Protective effects of sarsasapogenin against early stage of diabetic nephropathy in rats
Correction(s) for this article
-
Protective effects of sarsasapogenin against early stage of diabetic nephropathy in rats
- Volume 33Issue 9Phytotherapy Research
- pages: 2470-2470
- First Published online: July 15, 2019
Corresponding Author
Yao-Wu Liu
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004 Jiangsu, China
Department of Pharmacology, School of Pharmacy, Xuzhou Medical University, Xuzhou, 221004 Jiangsu, China
These authors contributed equally to this study.Correspondence
Yao-Wu Liu, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, No. 209, Tongshan Road, Xuzhou 221004, Jiangsu, China.
Email: [email protected]
Search for more papers by this authorYun-Chao Hao
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004 Jiangsu, China
These authors contributed equally to this study.Search for more papers by this authorYa-Jing Chen
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004 Jiangsu, China
Search for more papers by this authorShen-Yuan Yin
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004 Jiangsu, China
Search for more papers by this authorMeng-Ya Zhang
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004 Jiangsu, China
Search for more papers by this authorLi Kong
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004 Jiangsu, China
Search for more papers by this authorTao-Yun Wang
College of Chemistry, Biology and Material Engineering, Suzhou University of Science and Technology, Suzhou, 215009 China
Search for more papers by this authorCorresponding Author
Yao-Wu Liu
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004 Jiangsu, China
Department of Pharmacology, School of Pharmacy, Xuzhou Medical University, Xuzhou, 221004 Jiangsu, China
These authors contributed equally to this study.Correspondence
Yao-Wu Liu, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, No. 209, Tongshan Road, Xuzhou 221004, Jiangsu, China.
Email: [email protected]
Search for more papers by this authorYun-Chao Hao
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004 Jiangsu, China
These authors contributed equally to this study.Search for more papers by this authorYa-Jing Chen
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004 Jiangsu, China
Search for more papers by this authorShen-Yuan Yin
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004 Jiangsu, China
Search for more papers by this authorMeng-Ya Zhang
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004 Jiangsu, China
Search for more papers by this authorLi Kong
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004 Jiangsu, China
Search for more papers by this authorTao-Yun Wang
College of Chemistry, Biology and Material Engineering, Suzhou University of Science and Technology, Suzhou, 215009 China
Search for more papers by this authorAbstract
Rhizome of Anemarrhena asphodeloides Bunge (AA, family Liliaceae) has been widely used in China for thousands of years to treat febrile diseases and diabetes. Steroidal saponins from AA show good antidiabetes effects and ameliorate diabetic complications. This study was designed to investigate the effects of sarsasapogenin (Sar), a major sapogenin from AA, on diabetic nephropathy (DN) in rats, and to explore the possible mechanisms. Diabetic rats were divided into 3 groups treated orally with Sar (0, 20, or 60 mg/kg) and carboxymethylcellulose sodium, whereas normal rats for Sar (0 or 60 mg/kg) and carboxymethylcellulose sodium. We found that chronic treatment with Sar for 9 weeks significantly ameliorated renal dysfunction of diabetic rats, as evidenced by decreases in albuminuria, kidney weight index, serum uric acid, and morphologic changes such as extracellular matrix expansion and accumulation (fibronectin and collagen IV levels, etc.). Meanwhile, Sar treatment resulted in decreases in interleukin-18, NLRP3, and activated caspase 1 levels as well as advanced glycation endproducts (AGEs) and their receptor (RAGE) levels in the renal cortex of diabetic rats. However, Sar has no effects on the above indices in the normal rats. Therefore, Sar can markedly ameliorate diabetic nephropathy in rats via inhibition of NLRP3 inflammasome activation and AGEs–RAGE interaction.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
REFERENCES
- Abais, J. M., Zhang, C., Xia, M., Liu, Q., Gehr, T. W., Boini, K. M., & Li, P. L. (2013). NADPH oxidase-mediated triggering of inflammasome activation in mouse podocytes and glomeruli during hyperhomocysteinemia. Antioxidants & Redox Signaling, 18, 1537–1548.
- Kim, J. Y., Shin, J. S., Ryu, J. H., Kim, S. Y., Cho, Y. W., Choi, J. H., & Lee, K. T. (2009). Anti-inflammatory effect of anemarsaponin B isolated from the rhizomes of Anemarrhena asphodeloides in LPS-induced RAW 264.7 macrophages is mediated by negative regulation of the nuclear factor-kappaB and p38 pathways. Food and Chemical Toxicology, 47, 1610–1617.
- Kim, S. M., Lee, S. H., Kim, Y. G., Kim, S. Y., Seo, J. W., Choi, Y. W., … Moon, J. Y. (2015). Hyperuricemia-induced NLRP3 activation of macrophages contributes to the progression of diabetic nephropathy. American Journal of Physiology. Renal Physiology, 308, F993–F1003.
- King, F. W., Fong, S., Griffin, C., Shoemaker, M., Staub, R., Zhang, Y. L., … Shtivelman, E. (2009). Timosaponin AIII is preferentially cytotoxic to tumor cells through inhibition of mTOR and induction of ER stress. PLoS One, 4, e7283.
