Glucosidase inhibitor, Nimbidiol ameliorates renal fibrosis and dysfunction in type-1 diabetes
Open accessAbstract
Diabetic nephropathy is characterized by excessive accumulation of extracellular matrix (ECM) leading to renal fibrosis, progressive deterioration of renal function, and eventually to end stage renal disease. Matrix metalloproteinases (MMPs) are known to regulate synthesis and degradation of the ECM. Earlier, we demonstrated that imbalanced MMPs promote adverse ECM remodeling leading to renal fibrosis in type-1 diabetes. Moreover, elevated macrophage infiltration, pro-inflammatory cytokines and epithelial‒mesenchymal transition (EMT) are known to contribute to the renal fibrosis. Various bioactive compounds derived from the medicinal plant, Azadirachta indica (neem) are shown to regulate inflammation and ECM proteins in different diseases. Nimbidiol is a neem-derived diterpenoid that is considered as a potential anti-diabetic compound due to its glucosidase inhibitory properties. We investigated whether Nimbidiol mitigates adverse ECM accumulation and renal fibrosis to improve kidney function in type-1 diabetes and the underlying mechanism. Wild-type (C57BL/6J) and type-1 diabetic (C57BL/6‐Ins2Akita/J) mice were treated either with saline or with Nimbidiol (0.40 mg kg−1 d−1) for eight weeks. Diabetic kidney showed increased accumulation of M1 macrophages, elevated pro-inflammatory cytokines and EMT. In addition, upregulated MMP-9 and MMP-13, excessive collagen deposition in the glomerular and tubulointerstitial regions, and degradation of vascular elastin resulted to renal fibrosis in the Akita mice. These pathological changes in the diabetic mice were associated with functional impairments that include elevated resistive index and reduced blood flow in the renal cortex, and decreased glomerular filtration rate. Furthermore, TGF-β1, p-Smad2/3, p-P38, p-ERK1/2 and p-JNK were upregulated in diabetic kidney compared to WT mice. Treatment with Nimbidiol reversed the changes to alleviate inflammation, ECM accumulation and fibrosis and thus, improved renal function in Akita mice. Together, our results suggest that Nimbidiol attenuates inflammation and ECM accumulation and thereby, protects kidney from fibrosis and dysfunction possibly by inhibiting TGF-β/Smad and MAPK signaling pathways in type-1 diabetes.
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Renal function indicators are highly specific to diabetic nephropathy.
“Comparative analyses across complications reveal differing key predictors: retinal imaging features are critical for DR [154], renal function indicators are highly specific to DN [155], while hypertension and dyslipidemia serve as strong predictors for CVD [156] but also overlap with DR and DN [157].”
From Artificial intelligence-powered prediction of diabetic complications: from clinical data to molecular omics (2026) · cites this paper as [155]
The Results section reports reduced GFR in diabetic mice, supporting the relevance of renal function indicators to diabetic nephropathy. It does not establish that those indicators are highly specific to diabetic nephropathy; the Discussion also associates increased renal resistive index and poor renal function with chronic kidney disease more broadly. Page numbers are unavailable in our copy. (LLM, conf=0.86)
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Cites
The basics of epithelial-mesenchymal transition
Kalluri, R., & Weinberg, R. A. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39104 · Cited by 10,196 · see citing works
