Liquiritin Attenuates Diabetic Nephropathy in Type 2 Diabetic Male Rats Irrespective of Antihyperglycemic Effect
DOI:
https://doi.org/10.31351/vol34iss4pp13-22Keywords:
diabetes mellitus, diabetic nephropathy, flavonoids, liquiritin, oxidative stressAbstract
Diabetic nephropathy represents one of the common and serious complications of diabetes mellitus and it’s a leading cause of renal failure. Liquiritin is one of the main flavonoids found in Glycyrrhiza glabra that has been shown to have several pharmacological effects, such as the antioxidant, anti-inflammatory, anti-tumor, cardiovascular protection, hepatoprotection, and attenuation of rheumatoid arthritis in experimental animals. The present study investigated the protective effect of liquiritin against diabetic nephropathy in high fat diet and streptozotocin (STZ) induced diabetes mellitus in male rats.
In the present study, the type 2 diabetes model was induced by feeding the animals with the high fat diet for four weeks, after that the animals were fasted overnight and injected with a single intraperitoneal dose of STZ 30 mg/kg. Liquiritin was administered daily at a dose of 40 mg/kg for 15 weeks. At the end of the experimental period, blood glucose level, glycated hemoglobin A1 (HbA1c), lipid profile markers, serum renal function parameters, renal index were assed, levels of inflammatory and oxidative markers namely interleukin-1beta (IL-1β), interleukin -6 (IL-6), tumor necrosis factor-alpha (TNF- α), and transforming growth factor-beta (TGF-β1), glutathione (GSH), and malondialdehyde (MDA) were determined in the renal homogenate, and the histopathological examination was performed by the use of hematoxylin and eosin staining, where the histopathological changes in kidney tissues were semi-quantitatively calculated according to a renal pathology scoring system.
The diabetic control group showed a significant increase in the glycemic control parameters, and renal function parameters, and showed significant histopathological changes compared with the normal control group. The results revealed that liquiritin significantly improves histopathological changes while doesn’t affect the glycemic control parameters with a reduction in the inflammatory markers and oxidative stress in the renal homogenate.
Liquiritin has an ameliorating effect against DN and it can significantly decrease most of the histopathological changes, and oxidative, and inflammatory markers.
How to Cite
Publication Dates
Received
Revised
Accepted
Published Online First
References
Tang SCW, Chan GCW, Lai KN. Recent advances in managing and understanding diabetic nephropathy. F1000Research. 2016; 5: 1-9.
Warren AM, Knudsen ST, Cooper ME. Diabetic nephropathy: an insight into molecular mechanisms and emerging therapies. Expert Opinion on Therapeutic Targets. 2019; 23(7):579–91.
Doshi S, Society AF-CJ of the A. Diagnosis and management of type 2 diabetic kidney disease. Am Soc Nephrol. 2017; 12(8): 1366–1373.
Johansen KL, Chertow GM, Gilbertson DT, et al. US Renal Data System 2021 Annual Data Report: Epidemiology of Kidney Disease in the United States. American Journal of Kidney Diseases. 2022;79(4):A8–12.
Stoumpos S, Jardine AG, Mark PB. Cardiovascular morbidity and mortality after kidney transplantation. Transplant International. 2015; 28(1):10–21.
Herman-Edelstein M, Doi SQ. Pathophysiology of diabetic nephropathy. Proteinuria: Basic Mechanisms, Pathophysiology and Clinical Relevance. 2016; 4:1–65.
Navarro-González JF, Mora-Fernández C, De Fuentes MM, García-Pérez J. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nature Reviews Nephrology 2011 7:6. 2011;7(6):327–40.
Alicic RZ, Johnson EJ, Tuttle KR. Inflammatory Mechanisms as New Biomarkers and Therapeutic Targets for Diabetic Kidney Disease. Advances in Chronic Kidney Disease. 2018; 25(2):181–91.
Bhattacharjee N, Barma S, Konwar N, Dewanjee S, Manna P. Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: An update. European Journal of Pharmacology. 2016;791: 8–24.
Loeffler I, Wolf G. Mechanisms of interstitial fibrosis in diabetic nephropathy. Diabetic Nephropathy: Pathophysiology and Clinical Aspects. 2018; 227–51.
Tuttle KR, Agarwal R, Alpers CE, et al. Molecular mechanisms and therapeutic targets for diabetic kidney disease. Kidney International. 2022;102(2): 248–60.
Chen HW, Yang MY, Hung TW, Chang YC, Wang CJ. Nelumbo nucifera leaves extract attenuate the pathological progression of diabetic nephropathy in high-fat diet-fed and streptozotocin-induced diabetic rats. Journal of Food and Drug Analysis. 2019;27(3):736–48.
Hu Q, Chen Y, Deng X, et al. Diabetic nephropathy: Focusing on pathological signals, clinical treatment, and dietary regulation. Biomedicine & Pharmacotherapy. 2023;159:114252.
Barrera-Chimal J, Jaisser F. Pathophysiologic mechanisms in diabetic kidney disease: A focus on current and future therapeutic targets. Diabetes, Obesity and Metabolism. 2020; 22(S1):16–31.
Naaman SC, Bakris GL. Slowing Diabetic Kidney Disease Progression: Where Do We Stand Today? Compendia. 2021; 2021(1): 28–32.
Swayeh, Noor Hassoon; Kadhim HM. Effects of iraqi abelmoschus esculentus methanol extract on high fat diet plus streptozotocin induced type 2 diabetes mellitus in rats. Biochemical & Cellular Archives. 2022; 22(1): 1281.
researchgatenetAR Abu-Raghif, BJ Qasim, AH Abady, HB Sahib. Effects of aqueous thyme extract against cisplatin induced nephrotoxicity in rabbits. International Journal of Pharmaceutical Sciences Review and Research. 2015; 30(1):190–4.