- Kite, G. C., Porter, E. A., & Simmonds, M. S. (2007). Chromatographic behaviour of steroidal saponins studied by high-performance liquid chromatography-mass spectrometry. Journal of Chromatography. A, 1148, 177–183.
- Kumar Pasupulati, A., Chitra, P. S., & Reddy, G. B. (2016). Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy. Biomolecular Concepts, 7, 293–309.
- Lee, H. M., Kim, J. J., Kim, H. J., Shong, M., Ku, B. J., & Jo, E. K. (2013). Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes. Diabetes, 62, 194–204.
- Li, C. M., Gao, Y. L., Li, M., Han, B., & Liu, Z. F. (2005). Effects of saponins from Anemarrhean asphodeloides Bge. on blood glucose level in mice (in Chinese). Pharmacology and Clinics of Chinese Materia Medica, 21, 22–23.
- Lim, S. M., Jeong, J. J., Kang, G. D., Kim, K. A., Choi, H. S., & Kim, D. H. (2015). Timosaponin AIII and its metabolite sarsasapogenin ameliorate colitis in mice by inhibiting NF-kappaB and MAPK activation and restoring Th17/Treg cell balance. International Immunopharmacology, 25, 493–503.
- Liu, Y. W., Zhu, X., Lu, Q., Wang, J. Y., Li, W., Wei, Y. Q., & Yin, X. X. (2012). Total saponins from Rhizoma Anemarrhenae ameliorate diabetes-associated cognitive decline in rats: Involvement of amyloid-beta decrease in brain. Journal of Ethnopharmacology, 139, 194–200.
- Liu, Y. W., Zhu, X., Zhang, L., Lu, Q., Wang, J. Y., Zhang, F., … Yin, X. X. (2013). Up-regulation of glyoxalase 1 by mangiferin prevents diabetic nephropathy progression in streptozotocin-induced diabetic rats. European Journal of Pharmacology, 721, 355–364.
- Lu, Q., Zuo, W. Z., Ji, X. J., Zhou, Y. X., Liu, Y. Q., Yao, X. Q., … Yin, X. X. (2015). Ethanolic Ginkgo biloba leaf extract prevents renal fibrosis through Akt/mTOR signaling in diabetic nephropathy. Phytomedicine, 22, 1071–1078.
- Ma, D., Zhang, J., Sugahara, K., Sagara, Y., & Kodama, H. (2001). Effect of sarsasapogenin and its derivatives on the stimulus coupled responses of human neutrophils. Clinica Chimica Acta, 314, 107–112.
- Makino, H., Miyamoto, Y., Sawai, K., Mori, K., Mukoyama, M., Nakao, K., … Suga, S. (2006). Altered gene expression related to glomerulogenesis and podocyte structure in early diabetic nephropathy of db/db mice and its restoration by pioglitazone. Diabetes, 55, 2747–2756.
- Miura, T., Ichiki, H., Hashimoto, I., Iwamoto, N., Kato, M., Kubo, M., … Tanigawa, K. (2001). Antidiabetic activity of a xanthone compound, mangiferin. Phytomedicine, 8, 85–87.
- Miura, T., Ichiki, H., Iwamoto, N., Kato, M., Kubo, M., Sasaki, H., … Tanigawa, K. (2001). Antidiabetic activity of the rhizoma of Anemarrhena asphodeloides and active components, mangiferin and its glucoside. Biological & Pharmaceutical Bulletin, 24, 1009–1011.
- Muruganandan, S., Srinivasan, K., Gupta, S., Gupta, P. K., & Lal, J. (2005). Effect of mangiferin on hyperglycemia and atherogenicity in streptozotocin diabetic rats. Journal of Ethnopharmacology, 97, 497–501.
- Nakashima, N., Kimura, I., Kimura, M., & Matsuura, H. (1993). Isolation of pseudoprototimosaponin AIII from rhizomes of Anemarrhena asphodeloides and its hypoglycemic activity in streptozotocin-induced diabetic mice. Journal of Natural Products, 56, 345–350.
- Navarro-Gonzalez, J. F., Mora-Fernandez, C., Muros de Fuentes, M., & Garcia-Perez, J. (2011). Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nature Reviews. Nephrology, 7, 327–340.
- Qiu, Y. Y., & Tang, L. Q. (2016). Roles of the NLRP3 inflammasome in the pathogenesis of diabetic nephropathy. Pharmacological Research, 114, 251–264.
- Rivero, A., Mora, C., Muros, M., Garcia, J., Herrera, H., & Navarro-Gonzalez, J. F. (2009). Pathogenic perspectives for the role of inflammation in diabetic nephropathy. Clinical Science (London, England), 116, 479–492.
- Saraheimo, M., Teppo, A. M., Forsblom, C., Fagerudd, J., & Groop, P. H. (2003). Diabetic nephropathy is associated with low-grade inflammation in type 1 diabetic patients. Diabetologia, 46, 1402–1407.
