Effect of Borreria hispida Extract on SIRT1, HIF-1α, ET-1 and VEGFR-2 Gene Expression in NRK-52E Cells Subjected to Glucotoxicity
Abstract
This study aimed to investigate the impact of Borreria hispida extract on gene expression in NRK-52E cells under conditions of glucotoxicity. Gene expression analysis was conducted using RT-PCR following the exposure of cultured NRK-52E cells to glucotoxic conditions and varying concentrations of Borreria hispida extract. The results demonstrated a dose-dependent increase in SIRT1 gene expression and a concomitant decrease in HIF-1λ, ET-1, and VEGFR-2 gene expressions upon treatment with Borreria hispida extract. Additionally, molecular docking studies suggested the potential inhibition of Rho-kinase as a mechanistic explanation for these effects. Borreria hispida extract may confer renoprotective benefits against glucotoxicity-induced cellular damage. The potential therapeutic utility of Borreria hispida extracts in managing renal complications associated with conditions such as diabetes. Furthermore, our docking studies shed light on the potential molecular mechanisms underlying the observed effects, suggesting interactions between phytochemicals present in Borreria hispida extract and the JNK-1 protein. These interactions may contribute to the augmentation of SIRT1 activity, further bolstering the extract's therapeutic utility in DKD.
References
Acharya, C.K., Das, B., Madhu, N.R., Sau, S., Manna De, M., & Sarkar, B. (2023). A Comprehensive Pharmacological Appraisal of Indian Traditional Medicinal Plants with Anti-diabetic Potential. Springer Nature Singapore Pte Ltd., Advances in Diabetes Research and Management, pp. 163–193, Online ISBN-978-981-19-0027-3. https://doi.org/10.1007/978-981-19-0027-3_8
Altunkaya, A., Bi, C., Bradley, A. R., Rose, P. W., Prli, A., Christie, H., Costanzo, L. Di, Duarte, J. M., Dutta, S., Feng, Z., Green, R. K., Goodsell, D. S., Hudson, B., Kalro, T., Lowe, R., Peisach, E., Randle, C., Rose, A. S., Shao, C., … Burley, S. K. (2016). OUP accepted manuscript. Nucleic Acids Research, 1–11. https://doi.org/10.1093/nar/gkw1000
Andersen, A. R., Christiansen, J. S., Andersen, J. K., Kreiner, S., & Deckert, T. (1983). Diabetic nephropathy in type 1 (insulin-dependent) diabetes: An epidemiological study. Diabetologia, 25(6), 496–501. https://doi.org/10.1007/BF00284458
Biswas, T., Behera, B. K., & Madhu, N.R. (2023). Technology in the Management of Type 1 and Type 2 Diabetes Mellitus: Recent Status and Future Prospects. 26 pages, Springer Nature Singapore Pte Ltd., Advances in Diabetes Research and Management. pp. 111–136. Online ISBN-978-981-19-0027-3. https://doi.org/10.1007/978-981-19-0027-3_6
Chakrovorty, A., Bhattacharjee, B., Dey, R., Samadder, A., & Nandi, S. (2021). Graphene: the magic carbon derived biological weapon for human welfare. Int. J. Exp. Res. Rev., 25, 9-17. https://doi.org/10.52756/ijerr.2021.v25.002
Chiang, S. K., Chen, S. E., & Chang, L. C. (2019). A dual role of heme oxygenase-1 in cancer cells. International Journal of Molecular Sciences, 20(1), 1–18. https://doi.org/10.3390/ijms20010039
