,
Minghao Zhang,
Zijuan Zhang,
Xiaowei Zhang,
Wenhui Rong,
Juan Zhang,
Mengmeng Yang,
Jiangyan Xu*
Rhubarb has been found to have a certain protective effect on improving the kidney function. However, the specific mechanism is still unclear. In this study, network pharmacology, molecular docking spontaneous binding technology and molecular biology experiments were used to verify the mechanism of rhubarb and its active ingredients in the treatment of DKD. A total of 10 active compounds and 121 (larger than average) target proteins were collected. The target proteins with higher degree value were screened by PPI according to degree value as follows: AKT1, STAT3, EGFR, NFKB1, SRC, etc. GO and KEGG enrichment analysis suggest that rhubarb therapy for DKD mainly involves Pathways in cancer, Prostate cancer, Proteoglycans in cancer, Chemokine signaling pathway, PI3K-Akt signaling pathway, PD-L1 expression and PD-1 checkpoint pathway in cancer, EGFR tyrosine kinase inhibitor resistance signaling pathway and so on. Furthermore, molecular docking results suggest that hydrogen bonding, salt bridge and hydrophobic interactions contribute to spontaneous binding of the compound to the target protein. Experimental verification shows that rhubarb and aloe emodin affect the mechanism of pyroptosis in diabetic kidney disease by regulating STAT3/Caspase11 axis. In conclusion, this study comprehensively elaborated the active compounds, potential targets and molecular experimental mechanisms of rhubarb to provide the basic experimental theory for clinical treatment of DKD.
| Published in | American Journal of Clinical and Experimental Medicine (Volume 12, Issue 3) |
| DOI | 10.11648/j.ajcem.20241203.12 |
| Page(s) | 28-44 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2024. Published by Science Publishing Group |
Network Pharmacology, Rhubarb, SATA3, Pyroptosis, DKD
| [1] | Zhang X, Zhang J, Ren Y, Sun R, Zhai X. Unveiling the pathogenesis and therapeutic approaches for diabetic nephropathy: insights from panvascular diseases. Front Endocrinol (Lausanne). 2024 Feb 22; 15: 1368481. |
| [2] | Sun D, Wei S, Wang D, Zeng M, Mo Y, Li H, Liang C, Li L, Zhang JW, Wang L. Integrative analysis of potential diagnostic markers and therapeutic targets for glomerulus-associated diabetic nephropathy based on cellular senescence. Front Immunol. 2024 Jan 8; 14: 1328757. |
| [3] | Liang LL, He MF, Zhou PP, Pan SK, Liu DW, Liu ZS. GSK3β: A ray of hope for the treatment of diabetic kidney disease. FASEB J. 2024 Feb 15; 38(3): e23458. |
| [4] | Bell DSH, Jerkins T. The potential for improved outcomes in the prevention and therapy of diabetic kidney disease through 'stacking' of drugs from different classes. Diabetes Obes Metab. 2024 Jun; 26(6): 2046-2053. |
| [5] | Hu X, Chen S, Ye S, Chen W, Zhou Y. New insights into the role of immunity and inflammation in diabetic kidney disease in the omics era. Front Immunol. 2024 Feb 29; 15: 1342837. |
| [6] | Cai L, Chen Y, Xue H, Yang Y, Wang Y, Xu J, Zhu C, He L, Xiao Y. Effect and pharmacological mechanism of Salvia miltiorrhiza and its characteristic extracts on diabetic nephropathy. J Ethnopharmacol. 2024 Jan 30; 319(Pt 3): 117354. |
| [7] | Ma X, Ma J, Leng T, Yuan Z, Hu T, Liu Q, Shen T. Advances in oxidative stress in pathogenesis of diabetic kidney disease and efficacy of TCM intervention. Ren Fail. 2023 Dec; 45(1): 2146512. |
| [8] | Shen S, Zhong H, Zhou X, Li G, Zhang C, Zhu Y, Yang Y. Advances in Traditional Chinese Medicine research in diabetic kidney disease treatment. Pharm Biol. 2024 Dec; 62(1): 222-232. |
| [9] | Hu Q, Chen Y, Deng X, Li Y, Ma X, Zeng J, Zhao Y. Diabetic nephropathy: Focusing on pathological signals, clinical treatment, and dietary regulation. Biomed Pharmacother. 2023 Mar; 159: 114252. |
| [10] | Li P, Lu Q, Jiang W, Pei X, Sun Y, Hao H, Hao K. Pharmacokinetics and pharmacodynamics of rhubarb anthraquinones extract in normal and disease rats. Biomed Pharmacother. 2017 Jul; 91: 425-435. |
| [11] | Zhang F, Wu R, Liu Y, Dai S, Xue X, Li Y, Gong X. Nephroprotective and nephrotoxic effects of Rhubarb and their molecular mechanisms. Biomed Pharmacother. 2023 Apr; 160: 114297. |
| [12] | Xiang H, Zuo J, Guo F, Dong D. What we already know about rhubarb: a comprehensive review. Chin Med. 2020 Aug 26; 15: 88. |
| [13] | Yang F, Li X, Zhang Y, Ren Y, Zhang J, Xiao K. Prediction of potential mechanisms of rhubarb therapy for colorectal cancer based on network pharmacological analysis and molecular docking. Medicine (Baltimore). 2024 Mar 22; 103(12): e37477. |
| [14] | Zhang X, Zhao L, Xiang S, Sun Y, Wang P, Chen JJ, Teo BS, Xie Z, Zhang Z, Xu J. Yishen Tongluo formula alleviates diabetic kidney disease through regulating Sirt6/TGF-β1/Smad2/3 pathway and promoting degradation of TGF-β1. J Ethnopharmacol. 2023 May 10; 307: 116243. |
| [15] | CAI Rushuang, Yi Yan. Research progress of TCM in the prevention and treatment of diabetes mellitus and its complications [J/OL]. Chinese Journal of Experimental Formulae: 1-10 [2024-03-23]. |
| [16] | Liu XY, Zhang XB, Zhao YF, Qu K, Yu XY. Research Progress of Chinese Herbal Medicine Intervention in Renal Interstitial Fibrosis. Front Pharmacol. 2022 Jun 13; 13: 900491. |
| [17] | Hu Y, Zhang S, Lou H, Mikaye MS, Xu R, Meng Z, Du M, Tang P, Chen Z, Chen Y, Liu X, Du Z, Zhang Y. Aloe-Emodin Derivative, an Anthraquinone Compound, Attenuates Pyroptosis by Targeting NLRP3 Inflammasome in Diabetic Cardiomyopathy. Pharmaceuticals (Basel). 2023 Sep 8; 16(9): 1275. |
| [18] | Fang X, Chen Z, Zhou W, Li T, Wang M, Gao Y, Ma S, Feng Y, Du S, Lan P, Chen H, Wei J, Zhang S, Li Z, Liu X, Zhang H, Guo X, Luo J. Boosting Glioblastoma Therapy with Targeted Pyroptosis Induction. Small. 2023 Jul; 19(30): e2207604. |
| [19] | Li T, Shi L, Liu W, Hu X, Hui Y, Di M, Xue S, Zheng Y, Yao M, Li C, Meng K. Aloe-Emodin Induces Mitochondrial Dysfunction and Pyroptosis by Activation of the Caspase-9/3/Gasdermin E Axis in HeLa Cells. Front Pharmacol. 2022 May 17; 13: 854526. |
| [20] | Xu W, Wang Y, Jin C, Zhang W, Chen J, Chen X, Gao J, Gao J, Wang H. IL-17 Imbalance Promotes the Pyroptosis in Immune-Mediated Liver Injury Through STAT3-IFI16 Axis. Immune Netw. 2023 Dec 11; 23(6): e46. |
| [21] | Tao Y, Xu X, Yang B, Zhao H, Li Y. Mitigation of Sepsis-Induced Acute Lung Injury by BMSC-Derived Exosomal miR-125b-5p Through STAT3-Mediated Suppression of Macrophage Pyroptosis. Int J Nanomedicine. 2023 Nov 29; 18: 7095-7113. |
| [22] | Tang N, Zhu Y, Yu J. Xihuang pill facilitates glioma cell pyroptosis via the POU4F1/STAT3 axis. Funct Integr Genomics. 2023 Nov 14; 23(4): 334. |
| [23] | Ren Y, Yu M, Zheng D, He W, Jin J. Lysozyme promotes renal fibrosis through the JAK/STAT3 signal pathway in diabetic nephropathy. Arch Med Sci. 2023 Jul 31; 20(1): 233-247. |
| [24] | Xiang L, Cai X, Zhao X, Liu Y, Xiao Y, Jiang P, Yin L, Song D, Jiang X. Uncovering the mechanism of Qidan Dihuang Granule in the treat-ment of diabetic kidney disease combined network pharmacology, UHPLC-MS/MS with experimental validation. Heliyon. 2023 Oct 28; 9(11): e21714. |