Smad-dependent and Smad-independent pathways in TGF-β family signalling
Derynck, R., & Zhang, Y. E. (2003) · Nature · doi:10.1038/nature02006 · Cited by 5,370 · see citing works
Mechanisms of fibrosis: therapeutic translation for fibrotic disease
Wynn, T. A., & Ramalingam, T. R. (2012) · Nature Medicine · doi:10.1038/nm.2807 · Cited by 3,541 · see citing works
The Versatile Role of microRNA-30a in Human Cancer
Wang, C., Yang, X., Chen, Y., & Chen, L. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000471111 · Cited by 3,409 · see citing works
On the Dependency of Cellular Protein Levels on mRNA Abundance
Liu, Y., Beyer, A., & Aebersold, R. (2016) · Cell · doi:10.1016/j.cell.2016.03.014 · Cited by 3,221 · see citing works
Massagué, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3434 · Cited by 3,130 · see citing works
Epithelial-mesenchymal transition and its implications for fibrosis
Kalluri, R., & Neilson, E. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci20530 · Cited by 2,651 · see citing works
Non-Transgenic Mouse Models of Kidney Disease
Rabe, M., & Schaefer, F. S. (2016) · The Nephron journals/Nephron journals · doi:10.1159/000445171 · Cited by 1,927 · see citing works
Correlation of mRNA and protein in complex biological samples
Maier, T., Güell, M., & Serrano, L. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.10.036 · Cited by 1,802 · see citing works
Comparing protein abundance and mRNA expression levels on a genomic scale
Greenbaum, D. (2003) · Genome biology · doi:10.1186/gb-2003-4-9-117 · Cited by 1,692 · see citing works
New insights into TGF-β/Smad signaling in tissue fibrosis
Hu, H.-H., Chen, D., Wang, Y., Feng, Y., Cao, G., Vaziri, N. D., & Zhao, Y. (2018) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2018.07.008 · Cited by 1,188 · see citing works
Epithelial to Mesenchymal Transition in Renal Fibrogenesis
Liu, Y. (2004) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000106015.29070.e7 · Cited by 1,054 · see citing works
Macrophages: versatile players in renal inflammation and fibrosis
Tang, P. M.-K., Nikolic-Paterson, D. J., & Lan, H.-Y. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0110-2 · Cited by 1,033 · see citing works
Yang, J., & Liu, Y. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)62533-3 · Cited by 751 · see citing works
Inflammatory processes in renal fibrosis
Meng, X., Nikolic‐Paterson, D. J., & Lan, H. Y. (2014) · Nature Reviews Nephrology · doi:10.1038/nrneph.2014.114 · Cited by 693 · see citing works
TGF-β/Smad signaling in renal fibrosis
Meng, X., Tang, P. M., Li, J., & Lan, H. Y. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00082 · Cited by 671 · see citing works
Extracellular Matrix Metabolism in Diabetic Nephropathy
Mason, R. M., & Wahab, N. A. (2003) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000065640.77499.d7 · Cited by 653 · see citing works
Yoshioka, M., Kayo, T., Ikeda, T., & Koizuni, A. (1997) · Diabetes · doi:10.2337/diab.46.5.887 · Cited by 536 · see citing works
Oldfield, M. D., Bach, L. A., Forbes, J. M., Nikolic‐Paterson, D. J., McRobert, E. A., Thallas, V., Atkins, R. C., Osicka, T. M., Jerums, G., & Cooper, M. E. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11951 · Cited by 469 · see citing works
Ng, Y.-Y., Huang, T., Yang, W.-C., Chen, Z.-P., Yang, A., Mu, W., Nikolic‐Paterson, D. J., Atkins, R. C., & Lan, H. Y. (1998) · Kidney International · doi:10.1046/j.1523-1755.1998.00076.x · Cited by 396 · see citing works
Role of the TGF-β/BMP-7/Smad pathways in renal diseases
