Lipid-Lowering Potential of Almond Hulls (Quercetin, Baicalein, and Kaempferol): Insights from Network Pharmacology and Molecular Dynamics

The advancement of modern lifestyles has precipitated excessive consumption of energy-dense foods, driving the escalating global burden of lipid metabolism dysregulation-related pathologies—including obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascu...

Full description

Saved in:
Bibliographic Details
Main Authors: Qiming Miao, Lu Sun, Jiayuan Wu, Xinyue Zhu, Juer Liu, Roger Ruan, Guangwei Huang, Shengquan Mi, Yanling Cheng
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Current Issues in Molecular Biology
Subjects:
Online Access:https://www.mdpi.com/1467-3045/47/6/450
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850156246311632896
author Qiming Miao
Lu Sun
Jiayuan Wu
Xinyue Zhu
Juer Liu
Roger Ruan
Guangwei Huang
Shengquan Mi
Yanling Cheng
author_facet Qiming Miao
Lu Sun
Jiayuan Wu
Xinyue Zhu
Juer Liu
Roger Ruan
Guangwei Huang
Shengquan Mi
Yanling Cheng
author_sort Qiming Miao
collection DOAJ
description The advancement of modern lifestyles has precipitated excessive consumption of energy-dense foods, driving the escalating global burden of lipid metabolism dysregulation-related pathologies—including obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disorders—which collectively pose a formidable challenge to global public health systems. The almond hull, as a by-product of almond processing, is rich in polyphenolic compounds with demonstrated antioxidant, anti-inflammatory, and lipid-lowering potential, though its precise hypo-lipidemic mechanisms remain elusive. In this study, polyphenols were extracted from almond hulls using 50% ethanol with ultrasound-assisted extraction, followed by preliminary purification via solvent partitioning. The ethyl acetate fraction was analyzed by liquid chromatography–mass spectrometry (LC-MS). Network pharmacology and molecular docking were employed to investigate the interactions between key bioactive constituents (e.g., quercetin, baicalein, and kaempferol) and targets in lipid metabolism-related pathways. Molecular dynamics (MD) simulations further evaluated the stability of the lowest-energy complexes. Results revealed that the ethyl acetate fraction exhibited potent pancreatic lipase inhibitory activity (IC50 = 204.2 µg/mL). At 0.1 mg/mL after 24 h treatment, it significantly reduced free fatty acids (FFAs)-induced intracellular triglyceride accumulation (<i>p</i> < 0.01) and enhanced cellular antioxidant capacity. Network pharmacology and in vitro studies suggest almond hull extract modulates PI3K-AKT signaling and improves insulin resistance, demonstrating lipid-lowering effects. These findings support its potential in functional foods and pharmaceuticals, though further in vivo validation and mechanistic investigations are required.
format Article
id doaj-art-759b659f413843cca2b494adc080d6f9
institution OA Journals
issn 1467-3037
1467-3045
language English
publishDate 2025-06-01
publisher MDPI AG
record_format Article
series Current Issues in Molecular Biology
spelling doaj-art-759b659f413843cca2b494adc080d6f92025-08-20T02:24:37ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-06-0147645010.3390/cimb47060450Lipid-Lowering Potential of Almond Hulls (Quercetin, Baicalein, and Kaempferol): Insights from Network Pharmacology and Molecular DynamicsQiming Miao0Lu Sun1Jiayuan Wu2Xinyue Zhu3Juer Liu4Roger Ruan5Guangwei Huang6Shengquan Mi7Yanling Cheng8Biochemical Engineering College, Beijing Union University, Beijing 100101, ChinaBiochemical Engineering College, Beijing Union University, Beijing 100101, ChinaBiochemical Engineering College, Beijing Union University, Beijing 100101, ChinaBiochemical Engineering College, Beijing Union University, Beijing 100101, ChinaCenter for Biorefining & Department of Bioproducts and Biosystems Engineering, University of Minnesota, St. Paul, MN 55108, USACenter for Biorefining & Department of Bioproducts and Biosystems Engineering, University of Minnesota, St. Paul, MN 55108, USAAlmond Board of California, Modesto, CA 95354, USABiochemical Engineering College, Beijing Union University, Beijing 100101, ChinaBiochemical Engineering College, Beijing Union University, Beijing 100101, ChinaThe advancement of modern lifestyles has precipitated excessive