Potential of Bombyx Batryticatus for Chronic Atrophic Gastritis Precancerous Lesions via the PI3K/AKT/mTOR Pathway Based on Network Pharmacology of Blood-Entering Components
title_fullStr The Therapeutic Potential of Bombyx Batryticatus for Chronic Atrophic Gastritis Precancerous Lesions via the PI3K/AKT/mTOR Pathway Based on Network Pharmacology of Blood-Entering Components
title_full_unstemmed The Therapeutic Potential of Bombyx Batryticatus for Chronic Atrophic Gastritis Precancerous Lesions via the PI3K/AKT/mTOR Pathway Based on Network Pharmacology of Blood-Entering Components
title_short The Therapeutic Potential of Bombyx Batryticatus for Chronic Atrophic Gastritis Precancerous Lesions via the PI3K/AKT/mTOR Pathway Based on Network Pharmacology of Blood-Entering Components
title_sort therapeutic potential of bombyx batryticatus for chronic atrophic gastritis precancerous lesions via the pi3k akt mtor pathway based on network pharmacology of blood entering components
topic chronic atrophic gastritis precancerous lesions
Bombyx Batryticatus
UPLC-QE-Orbitrap-MS/MS
network pharmacology
PI3K/AKT/mTOR pathway
Bombyx Batryticatus
url https://www.mdpi.com/1424-8247/18/6/791
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