open access
The Effect of Hydroalcoholic Seed Extract of Securigera Securidaca on the Hepatic Renin-Angiotensin System in the Streptozotocin-Induced Diabetic Animal Model
Affiliations- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran, Islamic Republic Of
- Nephrology and Kidney Transplant Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran, Islamic Republic Of
- Department of Clinical Sciences, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan, Iran, Islamic Republic Of
- Institute of Biology, Biotechnology and Environmental Protection, Faculty of Natural Sciences, University of Silesia, Katowice, Poland
- Department of Pathobiology, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan, Iran, Islamic Republic Of
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran, Islamic Republic Of
open access
Abstract
Background: The aim of the study was to investigate the effect of hydroalcoholic seed extract of Securigera securidaca (S. securidaca) (HESS) on liver local reninangiotensin system (RAS) in streptozotocin-induced diabetic rats. Methods: Three groups of diabetic male Wistar rats were treated with different doses of HESS (100, 200, 400 mg/Kg-BW), and the results were compared with diabetic and healthy control groups. To test the effects of HESS on liver local RAS as well as its alternative pathway, the tissue levels of renin, angiotensin-converting enzyme (ACE), ACE2, angiotensin-II (Ang-II), and Ang-(1-7) were measured. The oxidative state of liver tissue was evaluated by biomarkers of malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant status (TAS). Due to the association between local RAS activity and tissue inflammation, the production of interleukins (IL) IL-1, IL-6, tumor necrosis factor alfa (TNF-a), and IL-10 in the liver was assayed in the experimental group. Results: Dose-dependent effects of HESS showed that the highest dose of the extract had a reducing effect on the hepatic levels of local RAS components including angiotensinogen, ACE, and Ang-II. Surprisingly, despite the decrease in tissue level of ACE2, an increase in Ang-(1-7) tissue concentration was observed. Decreased local RAS activity through treatment with the highest dose of HESS was associated with decreased tissue levels of proinflammatory cytokines (IL-1, IL-6, TNF-a), and increased anti-inflammatory cytokine (IL-10). Most of the effects of the extract are attributed to its antioxidant properties. Conclusions: S. securidaca seed can be suggested as a suitable drug supplement to prevent hepatic complications of diabetes.
Abstract
Background: The aim of the study was to investigate the effect of hydroalcoholic seed extract of Securigera securidaca (S. securidaca) (HESS) on liver local reninangiotensin system (RAS) in streptozotocin-induced diabetic rats. Methods: Three groups of diabetic male Wistar rats were treated with different doses of HESS (100, 200, 400 mg/Kg-BW), and the results were compared with diabetic and healthy control groups. To test the effects of HESS on liver local RAS as well as its alternative pathway, the tissue levels of renin, angiotensin-converting enzyme (ACE), ACE2, angiotensin-II (Ang-II), and Ang-(1-7) were measured. The oxidative state of liver tissue was evaluated by biomarkers of malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant status (TAS). Due to the association between local RAS activity and tissue inflammation, the production of interleukins (IL) IL-1, IL-6, tumor necrosis factor alfa (TNF-a), and IL-10 in the liver was assayed in the experimental group. Results: Dose-dependent effects of HESS showed that the highest dose of the extract had a reducing effect on the hepatic levels of local RAS components including angiotensinogen, ACE, and Ang-II. Surprisingly, despite the decrease in tissue level of ACE2, an increase in Ang-(1-7) tissue concentration was observed. Decreased local RAS activity through treatment with the highest dose of HESS was associated with decreased tissue levels of proinflammatory cytokines (IL-1, IL-6, TNF-a), and increased anti-inflammatory cytokine (IL-10). Most of the effects of the extract are attributed to its antioxidant properties. Conclusions: S. securidaca seed can be suggested as a suitable drug supplement to prevent hepatic complications of diabetes.
