GNPS-assisted identification of bioactive constituents from Scoparia dulcis and their anti-inflammatory mechanisms via network pharmacology and experimental validation.
14 affiliations
- 1Department of Pharmacognosy and Traditional Pharmacy, School of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City Ho Chi Minh City 700000 Vietnam.
- 2PhD Program in Clinical Drug Development of Herbal Medicine, College of Pharmacy, Taipei Medical University Taipei 110301 Taiwan [email protected].
- 3Food Technology Faculty, Saigon Technology University Ho Chi Minh City 700000 Vietnam.
- 4Faculty of Pharmacy, Lac Hong University 10 Huynh Van Nghe Street, Tran Bien Ward Dong Nai City Vietnam.
- 5Institute of Pharmaceutical Education and Research, Binh Duong University Ho Chi Minh City Vietnam.
- 6Faculty of Pharmacy, Ton Duc Thang University Ho Chi Minh City Vietnam.
- 7International PhD Program in Medicine, College of Medicine, Taipei Medical University Taipei 110301 Taiwan.
- 8Vietnam University of Traditional Medicine 2 Tran Phu, Dai Mo Hanoi Vietnam.
- 9University of Information Technology, Computer Science Ho Chi Minh City Vietnam.
- 10National Research Institute of Chinese Medicine, Ministry of Health and Welfare Taipei 112026 Taiwan [email protected].
- 11Department of Life Sciences, Institute of Genome Sciences, National Yang Ming Chiao Tung University No. 155, Sec. 2, Li-Nong Street, Beitou Taipei 112304 Taiwan.
- 12Traditional Herbal Medicine Research Center, Taipei Medical University Hospital Taipei 110301 Taiwan.
- 13National Museum of Marine Biology and Aquarium Pingtung 944401 Taiwan.
- 14Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University Taipei 110301 Taiwan.
Abstract
Scoparia dulcis L. (SD) is an edible medicinal herb traditionally consumed as a cooling beverage in tropical Asia for the management of metabolic and inflammatory disorders; however, its dietary bioactive constituents and anti-inflammatory mechanisms have not yet been fully elucidated. In the present study, the metabolite profile of the aerial parts of SD (ASD) was characterized, and their anti-inflammatory potential was evaluated through an integrated approach incorporating LC-HRMS/MS-based molecular networking, network pharmacology, molecular docking, molecular dynamics simulations, and in vitro validation in macrophages. Untargeted LC-HRMS/MS combined with GNPS feature-based molecular networking enabled the annotation of 184 metabolites in the ASD extract, mainly comprising shikimates and phenylpropanoids (44.0%) and terpenoids (39.7%), with flavonoids constituting the most abundant superclass and including known food bioactives such as β-sitosterol, pentamethoxyflavone, naringin, and catechin. ADMET-based screening prioritized 31 absorbable constituents, while network pharmacology identified 179 inflammation-related targets, with TNF-α, IL6, STAT3, AKT1, and JAK2 emerging as key hubs. Enrichment analysis highlighted the TNF, PI3K-AKT, JAK-STAT, and AGE-RAGE pathways as major signaling routes associated with low-grade diet-related inflammation. Molecular docking and 300 ns molecular dynamics simulations further identified zeorinone as a stable dual binder of TNF-α and IL6, exhibiting the most favorable MM-PBSA binding free energies among the compounds selected for molecular dynamics analysis. Consistent with these computational findings, the ASD extract showed no cytotoxicity in RAW264.7 macrophages at 10-100 µg mL⁻¹ and significantly reduced LPS-induced TNF-α and IL6 secretion at 50-100 µg mL⁻¹, with effects comparable to dexamethasone. Overall, these findings establish SD as a promising source of dietary anti-inflammatory bioactives and provide a chemical and mechanistic basis for its potential development as a functional food ingredient or herbal beverage targeting chronic diet-related inflammation.
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BibTeX
@article{pham2026gnpsassisted,
title = {{GNPS-assisted identification of bioactive constituents from Scoparia dulcis and their anti-inflammatory mechanisms via network pharmacology and experimental validation.}},
author = {Ngoc-Thac Pham and Thanh-Sang Nguyen and Ngo Thi My Duyen and Huong-Giang Le and Thuy-Tien Thi Phan and Quoc Dung Huynh Tran and Phuong Vu Luu and Quang-Hien Kha and Vu Duc Loi and Duc-Toan Nguyen and Chung-Kuang Lu and Kuei-Hung Lai},
journal = {RSC advances},
year = {2026},
month = oct,
doi = {10.1039/d6ra06433g},
url = {https://europepmc.org/article/MED/42846252},
note = {CC BY},
}
RIS
TY - JOUR
TI - GNPS-assisted identification of bioactive constituents from Scoparia dulcis and their anti-inflammatory mechanisms via network pharmacology and experimental validation.
AU - Ngoc-Thac Pham
AU - Thanh-Sang Nguyen
AU - Ngo Thi My Duyen
AU - Huong-Giang Le
AU - Thuy-Tien Thi Phan
AU - Quoc Dung Huynh Tran
AU - Phuong Vu Luu
AU - Quang-Hien Kha
AU - Vu Duc Loi
AU - Duc-Toan Nguyen
AU - Chung-Kuang Lu
AU - Kuei-Hung Lai
PY - 2026
DA - 2026/10/07
JO - RSC advances
DO - 10.1039/d6ra06433g
UR - https://europepmc.org/article/MED/42846252
AB - Scoparia dulcis L. (SD) is an edible medicinal herb traditionally consumed as a cooling beverage in tropical Asia for the management of metabolic and inflammatory disorders; however, its dietary bioactive constituents and anti-inflammatory mechanisms have not yet been fully elucidated. In the present study, the metabolite profile of the aerial parts of SD (ASD) was characterized, and their anti-inflammatory potential was evaluated through an integrated approach incorporating LC-HRMS/MS-based molecular networking, network pharmacology, molecular docking, molecular dynamics simulations, and in vitro validation in macrophages. Untargeted LC-HRMS/MS combined with GNPS feature-based molecular networking enabled the annotation of 184 metabolites in the ASD extract, mainly comprising shikimates and phenylpropanoids (44.0%) and terpenoids (39.7%), with flavonoids constituting the most abundant superclass and including known food bioactives such as β-sitosterol, pentamethoxyflavone, naringin, and catechin. ADMET-based screening prioritized 31 absorbable constituents, while network pharmacology identified 179 inflammation-related targets, with TNF-α, IL6, STAT3, AKT1, and JAK2 emerging as key hubs. Enrichment analysis highlighted the TNF, PI3K-AKT, JAK-STAT, and AGE-RAGE pathways as major signaling routes associated with low-grade diet-related inflammation. Molecular docking and 300 ns molecular dynamics simulations further identified zeorinone as a stable dual binder of TNF-α and IL6, exhibiting the most favorable MM-PBSA binding free energies among the compounds selected for molecular dynamics analysis. Consistent with these computational findings, the ASD extract showed no cytotoxicity in RAW264.7 macrophages at 10-100 µg mL⁻¹ and significantly reduced LPS-induced TNF-α and IL6 secretion at 50-100 µg mL⁻¹, with effects comparable to dexamethasone. Overall, these findings establish SD as a promising source of dietary anti-inflammatory bioactives and provide a chemical and mechanistic basis for its potential development as a functional food ingredient or herbal beverage targeting chronic diet-related inflammation.
SN - 2046-2069
ER -