Meng, X., Chung, A. C. K., & Lan, H. Y. (2012) · Clinical Science · doi:10.1042/cs20120252 · Cited by 356 · see citing works
Qian, Y., Feldman, E. L., Pennathur, S., Kretzler, M., & Brosius, F. C. (2008) · Diabetes · doi:10.2337/db08-0061 · Cited by 327 · see citing works
Yang, J., & Liu, Y. (2002) · Journal of the American Society of Nephrology · doi:10.1681/asn.v13196 · Cited by 324 · see citing works
Urinary excretion of podocytes in patients with diabetic nephropathy
Nakamura, T., Ushiyama, C., Suzuki, S., Hara, M., Shimada, N., Ebihara, I., & Koide, H. (2000) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/15.9.1379 · Cited by 302 · see citing works
Diverse origins of the myofibroblast—implications for kidney fibrosis
Falke, L. L., Gholizadeh, S., Goldschmeding, R., Kok, R. J., & Nguyen, T. Q. (2015) · Nature Reviews Nephrology · doi:10.1038/nrneph.2014.246 · Cited by 297 · see citing works
Zeisberg, M., Bonner, G., Maeshima, Y., Colorado, P. C., Muller, G. A., Strutz, F. M., & Kalluri, R. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)62518-7 · Cited by 295 · see citing works
Macrophages promote renal fibrosis through direct and indirect mechanisms
Nikolic‐Paterson, D. J., Wang, S., & Lan, H. Y. (2014) · Kidney International Supplements · doi:10.1038/kisup.2014.7 · Cited by 280 · see citing works
Role of TGF-β in chronic kidney disease: an integration of tubular, glomerular and vascular effects
López-Hernández, F. J., & López-Novoa, J. M. (2011) · Cell and Tissue Research · doi:10.1007/s00441-011-1275-6 · Cited by 276 · see citing works
Matrix metalloproteinases in kidney homeostasis and diseases
Tan, R. J., & Liu, Y. (2012) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00037.2012 · Cited by 261 · see citing works
Wu, C.-F., Chiang, W., Lai, C., Chang, F., Chen, Y., Chou, Y., Wu, T.-H., Linn, G. R., Ling, H., Wu, K., et al. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.09.009 · Cited by 247 · see citing works
Lemos, D. R., McMurdo, M., Karaca, G., Wilflingseder, J., Leaf, I. A., Gupta, N. R., Miyoshi, T., Susa, K., Johnson, B. G., Soliman, K., et al. (2018) · Journal of the American Society of Nephrology · doi:10.1681/asn.2017121283 · Cited by 220 · see citing works
Transcutaneous measurement of renal function in conscious mice
Schreiber, A., Shulhevich, Y., Geraci, S., Hesser, J. W., Stsepankou, D., Neudecker, S., Koenig, S., Heinrich, R., Hoecklin, F., Pill, J., et al. (2012) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00279.2012 · Cited by 218 · see citing works
Signaling Pathways Involved in Diabetic Renal Fibrosis
Zhang, Y., Jin, D., Kang, X., Zhou, R., Sun, Y., Lian, F., & Tong, X. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.696542 · Cited by 214 · see citing works
Myofibroblasts and the progression of diabetic nephropathy
Essawy, M., Söylemezoğlu, O., Muchaneta-Kubara, E. C., Shortland, J. R., Brown, C., & Nahas, A. E. (1997) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/12.1.43 · Cited by 199 · see citing works
Obstructive nephropathy: towards biomarker discovery and gene therapy
Chevalier, R. L. (2006) · Nature Reviews Nephrology · doi:10.1038/ncpneph0098 · Cited by 178 · see citing works
Nonenzymatic glycation of type IV collagen and matrix metalloproteinase susceptibility
Mott, J. D., Khalifah, R. G., Nagase, H., Shield, C. F., Hudson, J. K., & Hudson, B. G. (1997) · Kidney International · doi:10.1038/ki.1997.455 · Cited by 170 · see citing works