| [25] | Sun Y, Zhao Y, Lu Y, Li H, Xiang J, Yang D, Wang J, Gao X, Wang Y. Urinary stem cell-derived exocrine circRNA ATG7 regulates the SOCS1/STAT3 signaling pathway through miR-4500, inhibits M1 macrophage polarization, and alleviates the progression of diabetes nephropathy. Int Urol Nephrol. 2024 Apr; 56(4): 1449-1463. |
| [26] | Fang X, Huang W, Sun Q, Zhao Y, Sun R, Liu F, Huang D, Zhang Y, Gao F, Wang B. Melatonin attenuates cellular senescence and apoptosis in diabetic nephropathy by regulating STAT3 phosphorylation. Life Sci. 2023 Nov 1; 332: 122108. |
APA Style
Mao, Y., Zhang, M., Zhang, Z., Zhang, X., Rong, W., et al. (2024). Study on the Effect of Rhubarb and Its Active Components on Pyroptosis in DKD by Regulating STAT3/Caspase-11 Axis. American Journal of Clinical and Experimental Medicine, 12(3), 28-44. https://doi.org/10.11648/j.ajcem.20241203.12
ACS Style
Mao, Y.; Zhang, M.; Zhang, Z.; Zhang, X.; Rong, W., et al. Study on the Effect of Rhubarb and Its Active Components on Pyroptosis in DKD by Regulating STAT3/Caspase-11 Axis. Am. J. Clin. Exp. Med. 2024, 12(3), 28-44. doi: 10.11648/j.ajcem.20241203.12
AMA Style
Mao Y, Zhang M, Zhang Z, Zhang X, Rong W, et al. Study on the Effect of Rhubarb and Its Active Components on Pyroptosis in DKD by Regulating STAT3/Caspase-11 Axis. Am J Clin Exp Med. 2024;12(3):28-44. doi: 10.11648/j.ajcem.20241203.12
Share This Article
Twitter
Linked In
Facebook
Copy
Download@article{10.11648/j.ajcem.20241203.12,
author = {Yanwen Mao and Minghao Zhang and Zijuan Zhang and Xiaowei Zhang and Wenhui Rong and Juan Zhang and Mengmeng Yang and Jiangyan Xu},
title = {Study on the Effect of Rhubarb and Its Active Components on Pyroptosis in DKD by Regulating STAT3/Caspase-11 Axis
},
journal = {American Journal of Clinical and Experimental Medicine},
volume = {12},
number = {3},
pages = {28-44},
doi = {10.11648/j.ajcem.20241203.12},
url = {https://doi.org/10.11648/j.ajcem.20241203.12},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20241203.12},
abstract = {Rhubarb has been found to have a certain protective effect on improving the kidney function. However, the specific mechanism is still unclear. In this study, network pharmacology, molecular docking spontaneous binding technology and molecular biology experiments were used to verify the mechanism of rhubarb and its active ingredients in the treatment of DKD. A total of 10 active compounds and 121 (larger than average) target proteins were collected. The target proteins with higher degree value were screened by PPI according to degree value as follows: AKT1, STAT3, EGFR, NFKB1, SRC, etc. GO and KEGG enrichment analysis suggest that rhubarb therapy for DKD mainly involves Pathways in cancer, Prostate cancer, Proteoglycans in cancer, Chemokine signaling pathway, PI3K-Akt signaling pathway, PD-L1 expression and PD-1 checkpoint pathway in cancer, EGFR tyrosine kinase inhibitor resistance signaling pathway and so on. Furthermore, molecular docking results suggest that hydrogen bonding, salt bridge and hydrophobic interactions contribute to spontaneous binding of the compound to the target protein. Experimental verification shows that rhubarb and aloe emodin affect the mechanism of pyroptosis in diabetic kidney disease by regulating STAT3/Caspase11 axis. In conclusion, this study comprehensively elaborated the active compounds, potential targets and molecular experimental mechanisms of rhubarb to provide the basic experimental theory for clinical treatment of DKD.