Chuang, P. Y., Dai, Y., Liu, R., He, H., Kretzler, M., Jim, B., Cohen, C. D., & He, J. C. (2011). Alteration of forkhead box o (foxo4) acetylation mediates apoptosis of podocytes in diabetes mellitus. PLoS ONE, 6(8). https://doi.org/10.1371/journal.pone.0023566
de Boer, V. C. J., de Goffau, M. C., Arts, I. C. W., Hollman, P. C. H., & Keijer, J. (2006). SIRT1 stimulation by polyphenols is affected by their stability and metabolism. Mechanisms of Ageing and Development, 127(7), 618–627. https://doi.org/10.1016/j.mad.2006.02.007
Feng, X., Wang, S., Sun, Z., Dong, H., Yu, H., Huang, M., & Gao, X. (2021). Ferroptosis Enhanced Diabetic Renal Tubular Injury via HIF-1α/HO-1 Pathway in db/db Mice. Frontiers in Endocrinology, 12(February), 1–12. https://doi.org/10.3389/fendo.2021.626390
Gao, Z., Zhang, J., Kheterpal, I., Kennedy, N., Davis, R. J., & Ye, J. (2011). Sirtuin 1 (SIRT1) protein degradation in response to persistent c-Jun N-terminal Kinase 1 (JNK1) activation contributes to hepatic steatosis in obesity. Journal of Biological Chemistry, 286(25), 22227–22234. https://doi.org/10.1074/jbc.M111.228874
Guo, Z., Liao, Z., Huang, L., Liu, D., Yin, D., & He, M. (2015). Kaempferol protects cardiomyocytes against anoxia/reoxygenation injury via mitochondrial pathway mediated by SIRT1. European Journal of Pharmacology, 761, 245–253. https://doi.org/10.1016/j.ejphar.2015.05.056
Hallows, W. C., Yu, W., & Denu, J. M. (2012). Regulation of glycolytic enzyme phosphoglycerate mutase-1 by Sirt1 protein-mediated deacetylation. Journal of Biological Chemistry, 287(6), 3850–3858. https://doi.org/10.1074/jbc.M111.317404
Hasegawa, K., Wakino, S., Simic, P., Sakamaki, Y., Minakuchi, H., Fujimura, K., Hosoya, K., Komatsu, M., Kaneko, Y., Kanda, T., Kubota, E., Tokuyama, H., Hayashi, K., Guarente, L., & Itoh, H. (2013). Renal tubular sirt1 attenuates diabetic albuminuria by epigenetically suppressing claudin-1 overexpression in podocytes. Nature Medicine, 19(11), 1496–1504. https://doi.org/10.1038/nm.3363
Huang, L., He, H., Liu, Z., Liu, D., Yin, D., & He, M. (2016). Protective Effects of Isorhamnetin on Cardiomyocytes Against Anoxia/Reoxygenation-induced Injury Is Mediated by SIRT1. Journal of Cardiovascular Pharmacology, 67(6), 526–537. https://doi.org/10.1097/FJC.0000000000000376
Isoe, T., Makino, Y., Mizumoto, K., Sakagami, H., Fujita, Y., Honjo, J., Takiyama, Y., Itoh, H., & Haneda, M. (2010). High glucose activates HIF-1-mediated signal transduction in glomerular mesangial cells through a carbohydrate response element binding protein. Kidney International, 78(1), 48–59. https://doi.org/10.1038/ki.2010.99
Kume, S., Haneda, M., Kanasaki, K., Sugimoto, T., Araki, S. I., Isshiki, K., Isono, M., Uzu, T., Guarente, L., Kashiwagi, A., & Koya, D. (2007). SIRT1 inhibits transforming growth factor β-induced apoptosis in glomerular mesangial cells via Smad7 deacetylation. Journal of Biological Chemistry, 282(1), 151–158. https://doi.org/10.1074/jbc.M605904200
DeLano, W. (2002). Pymol: An open-source molecular graphics tool. {CCP4} Newsletter On Protein Crystallography, 40, 1–8. http://www.ccp4.ac.uk/newsletters/newsletter40/11_pymol.pdf
Lavoz, C., Rodrigues-diez, R. R., Plaza, A., Carpio, D., Egido, J., Ruiz-ortega, M., & Mezzano, S. (2020). VEGFR2 blockade improves renal damage in an experimental model of type 2 diabetic nephropathy. Journal of Clinical Medicine, 9(2), 1–21. https://doi.org/10.3390/jcm9020302