Keywords
local renin-angiotensin system (RAS), angiotensin-converting enzyme, renin, angiotensin-II, angiotensin-(1–7), angiotensinogen
About this articleTitle
The Effect of Hydroalcoholic Seed Extract of Securigera Securidaca on the Hepatic Renin-Angiotensin System in the Streptozotocin-Induced Diabetic Animal Model
Journal
Issue
Article type
Research paper
Pages
97-106
Published online
2022-03-03
Page views
3564
Article views/downloads
259
DOI
10.5603/DK.a2022.0013
Bibliographic record
CD 2022;11(2):97-106.
Keywords
local renin-angiotensin system (RAS)
angiotensin-converting enzyme
renin
angiotensin-II
angiotensin-(1–7)
angiotensinogen
Authors
Bahar Kiani
Shahin Alizadeh-Fanalou
Fatemeh Khomari
Mohammad Babaei
Iraj Alipourfard
Ali Kalantari Hesari
Mohammad Najafi
Ali-Mohammad Sharifi
Elham Bahreini
References (29)- Hayden MR, Sowers KM, Pulakat L, et al. Possible Mechanisms of Local Tissue Renin-Angiotensin System Activation in the Cardiorenal Metabolic Syndrome and Type 2 Diabetes Mellitus. Cardiorenal Medicine. 2011; 1(3): 193–210.
- Ager EI, Neo J, Christophi Ch. The renin-angiotensin system and malignancy. Carcinogenesis. 2008; 29(9): 1675–1684.
- Koh SL, Ager EI, Christophi Ch. Liver regeneration and tumour stimulation: implications of the renin-angiotensin system. Liver International. 2010; 30(10): 1414–1426.
- Moreira de Macêdo S, Guimarães TA, Feltenberger JD, et al. The role of renin-angiotensin system modulation on treatment and prevention of liver diseases. Peptides. 2014; 62: 189–196.
- Afroze SH, Munshi MK, Martínez AK, et al. Activation of the renin-angiotensin system stimulates biliary hyperplasia during cholestasis induced by extrahepatic bile duct ligation. Am J Physiol Gastrointest Liver Physiol. 2015; 308(8): 691–701.
- Warner FJ, Lubel JS, McCaughan GW, et al. Liver fibrosis: a balance of ACEs? Clin Sci (Lond). 2007; 113(3): 109–118.
- Takeshita Y, Takamura T, Ando H, et al. Cross talk of tumor necrosis factor-α and the renin–angiotensin system in tumor necrosis factor-α-induced plasminogen activator inhibitor-1 production from hepatocytes. Eur J Pharmacol. 2008; 579(1-3): 426–432.
- Renna NF, Lembo C, Diez E, et al. Role of renin-angiotensin system and oxidative stress on vascular inflammation in insulin resistence model. Int J Hypertens. 2013; 2013: 420979.
- Leung PoS, Suen PoM, Ip SPo, et al. Expression and localization of AT1 receptors in hepatic Kupffer cells: its potential role in regulating a fibrogenic response. Regul Pept. 2003; 116(1-3): 61–69.
- Loizzo MR, Said A, Tundis R. Inhibition of angiotensin converting enzyme (ACE) by flavonoids isolated from Ailanthus excelsa (Roxb) (Simaroubaceae). Phytother Res. 2007; 21(1): 32–36.
- Alizadeh-Fanalou S, Babaei M, Hosseini A, et al. Effects of Securigera Securidaca seed extract in combination with glibenclamide on antioxidant capacity, fibroblast growth factor 21 and insulin resistance in hyperglycemic rats. J Ethnopharmacol. 2020; 248: 112331.
- Singleton VL, Rossi JA. Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am. J. of Enol. and Viticult. 1965; 16: 144–158.
- Chandra S, Khan S, Avula B, et al. Assessment of total phenolic and flavonoid content, antioxidant properties, and yield of aeroponically and conventionally grown leafy vegetables and fruit crops: a comparative study. Evid Based Complement Alternat Med. 2014; 2014: 253875.