Tan, T. K., Zheng, G., Hsu, T.-T., Lee, S. R., Zhang, J., Zhao, Y., Tian, X., Wang, Y., Wang, Y. M., Cao, Q., et al. (2013) · Laboratory Investigation · doi:10.1038/labinvest.2013.3 · Cited by 165 · see citing works
Renal Structural and Functional Repair in a Mouse Model of Reversal of Ureteral Obstruction
Cochrane, A. L., Kett, M. M., Samuel, C. S., Campanale, N., Anderson, W. P., Hume, D. A., Little, M. H., Bertram, J. F., & Ricardo, S. D. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2004090771 · Cited by 164 · see citing works
Ohta, Y., Fujii, K., Arima, H., Matsumura, K., Tsuchihashi, T., Tokumoto, M., Tsuruya, K., Kanai, H., Iwase, M., Hirakata, H., et al. (2005) · Journal of Hypertension · doi:10.1097/01.hjh.0000181323.44162.01 · Cited by 162 · see citing works
Tan, T. K., Zheng, G., Hsu, T.-T., Wang, Y., Lee, V. W., Tian, X., Wang, Y., Cao, Q., Wang, Y., & Harris, D. C. H. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090188 · Cited by 160 · see citing works
Matrix metalloproteinases contribute to kidney fibrosis in chronic kidney diseases
Zhao, H. (2013) · World Journal of Nephrology · doi:10.5527/wjn.v2.i3.84 · Cited by 148 · see citing works
TGF-β1 → SMAD/p53/USF2 → PAI-1 transcriptional axis in ureteral obstruction-induced renal fibrosis
Samarakoon, R., Overstreet, J. M., Higgins, S. P., & Higgins, P. J. (2011) · Cell and Tissue Research · doi:10.1007/s00441-011-1181-y · Cited by 143 · see citing works
Zeisberg, M., Maeshima, Y., Mosterman, B., & Kalluri, R. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)61150-9 · Cited by 142 · see citing works
Li, S., Huang, P., Yang, A., Tarng, D., Yang, W.-C., Lin, C., Chen, J., Schmid‐Schönbein, G. W., & Lin, S. (2014) · Kidney International · doi:10.1038/ki.2014.67 · Cited by 135 · see citing works
Zhang, X., Guo, Y., Song, Z., & Zhou, M. (2014) · Endocrinology · doi:10.1210/en.2014-1020 · Cited by 126 · see citing works
Rane, M. J., Song, Y., Jin, S., Barati, M. T., Wu, R., Kausar, H., Tan, Y., Wang, Y., Zhou, G., Klein, J. B., et al. (2009) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00032.2009 · Cited by 126 · see citing works
A study of hypoglycaemic effects of Azadirachta indica (Neem) in normaland alloxan diabetic rabbits.
Khosla, P., Bhanwra, S., Singh, J., Seth, S., & Srivastava, R. K. (2000) · PubMed · Cited by 126 · see citing works
Resident fibroblasts in the kidney: a major driver of fibrosis and inflammation
Sato, Y., & Yanagita, M. (2017) · Inflammation and Regeneration · doi:10.1186/s41232-017-0048-3 · Cited by 124 · see citing works
Zhang, L., Pang, S., Deng, B., Qian, L., Chen, J., Zou, J., Zheng, J., Linghui, Y., Zhang, C., Chen, X., et al. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.01.001 · Cited by 123 · see citing works
Wang, X., Zhou, Y., Tan, R., Xiong, M., He, W., Fang, L., Wen, P., Jiang, L., & Yang, J. (2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00216.2010 · Cited by 122 · see citing works
Bigé, N., Lévy, P., Callard, P., Faintuch, J.-M., Chigot, V., Jousselin, V., Ronco, P. M., & Boffa, J. (2012) · BMC Nephrology · doi:10.1186/1471-2369-13-139 · Cited by 116 · see citing works
Matrix Metalloproteinases in Renal Diseases: A Critical Appraisal
Zakiyanov, O., Kalousová, M., Zima, T., & Tesař, V. (2019) · Kidney & Blood Pressure Research · doi:10.1159/000499876 · Cited by 114 · see citing works
Hanamura, K., Tojo, A., Kinugasa, S., Asaba, K., & Fujita, T. (2012) · International Journal of Nephrology · doi:10.1155/2012/139565 · Cited by 110 · see citing works
Babykutty, S., Priya, P. S., Nandini, R. J., Kumar, M. A. S., Nair, M. S., Srinivas, P., & Gopala, S. (2011) · Molecular Carcinogenesis · doi:10.1002/mc.20812 · Cited by 108 · see citing works
