Advanced Search

Journal of Traditional Chinese Medicine >

2026 , Vol. 46 >Issue 2: 382 - 391

DOI: https://doi.org/10.19852/j.cnki.jtcm.2026.02.010

Original Articles

Mechanism of Shaofu Zhuyu decoction (少腹逐瘀汤) in improving diabetic mellitus erectile dysfunction via inhibition of ferroptosis based on network pharmacology and experimental validation

  • WANG Zhuo ,
  • MAO Yinhui ,
  • ZANG Yueyue ,
  • HE Shuangyan ,
  • SUN Juntao ,
  • WEI Zhitao ,
  • WANG Mingxing ,
  • YANG Yong
Expand
  • 1 Changchun University of Chinese Medicine, Changchun 130117, China
    2 Department of Urology, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China
    3 Department of Experimental Center, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China
WANG Mingxing, Department of Experimental Center, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China. 578658688@qq.com;
YANG Yong, Department of Urology, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China. yongyang301@163.com; Telephone: +86-18946546330

Received date: 2025-05-09

  Accepted date: 2026-01-12

  Online published: 2026-04-04

Supported by

National Natural Science Foundation of China (Mechanism of Ginsenoside Rk1 in Treating Ulcerative Colitis by Regulating Macrophage Polarization Based on Epidermal Growth Factor Receptor Phosphorylation)(82374128);Department of Science and Technology of Jilin Province (Research on the Mechanism of Endogenous Stem Cells in Mechanical Force Therapy for Neurogenic Erectile Dysfunction)(ydzj202301zyts138);Projects in Health Commission of Jilin Province (Research on the Mechanism of Low-intensity Pulsed Ultrasound in the Treatment of Late-onset Hypogonadism via the Wnt Family Member 5a/beta-Catenin Axis(2022jc043);Projects in Health Commission of Jilin Province (Research on the Mechanism of Microencapsulated Adipose-Derived Stem Cells in the Treatment of Neurogenic Erectile Dysfunction)(2022jc048)

Fold

Abstract

OBJECTIVE: To explore the medication patterns and mechanisms of action of Shaofu Zhuyu decoction (少腹逐瘀汤, SFZYD) in inhibiting ferroptosis through the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1)/glutathione peroxidase 4 (GPX4) pathway to improve diabetes mellitus-induced erectile dysfunction (DMED).

METHODS: Firstly, data mining was employed to identify the medication patterns of Traditional Chinese Medicine (TCM) in treating DMED. Secondly, network pharmacology combined with a ferroptosis database was used to predict the targets. Subsequently, cell counting kit-8, 4',6-diamidino-2-phenylindole staining, reverse transcription-polymerase chain reaction (RT-PCR), and reagent kits were utilized to assess the repair effects of SFZYD on corpus cavernosum endothelial cells (CCECs) induced by high glucose (HG). Metabolic indicators, hematoxylin-eosin staining, and Masson staining were performed to observe the restorative effects of SFZYD on erectile function and penile tissue in diabetic rats. Finally, using Nrf2 inhibitors, the expression of related proteins and mRNAs was detected through Western blotting and RT-PCR. Reactive oxygen species levels and mitochondrial membrane potential were detected by flow cytometry.

RESULTS: Data mining revealed that the prescription rules for blood stasis-type DMED coincide with the treatment principles of SFZYD. Network pharmacology identified 48 ferroptosis-related targets, primarily heme oxygenase 1 (HMOX1) and GPX4. Kyoto Encyclopedia of Genes and Genomes enrichment analysis associated these targets with the ferroptosis pathway. SFZYD repaired HG-induced CCECs damage and restored HMOX1 and GPX4 mRNA levels. in vivo, SFZYD effectively alleviated erectile dysfunction and repaired blood sinuses and fibrosis in diabetic rats. Following Nrf2 inhibition, the expression of Nrf2, HMOX1, and GPX4 decreased, while SFZYD intervention reversed these effects, improving ferroptosis and oxidative stress indicators.

CONCLUSION: This study explored the potential mechanisms and efficacy of the TCM prescription SFZYD in treating DMED through data mining, network pharmacology analysis, cellular experiments, and animal experiments. It verified its effectiveness in repairing HG-induced CCECs damage, improving the pathological state of penile tissue in diabetic rats, and restoring erectile function by regulating the Nrf2/HO-1/GPX4 signaling pathway. This provides new insights and scientific evidence for treating DMED with TCM.