- Shahzad, K., Bock, F., Al-Dabet, M. M., Gadi, I., Kohli, S., Nazir, S., … Isermann, B. (2016). Caspase-1, but not caspase-3, promotes diabetic nephropathy. Journal of the American Society of Nephrology, 27, 2270–2275.
- Shahzad, K., Bock, F., Dong, W., Wang, H., Kopf, S., Kohli, S., … Isermann, B. (2015). Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy. Kidney International, 87, 74–84.
- Susztak, K., Bottinger, E., Novetsky, A., Liang, D., Zhu, Y., Ciccone, E., … Sharma, K. (2004). Molecular profiling of diabetic mouse kidney reveals novel genes linked to glomerular disease. Diabetes, 53, 784–794.
- Tanji, N., Markowitz, G. S., Fu, C., Kislinger, T., Taguchi, A., Pischetsrieder, M., … D'Agati, V. D. (2000). Expression of advanced glycation end products and their cellular receptor RAGE in diabetic nephropathy and nondiabetic renal disease. Journal of the American Society of Nephrology, 11, 1656–1666.
- Tesch, G. H., Yang, N., Yu, H., Lan, H. Y., Foti, R., Chadban, S. J., … Nikolic-Paterson, D. J. (1997). Intrinsic renal cells are the major source of interleukin-1 beta synthesis in normal and diseased rat kidney. Nephrology, Dialysis, Transplantation, 12, 1109–1115.
- Tuttle, K. R. (2005). Linking metabolism and immunology: Diabetic nephropathy is an inflammatory disease. Journal of the American Society of Nephrology, 16, 1537–1538.
- Wada, J., & Makino, H. (2013). Inflammation and the pathogenesis of diabetic nephropathy. Clinical Science (London, England), 124, 139–152.
- Wang, C., Pan, Y., Zhang, Q. Y., Wang, F. M., & Kong, L. D. (2012). Quercetin and allopurinol ameliorate kidney injury in STZ-treated rats with regulation of renal NLRP3 inflammasome activation and lipid accumulation. PLoS One, 7, e38285.
- Wang, F., Yan, J., Niu, Y., Li, Y., Lin, H., Liu, X., … Li, L. (2014). Mangiferin and its aglycone, norathyriol, improve glucose metabolism by activation of AMP-activated protein kinase. Pharmaceutical Biology, 52, 68–73.
- Wang, Y., Dan, Y., Yang, D., Hu, Y., Zhang, L., Zhang, C., … Liu, Y. (2014). The genus Anemarrhena Bunge: A review on ethnopharmacology, phytochemistry and pharmacology. Journal of Ethnopharmacology, 153, 42–60.
- Yang, S. M., Ka, S. M., Wu, H. L., Yeh, Y. C., Kuo, C. H., Hua, K. F., … Chen, A. (2014). Thrombomodulin domain 1 ameliorates diabetic nephropathy in mice via anti-NF-kappaB/NLRP3 inflammasome-mediated inflammation, enhancement of NRF2 antioxidant activity and inhibition of apoptosis. Diabetologia, 57, 424–434.
- Yeh, W. J., Yang, H. Y., Pai, M. H., Wu, C. H., & Chen, J. R. (2017). Long-term administration of advanced glycation end-product stimulates the activation of NLRP3 inflammasome and sparking the development of renal injury. The Journal of Nutritional Biochemistry, 39, 68–76.
- Yi, H., Peng, R., Zhang, L. Y., Sun, Y., Peng, H. M., Liu, H. D., … Zhang, Z. (2017). LincRNA-Gm4419 knockdown ameliorates NF-kappaB/NLRP3 inflammasome-mediated inflammation in diabetic nephropathy. Cell Death & Disease, 8, e2583.
- Yuan, Y. L., Guo, C. R., Cui, L. L., Ruan, S. X., Zhang, C. F., Ji, D., … Li, F. (2015). Timosaponin B-II ameliorates diabetic nephropathy via TXNIP, mTOR, and NF-kappaB signaling pathways in alloxan-induced mice. Drug Design, Development and Therapy, 9, 6247–6258.
- Yuan, Y. L., Lin, B. Q., Zhang, C. F., Cui, L. L., Ruan, S. X., Yang, Z. L., … Ji, D. (2016). Timosaponin B-II Ameliorates Palmitate-Induced Insulin Resistance and Inflammation via IRS-1/PI3K/Akt and IKK/NF-[Formula: see text]B Pathways. The American Journal of Chinese Medicine, 44, 755–769.
- Zhou, X., Wang, B., Zhu, L., & Hao, S. (2012). A novel improved therapy strategy for diabetic nephropathy: Targeting AGEs. Organogenesis, 8, 18–21.
- Zu, Y., Wan, L. J., Cui, S. Y., Gong, Y. P., & Li, C. L. (2015). The mitochondrial Na(+)/Ca(2+) exchanger may reduce high glucose-induced oxidative stress and nucleotide-binding oligomerization domain receptor 3 inflammasome activation in endothelial cells. Journal of Geriatric Cardiology, 12, 270–278.