Next Article in Journal
Chelerythrine Protects Against Acetaminophen-Induced Acute Liver Injury: Insights from Gut Microbiota and Multi-Omics Analysis
Previous Article in Journal
Early-Life Hydrogen Sulfide Signaling as a Target for Cardiovascular–Kidney–Metabolic Syndrome Reprogramming
Previous Article in Special Issue
The MiBlend Randomized Trial: Investigating Genetic Polymorphisms in Personalized Responses to Fruit and Vegetable Interventions for Chronic Disease Prevention
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Antioxidants
Volume 14
Issue 9
10.3390/antiox14091065
antioxidants-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Elucidating Key Components and Mechanisms Underlying the Synergistic Anti-Type 2 Diabetes Effect of Morus alba L. and Siraitia grosvenorii Combination: An Integrated In Vitro Enzymology, Untargeted Metabolomics, and Network Pharmacology Approach

by
Fang He
1,†,
Shenglan Su
1,†,
Ruihan Song
1,
Yan Li
1,
Luyan Zou
1,
Zongjun Li
1,2,
Yu Xiao
1,2,
Aixiang Hou
1,2,
Ke Li
1,2 and
Yuanxiang Wang
1,2,*
1
College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China
2
Hunan Province Key Laboratory of Food Science and Biotechnology, Changsha 410128, China
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Antioxidants 2025, 14(9), 1065; https://doi.org/10.3390/antiox14091065
Submission received: 16 July 2025 / Revised: 15 August 2025 / Accepted: 28 August 2025 / Published: 29 August 2025
(This article belongs to the Special Issue Potential Health Benefits of Dietary Antioxidants)
Versions Notes

Abstract

Although mulberry leaf (Morus alba L., ML) and Siraitia grosvenorii (SG) individually demonstrate anti-diabetic properties, their combined efficacy against type 2 diabetes mellitus (T2DM) remains unexplored. This study systematically explored the multi-target mechanisms and synergistic potential of the MLSG combination (MLSG) for T2DM intervention. We evaluated the in vitro inhibitory activities of MLSG, ML, and SG on α-amylase and α-glucosidase, alongside antioxidant capacity assessments through DPPH/ABTS radical scavenging, reducing power, and FRAP assays. Bioactive metabolites were identified using non-targeted metabolomics, while core targets and pathways were predicted using network pharmacology and validated through molecular docking. The results reveal MLSG’s significantly enhanced inhibition of α-amylase (IC50 = 14.06 mg/mL) and α-glucosidase (IC50 = 0.02 mg/mL) compared to individual extracts, exhibiting 1.3–15.5-fold higher potency with synergistic effects (combination index < 1). MLSG also showed improved antioxidant capacity, outperforming SG in DPPH/ABTS+ scavenging and reducing power (p < 0.05), and surpassing ML in ABTS+ scavenging, reducing power, and FRAP values (p < 0.05). Metabolomics identified 26 MLSG-derived metabolites with anti-T2DM potential, and network analysis pinpointed 26 active components primarily targeting STAT3, AKT1, PIK3CA, EGFR, and MAPK1 to regulate T2DM pathways. Molecular docking confirmed strong binding affinities between these components and core targets. Collectively, MLSG exerts potent synergistic anti-T2DM effects through dual-enzyme inhibition, elevated antioxidant activity, and multi-target pathway regulation, providing a solid foundation for developing MLSG as functional food ingredients.
Keywords: mulberry leaf; Siraitia grosvenorii; type 2 diabetes; untargeted metabolomics; network pharmacology; functional food mulberry leaf; Siraitia grosvenorii; type 2 diabetes; untargeted metabolomics; network pharmacology; functional food

Share and Cite

MDPI and ACS Style

He, F.; Su, S.; Song, R.; Li, Y.; Zou, L.; Li, Z.; Xiao, Y.; Hou, A.; Li, K.; Wang, Y. Elucidating Key Components and Mechanisms Underlying the Synergistic Anti-Type 2 Diabetes Effect of Morus alba L. and Siraitia grosvenorii Combination: An Integrated In Vitro Enzymology, Untargeted Metabolomics, and Network Pharmacology Approach. Antioxidants 2025, 14, 1065. https://doi.org/10.3390/antiox14091065

AMA Style

He F, Su S, Song R, Li Y, Zou L, Li Z, Xiao Y, Hou A, Li K, Wang Y. Elucidating Key Components and Mechanisms Underlying the Synergistic Anti-Type 2 Diabetes Effect of Morus alba L. and Siraitia grosvenorii Combination: An Integrated In Vitro Enzymology, Untargeted Metabolomics, and Network Pharmacology Approach. Antioxidants. 2025; 14(9):1065. https://doi.org/10.3390/antiox14091065

Chicago/Turabian Style

He, Fang, Shenglan Su, Ruihan Song, Yan Li, Luyan Zou, Zongjun Li, Yu Xiao, Aixiang Hou, Ke Li, and Yuanxiang Wang. 2025. "Elucidating Key Components and Mechanisms Underlying the Synergistic Anti-Type 2 Diabetes Effect of Morus alba L. and Siraitia grosvenorii Combination: An Integrated In Vitro Enzymology, Untargeted Metabolomics, and Network Pharmacology Approach" Antioxidants 14, no. 9: 1065. https://doi.org/10.3390/antiox14091065

APA Style

He, F., Su, S., Song, R., Li, Y., Zou, L., Li, Z., Xiao, Y., Hou, A., Li, K., & Wang, Y. (2025). Elucidating Key Components and Mechanisms Underlying the Synergistic Anti-Type 2 Diabetes Effect of Morus alba L. and Siraitia grosvenorii Combination: An Integrated In Vitro Enzymology, Untargeted Metabolomics, and Network Pharmacology Approach. Antioxidants, 14(9), 1065. https://doi.org/10.3390/antiox14091065

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop