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Cited by 30Chronic Kidney Disease and DiabetesGenomics, phytochemicals, and oxidative stressNatural Antidiabetic Agents Studies

Effects of Compound Centella on Oxidative Stress and Keap1‐Nrf2‐ARE Pathway Expression in Diabetic Kidney Disease Rats

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Zhu, Qin, Zeng, Jiali, Li, Jian, Chen, Xueming, Miao, Jianxia, Jin, Qinyang, Chen, Hongyu·2020·Evidence-Based Complementary and Alternative Medicine
DOI 10.1155/2020/9817932PMC PMC7277064
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Abstract

The formula of Compound Centella mainly contains 3 traditional Chinese herbs: Centella asiatica (L.) Urb. (JiXueCao), Astragalus Membranaceus Fish. (HuangQi), and Tripterygium wilfordii Hook. f. (LeiGongTeng). Though this formula is effective for treating diabetic kidney disease (DKD) in clinic, the exact mechanism is still unclear. This study aims to investigate the effect and antioxidant mechanism of Compound Centella on DKD rats. High‐performance liquid chromatography (HPLC) was applied to analyse 3 herbs in Compound Centella. Sprague‐Dawley rats were divided into the normal group (NG), DKD group (DKDG), Compound Centella group (CCG), and losartan group (LG), with 8 rats in each group. On the first day of the experiment, rats in the NG were fed with ordinary –feed, while the other groups were fed with high‐fat and high‐sugar feed. On the 29 th day, except the NG, the other 3 groups received a single intraperitoneal injection of streptozocin (STZ, 35 mg/kg). Fasting blood glucose (FBG) was measured on the 1 st day, 32 nd day, 46 th day, 56 th day, 84 th day, and 112 th day. Total protein/creatinine ratio of urine was determined by the phenol red assay on the 1 st day and 112 th day. Serum creatinine (Scr) was determined by an automatic biochemical analyser on the 112 th day. Kidneys were collected on the 112 th day for analysis and evaluation. Periodic acid‐Schiff (PAS) staining, hematoxylin‐eosin (HE) staining, and transmission electron microscopy were used to observe kidney pathological changes. The mRNA and protein expressions of Kelch‐like ECH‐associated protein 1 (Keap1) and nuclear factor‐erythroid 2‐related factor 2 (Nrf2) in renal tissues were detected by RT‐qPCR, Western blot, and immunohistochemistry. Oxidative stress was evaluated by detecting the levels of malondialdehyde (MDA) and heme oxidase‐1 (HO‐1). The results showed that the content of asiaticoside, astragaloside, and triptolide in the herb was 5960, 809, and 2.42 μ g/g and in the Compound Centella was 340, 64, and 0.1403 μ g/mL by HPLC. Compound Centella reduced the urine protein/creatinine ratio and improved renal pathology in the kidneys of DKD rats. In addition, the mRNA and protein expressions of Keap1 and Nrf2 in kidneys were upregulated by Compound Centella. The expressions of MDA were downregulated but HO‐1 were upregulated by Compound Centella. Therefore, the protective effect of Compound Centella in the kidney of DKD rats may be related to regulating the Keap1‐Nrf2‐ARE pathway under oxidative stress, suggesting Compound Centella as a promising treatment against DKD.

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  • Asiaticoside is major constituent of formula Compound Centella, which lowers urine protein/creatinine ratio in diabetic rats and improves renal pathology of diabetic kidney disease by regulating oxidative stress signalling.

    “Asiaticoside is the major constituent of the formula Compound Centella, which has proved effective in lowering the urine protein/creatinine ratio in diabetic rats and can improve the renal pathology of diabetic kidney disease by regulating oxidative stress signalling.”

    From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [123]

    The Abstract and Conclusion report that Compound Centella lowered the urine protein/creatinine ratio and improved renal pathology in DKD rats. The Abstract identifies asiaticoside as a measured component, but does not establish it as the formula’s major constituent; the Conclusion says regulation of oxidative-stress signalling *may* explain the protective effect, rather than establishing it as the mechanism. (LLM, conf=0.86)

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  1. [1]Majewski C. Bakris G. Managing diabetic nephropathies in clinical practice: emerging and future therapies Managing Diabetic Nephropathies in Clinical Practice 2017 Cham, Switzerland Springer International Publishing 117 129
  2. [2]Cooper M. Warren A. M. A promising outlook for diabetic kidney disease Nature Reviews Nephrology 2019 15 2 68 70 10.1038/s41581-018-0092-5 2-s2.0-85058272196 30532022 · DOI
  3. [3]Critchley J. Zhao H. L. Tomlinson B. Management of nephropathy in patients with type 2 diabetes Chinese Medical Journal 2002 115 1 129 135 in Chinese 11930647
  4. [4]Maulidiani F. Abas F. Khatib A. Metabolic alteration in obese diabetes rats upon treatment with Centella asiatica extract Journal of Ethnopharmacology 2016 180 60 69 10.1016/j.jep.2016.01.001 2-s2.0-84956746404 26775274 · DOI
  5. [5]Masola B. Oguntibeju O. O. Oyenihi A. B. Centella asiatica ameliorates diabetes-induced stress in rat tissues via influences on antioxidants and inflammatory cytokines Biomedicine & Pharmacotherapy 2018 101 447 457 10.1016/j.biopha.2018.02.115 2-s2.0-85042647276 29501767 · DOI · Paper page
  6. [6]Lu M.-C. Ji J.-A. Jiang Z.-Y. You Q.-D. The Keap1-nrf2-ARE pathway as a potential preventive and therapeutic target: an update Medicinal Research Reviews 2016 36 5 924 963 10.1002/med.21396 2-s2.0-85028271428 27192495 · DOI
  7. [7]Spiers D. E. Candas V. Relationship of skin surface area to body mass in the immature rat: a reexamination Journal of Applied Physiology 1984 56 1 240 243 10.1152/jappl.1984.56.1.240 6693327 · DOI
  8. [8]Zhu X. Chen Y. Chen Q. Yang H. Xie X. Astaxanthin promotes Nrf2/ARE signaling to alleviate renal fibronectin and collagen IV accumulation in diabetic rats Journal of Diabetes Research 2018 2018 7 6730315 10.1155/2018/6730315 2-s2.0-85054346640 PMC5884145 29744366 · DOI
  9. [9]Liu H.-F. Guo L.-Q. Huang Y.-Y. hiazolidinedione attenuate proteinuria and glomerulosclerosis in adriamycin-induced nephropathy rats via slit diaphragm protection Nephrology 2010 15 1 75 83 10.1111/j.1440-1797.2009.01146.x 2-s2.0-77149145181 20377774 · DOI
  10. [10]Löffler I. Wolf G. Pathophysiologie der diabetischen nephropathie Der Nephrologe 2017 12 6 391 399 10.1007/s11560-017-0191-5 2-s2.0-85029459935 · DOI
  11. [11]Mogensen C. E. Christensen C. K. Vittinghus E. The stages in diabetic renal disease: with emphasis on the stage of incipient diabetic nephropathy Diabetes 1983 32 Supplement_2 64 78 10.2337/diab.32.2.s64 6400670 · DOI
  12. [12]Forbes J. M. Coughlan M. T. Cooper M. E. Oxidative stress as a major culprit in kidney disease in diabetes Diabetes 2008 57 6 1446 1454 10.2337/db08-0057 2-s2.0-48249085391 18511445 · DOI · Paper page
  13. [13]Finkel T. Holbrook N. J. Oxidants, oxidative stress and the biology of ageing Nature 2000 408 6809 239 247 10.1038/35041687 2-s2.0-0034626735 11089981 · DOI · Paper page
  14. [15]Bee O. Bey G. Wei Y. Oxidative stress in cardiovascular diseases: involvement of Nrf2 antioxidant redox signaling in macrophage foam cells formation International Journal of Molecular Sciences 2017 18 11 p. 2336 PMC5713305 29113088
  15. [17]Giorda C. B. Carnà P. Salomone M. Ten-year comparative analysis of incidence, prognosis, and associated factors for dialysis and renal transplantation in type 1 and type 2 diabetes versus non-diabetes Acta Diabetologica 2018 55 7 733 740 10.1007/s00592-018-1142-y 2-s2.0-85045741849 29679150 · DOI
  16. [18]Kovac S. Angelova P. R. Holmström K. M. Zhang Y. Dinkova-Kostova A. T. Abramov A. Y. Nrf2 regulates ROS production by mitochondria and NADPH oxidase Biochimica et Biophysica Acta (BBA)—General Subjects 2015 1850 4 794 801 10.1016/j.bbagen.2014.11.021 2-s2.0-84921814081 25484314 PMC4471129 · DOI
  17. [19]Kaefer M. De Carvalho J. A. Piva S. J. Plasma malondialdehyde levels and risk factors for the development of chronic complications in type 2 diabetic patients on insulin therapy Clinical Laboratory 2012 58 9-10 973 978 23163113
  18. [20]Rasheed N. O. A. Ahmed L. A. Abdallah D. M. Nephro-toxic effects of intraperitoneally injected EGCG in diabetic mice: involvement of oxidative stress, inflammation and apoptosis Scientific Reports 2017 7 1 p. 40617 10.1038/srep40617 2-s2.0-85010058663 28098182 PMC5241811 · DOI
  19. [21]Duan J. Guan Y. Mu F. Protective effect of butin against ischemia/reperfusion-induced myocardial injury in diabetic mice: involvement of the AMPK/GSK-3β/Nrf2 signaling pathway Scientific Reports 2017 7 1 p. 41491 10.1038/srep41491 2-s2.0-85010993726 PMC5269748 28128361 · DOI
  20. [22]Kim Y. J. Kim Y. A. Yokozawa T. Pycnogenol modulates apoptosis by suppressing oxidative stress and inflammation in high glucose-treated renal tubular cells Food and Chemical Toxicology 2011 49 9 2196 2201 10.1016/j.fct.2011.06.012 2-s2.0-79960838959 21689714 · DOI
  21. [23]Huang K. Huang J. Xie X. Sirt1 resists advanced glycation end products-induced expressions of fibronectin and TGF-β1 by activating the Nrf2/ARE pathway in glomerular mesangial cells Free Radical Biology and Medicine 2013 65 528 540 10.1016/j.freeradbiomed.2013.07.029 2-s2.0-84884519280 23891678 · DOI