consumption of energy-dense foods, driving the escalating global burden of lipid metabolism dysregulation-related pathologies—including obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disorders—which collectively pose a formidable challenge to global public health systems. The almond hull, as a by-product of almond processing, is rich in polyphenolic compounds with demonstrated antioxidant, anti-inflammatory, and lipid-lowering potential, though its precise hypo-lipidemic mechanisms remain elusive. In this study, polyphenols were extracted from almond hulls using 50% ethanol with ultrasound-assisted extraction, followed by preliminary purification via solvent partitioning. The ethyl acetate fraction was analyzed by liquid chromatography–mass spectrometry (LC-MS). Network pharmacology and molecular docking were employed to investigate the interactions between key bioactive constituents (e.g., quercetin, baicalein, and kaempferol) and targets in lipid metabolism-related pathways. Molecular dynamics (MD) simulations further evaluated the stability of the lowest-energy complexes. Results revealed that the ethyl acetate fraction exhibited potent pancreatic lipase inhibitory activity (IC50 = 204.2 µg/mL). At 0.1 mg/mL after 24 h treatment, it significantly reduced free fatty acids (FFAs)-induced intracellular triglyceride accumulation (<i>p</i> < 0.01) and enhanced cellular antioxidant capacity. Network pharmacology and in vitro studies suggest almond hull extract modulates PI3K-AKT signaling and improves insulin resistance, demonstrating lipid-lowering effects. These findings support its potential in functional foods and pharmaceuticals, though further in vivo validation and mechanistic investigations are required.https://www.mdpi.com/1467-3045/47/6/450almond hullextractionmechanismsHepG2 cells
spellingShingle Qiming Miao
Lu Sun
Jiayuan Wu
Xinyue Zhu
Juer Liu
Roger Ruan
Guangwei Huang
Shengquan Mi
Yanling Cheng
Lipid-Lowering Potential of Almond Hulls (Quercetin, Baicalein, and Kaempferol): Insights from Network Pharmacology and Molecular Dynamics
Current Issues in Molecular Biology
almond hull
extraction
mechanisms
HepG2 cells
title Lipid-Lowering Potential of Almond Hulls (Quercetin, Baicalein, and Kaempferol): Insights from Network Pharmacology and Molecular Dynamics
title_full Lipid-Lowering Potential of Almond Hulls (Quercetin, Baicalein, and Kaempferol): Insights from Network Pharmacology and Molecular Dynamics
title_fullStr Lipid-Lowering Potential of Almond Hulls (Quercetin, Baicalein, and Kaempferol): Insights from Network Pharmacology and Molecular Dynamics
title_full_unstemmed Lipid-Lowering Potential of Almond Hulls (Quercetin, Baicalein, and Kaempferol): Insights from Network Pharmacology and Molecular Dynamics
title_short Lipid-Lowering Potential of Almond Hulls (Quercetin, Baicalein, and Kaempferol): Insights from Network Pharmacology and Molecular Dynamics
title_sort lipid lowering potential of almond hulls quercetin baicalein and kaempferol insights from network pharmacology and molecular dynamics
topic almond hull
extraction
mechanisms
HepG2 cells
url https://www.mdpi.com/1467-3045/47/6/450
work_keys_str_mv AT qimingmiao lipidloweringpotentialofalmondhullsquercetinbaicaleinandkaempferolinsightsfromnetworkpharmacologyandmoleculardynamics
AT lusun lipidloweringpotentialofalmondhullsquercetinbaicaleinandkaempferolinsightsfromnetworkpharmacologyandmoleculardynamics
AT jiayuanwu lipidloweringpotentialofalmondhullsquercetinbaicaleinandkaempferolinsightsfromnetworkpharmacologyandmoleculardynamics
AT xinyuezhu lipidloweringpotentialofalmondhullsquercetinbaicaleinandkaempferolinsightsfromnetworkpharmacologyandmoleculardynamics
AT juerliu lipidloweringpotentialofalmondhullsquercetinbaicaleinandkaempferolinsightsfromnetworkpharmacologyandmoleculardynamics
AT rogerruan lipidloweringpotentialofalmondhullsquercetinbaicaleinandkaempferolinsightsfromnetworkpharmacologyandmoleculardynamics
AT guangweihuang lipidloweringpotentialofalmondhullsquercetinbaicaleinandkaempferolinsightsfromnetworkpharmacologyandmoleculardynamics
AT shengquanmi lipidloweringpotentialofalmondhullsquercetinbaicaleinandkaempferolinsightsfromnetworkpharmacologyandmoleculardynamics
AT yanlingcheng lipidloweringpotentialofalmondhullsquercetinbaicaleinandkaempferolinsightsfromnetworkpharmacologyandmoleculardynamics