Medhi, J., Karmakar, M., Barman, A., Mondal, S., & Nag, A. (2023). Diabetic retinopathy stage detection using convolutional fine-tuned transfer Learning model. Int. J. Exp. Res. Rev., 31(Spl Volume), 33-41. https://doi.org/10.52756/10.52756/ijerr.2023.v31spl.004
Moynihan, K. A., Grimm, A. A., Plueger, M. M., Bernal-Mizrachi, E., Ford, E., Cras-Méneur, C., Permutt, M. A., & Imai, S. I. (2005). Increased dosage of mammalian Sir2 in pancreatic β cells enhances glucose-stimulated insulin secretion in mice. Cell Metabolism, 2(2), 105–117. https://doi.org/10.1016/j.cmet.2005.07.001
Nihalani, D., & Susztak, K. (2013). Sirt1-claudin-1 crosstalk regulates renal function. Nature Medicine, 19(11), 1371–1372. https://doi.org/10.1038/nm.3386
Muhammad, T., Ikram, M., Ullah, R., Rehman, S. U., & Kim, M. O. (2019). Hesperetin, a citrus flavonoid, attenuates LPS-induced neuroinflammation, apoptosis and memory impairments by modulating TLR4/NF-κB signaling. Nutrients, 11(3), 1–20. https://doi.org/10.3390/nu11030648
Pawar, S., Pawade, K., Nipate, S., Balap, A., Pimple, B., Wagh, V., Kachave, R., & Gaikwad, A. (2023). Preclinical evaluation of the diabetic wound healing activity of phytoconstituents extracted from Ficus racemosa Linn. leaves. Int. J. Exp. Res. Rev., 32, 365-377. https://doi.org/10.52756/ijerr.2023.v32.032
Peppa-Patrikiou, M., Dracopoulou, M., & Dacou-Voutetakis, C. (1998). Urinary endothelin in adolescents and young adults with insulin- dependent diabetes mellitus: Relation to urinary albumin, blood pressure, and other factors. Metabolism: Clinical and Experimental, 47(11), 1408–1412. https://doi.org/10.1016/S0026-0495(98)90314-6
Price, N. L., Gomes, A. P., Ling, A. J. Y., Duarte, F. V., Martin-Montalvo, A., North, B. J., Agarwal, B., Ye, L., Ramadori, G., Teodoro, J. S., Hubbard, B. P., Varela, A. T., Davis, J. G., Varamini, B., Hafner, A., Moaddel, R., Rolo, A. P., Coppari, R., Palmeira, C. M., … Sinclair, D. A. (2012). SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metabolism, 15(5), 675–690. https://doi.org/10.1016/j.cmet.2012.04.003
Purushotham, A., Schug, T. T., Xu, Q., Surapureddi, S., Guo, X., & Li, X. (2009). Hepatocyte-Specific Deletion of SIRT1 Alters Fatty Acid Metabolism and Results in Hepatic Steatosis and Inflammation.
Cell Metabolism, 9(4), 327–338. https://doi.org/10.1016/j.cmet.2009.02.006
Qi, F., Sun, J. hao, Yan, J. qun, Li, C. mei, & Lv, X. chao. (2018). Anti-inflammatory effects of isorhamnetin on LPS-stimulated human gingival fibroblasts by activating Nrf2 signaling pathway. Microbial Pathogenesis, 120, 37–41. https://doi.org/10.1016/j.micpath.2018.04.049
Roy, R., Chakraborty, A., Jana, K., Sarkar, B., Biswas, P., & Madhu, N.R. (2023). The Broader Aspects of Treating Diabetes with the Application of Nanobiotechnology. Springer Nature Singapore Pte Ltd., Advances in Diabetes Research and Management, pp. 137–162, Online ISBN-978-981-19-0027-3, https://doi.org/10.1007/978-981-19-0027-3_7
Sarkar, S., Sadhu, S., Roy, R., Tarafdar, S., Mukherjee, N., Sil, M., Goswami, A., & Madhu, N.R. (2023). Contemporary Drifts in Diabetes Management. Int. J. App. Pharm., 15(2): 1-9.