Zangeneh MM, Mohammadi G, Salmani S, Razeghi Tehrani P, Rashidi K, Zangeneh* A. A Comparative Evaluation of Nephroprotective Property of Urtica dioica L. Aqueous Extract and Glibenclamide in Diabetic Mice. Research Journal of Pharmacognosy. 2020; 7(1):31–40.
Lin -L ;, Hammes J-H;, Zhang H-P;, et al. Flavonoids in Treatment of Chronic Kidney Disease. Molecules. 2022; 27(7):2365.
Wahab S, Annadurai S, Abullais SS, et al. Glycyrrhiza glabra (Licorice): A Comprehensive Review on Its Phytochemistry, Biological Activities, Clinical Evidence and Toxicology. 2021;10(12):2751.
Noreen S, Mubarik F, Farooq F, Khan M, Khan AU, Pane YS. Medicinal uses of licorice (Glycyrrhiza glabra L.): A comprehensive review. Open Access Macedonian Journal of Medical Sciences. 2021; 9:668–75.
Zhai KF, Duan H, Cui CY, et al. Liquiritin from Glycyrrhiza uralensis Attenuating Rheumatoid Arthritis via Reducing Inflammation, Suppressing Angiogenesis, and Inhibiting MAPK Signaling Pathway. Journal of Agricultural and Food Chemistry. 2019; 67(10):2856–64.
Qin J, Chen J, Peng F, et al. Pharmacological activities and pharmacokinetics of liquiritin: A review. Journal of Ethnopharmacology. 2022; 293:115257.
Liu L, Tang D, Zhao H, Xin X, Aisa HA. Hypoglycemic effect of the polyphenols rich extract from Rose rugosa Thunb on high fat diet and STZ induced diabetic rats. Journal of Ethnopharmacology. 2017; 200:174–81.
Furman BL. Streptozotocin-Induced Diabetic Models in Mice and Rats. 2021; 1: e78.
Jia SL, Wu XL, Li XX, et al.Neuroprotective effects of liquiritin on cognitive deficits induced by soluble amyloid-β1–42 oligomers injected into the hippocampus. 2016; 18(12):1186-1199.
Aal-Aaboda M, Raghif AR, Almudhafer RH, Hadi NR. Lipopolysaccharide from Rhodobacter spheroids modulate toll-like receptors expression and tissue damage in an animal model of bilateral renal ischemic reperfusion injury. Journal of Medicine and Life. 2022; 15(5):685.
Kuttancheri T, Das SK, Shetty MS, Satish S, Bathrenathh B. Renal resistive index as a marker of histopathological damage in diabetic and non-diabetic chronic kidney disease. Egyptian Journal of Radiology and Nuclear Medicine. 2023; 54:159.
Wong MG, Group for the A-OC, Perkovic V, et al. Long-term Benefits of Intensive Glucose Control for Preventing End-Stage Kidney Disease: advance-on. Diabetes Care. 2016; 39(5):694–700.
Wang X, Gao L, Lin H, et al. Mangiferin prevents diabetic nephropathy progression and protects podocyte function via autophagy in diabetic rat glomeruli. European Journal of Pharmacology. 2018; 824:170–8.
Olatunji OJ, Chen H, Zhou Y. Lycium chinense leaves extract ameliorates diabetic nephropathy by suppressing hyperglycemia mediated renal oxidative stress and inflammation. Biomedicine & Pharmacotherapy. 2018; 102:1145–51.
Han Y, Xu X, Tang C, et al. Reactive oxygen species promote tubular injury in diabetic nephropathy: The role of the mitochondrial ros-txnip-nlrp3 biological axis. Redox Biology. 2018; 16:32–46.
Shahzad K, Bock F, Dong W, et al. Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy. Kidney International. 2015; 87(1):74–84.
Lee MJ, Rao YK, Chen K, Lee YC, Chung YS, Tzeng YM. Andrographolide and 14-deoxy-11,12-didehydroandrographolide from Andrographis paniculata attenuate high glucose-induced fibrosis and apoptosis in murine renal mesangeal cell lines. Journal of Ethnopharmacology. 2010; 132(2):497–505.
Wang T, Zheng L, Liu X, Zhao M. Sea cucumber (Holothuria nobilis) hydrolysates improve diabetic nephropathy via suppression of oxidative stress in high-fat diet/streptozotocin-induced diabetic rats. Journal of Functional Foods. 2023; 106:105589.
Zhang C, Li Q, Lai S, et al. Attenuation of diabetic nephropathy by Sanziguben Granule inhibiting EMT through Nrf2-mediated anti-oxidative effects in streptozotocin (STZ)-induced diabetic rats. Journal of Ethnopharmacology. 2017; 205:207–16.
Song W, Wei L, Du Y, Wang Y, Jiang S. Protective effect of ginsenoside metabolite compound K against diabetic nephropathy by inhibiting NLRP3 inflammasome activation and NF-κB/p38 signaling pathway in high-fat diet/streptozotocin-induced diabetic mice. International Immunopharmacology. 2018; 63:227–38.Wang DD, Zhang GY, Chen X, Wei T, Liu CX, Chen C. et al. Sitagliptin ameliorates diabetic nephropathy by blocking TGF-β1/Smad signaling pathway. 2018; 41:2784–92.
Gao F, He X, Liang S, et al. Quercetin ameliorates podocyte injury via inhibition of oxidative stress and the TGF-β1/Smad pathway in DN rats. RSC advances. 2018; 8(62):35413–21.
Published
Issue
Section
License
Copyright (c) 2025 Iraqi Journal of Pharmaceutical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