Ng, Y.-Y., Fan, J., Mu, W., Nikolic‐Paterson, D. J., Yang, W.-C., Huang, T., Atkins, R. C., & Lan, H. Y. (1999) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/14.12.2860 · Cited by 103 · see citing works
Gupta, S. C., Prasad, S., Reuter, S., Kannappan, R., Yadav, V. R., Ravindran, J., Hema, P. S., Chaturvedi, M. M., Nair, M. S., & Aggarwal, B. B. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.161984 · Cited by 103 · see citing works
TGF-β-activated kinase-1: New insights into the mechanism of TGF-β signaling and kidney disease
Kim, S. I., & Choi, M. E. (2012) · Kidney Research and Clinical Practice · doi:10.1016/j.krcp.2012.04.322 · Cited by 96 · see citing works
Bhat, M., Kothiwale, S. K., Tirmale, A. R., Bhargava, S., & Joshi, B. N. (2009) · Evidence-based Complementary and Alternative Medicine · doi:10.1093/ecam/nep033 · Cited by 92 · see citing works
Hydrogen sulfide deficiency and diabetic renal remodeling: role of matrix metalloproteinase-9
Kundu, S., Pushpakumar, S. B., Tyagi, A. C., Coley, D. M., & Sen, U. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00604.2012 · Cited by 88 · see citing works
Self-citationIL-1RI deficiency ameliorates early experimental renal interstitial fibrosis
Jones, L. K., O’Sullivan, K. M., Semple, T. J., Kuligowski, M., Fukami, K., Ma, F. Y., Nikolic‐Paterson, D. J., Holdsworth, S. R., & Kitching, A. R. (2009) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfp214 · Cited by 87 · see citing works
Gutiérrez, R. M. P., & Damian-Guzman, M. (2012) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b12-00246 · Cited by 84 · see citing works
Therrien, F., Agharazii, M., Lebel, M., & Larivière, R. (2012) · American Journal of Nephrology · doi:10.1159/000340033 · Cited by 77 · see citing works
Nimbolide, a Neem Limonoid, Is a Promising Candidate for the Anticancer Drug Arsenal
Nagini, S., Nivetha, R., Palrasu, M., & Mishra, R. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c02239 · Cited by 76 · see citing works
Meng, X., Mak, T. S., & Lan, H.-Y. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-8871-2_13 · Cited by 67 · see citing works
Nelson, C., Karschimkus, C. S., Dragicevic, G., Packham, D., Wilson, A., O'Neal, D. N., Becker, G. J., Best, J. D., & Jenkins, A. J. (2005) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfi067 · Cited by 63 · see citing works
New and old markers of progression of diabetic nephropathy
Jerums, G., Premaratne, E., Panagiotopoulos, S., Clarke, S., Power, D. A., & MacIsaac, R. J. (2008) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2008.09.032 · Cited by 60 · see citing works
GYY4137, a Hydrogen Sulfide Donor Modulates miR194-Dependent Collagen Realignment in Diabetic Kidney
John, A. S. P., Kundu, S., Pushpakumar, S. B., Fordham, M., Weber, G. J., Mukhopadhyay, M., & Sen, U. (2017) · Scientific Reports · doi:10.1038/s41598-017-11256-3 · Cited by 59 · see citing works
Self-citationKluger, M. A., Zahner, G., Paust, H., Schaper, M., Magnus, T. U., Panzer, U., & Stahl, R. A. K. (2013) · Kidney International · doi:10.1038/ki.2012.483 · Cited by 53 · see citing works
Qian, X., Li, X., Ma, F., Luo, S., Ge, R., & Zhu, Y. Z. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.03.154 · Cited by 52 · see citing works
Chung, C. H., Fan, J., Lee, E. Y., Kang, J. S., Lee, S. J., Pyagay, P. E., Khoury, C. C., Yeo, T.-K., Khayat, M. F., Wang, A., et al. (2015) · Nephron Extra · doi:10.1159/000369576 · Cited by 49 · see citing works