Shokri Afra, H., Zangooei, M., Meshkani, R., Ghahremani, M. H., Ilbeigi, D., Khedri, A., Shahmohamadnejad, S., Khaghani, S., & Nourbakhsh, M. (2019). Hesperetin is a potent bioactivator that activates SIRT1-AMPK signaling pathway in HepG2 cells. Journal of Physiology and Biochemistry, 75(2), 125–133. https://doi.org/10.1007/s13105-019-00678-4
Simms, D., Cizdziel, P., & Chomczynski, P. (1993). TRIzol: a new reagent for optimal single-step isolation of RNA. Focus, 99–102. http://www.invitrogen.co.jp/focus/154099.pdf%5Cnpapers2://publication/uuid/B68F1A0C-FB1A-4A64-8567-DE4CA8297D16
Song, L., Wang, K., Yin, J., Yang, Y., Li, B., Zhang, D., Wang, H., Wang, W., Zhan, W., Guo, C., Gu, Z., Wang, L., Zeng, Z., Bei, W., Rong, X., & Guo, J. (2022). Traditional Chinese Medicine Fufang-Zhenzhu-Tiaozhi capsule prevents renal injury in diabetic minipigs with coronary heart disease. Chinese Medicine (United Kingdom), 17(1), 1–14. https://doi.org/10.1186/s13020-022-00648-x
Sun, H. K., Lee, Y. M., Han, K. H., Kim, H. S., Ahn, S. H., & Han, S. Y. (2012). Phosphodiesterase inhibitor improves renal tubulointerstitial hypoxia of the diabetic rat kidney. Korean Journal of Internal Medicine, 27(2), 163–170. https://doi.org/10.3904/kjim.2012.27.2.163
Sur, T., Das, A., Bashar, S., Tarafdar, S., Sarkar, B., & Madhu, N.R. (2023). Biochemical Assay for Measuring Diabetes Mellitus. Springer Nature Singapore Pte Ltd., Advances in Diabetes Research and Management, pp. 1–20. Online ISBN-978-981-19-0027-3, https://doi.org/10.1007/978-981-19-0027-3_1
Susztak, K., Raff, A. C., Schiffer, M., & Böttinger, E. P. (2006). Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes, 55(1), 225–233. https://doi.org/10.2337/diabetes.55.01.06.db05-0894
Thomas, M. C., Tikellis, C., Kantharidis, P., Burns, W. C., Cooper, M. E., & Forbes, J. M. (2004). The role of advanced glycation in reduced organic cation transport associated with experimental diabetes. Journal of Pharmacology and Experimental Therapeutics, 311(2), 456–466. https://doi.org/10.1124/jpet.104.070672
Trott, O., & Olson, A. J. (2009). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455–461. Portico. https://doi.org/10.1002/jcc.21334
van Horssen, J., Schreibelt, G., Drexhage, J., Hazes, T., Dijkstra, C. D., van der Valk, P., & de Vries, H. E. (2008). Severe oxidative damage in multiple sclerosis lesions coincides with enhanced antioxidant enzyme expression. Free Radical Biology and Medicine, 45(12), 1729–1737. https://doi.org/10.1016/j.freeradbiomed.2008.09.023
Wang, J., Liu, W., Luo, G., Li, Z., Zhao, C., Zhang, H., Zhu, M., Xu, Q., Wang, X., Zhao, C., Qu, Y., Yang, Z., Yao, T., Li, Y., Lin, Y., Wu, Y., & Li, Y. (2018). Synergistic effect of well-defined dual sites boosting the oxygen reduction reaction. Energy and Environmental Science, 11(12), 3375–3379. https://doi.org/10.1039/c8ee02656d
Wenzel, R. R., Czyborra, P., Lüscher, T. F., & Philipp, T. (1999). Endothelin in cardiovascular control: The role of endothelin antagonists. Current Hypertension Reports, 1(1), 79–87. https://doi.org/10.1007/s11906-999-0077-7
Yoshino, J., Mills, K. F., Yoon, M. J., & Imai, S. I. (2011). Nicotinamide mononucleotide, a key NAD + intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metabolism, 14(4), 528–536. https://doi.org/10.1016/j.cmet.2011.08.014
Yu, L., Wang, Y., Guo, Y. H., Wang, L., Yang, Z., Zhai, Z. H., & Tang, L. (2022). HIF-1α Alleviates High-Glucose-Induced Renal Tubular Cell Injury by Promoting Parkin/PINK1-Mediated Mitophagy. Frontiers in Medicine, 8, 1–8. https://doi.org/10.3389/fmed.2021.803874
Zhuo, L., Fu, B., Bai, X., Zhang, B., Wu, L., Cui, J., Cui, S., Wei, R., Chen, X., & Cai, G. (2011). NAD blocks high glucose induced mesangial hypertrophy via activation of the sirtuins-AMPK-mTOR pathway. Cellular Physiology and Biochemistry, 27(6), 681–690. https://doi.org/10.1159/000330077
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