Key words： diabetes mellitus; erectile dysfunction; ferroptosis; NF-E2-related factor 2; heme oxygenase 1; phospholipid hydroperoxide glutathione peroxidase; network pharmacology

Cite this article

WANG Zhuo , MAO Yinhui , ZANG Yueyue , HE Shuangyan , SUN Juntao , WEI Zhitao , WANG Mingxing , YANG Yong . Mechanism of Shaofu Zhuyu decoction (少腹逐瘀汤) in improving diabetic mellitus erectile dysfunction via inhibition of ferroptosis based on network pharmacology and experimental validation[J]. Journal of Traditional Chinese Medicine, 2026 , 46(2) : 382 -391 . DOI: 10.19852/j.cnki.jtcm.2026.02.010

References

1. Zhu B, Zhang X, Niu L, Yang C, Jin X, Liu F. Nlrp 3 inhibitor combined with yimusake improves erectile dysfunction in rats with diabetes mellitus through the attenuation of pyroptosis. Heliyon 2024; 10: e38626.
2. Li B, Hu P, Liu K, et al. Mirna-100 ameliorates diabetes mellitus-induced erectile dysfunction by modulating autophagy, anti-inflammatory, and antifibrotic effects. Andrology 2024; 12: 1280-93.
3. Castela A, Costa C. Molecular mechanisms associated with diabetic endothelial-erectile dysfunction. Nat Rev Urol 2016; 13: 266-74.
4. Zhang XH, Filippi S, Morelli A, et al. Testosterone restores diabetes-induced erectile dysfunction and sildenafil responsiveness in two distinct animal models of chemical diabetes. J Sex Med 2006; 3: 253-64.
5. Chen YL, Ouyang L, Meng LL, et al. Electroacupuncture ameliorates blood-brain barrier disruption after ischemic stroke through histone acetylation regulation at the matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 2 genes. J Tradit Chin Med 2024; 44: 734-44.
6. Zuo S, Yu J, Pan H, Lu L. Novel insights on targeting ferroptosis in cancer therapy. Biomark Res 2020; 8: 50.
7. Liang C, Zhang X, Yang M, Dong X. Recent progress in ferroptosis inducers for cancer therapy. Adv Mater 2019; 31: e1904197.
8. Zou Y, Schreiber SL. Progress in understanding ferroptosis and challenges in its targeting for therapeutic benefit. Cell Chem Biol 2020; 27: 463-71.
9. Zupo V, Costantini M, Aflalo ED, et al. Ferroptosis precedes apoptosis to facilitate specific death signalling by fatty acids. Proc Biol Sci 2023; 290: 20231327.
10. Sun LJ, Li CF, Liu JG, et al. Efficacy of Sailuotong on neurovascular unit in amyloid precursor protein/presenilin-1 transgenic mice with Alzheimer’s disease. J Tradit Chin Med 2024; 44: 289-302.
11. Xu W, Sun T, Wang J, et al. Ferroptosis is involved in corpus cavernosum smooth muscle cells impairment in diabetes mellitus-induced erectile dysfunction. Andrology 2023; 11: 332-43.
12. Liu P, Zhang Z, Cai Y, Li Z, Zhou Q, Chen Q. Ferroptosis: mechanisms and role in diabetes mellitus and its complications. Ageing Res Rev 2024; 94: 102201.
13. Feng H, Liu Q, Deng Z, et al. Human umbilical cord mesenchymal stem cells ameliorate erectile dysfunction in rats with diabetes mellitus through the attenuation of ferroptosis. Stem Cell Res Ther 2022; 13: 450.
14. Yang R, Liu C, Li Q, et al. Artificial intelligence based identification of the functional role of hirudin in diabetic erectile dysfunction treatment. Pharmacol Res 2021; 163: 105244.
15. Su S, Cui W, Duan JA, et al. Uhplc-ms simultaneous determination and pharmacokinetic study of three aromatic acids and one monoterpene in rat plasma after oral administration of Shaofu Zhuyu decoction. Am J Chin Med 2013; 41: 697-715.
16. Liu L, Duan JA, Tang YP, et al. The protective effects of the active fraction of Shaofu Zhuyu decoction on hydrogen peroxide-induced oxidative injury in vascular smooth muscle cells. Molecules 2010; 15: 5066-78.