Kundu, S., Pushpakumar, S. B., & Sen, U. (2015) · Nitric Oxide · doi:10.1016/j.niox.2015.02.003 · Cited by 48 · see citing works
Self-citationSanni, O., Erukainure, O. L., Chukwuma, C. I., Koorbanally, N. A., Ibeji, C. U., & Islam, M. S. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.10.171 · Cited by 47 · see citing works
Pingali, U., Ali, M. A., Gundagani, S., & Nutalapati, C. (2020) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s274378 · Cited by 46 · see citing works
Annaldas, S., Saifi, M. A., Khurana, A., & Godugu, C. (2019) · Molecular Immunology · doi:10.1016/j.molimm.2019.06.003 · Cited by 46 · see citing works
Goswami, K. K., Barik, S., Sarkar, M., Bhowmick, A. K., Biswas, J. K., Bose, A., & Baral, R. (2014) · Molecular Immunology · doi:10.1016/j.molimm.2014.01.015 · Cited by 44 · see citing works
Morris, J., Gonzales, C. B., Chapa, J. J. D. L., Cabang, A. B., Fountzilas, C. K., Patel, M., Orozco, S., & Wargovich, M. J. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00890 · Cited by 44 · see citing works
Huang, J., Chuang, C., Liu, M.-H., Lin, S.-H., Guh, J., & Chuang, L. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.04.001 · Cited by 43 · see citing works
Schwalm, S. A., Beyer, S., Frey, H., Haceni, R., Grammatikos, G., Thomas, D., Geißlinger, G., Schaefer, L., Huwiler, A., & Pfeilschifter, J. M. (2017) · American Journal Of Pathology · doi:10.1016/j.ajpath.2017.06.017 · Cited by 43 · see citing works
Kudalkar, M., Nayak, A., Bhat, K., & Nayak, R. N. (2014) · AYU (An International Quarterly Journal of Research in Ayurveda) · doi:10.4103/0974-8520.141947 · Cited by 43 · see citing works
Jun, J. Y., Ma, Z., & Segar, L. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00034.2011 · Cited by 40 · see citing works
Surse, V. M., Gupta, J., & Tikoo, K. (2011) · Journal of Molecular Endocrinology · doi:10.1530/jme-10-0154 · Cited by 38 · see citing works
Pushpakumar, S. B., Kundu, S., & Sen, U. (2019) · Scientific Reports · doi:10.1038/s41598-018-38467-6 · Cited by 37 · see citing works
Self-citationMukherjee, A., & Sengupta, S. (2012) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.3109/14756366.2012.694877 · Cited by 34 · see citing works
Perumal, E., Mercy, A. B., Arunkamar, R., Sharmila, G., Bhat, F. A., Balakrishnan, S., Singh, P., & Arunakaran, J. (2014) · Cell Proliferation · doi:10.1111/cpr.12148 · Cited by 33 · see citing works
Nimbolide induces apoptosis in human nasopharyngeal cancer cells
Chien, S., Hsu, C.-H., Lin, C., Chuang, Y., Lo, Y., Hsi, Y., Hsieh, M., & Chen, M. (2017) · Environmental Toxicology · doi:10.1002/tox.22423 · Cited by 30 · see citing works
Bansod, S., Saifi, M. A., Khurana, A., & Godugu, C. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104756 · Cited by 29 · see citing works
Youssef, D. M., & Fawzy, F. (2012) · Saudi Journal of Kidney Diseases and Transplantation · doi:10.4103/1319-2442.100880 · Cited by 28 · see citing works
Grutzmacher, C. K., Park, S., Zhao, Y. F., Morrison, M. E., Sheibani, N., & Sorenson, C. M. (2012) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00036.2012 · Cited by 28 · see citing works
Diddi, S., Bale, S., Pulivendala, G., & Godugu, C. (2018) · Inflammopharmacology · doi:10.1007/s10787-018-0527-4 · Cited by 26 · see citing works
Tubular biomarkers to assess progression of diabetic nephropathy
Tramonti, G., & Kanwar, Y. S. (2011) · Kidney International · doi:10.1038/ki.2011.9 · Cited by 25 · see citing works
