Advanced Search

Journal of Traditional Chinese Medicine >

2023 , Vol. 43 >Issue 4: 667 - 675

DOI: https://doi.org/10.19852/j.cnki.jtcm.20230428.001

Qizhi Jiangtang capsule (芪蛭降糖胶囊) activates podocyte autophagy in diabetic kidney disease by inhibiting phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways

  • Zhaoan GUO ,
  • Lina SUN ,
  • Yingying LIU ,
  • Ruifeng LI ,
  • Chong LIU ,
  • Ke DIAO ,
  • Jing SHI ,
  • Jun SUN
Expand
  • 1 Department of Nephrology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, China
    2 Department of Nephrology, Linyi People’s Hospital, Linyi 276003, China
    3 Shandong University of Traditional Chinese Medicine, Jinan 250355, China
    4 Shandong GuoxinYiyang Group Zibo Hospital, Zibo 255051, China

Received date: 2022-01-02

  Accepted date: 2022-07-27

  Online published: 2023-04-28

Supported by

National Natural Science Foundation of China Project: Experimental Research on Podocyte Autophagy of Diabetic Nephropathy Regulated by Qizhi Jiangtang Capusul(81874440);Natural Science Foundation of Shandong Province Project: Curcumin Ameliorates Diabetic Nephropathy via Regulating the Intestinal Barrier-Inflammation “cross-talk”(ZR2020QH063)

Fold

Abstract

OBJECTIVE: To investigate the therapeutic action and mechanism of the Qizhi Jiangtang capsule (芪蛭降糖胶囊, QZJT) on diabetic kidney disease (DKD) treatment.

METHODS: This experiment used db/db mice and podocytes (MPC5) to develop DKD model. Evaluation of the effect of the QZJT on db/db mice by testing urine and blood biochemical parameters (24-h urinary albumin, serum creatinine, blood urine nitrogen), pathological kidney injury, and podocyte integrity. Moreover, autophagosomes in podocytes of DKD mice and cultured podocytes were detected using electron microscopy. Additionally, Western blotting was applied to detect the expression of podocyte marker protein (podocin), autophagy-associated proteins, and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway changes in vivo and in vitro.

RESULTS: QZJT significantly reduced urine protein, blood nitrogen urea, and serum creatinine and showed histological restoration of renal tissues. QZJT also significantly improved the down-regulation of podocin and foot fusion and effacement in db/db mice. QZJT increased autophagic vesicles in mice and cultured podocytes. QZJT also upregulated microtubule-associated protein 1 light chain 3-II (LC3-II) / (LC3-I) and Beclin-1 and downregulated phosphorylated-PI3K (p-PI3K), p-AKT, and p-mTOR in db/db mice and MPC5 cells. However, autophagy inhibitor 3-methyladenine partially alleviated the above effects in MPC5 cells.

CONCLUSIONS: These results showed that the QZJT can enhance podocyte autophagy and ameliorate podocyte injury in DKD by inhibiting the PI3K/AKT/mTOR signaling pathway.

Key words： diabetic kidney disease; podocytes; autophagy; AKT; Qizhi Jiangtang capsule

Cite this article

Zhaoan GUO , Lina SUN , Yingying LIU , Ruifeng LI , Chong LIU , Ke DIAO , Jing SHI , Jun SUN . Qizhi Jiangtang capsule (芪蛭降糖胶囊) activates podocyte autophagy in diabetic kidney disease by inhibiting phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways[J]. Journal of Traditional Chinese Medicine, 2023 , 43(4) : 667 -675 . DOI: 10.19852/j.cnki.jtcm.20230428.001

