Network pharmacology: Anti-obesity and insulin-sensitizing effects of Danggui-Huangjing herb-pair via epidermal growth factor receptor/phosphatidylinositol 3-kinase/protein kinase B pathway

doi:10.4239/wjd.v17.i5.118275

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May 15, 2026 (publication date) through May 14, 2026

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World Journal of Diabetes

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1948-9358

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Diabetes. May 15, 2026; 17(5): 118275
Published online May 15, 2026. doi: 10.4239/wjd.v17.i5.118275

Network pharmacology: Anti-obesity and insulin-sensitizing effects of Danggui-Huangjing herb-pair via epidermal growth factor receptor/phosphatidylinositol 3-kinase/protein kinase B pathway

Wen-Jing Li, Jing-Jing Xu, Hannah Shi Tiang, Tong-Hua Liu, Li-Li Wu

Wen-Jing Li, Jing-Jing Xu, Tong-Hua Liu, Li-Li Wu, Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing 102488, China

Jing-Jing Xu, College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China

Hannah Shi Tiang, Holistic Acupuncture and TCM Centre, Sibu 96000, Sarawak, Malaysia

Co-first authors: Wen-Jing Li and Jing-Jing Xu.

Author contributions: Li WJ and Xu JJ performed validation (for western blot experiments) as co-first authors; Li WJ, Xu JJ, and Tiang HS performed the experiments, and curated and analyzed data; Li WJ, Xu JJ, and Liu TH conceptualized and coordinated the study; Xu JJ wrote the original draft of the manuscript, performed software (for molecular dynamics simulation using GROMACS 2022); Tiang HS, Liu TH, and Wu LL reviewed and edited the manuscript; Wu LL acquired funding and supervised the project; all authors read and approved the final version of the article.

Supported by Innovation Base for Integrating International Expertise in TCM Prevention and Management of Diabetes Mellitus and Complications, No. B20055; Traditional Chinese Medicine Intervention of Metabolic Diseases Research Project, No. 90020165120003; and Key Laboratory of Health Cultivation of the Ministry of Education Project, No. 2024-JYB-KYPT-002.

Institutional animal care and use committee statement: The animal experimental protocol was reviewed and approved by the Experimental Animal Ethics Subcommittee of Beijing University of Chinese Medicine (No. BUCM-2024091301-3253). All procedures were performed in strict accordance with the ethical standards for experimental animal care.

Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: The datasets supporting the findings of this study are available from the corresponding author upon reasonable request.

Corresponding author: Li-Li Wu, PhD, Associate Professor, Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, No. 11 North 3^rd-Ring East Road, Chaoyang District, Beijing 102488, China. qingniao_566@163.com

Received: December 30, 2025
Revised: February 8, 2026
Accepted: March 16, 2026
Published online: May 15, 2026
Processing time: 132 Days and 17.7 Hours

Abstract

BACKGROUND

Clinical obesity, a major type 2 diabetes mellitus risk factor linked to insulin resistance and dyslipidemia, responds poorly to single-target therapies. Danggui (Angelica sinensis, DG) and Huangjing (Polygonatum sibiricum, HJ) are traditional Chinese medicine herbs combined to regulate glucose-lipid metabolism.

AIM

To elucidate the synergistic anti-obesity/insulin-sensitizing effects of the DG-HJ (DH) pair and identify epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)-mediated mechanisms via network pharmacology and experimental validation.

METHODS

Network pharmacology, molecular docking, 100 nanosecond molecular dynamics simulation, and in vivo experiments in high-fat diet-fed mice (normal control/model control/DG/HJ/DH groups) were performed. Metabolic phenotypes, histopathology, serum cytokines, and hepatic EGFR/PI3K/AKT-related expression were assessed after an 8-week intervention.

RESULTS

Network pharmacology analysis identified 15 core components, 73 targets, and PI3K/AKT as the core pathway, with key components showing high affinity to estrogen receptor 1/EGFR/signal transducer and activator of transcription 3. In vivo, DH reduced body weight and fat mass, improved glucose-lipid profiles, alleviated steatosis and inflammation, enhanced insulin sensitivity, normalized leptin/adiponectin balance, and regulated EGFR/PI3K/AKT signaling (P < 0.05 or P < 0.01 vs model control), with superior efficacy to DG/HJ alone.

CONCLUSION

DH exerts additive or synergistic anti-obesity effects via the EGFR/PI3K/AKT pathway, ameliorating metabolic disorders and insulin resistance, providing a scientific basis for traditional Chinese medicine-Western medicine integration and type 2 diabetes mellitus prevention.

Keywords: Danggui-Huangjing herb pair; Clinical obesity; Insulin resistance; Epidermal growth factor receptor/phosphatidylinositol 3-kinase/protein kinase B signaling pathway; Metabolic disorder; Network pharmacology; Translational medicine

Core Tip: Clinical obesity, a major type 2 diabetes mellitus risk factor with insulin resistance and inflammation, responds poorly to single-target therapies. This study integrated network pharmacology, molecular docking, 100 nanosecond molecular dynamics simulation, and high-fat diet-fed mouse experiments to clarify the synergistic mechanism of Danggui-Huangjing herb pair. Danggui-Huangjing targets epidermal growth factor receptor/estrogen receptor 1/signal transducer and activator of transcription 3 via the phosphatidylinositol 3-kinase/protein kinase B pathway, reducing body weight/fat, improving glucose-lipid metabolism, and alleviating inflammation – efficacy superior to single herbs – providing a scientific basis for clinical application.