17. Hong M, Jung J, Park HS, et al. Shaofu Zhuyu decoction ameliorates obesity-mediated hepatic steatosis and systemic inflammation by regulating metabolic pathways. PLoS One 2017; 12: e0178514.
18. Zhang Y, Kang A, Deng H, et al. Simultaneous determination of sulfur compounds from the sulfur pathway in rat plasma by liquid chromatography tandem mass spectrometry: application to the study of the effect of Shaofu Zhuyu decoction. Anal Bioanal Chem 2018; 410: 3743-55.
19. Huang HM, Yang MJ, Li T, et al. Neferine inhibits the progression of diabetic nephropathy by modulating the mir-17-5p/nuclear factor e2-related factor 2 axis. J Tradit Chin Med 2024; 44: 44-53.
20. Xia XC, Xue SP, Song GY, et al.Anti-oxidative and immunological role of cyclocarya paliurus polysaccharide on the liver injury of diabetic rats. J Tradit Chin Med 2024; 44: 1146-52.
21. Zuo X, Zeng H, Yang X, He D, Wang B, Yuan J. Atg5-mediated lipophagy induces ferroptosis in corneal epithelial cells in dry eye disease. Invest Ophthalmol Vis Sci 2024; 65: 12.
22. Zou Z, Hu W, Kang F, et al. Interplay between lipid dysregulation and ferroptosis in chondrocytes and the targeted therapy effect of metformin on osteoarthritis. J Adv Res 2024; 57: 1-16.
23. Zhu LH, Sun ZW, Guan YY, et al. Differences in vascular endothelial function and serum proteome between obese people with phlegm-dampness constitution and balanced constitution. J Tradit Chin Med 2024; 44: 188-96.
24. Zou Y, Palte MJ, Deik AA, et al. A gpx4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis. Nat Commun 2019; 10: 1617.
25. Zou P, Lin R, Fang Z, et al. Implanted, wireless, self-powered photodynamic therapeutic tablet synergizes with ferroptosis inducer for effective cancer treatment. Adv Sci (Weinh) 2023; 10: e2302731.
26. Zi Y, Wang X, Zi Y, et al. Cigarette smoke induces the ros accumulation and inos activation through deactivation of nrf-2/sirt3 axis to mediate the human bronchial epithelium ferroptosis. Free Radic Biol Med 2023; 200: 73-86.
27. Zhu Z, Li J, Song Z, Li T, Li Z, Gong X. Tetramethylpyrazine attenuates renal tubular epithelial cell ferroptosis in contrast-induced nephropathy by inhibiting transferrin receptor and intracellular reactive oxygen species. Clin Sci (Lond) 2024; 138: 235-49.
28. Sun CB, Xu GP, Jiang P, et al. Protective effect of Zhizi Huangqi Shanzha formula on aflatoxin poisoning in mice and its effect on intestinal flora. J Tradit Chin Med 2024; 44: 926-33.
29. Zou J, Zheng Z, Ye W, et al. Targeting the smooth muscle cell KEAP1-Nrf2-STING axis with pterostilbene attenuates abdominal aortic aneurysm. Phytomedicine 2024; 130: 155696.
30. Zou W, Chen C, Zhong Y, Zhang Z, Gu J, Wei Y. PI3K/Akt pathway mediates Nrf2/ARE activation in human L02 hepatocytes exposed to low-concentration HBCDs. Environ Sci Technol 2013; 47: 12434-40.
31. Zuo T, Fang T, Zhang J, et al. Ph-sensitive molecular-switch-containing polymer nanoparticle for breast cancer therapy with ferritinophagy-cascade ferroptosis and tumor immune activation. Adv Healthc Mater 2021; 10: e2100683.
32. Lü QK, Tao KX, Yao XY, et al. Melatonin MT1 receptors regulate the Sirt1/Nrf2/Ho-1/Gpx4 pathway to prevent α-synuclein-induced ferroptosis in Parkinson's disease. J Pineal Res 2024; 76: e12948.
33. Zhao X, Huang H, Jiang X, et al. Supramolecular nanoparticle loaded with bilirubin enhances cartilage protection and alleviates osteoarthritis via modulating oxidative stress and inflammatory responses. Colloids Surf B Biointerfaces 2025; 245: 114243.
Options
Outlines

/

〈 〉