Yadav, D. K., Bharitkar, Y. P., Hazra, A., Pal, U., Verma, S., Jana, S., Singh, U., Maiti, N. C., Mondal, N. B., & Swarnakar, S. (2017) · Journal of Natural Products · doi:10.1021/acs.jnatprod.6b00957 · Cited by 25 · see citing works
The kidney expression of matrix metalloproteinase-9 in the diabetic nephropathy of Kkay mice
Qing-Hua, G., Ju-ming, L., Chang-yu, P., Zhao-Hui, L., Xiao-man, Z., & Yiming, M. (2008) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2007.10.002 · Cited by 24 · see citing works
Li, Q., Li, K., Chen, Z., & Zhou, B. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2019.103748 · Cited by 23 · see citing works
Methylation-dependent antioxidant-redox imbalance regulates hypertensive kidney injury in aging
Pushpakumar, S. B., Ren, L., Juin, S. K., Majumder, S., Kulkarni, R. N., & Sen, U. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101754 · Cited by 23 · see citing works
Self-citationShin, S., Hwang, B., Muhammad, K., Gho, Y., Song, J., Kim, W., Kim, G., & Moon, S. (2019) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2019/3753587 · Cited by 23 · see citing works
Park, J., Jang, K. M., An, H. J., Kim, J., Gwon, M., Gu, H., Park, B., & Park, K. (2018) · Molecules · doi:10.3390/molecules23092236 · Cited by 22 · see citing works
Arumugam, A., Subramani, R., & Lakshmanaswamy, R. (2021) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2021.02.014 · Cited by 22 · see citing works
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Self-citationOhta, M. Y., Nagai, Y., Takamura, T., Nohara, E., & KOBAYASHI, K. P. (2000) · Metabolism · doi:10.1016/s0026-0495(00)91143-0 · Cited by 17 · see citing works
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Pendse, A. A., Johnson, L. A., Tsai, Y.-S., & Maeda, N. (2010) · Diabetes · doi:10.2337/db10-0673 · Cited by 10 · see citing works
Chugh, N., & Koul, A. (2020) · Journal of Traditional and Complementary Medicine · doi:10.1016/j.jtcme.2020.03.006 · Cited by 5 · see citing works
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Chen, C., Lin, M. C., Xie, X.-Y., Lin, C., Yang, C., Wu, P.-C., Liu, D.-H., Wu, C., & Lin, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010329 · Cited by 7 · see citing works
Xie, X., Wu, C., Huang, Z., Zhou, Y., Huang, J., Dao, F., Yan, D., Deng, K., Lyu, H., Ma, C., et al. (2026) · Briefings in Bioinformatics · doi:10.1093/bib/bbag083 · Cited by 4 · see citing works
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- Authors
- Juin, S. K., Pushpakumar, S., Tyagi, S. C., & Sen, U.
- Affiliations
- University of Louisville (US)
- Corresponding author
- Sen, Utpal
- Venue
- Scientific Reports
- Published
- 2022-12-15
- Volume
- 12
- Issue
- 1
- Pages
- 21707-21707
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC9755213
- OpenAlex
- W4311749438
- Cited by
- 18
- References
- 104
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 7
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (DK116591)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Keywords
- Azadirachta indica, type 1 diabetes, diabetic nephropathy, renal fibrosis, extracellular matrix accumulation, matrix metalloproteinases, MMP-9, MMP-13, macrophage infiltration, epithelial-mesenchymal transition, TGF-β/Smad signaling, MAPK signaling, glucosidase inhibitors, diterpenoids, Akita mice, renal function
- MeSH terms
- Animals, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Diabetic Nephropathies, Diterpenes, Fibrosis, Glucosidases, Inflammation, Kidney, Mice, Inbred C57BL, Mice, Transforming Growth Factor beta1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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