Author(s)

Wei Tao ¹, Zhang Yu ²

Affiliation(s)

¹ Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, China
² Chengdu First People's Hospital, Chengdu, Sichuan, 610041, China

Corresponding Author

Zhang Yu

ABSTRACT

This study aimed to systematically investigate the active ingredients, key targets, and potential molecular mechanisms of Liuwei Dihuang Decoction (LWDHD) in the treatment of osteoporosis (OP) using a network pharmacology approach. We identified the active ingredients and corresponding targets of LWDHD from the TCMSP database and collected OP-related targets from the GeneCards database. A protein-protein interaction (PPI) network was constructed using the STRING database to screen for key targets. Finally, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID platform. Resultly, the results indicated that LWDHD likely exerts its therapeutic effects primarily through core active ingredients such as quercetin, kaempferol, and beta-sitosterol. These compounds act on key targets including TNF, IL6, and CASP3, modulating pathways such as the TNF signaling pathway and HIF-1 signaling pathway. The potential mechanisms involve anti-inflammatory and antioxidant effects, as well as the regulation of apoptosis. In conclusion, this study preliminarily reveals that LWDHD treats OP through a "multi-component, multi-target, multi-pathway" collaborative network, laying a theoretical foundation for subsequent experimental validation and clinical application.

KEYWORDS

Osteoporosis; Liuwei Dihuang Decoction; Network Pharmacology; Mechanism of Action

CITE THIS PAPER

Wei Tao, Zhang Yu. Investigating the Therapeutic Mechanisms of Liuwei Dihuang Decoction for Osteoporosis via Network Pharmacology. MEDS Chinese Medicine (2026) Vol. 8: 9-19. DOI: http://dx.doi.org/10.23977/medcm.2026.080102.

REFERENCES

[1] Amin U, McPartland A, O'Sullivan M, Silke C. An overview of the management of osteoporosis in the aging female population. Womens Health (Lond). 2023;19:17455057231176655.
[2] Ensrud KE, Crandall CJ. Osteoporosis. Ann Intern Med. 2017;167(3):ITC17-ITC32.
[3] Martín-Merino E, Petersen I, Hawley S, et al. Risk of venous thromboembolism among users of different anti-osteoporosis drugs: a population-based cohort analysis including over 200,000 participants from Spain and the UK. Osteoporos Int. 2018;29(2):467-478.
[4] Li C, Lyu WH, Wang TT, et al. An epidemiological study on osteoporosis among 1088 medical staff. Chin J Osteoporos. 2015;21(10):1217-1220.
[5] Qaseem A, Forciea MA, McLean RM, et al. Treatment of low bone density or osteoporosis to prevent fractures in men and women: A clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017;166(11):818-839.
[6] Li LX, Wu LG, Liang BC, et al. Clinical efficacy evaluation of Liuwei Dihuang Pill in preventing and treating postmenopausal osteoporosis of kidney-yin deficiency type. Chin J Gen Pract. 2022;20(8):1392-1395.
[7] Zhang AQ, Cai XY, Xie YX. Analysis of the clinical efficacy of Liuwei Dihuang Pill in treating primary osteoporosis of liver-kidney yin deficiency type. Heilongjiang Med J. 2023;36(4):870-873.
[8] Zhang H, Zhou C, Zhang Z, et al. Integration of network pharmacology and experimental validation to explore the pharmacological mechanisms of Zhuanggu Busui Formula against osteoporosis. Front Endocrinol (Lausanne). 2022;12:841668.
[9] Zhang X, Zhang GQ, Gu BL, et al. Research progress on the effects of Salvia miltiorrhiza and its active components on bone metabolism. Chin J Osteoporos. 2015;21(1):112-116.
[10] Jian H, Yuan L, Wang X, et al. Icaritin and its glycosides enhance osteoblastic, but suppress osteoclastic, differentiation and activity in vitro. Life Sci. 2007;81(10):832-840.
[11] Gu YQ, Fu JY, Wu WQ, et al. Quercetin alleviates estrogen deficiency-induced osteoporosis through anti-senescence effect on bone cells. J Tongji Univ (Med Sci). 2019;40(3):274-280.
[12] Zeng YR, Zeng JC, Fan YG, et al. Effect of kaempferol on proliferation and differentiation of osteoblast MG-63. Lishizhen Med Mater Med Res. 2012;23:1463-1465.
[13] Rajavel T, Packiyaraj P, Suryanarayanan V, et al. β-Sitosterol targets Trx/Trx1 reductase to induce apoptosis in A549 cells via ROS mediated mitochondrial dysregulation and p53 activation. Sci Rep. 2018;8(1):584.
[14] Lin MZ, Zhao Y, Cai EB, et al. Antitumor effect of β-sitosterol on H22 tumor-bearing mice in vivo. Chin J Public Health. 2017;33(12):1797-1800.
[15] Wang S, Zhang H, Zhu Y, et al. Progranulin protects against osteoporosis by regulating osteoclast and osteoblast balance via TNFR pathway. J Cell Mol Med. 2025;29(3):e70385.
[16] He Y, Liu SQ, Wang CJ, et al. Role of IL-6 and TNF-α in the pathogenesis of postmenopausal osteoporosis. Chin J Clin Healthc. 2007;(1):41-43.
[17] Srivastava RK, Sapra L. The rising era of "immunoporosis": role of immune system in the pathophysiology of osteoporosis. J Inflamm Res. 2022;15:1667-1698.
[18] Yang XF, Hao YM, Lu K, et al. Mechanism of inflammatory bone marrow microenvironment affecting the occurrence and development of osteoporosis. Chin J Osteoporos. 2022;28(11):1614-1619.
[19] Ru JY, Wang YF. Osteocyte apoptosis: the roles and key molecular mechanisms in resorption-related bone diseases. Cell Death Dis. 2020;11(10):846.
[20] Djavaheri-Mergny M, Maiuri MC, Kroemer G. Cross talk between apoptosis and autophagy by caspase-mediated cleavage of Beclin 1. Oncogene. 2010;29(12):1717-1719.
[21] Ji YF, Jiang X, Li W, et al. Impact of interleukin-6 gene polymorphisms and its interaction with obesity on osteoporosis risk in Chinese postmenopausal women. Environ Health Prev Med. 2019;24(1):48.
[22] Wang Y, Wan C, Deng L, et al. The hypoxia-inducible factor α pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest. 2007;117(6):1616-1626.
[23] Chen W, Wu P, Yu F, Luo G, Qing L, Tang J. HIF-1α regulates bone homeostasis and angiogenesis, participating in the occurrence of bone metabolic diseases. Cells. 2022;11(22):3552.
[24] Zhong H, Cao C, Yang J, et al. Study on the relationship between HIF-1 signaling pathway and postmenopausal osteoporosis. J Sichuan Univ (Med Sci). 2017;48(6):862-868.

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