Journal of Traditional Chinese Medicine >
Bushen Tongluo recipe (补肾通络方) improves oxidative stress homeostasis, inhibits transforming growth factor/Notch signaling pathway, and regulates the lncRNA maternally expressed gene 3/miR-145 axis to delay diabetic kidney disease
Received date: 2024-04-22
Accepted date: 2024-09-30
Online published: 2025-05-21
OBJECTIVES: To investigate the effect of Bushen Tongluo recipe (BSTLR, 补肾通络方) on rats with diabetic kidney disease (DKD) and to explore the underlying mechanism of action.
METHODS: The rat model of DKD was established, and rats were treated with different doses of BSTLR. Body weight and the levels of urinary protein, α1-microglobulin, glucose, blood urea nitrogen, creatinine, Cystatin C, superoxide dismutase, malondialdehyde, and catalase were analyzed biochemically or by enzyme-linked immunosorbent assay. The pathological damage to renal tissues was assessed by hematoxylin-eosin staining. Immunohistochemical staining was carried out to detect the expression levels of fibronectin, E-cadherin, α-smooth muscle actin, laminin, vimentin, collagen type Ⅳ in kidney tissues. Western blot analysis was conducted to analyze the expression levels of Nephrin, Desmin, Podocin, transforming growth factor-β1, mothers against decapentaplegic homolog 3 (Smad3), Notch1, jagged, hairy and enhancer of split 1 (Hes1) in kidney tissues, and the expression levels of maternally expressed gene 3 (MEG3) and miR-145 were measured by quantitative reverse transcription-polymerase chain reaction. Moreover, dual-luciferase reporter assay was employed to verify the binding of miR-145 to MEG3.
RESULTS: BSTLR increased the body weight of DKD rats, effectively ameliorated the renal function and pathological injury in DKD, regulated the balance of renal oxidative stress, inhibited the TGF/Notch signaling pathway, and affected the variations in the lncRNA MEG3/miR-145 axis.
CONCLUSION: BSTLR improved oxidative stress homeostasis, inhibited the TGF/Notch signaling pathway, and regulated the lncRNA MEG3/miR-145 axis, effectively delaying the progression of DKD.
Bojun XU , Tian TAO , Liangbin ZHAO , Hui ZHENG , huakui ZHAN , Julan GUO . Bushen Tongluo recipe (补肾通络方) improves oxidative stress homeostasis, inhibits transforming growth factor/Notch signaling pathway, and regulates the lncRNA maternally expressed gene 3/miR-145 axis to delay diabetic kidney disease[J]. Journal of Traditional Chinese Medicine, 2025 , 45(3) : 561 -570 . DOI: 10.19852/j.cnki.jtcm.2025.03.011
| 1. | Tinajero MG, Malik VS. An update on the epidemiology of type 2 diabetes: a global perspective. Endocrinol Metab Clin North Am 2021; 50: 337-55. |
| 2. | Guo W, Song Y, Sun Y, et al. Systemic immune-inflammation index is associated with diabetic kidney disease in type 2 diabetes mellitus patients: evidence from NHANES 2011-2018. Front Endocrinol (Lausanne) 2022; 13: 1071465. |
| 3. | Rayego-Mateos S, Rodrigues-Diez RR, Fernandez-Fernandez B, et al. Targeting inflammation to treat diabetic kidney disease: the road to 2030. Kidney Int 2023; 103: 282-96. |
| 4. | Barrera-Chimal J, Lima-Posada I, Bakris GL, et al. Mineralocorticoid receptor antagonists in diabetic kidney disease -mechanistic and therapeutic effects. Nat Rev Nephrol 2022; 18: 56-70. |
| 5. | Park EG, Pyo SJ, Cui Y, et al. Tumor immune microenvironment lncRNAs. Brief Bioinform 2022; 23: bbab504. |
| 6. | Chen T, Shi Z, Zhao Y, et al. LncRNA Airn maintains LSEC differentiation to alleviate liver fibrosis via the KLF2-eNOS-sGC pathway. BMC Med 2022; 20: 335. |
| 7. | Wu YY, Wu S, Li XF, et al. LncRNA MEG3 reverses CCl(4)-induced liver fibrosis by targeting NLRC5. Eur J Pharmacol 2021; 911: 174462. |
| 8. | He Y, Dan Y, Gao X, et al. DNMT1-mediated lncRNA MEG3 methylation accelerates endothelial-mesenchymal transition in diabetic retinopathy through the PI3K/Akt/mTOR signaling pathway. Am J Physiol Endocrinol Metab 2021; 320: E598-e608. |
| 9. | Xu BW, Rao Y, Wang L, et al. LncRNA MEG3 inhibits renal fibrinoid necrosis of diabetic nephropathy via the MEG3/miR-21/ORAI1 axis. Mol Biol Rep 2023; 50: 3283-295. |
| 10. | Zha F, Qu X, Tang B, et al. Long non-coding RNA MEG3 promotes fibrosis and inflammatory response in diabetic nephropathy via miR-181a/Egr-1/TLR4 axis. Mol Biol Rep 2019; 11: 3716-730. |
| 11. | Mahtal N, Lenoir O. MicroRNAs in kidney injury and disease. Nat Rev Nephrol 2022; 18: 643-62. |
| 12. | Qin R, Huang W, Huang Y, et al. lncRNA MEG3 modulates hepatic stellate cell activation by sponging miR-145 to regulate PPARγ. Mol Med Rep 2022; 25: 3. |
