Advanced Search

Journal of Traditional Chinese Medicine >

2026 , Vol. 46 >Issue 3: 641 - 651

DOI: https://doi.org/10.19852/j.cnki.jtcm.2026.03.008

Original Articles

Network pharmacology and experimental validation of asiaticoside protecting against diabetic kidney disease by regulating 11β-hydroxysteroid dehydrogenase type 2

  • ZHU Qin ,
  • BI Peng ,
  • ZENG Jiali ,
  • ZHANG Yang ,
  • HU Lidan ,
  • CAO Zhongkai ,
  • ZHU Jingyu ,
  • JIN Qinyang
Expand
  • 1 Department of Nephrology (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310007, China
    2 the Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China
    3 Geriatric Medicine Center, Department of Geriatric Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China
First author contact:

ZHU Qin and BI Peng are co-first authors and contributed equally to this work

JIN Qinyang, Geriatric Medicine Center, Department of Geriatric Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China. jqy119@163.com, Telephone: +86-13777877613

Received date: 2024-12-22

  Accepted date: 2025-07-05

  Online published: 2026-06-08

Supported by

National Natural Science Foundation of China for Young Scholars: Study on the Mechanism of Compound Centella Asiatica Mediate 24-dehydrocholesterol Reductase (DHCR24)/Liver X Receptor (LXR) Signaling Axis to Regulate Macrophage Activation and Alleviate Microinflammation in Diabetic Kidney Disease(82205008);Medical Scientific Research Foundation of Zhejiang Province, China: Mechanistic Study of Asiaticoside in Regulating Macrophage Innate Immune Response in Diabetic Kidney Disease by Maintaining Cholesterol Homeostasis via the DHCR24/Desmosterol/ LXR Signaling Axis(2023RC242);Zhejiang Traditional Medicine and Technology Program, China: Research on the Construction of a Knowledge Graph for the Academic Thoughts and Clinical Experience of Famous Traditional Chinese Medicine Practitioner Chen Hongyu in Diagnosing and Treating Diabetic Kidney Disease(2023ZF137);Hangzhou Science and Technology Bureau project: Precise Diagnosis of Prostate Malignancies Using Artificial Intelligence(20231203A12);Special key research project of the Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine: Study on Clinical Auxiliary Decision-Making Model for Professor Wang Yongjun in Diagnosis and Treatment of Diabetic Kidney Disease Based on Graph Convolutional Neural Network(2022FSYYZZ14)

Fold

Abstract

OBJECTIVE: To explore the protective effects and mechanisms of Asiaticoside (AC) against diabetic kidney disease (DKD) through network pharmacology combined with in vitro and in vivoexperiments.

METHODS: Based on network pharmacology and RNA sequencing (RNA-Seq) analyses, combined with molecular docking, the core targets and signaling pathways of AC in the treatment of DKD were predicted and screened. Subsequently, the therapeutic effect of AC on DKD was validated in db/db mice and SV40-MES-13 cells, and its molecular mechanism was evaluated.

RESULTS: Network pharmacology and protein-protein interaction analyses identified 11-beta hydroxysteroid dehydrogenase type 2 (HSD11B2) as a potential key target for AC treatment of DKD. Molecular docking indicated strong affinity between AC derivative and HSD11B2. RNA-Seq analysis showed that AC significantly regulated steroid metabolism under diabetic conditions. In db/db mice, AC reduced urinary protein excretion, improved renal morphology, and protected renal function. AC also dose-dependently inhibited excessive proliferation of SV40-MES-13 cells in a high-glucose environment. Further validation showed that AC upregulated Hsd11b2 mRNA expression and HSD11B2 protein levels.

CONCLUSION: AC may alleviate DKD-related pathological processes by regulating Hsd11b2 gene expression and HSD11B2 protein levels.