References

1. Collins AJ, Foley RN, Chavers B, et al. US renal data system 2013 Annual Data Report. Am J Kidney Dis 2014; 63: A7.
2. Altintas MM, Reiser J. Podocytes: way to go. Am J Pathol 2019; 189: 226-8.
3. Sai YP, Song YC, Chen XX, Luo X, Liu J, Cui WJ. Protective effect of astragalosides from radix astragali on adriamycin-induced podocyte injury. Exp Ther Med 2018; 15: 4485-90.
4. Kim Y, Park CW. New therapeutic agents in diabetic nephropathy. Korean J Intern Med 2017; 32: 11-25.
5. Kawakami T, Gomez IG, Ren S, et al. Deficient autophagy results in mitochondrial dysfunction and FSGS. J Am Soc Nephrol 2015; 26: 1040-52.
6. Bork T, Liang W, Yamahara K, et al. Podocytes maintain high basal levels of autophagy independent of mtor signaling. Autophagy 2020; 16: 1932-48.
7. Lin TA, Wu VC, Wang CY. Autophagy in chronic kidney diseases. Cells 2019; 8.
8. Tagawa A, Yasuda M, Kume S, et al. Impaired podocyte autophagy exacerbates proteinuria in diabetic nephropathy. Diabetes 2016; 65: 755-67.
9. Zhang Y, Wang Y, Luo M, et al. Elabela protects against podocyte injury in mice with streptozocin-induced diabetes by associating with the PI3K/Akt/mTOR pathway. Peptides 2019; 114: 29-37.
10. Zheng D, Tao M, Liang X, Li Y, Jin J, He Q. p66Shc regulates podocyte autophagy in high glucose environment through the Notch-PTEN-PI3K/Akt/mTOR pathway. Histol Histopathol 2020; 35: 405-15.
11. Guo ZA, Yu CJ, Liu G, Meng FC, Li Y, Peng SL. Treatment of stage 3b diabetic kidney disease patients with macroalbuminuria by Qizhi Jiangtang capsule: a multicenter randomized control clinical study. Zhong Guo Zhong Xi Yi Jie He Za Zhi 2014; 34: 1047-52.
12. Li Y, Yu C, Guo Z, et al. Effect of Qizhi Jiangtang capsule on the ratio of intima/media thickness and inflammatory factors in renal small artery of diabetic nephropathy rats. Zhong Xi Yi Jie He Shen Bing Za Zhi 2013; 14: 858-63.
13. Guo Z, Meng F, Yu C. Effect of Qizhi Jiangtang capsule on function and structure of kidney in diabetic nephropathy rats. Zhong Guo Yi Yao Ke Xue 2015; 5: 31-6.
14. Lavoz C, Matus YS, Orejudo M, et al. Interleukin-17A blockade reduces albuminuria and kidney injury in an accelerated model of diabetic nephropathy. Kidney Int 2019; 95: 1418-32.
15. Thomas B. The global burden of diabetic kidney disease: time trends and gender gaps. Curr Diab Rep 2019; 19: 18.
16. Wang B, Qian JY, Tang TT, et al. VDR/Atg3 axis regulates slit diaphragm to tight junction transition via p62-mediated autophagy pathway in diabetic nephropathy. diabetes 2021; 70: 2639-51.
17. Zheng X, Feng Y, Han L. Clinical curative effect analysis of Qizhi Jiangtang capsule for diabetes nephrosis patients. Zhong Hua Zhong Yi Yao Xue Kan 2018; 36: 994-6.
18. Lu M, Wang P, Ge Y, et al. Activation of mineralocorticoid receptor by ecdysone, an adaptogenic and anabolic ecdysteroid, promotes glomerular injury and proteinuria involving overactive GSK3β pathway signaling. Sci Rep 2018; 8: 12225.
19. Dai H, Liu Q, Liu B. Research progress on mechanism of podocyte depletion in diabetic nephropathy. J Diabetes Res 2017; 2017: 2615286.
20. Xuan C, Xi YM, Zhang YD, Tao CH, Zhang LY, Cao WF. Yiqi Jiedu Huayu decoction alleviates renal injury in rats with diabetic nephropathy by promoting autophagy. Front Pharmacol 2021; 12: 624404.
21. Nagata M. Podocyte injury and its consequences. Kidney Int 2016; 89: 1221-30.
22. Liang W, Yamahara K, Hernando-Erhard C, et al. A reciprocal regulation of spermidine and autophagy in podocytes maintains the filtration barrier. Kidney Int 2020; 98: 1434-48.
23. Liu WJ, Huang WF, Ye L, et al. The activity and role of autophagy in the pathogenesis of diabetic nephropathy. Eur Rev Med Pharmacol Sci 2018; 22: 3182-9.
24. Jin J, Hu K, Ye M, Wu D, He Q. Rapamycin reduces podocyte apoptosis and is involved in autophagy and mTOR/ P70S6K/4EBP1 signaling. Cell Physiol Biochem 2018; 48: 765-72.
25. Fantus D, Rogers NM, Grahammer F, Huber TB, Thomson AW. Roles of mTOR complexes in the kidney: implications for renal disease and transplantation. Nat Rev Nephrol 2016; 12: 587-609.
26. Xiao T, Guan X, Nie L, et al. Rapamycin promotes podocyte autophagy and ameliorates renal injury in diabetic mice. Mol Cell Biochem 2014; 394: 145-54.
27. Bachar-Wikstrom E, Wikstrom JD, Ariav Y, et al. Stimulation of autophagy improves endoplasmic reticulum stress-induced diabetes. Diabetes 2013; 62: 1227-37.
28. Al-Bari MAA, Xu P. Molecular regulation of autophagy machinery by mTOR-dependent and -independent pathways. Ann N Y Acad Sci 2020; 1467: 3-20.
29. Yang F, Qu Q, Zhao C, et al. Paecilomyces cicadae-fermented radix astragali activates podocyte autophagy by attenuating PI3K/AKT/mTOR pathways to protect against diabetic nephropathy in mice. Biomed Pharmacother 2020; 129: 110479.
Options
Outlines

/

〈 〉