},
year = {2024}
}
TY - JOUR T1 - Study on the Effect of Rhubarb and Its Active Components on Pyroptosis in DKD by Regulating STAT3/Caspase-11 Axis AU - Yanwen Mao AU - Minghao Zhang AU - Zijuan Zhang AU - Xiaowei Zhang AU - Wenhui Rong AU - Juan Zhang AU - Mengmeng Yang AU - Jiangyan Xu Y1 - 2024/07/29 PY - 2024 N1 - https://doi.org/10.11648/j.ajcem.20241203.12 DO - 10.11648/j.ajcem.20241203.12 T2 - American Journal of Clinical and Experimental Medicine JF - American Journal of Clinical and Experimental Medicine JO - American Journal of Clinical and Experimental Medicine SP - 28 EP - 44 PB - Science Publishing Group SN - 2330-8133 UR - https://doi.org/10.11648/j.ajcem.20241203.12 AB - Rhubarb has been found to have a certain protective effect on improving the kidney function. However, the specific mechanism is still unclear. In this study, network pharmacology, molecular docking spontaneous binding technology and molecular biology experiments were used to verify the mechanism of rhubarb and its active ingredients in the treatment of DKD. A total of 10 active compounds and 121 (larger than average) target proteins were collected. The target proteins with higher degree value were screened by PPI according to degree value as follows: AKT1, STAT3, EGFR, NFKB1, SRC, etc. GO and KEGG enrichment analysis suggest that rhubarb therapy for DKD mainly involves Pathways in cancer, Prostate cancer, Proteoglycans in cancer, Chemokine signaling pathway, PI3K-Akt signaling pathway, PD-L1 expression and PD-1 checkpoint pathway in cancer, EGFR tyrosine kinase inhibitor resistance signaling pathway and so on. Furthermore, molecular docking results suggest that hydrogen bonding, salt bridge and hydrophobic interactions contribute to spontaneous binding of the compound to the target protein. Experimental verification shows that rhubarb and aloe emodin affect the mechanism of pyroptosis in diabetic kidney disease by regulating STAT3/Caspase11 axis. In conclusion, this study comprehensively elaborated the active compounds, potential targets and molecular experimental mechanisms of rhubarb to provide the basic experimental theory for clinical treatment of DKD. VL - 12 IS - 3 ER -
Academy of Medical, Henan University of Chinese Medicine, Zhengzhou, China
Academy of Medical, Henan University of Chinese Medicine, Zhengzhou, China
Academy of Medical, Henan University of Chinese Medicine, Zhengzhou, China
Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
Academy of Medical, Henan University of Chinese Medicine, Zhengzhou, China
Academy of Medical, Henan University of Chinese Medicine, Zhengzhou, China
School of Management, Henan University of Chinese Medicine, Zhengzhou, China
Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases with Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, China