| 13. | Wang T, Cui S, Liu X, et al. LncTUG1 ameliorates renal tubular fibrosis in experimental diabetic nephropathy through the miR-145-5p/dual-specificity phosphatase 6 axis. Ren Fail 2023; 45: 2173950. |
| 14. | Liu XJ, Hu XK, Yang H, et al. A review of Traditional Chinese Medicine on treatment of diabetic nephropathy and the involved mechanisms. Am J Chin Med 2022; 50: 1739-79. |
| 15. | Liu H, Wang G, Wang J, et al. Bushentongluo recipe (BSTL) attenuates bone destruction by inhibiting NF-κB/RANK/RANKL pathway in collagen-induced arthritis (CIA) rats. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021; 37: 205-11. |
| 16. | Yuan H, Xiao L, Min W, et al. Bu-Shen-Tong-Luo decoction prevents bone loss via inhibition of bone resorption and enhancement of angiogenesis in ovariectomy-induced osteoporosis of rats. J Ethnopharmacol 2018; 220: 228-38. |
| 17. | Xiang E, Han B, Zhang Q, et al. Human umbilical cord-derived mesenchymal stem cells prevent the progression of early diabetic nephropathy through inhibiting inflammation and fibrosis. Stem Cell Res Ther 2020; 11: 336. |
| 18. | Mohamed RH, Sedky AA. Sitagliptin's renoprotective effect in a diabetic nephropathy model in rats: the potential role of PI3K/AKT pathway. Fundam Clin Pharmacol 2022; 36: 324-37. |
| 19. | Wang Z, Fu W, Huo M, et al. Spatial-resolved metabolomics reveals tissue-specific metabolic reprogramming in diabetic nephropathy by using mass spectrometry imaging. Acta Pharm Sin B 2021; 11: 3665-77. |
| 20. | An X, Zhang Y, Cao Y, et al. Punicalagin protects diabetic nephropathy by inhibiting pyroptosis based on TXNIP/NLRP3 pathway. Nutrients 22 2020; 12: 1516. |
| 21. | Liu J, Zhang J, Hou MH, et al. Clinical efficacy of linagliptin combined with irbesartan in patients with diabetic nephropathy. Pak J Med Sci 2022; 38: 52-6. |
| 22. | Teuma L, Eshwaran R, Tawokam Fongang U, et al. Glucosamine inhibits extracellular matrix accumulation in experimental diabetic nephropathy. Front Nutr 2022; 9: 1048305. |
| 23. | Tang C, Wang M, Liu J, et al. A cyclopentanone compound attenuates the over-accumulation of extracellular matrix and fibrosis in diabetic nephropathy via downregulating the TGF-β/p38MAPK axis. Biomedicines 2022; 10: 3270. |
| 24. | Liu J, Sun M, Xia Y, et al. Phloretin ameliorates diabetic nephropathy by inhibiting nephrin and podocin reduction through a non-hypoglycemic effect. Food Funct 2022; 13: 6613-22. |
| 25. | Ashraf A, Akhtar T. Sitagliptin ameliorates diabetic nephropathy by upregulating renal nephrin and podocin expression through modulation of adipokines levels. Fundam Clin Pharmacol 2023; 37: 549-55. |
| 26. | Ma T, Li X, Zhu Y, et al. Excessive activation of Notch signaling in macrophages promote kidney inflammation, fibrosis, and necroptosis. Front Immunol 2022; 13: 835879. |
| 27. | Chen J, Ou Z, Gao T, et al. Ginkgolide B alleviates oxidative stress and ferroptosis by inhibiting GPX4 ubiquitination to improve diabetic nephropathy. Biomed Pharmacother 2022; 156: 113953. |
| 28. | Ma L, Wu F, Shao Q, et al. Baicalin alleviates oxidative stress and inflammation in diabetic nephropathy via Nrf2 and MAPK signaling pathway. Drug Des Devel Ther 2021; 15: 3207-21. |
| 29. | Sapian S, Budin SB, Taib IS, et al. Role of polyphenol in regulating oxidative stress, inflammation, fibrosis, and apoptosis in diabetic nephropathy. Drug Des Devel Ther 2022; 22: 453-70. |
| 30. | Wu H, Xu F, Huang X, et al. Lupenone improves type 2 diabetic nephropathy by regulating NF-κB pathway-mediated inflammation and TGF-β1/Smad/CTGF -associated fibrosis. Phytomedicine 2023; 118: 154959. |
| 31. | Luo J, Jiang J, Huang H, et al. C-peptide ameliorates high glucose-induced podocyte dysfunction through the regulation of the Notch and TGF-β signaling pathways. Drug Dev Res 2021; 142: 170557. |
| 32. | Liu B, Deng C, Tan P. Ombuin ameliorates diabetic nephropathy in rats by anti-inflammation and antifibrosis involving Notch 1 and PPAR γ signaling pathways. Drug Dev Res 2022; 83: 1270-80. |
| 33. | Li J, Jiang X, Duan L, et al. Long non-coding RNA MEG3 impacts diabetic nephropathy progression through sponging miR-145. Am J Transl Res 2019; 11: 6691-8. |
| 34. | Guo K, Qian K, Shi Y, et al. LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH 2 by sponging miR-150-5p. Cell Death Dis 2021; 12: 1097. |
| 35. | Karagkouni D, Karavangeli A, Paraskevopoulou MD, et al. Characterizing miRNA-lncRNA interplay. Methods Mol Biol 2021; 2372: 243-62. |
/
| 〈 |
|
〉 |