ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Bone Research
This article is part of the Research TopicRecent Advances in the Management of Osteoporosis: Prevention, Diagnosis and TreatmentView all 16 articles
Exploring the Mechanism of Heidihuang Pill in the Treatment of Osteoporosis Based on Network Pharmacology, Molecular Docking, and Experimental Validation
Provisionally accepted
- 1College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
- 2Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, China
- 3Shandong University of Traditional Chinese Medicine, Jinan, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Currently, studies have focused on exploring anti-osteoporosis (OP) therapies. As a classic prescription in traditional Chinese medicine (TCM), the Heidihuang Pill (HP) was clinically shown to alleviate OP. However, the mechanism behind its effect remains unclear. Methods: Network pharmacology was used to identify the active ingredients, targets, and mechanisms of action of HP in treating OP. Molecular docking technology was then used to verify the interactions between the active ingredients and target proteins. Finally, an OP rat model was established through in vivo experiments to validate the results obtained from network pharmacology. Results: Overall, 178 targets were retrieved, which are key targets of HP for treating OP. Protein-Protein Interaction network analysis showed that RAC-alpha serine/threonine-protein kinase (Akt1) (degree =132) was the most reliable target of HP for treating OP. Gene Ontology functional analysis revealed that the regulation of HP on OP mainly occurs as follows: it mainly manifests as a response to hormones in biological processes; it mainly acts on membrane rafts in cellular components; and it mainly involves the binding of transcription factors in molecular functions. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the Advanced Glycation End products/Receptor for Advanced Glycation End products (AGE-RAGE) signaling pathway in diabetic complications and the hypoxia-inducible factor (HIF)-1 signaling pathway are the main pathways involved in the HP treatment of OP. Molecular docking results showed that Akt1 has a good binding ability with peoniflorin, with a binding energy of -56.66 kcal/mol. In vivo experiments confirmed that the trabecular bone mineral density, trabecular number, and bone volume fraction of model rats treated with HP significantly increased (P < 0.05 vs. the model group). Histopathological staining showed that the number and morphology of the trabecular bones improved (vs. the model group). Additionally, the expression of HIF-1 signaling protein in rat bone tissue increased, while the expression of AGE/RAGE signaling protein decreased (P < 0.05, vs. the model group). Conclusion: Peoniflorin, the main active ingredient in HP, acts on Akt1 and treats OP through the AGE-RAGE and HIF-1 signaling pathways.
Keywords: Heidihuang Pill, Osteoporosis, AGE-RAGE signaling pathway, HIF-1signaling pathway, Network Pharmacology
Received: 11 Jul 2025; Accepted: 28 Nov 2025.
Copyright: © 2025 Tian, Cui, Tian, Chen, Liu, Zhang, Hao and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zeng-Hui Tian
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.