Key words： diabetic kidney disease; asiaticoside; hydroxysteroid 11-beta dehydrogenase 2; network pharmacology; RNA-sequencing; molecular docking

Cite this article

ZHU Qin , BI Peng , ZENG Jiali , ZHANG Yang , HU Lidan , CAO Zhongkai , ZHU Jingyu , JIN Qinyang . Network pharmacology and experimental validation of asiaticoside protecting against diabetic kidney disease by regulating 11β-hydroxysteroid dehydrogenase type 2[J]. Journal of Traditional Chinese Medicine, 2026 , 46(3) : 641 -651 . DOI: 10.19852/j.cnki.jtcm.2026.03.008

References

1. Magliano DJ, Boyko EJ, committee IDFDAtes. IDF Diabetes Atlas. Brussels: International Diabetes Federation, 2021: 4-12.
2. Cheng HT, Xu X, Lim PS, Hung KY. Worldwide epidemiology of diabetes-related end-stage renal disease, 2000-2015. Diabetes Care 2021; 44: 89-97.
3. Cooper M, Warren AM. A promising outlook for diabetic kidney disease. Nat Rev Nephrol 2019; 15: 68-70.
4. Yin B, Bi YM, Fan GJ, Xia YQ. Molecular mechanism of the effect of Huanglian Jiedu decoction on type 2 diabetes mellitus based on network pharmacology and molecular docking. J Diabetes Res 2020; 2020: 5273914.
5. Shen S, Zhong H, Zhou X, et al. Advances in Traditional Chinese Medicine research in diabetic kidney disease treatment. Pharm Biol 2024; 62: 222-32.
6. Sari DCR, Budiharjo S, Afifah H, et al. Centella asiatica extract attenuates kidney fibrosis through reducing mesenchymal transition and inflammation in ureteral ligation model in mice. Front Pharmacol 2021; 12: 621894.
7. Arfian N, Setyaningsih WAW, Anggorowati N, Romi MM, Sari DCR. Ethanol extract of Centella asiatica (Gotu Kola) attenuates tubular injury through inhibition of inflammatory cytokines and enhancement of anti-fibrotic factor in mice with 5/6 subtotal nephrectomy. Malays J Med Sci 2019; 26: 53-63.
8. Masola B, Oguntibeju OO, Oyenihi AB. Centella asiatica ameliorates diabetes-induced stress in rat tissues via influences on antioxidants and inflammatory cytokines. Biomed Pharmacother 2018; 101: 447-57.
9. Pittella F, Dutra RC, Junior DD, Lopes MTP, Barbosa NR. Antioxidant and cytotoxic activities of Centella asiatica (L) Urb. Int J Mol Sci 2009; 10: 3713-21.
10. Xu J, Wang S, Feng T, Chen Y, Yang G. Hypoglycemic and hypolipidemic effects of total saponins from Stauntonia chinensis in diabetic db/db mice. J Cell Mol Med 2018; 22: 6026-38.
11. Wang Z, Liu J, Sun W. Effects of asiaticoside on levels of podocyte cytoskeletal proteins and renal slit diaphragm proteins in adriamycin-induced rat nephropathy. Life Sci 2013; 93: 352-8.
12. Tang S, Xie X, Wang M, Yang L, Wei W. Protective effects of asiaticoside on renal ischemia reperfusion injury in vivo and in vitro. Bioengineered 2022; 13: 10235-43.
13. Lu JZ, Ye D, Ma BL. Constituents, pharmacokinetics, and pharmacology of Gegen-Qinlian decoction. Front Pharmacol 2021; 12: 668418.
14. Ru J, Li P, Wang J, et al. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 2014; 6: 13.
15. Inderbinen SG, Zogg M, Kley M, Smie?ko M, Odermatt A. Species-specific differences in the inhibition of 11β-hydroxysteroid dehydrogenase 2 by itraconazole and posaconazole. Toxicol Appl Pharmacol 2021; 412: 115387.