- Rajaei Z, Hadjzadeh MA, Moradi R, et al. Saghebi, Antihyperglycemic and antihyperlipidemic effects of hydroalcoholic extract of Securigera securidaca seeds in streptozotocin-induced diabetic rats. Adv Biomed Res. 2015; 4: 33.
- Alizadeh-Fanalou S, Nazarizadeh A, Babaei M, et al. Effects of Securigera securidaca (L.) Degen & Dorfl seed extract combined with glibenclamide on paraoxonase1 activity, lipid profile and peroxidation, and cardiovascular risk indices in diabetic rats. BioImpacts. 2020; 10(3): 159–167.
- Sharifzadeh M, Ranjbar A, Hosseini A. he effect of green tea extract on oxidative stress and spatial learning in streptozotocin-diabetic rats. Iran J Pharm Res. 2017; 16: 201–209.
- Skrabal F. Half-life of plasma renin activity in normal subjects and in malignant hypertension. Klin Wochenschr. 1974; 52(24): 1173–1174.
- Ibrahim RM, El-Halawany AM, Saleh DO, et al. HPLC-DAD-MS/MS profiling of phenolics from Securigera securidaca flowers and its anti-hyperglycemic and anti-hyperlipidemic activities. Revista Brasileira de Farmacognosia. 2015; 25(2): 134–141.
- Pan Li, Wang Y, Jones CA, et al. Enhancer-dependent inhibition of mouse renin transcription by inflammatory cytokines. Am J Physiol Renal Physiol. 2005; 288(1): F117–F124.
- Liu X, Shi Qi, Sigmund CD. Interleukin-1beta attenuates renin gene expression via a mitogen-activated protein kinase kinase-extracellular signal-regulated kinase and signal transducer and activator of transcription 3-dependent mechanism in As4.1 cells. Endocrinology. 2006; 147(12): 6011–6018.
- Ustündağ B, Canatan H, Çi̇nkilinç N, et al. Angiotensin converting enzyme (ACE) activity levels in insulin-independent diabetes mellitus and effect of ACE levels on diabetic patients with nephropathy. Cell Biochem Funct. 2000; 18(1): 23–28, doi: 10.1002/(sici)1099-0844(200001/03)18:1<23::aid-cbf843>3.0.co;2-0.
- Dell’Italia LJ, Collawn JF, Ferrario CM. Multifunctional role of chymase in acute and chronic tissue injury and remodeling. Circ Res. 2018; 122(2): 319–336.
- Takai S, Jin D. Chymase as a possible therapeutic target for amelioration of non-alcoholic steatohepatitis. Int J Mol Sci. 2020; 21(20): 7543.
- Brar GS, Barrow BM, Watson M, et al. Neprilysin is required for angiotensin-(1–7)’s ability to enhance insulin secretion via its proteolytic activity to generate angiotensin-(1–2). Diabetes. 2017; 66(8): 2201–2212.
- Rice GI, Thomas DA, Grant PJ, et al. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J. 2004; 383(1): 45–51.
- Singh KD, Karnik SS. Angiotensin receptors: structure, function, signaling and clinical applications. J Cell Signal. 2016; 1(2): 111.
- Afsar B, Afsar RE, Ertuglu LA, et al. Renin-angiotensin system and cancer: epidemiology, cell signaling, genetics and epigenetics. ClinTrans Oncol. 2021; 23(4): 682–696.
- Leon-Cabrera S, Arana-Lechuga Y, Esqueda-León E, et al. Reduced systemic levels of IL-10 are associated with the severity of obstructive sleep apnea and insulin resistance in morbidly obese humans. Mediators Inflamm. 2015; 2015: 493409.
- Kessler B, Rinchai D, Kewcharoenwong C, et al. Interleukin 10 inhibits pro-inflammatory cytokine responses and killing of Burkholderia pseudomallei. Sci Rep. 2017; 7: 42791.