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Authors
Zhu, Q., Zeng, J., Li, J., Chen, X., Miao, J., Jin, Q., & Chen, H.
Affiliations
  • Hangzhou Hospital of Traditional Chinese Medicine (CN)
  • Ningbo University (CN)
  • Zhejiang Provincial People's Hospital (CN)
Corresponding author
  • Jin, Qinyang
  • Chen, Hongyu
ORCID
Venue
Evidence-Based Complementary and Alternative Medicine
Publisher
Wiley
Published
2020-01
Volume
2020
Issue
1
Pages
9817932-9817932
ISSN
  • 1741-427X (ISSN-L)
  • 1741-4288
DOI
10.1155/2020/9817932
PMC
PMC7277064
OpenAlex
W3030056514
Cited by
30
References
2
Citations by year
2026: 3 · 2025: 7 · 2024: 7 · 2023: 5 · 2022: 5 · 2021: 3
FWCI
2.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Evidence-based Complementary and Alternative Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Natural Science Foundation of Zhejiang Province (LQ19H290005)
  • National Natural Science Foundation of China (81973760)
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
Keywords
diabetic nephropathy, oxidative stress, Nrf2/Keap1 pathway, Centella asiatica, Astragalus membranaceus, Tripterygium wilfordii, antioxidant defense, heme oxygenase-1, malondialdehyde, proteinuria, renal fibrosis, traditional Chinese medicine, streptozotocin-induced diabetes, losartan

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