16. Jiang J, Yin J, Liu X, Wang H, Lu G. Erzhi formula extracts reverse renal injury in diabetic nephropathy rats by protecting the renal podocytes. Evid Based Complement Alternat Med 2018; 2018: 1741924.
17. Zhu Q, Zeng J, Li J, et al. Effects of compound centella on oxidative stress and Keap1-Nrf2-ARE pathway expression in diabetic kidney disease rats. Evid Based Complement Alternat Med 2020; 2020: 9817932.
18. Sanaei-Ardekani M, Kamal S, Handy W, et al. Suppression of collagen Ⅳ alpha-2 subunit by prolyl hydroxylase domain inhibition via hypoxia-inducible factor-1 in chronic kidney disease. Pharmacol Res Perspect 2021; 9: e00872.
19. Khawaja N, Abu-Shennar J, Saleh M, Dahbour SS, Khader YS, Ajlouni KM. The prevalence and risk factors of peripheral neuropathy among patients with type 2 diabetes mellitus; the case of Jordan. Diabetol Metab Syndr 2018; 10: 8.
20. Welsh GI, Hale LJ, Eremina V, et al. Insulin signaling to the glomerular podocyte is critical for normal kidney function. Cell Metab 2010; 12: 329-40.
21. Ghosh P, Sahoo R, Vaidya A, Chorev M, Halperin JA. Role of complement and complement regulatory proteins in the complications of diabetes. Endocr Rev 2015; 36: 272-88.
22. Zhu Q, Li XH, Chen HY, Jin QY. The effects of compound centella formula on oxinflammation and silent information regulator 1 in a high-fat diet/streptozotocin-induced diabetic kidney disease rat model. Exp Ther Med 2021; 22: 962.
23. Maulidiani, Abas F, Khatib A, et al. Metabolic alteration in obese diabetes rats upon treatment with Centella asiatica extract. J Ethnopharmacol 2016; 180: 60-9.
24. Zhang Z, Ma J, Feng R, Wang Z. Centella asiatica inhibits renal interstitial fibrosis by regulating Smad3 and Smad7 expression in the TGFβ signaling pathway. Int J Clin Exp Pathol 2018; 11: 1009-17.
25. Jin L, Zheng D, Yang G, et al. Tilapia skin peptides ameliorate diabetic nephropathy in STZ-induced diabetic rats and HG-induced GMCs by improving mitochondrial dysfunction. Mar Drugs 2020: 18.
26. Alshahrani S. Renin-angiotensin-aldosterone pathway modulators in chronic kidney disease: a comparative review. Front Pharmacol 2023; 14: 1101068.
27. Homma M, Tanaka A, Hino K, et al. Assessing systemic 11β-hydroxysteroid dehydrogenase with serum cortisone/cortisol ratios in healthy subjects and patients with diabetes mellitus and chronic renal failure. Metabolism 2001; 50: 801-4.
28. Hunter RW, Ivy JR, Flatman PW, et al. Hypertrophy in the distal convoluted tubule of an 11β-hydroxysteroid dehydrogenase type 2 knockout model. J Am Soc Nephrol 2015; 26: 1537-48.
29. Evans LC, Livingstone DE, Kenyon CJ, et al. A urine-concentrating defect in 11β-hydroxysteroid dehydrogenase type 2 null mice. Am J Physiol Renal Physiol 2012; 303: F494-502.
30. Mune T, Suwa T, Morita H, et al. Longer HSD11B2 CA-repeat in impaired glucose tolerance and type 2 diabetes. Endocr J 2013; 60: 671-8.
31. Lavery GG, McTernan CL, Bain SC, Chowdhury TA, Hewison M, Stewart PM. Association studies between the HSD11B2 gene (encoding human 11β-hydroxysteroid dehydrogenase type 2), type 1 diabetes mellitus and diabetic nephropathy. Eur J Endocrinol 2002; 146: 553-8.
Options
Outlines

/

〈 〉