Abstract
Background
Type 2 diabetes mellitus (T2DM) is a major risk factor of atherosclerosis. Hyperglycemia in T2DM causes advanced formation of glycation end products (AGE) which leads to oxidative stress and chronic inflammation. Oxidative stress occurs due to increased levels of reactive oxygen species (ROS) such as H2O2. On the other hand, lipoprotein-associated phospholipase (Lp-PLA2) has pro-inflammatory effects, which cause instability of atherosclerosis plaques. This condition causes hypoxemic cells to stimulate HIFα induced vasa vasorum angiogenesis. This study aims to understand the potential of PSP as an anti-angiogenic agent through decreased levels of H2O2 and Lp-PLA2 leading to the decline of vasa vasorum angiogenesis in diabetic rat model. In addition, this study also measured the lipid profile of diabetic rat model in relation to vasa vasorum angiogenesis.
Methods
True laboratory experiment with randomized post-test control of group design using 25 wistar rats (Rattus norvegicus) were divided into five groups; one normal group and four group with High Fat Diet (HFD) and low dose streptozotocin (30 mg/kgBW) injection sc, treated with placebo and three various doses of PSP 50, 150, 300 mg/kgBW.
Results
ANOVA test (p < 0.05) shows that there is a significant influence of polysaccharide peptide (PSP) feeding on the decreased amount of vasa vasorum angiogenesis (p = 0.00), lipid profile (cholesterol total and triglyceride; p = 0.01, p = 0.001), and amount of H202 (p = 0.003). The amount of Lp-PLA2 declined to (p = 0.184). This result indicates that PSP prevents inflammation in atherosclerosis.
Conclusions
PSP of Ganoderma lucidum is an anti-angiogenic agent in T2DM.
Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: This study has been evaluated and approved by the Ethical Committee of Indonesian Health Research for the care and use of animals. (267/EC/KEPK-S1-PD/07/2017)
References
[1] Chan JC, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon KH, et al. Diabetes in asia: epidemiology, risk factors, and pathophysiology. J Am Med Assoc 2009;301:2129–40.10.1001/jama.2009.726Search in Google Scholar PubMed
[2] Nowotny K, Jung T, Höhn A, Weber D, Grune T. Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules 2015;5:194–222.10.3390/biom5010194Search in Google Scholar PubMed PubMed Central
[3] Chait A, Bornfeldt KE. Diabetes and atherosclerosis: Is there a role for hyperglycemia? J Lipid Res 2009;50:335–9.10.1194/jlr.R800059-JLR200Search in Google Scholar PubMed PubMed Central
[4] Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis epidemiology, pathophysiology, and management. J Am Med Assoc 2002;287:2570–81.10.1001/jama.287.19.2570Search in Google Scholar PubMed
[5] Wihastuti TA, Heriansyah T, Soraya M, Wijayanti MD, Firani NK, Iskandar A, et al. Inhibition of oxidative stress in hypercolesterolemic rats by soy milk. J Cardiovasc Dis Res 2016;7:74–82.10.5530/jcdr.2016.2.4Search in Google Scholar
[6] Heitzer T, Schlinzig T, Krohn K, Meinertz T, Münzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 2001;104:2673–8.10.1161/hc4601.099485Search in Google Scholar PubMed
[7] Heriansyah T, Wihastuti TA, Siswanto BB, Santoso A, Sukmawan R, Sargowo D, et al. Lowering inflammation level by lp-pla2 inhibitor (darapladib) in early atherosclerosis development: In vivo rat type 2 diabetes mellitus model. J Cardiovasc Dis Res 2017;8:56–61.10.5530/jcdr.2017.2.12Search in Google Scholar
[8] Wihastuti TA, Sargowo D, Tjokroprawiro A, Permatasari N, Widodo MA, Soeharto S. Vasa vasorum anti-angiogenesis through H2O2, HIF-1α, NF-κB, and iNOS inhibition by mangosteen pericarp ethanolic extract (Garcinia mangostana Linn) in hypercholesterol-diet-given Rattus norvegicus Wistar strain. Vasc Health Risk Manag 2014;10:523–31.10.2147/VHRM.S61736Search in Google Scholar PubMed PubMed Central
[9] Mulligan-Kehoe MJ, Simons M. Vasa vasorum in normal and diseased arteries. Circulation 2014;129:2557–66.10.1161/CIRCULATIONAHA.113.007189Search in Google Scholar PubMed
[10] Feinstein SB. Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. J Am Coll Cardiol 2006;48:236–43.10.1016/j.jacc.2006.02.068Search in Google Scholar PubMed
[11] Lakshmi B, Ajith TA, Sheena N, Gunapalan N, Janardhanan KK. Antiperoxidative, anti-inflammatory, and antimutagenic activities of ethanol extract of the mycelium of Ganoderma lucidum occurring in South India. Teratog Carcinog Mutagen 2003;23:85–97.10.1002/tcm.10065Search in Google Scholar PubMed
[12] You Y-H, Lin Z-B. Protective effects of Ganoderma lucidum polysaccharides peptide on injury of macrophages induced by reactive oxygen species. Acta Pharmacol Sin 2002;23:787–91.Search in Google Scholar
[13] Vlassara H, Uribarri J. Advanced glycation end products (AGE) and diabetes: Cause, effect, or both? Curr Diab Rep 2014;14:1–17.10.1007/s11892-013-0453-1Search in Google Scholar PubMed PubMed Central
[14] Ozougwu O. The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus. J Physiol Pathophysiol 2013;4:46–57.10.5897/JPAP2013.0001Search in Google Scholar
[15] Rambhade S, Chakraborty AK, Patil UK, Rambhade A. Diabetes mellitus- its complications, factors influencing complications and prevention-an overview. J Chem Pharm Res 2010;2:7–25.10.4103/0975-8453.83433Search in Google Scholar
[16] Kosti M, Kanakari M. Education and diabetes mellitus. Heal Sci J 2012;6:654–62.Search in Google Scholar
[17] Heriansyah T, Siswanto BB, Santoso A, Sargowo D, Subekti I, Aulani A, et al. Ox-LDL, lysophospatidy choline platelet activating factor, IL-6 expression level and foam cell number with darappabdib treatment in early development of atherosclerosis: In vivo study for type 2 diabetes mellitus model. J Hong Kong Coll Cardiol 2016;24:64–73.10.55503/2790-6744.1025Search in Google Scholar
[18] Heriansyah T, Wihastuti TA, Sargowo D, Widodod M, Anjanie PM, Suparnoe TD, et al. Reduction of histopathological images through a decrease in H2O2 levels in diabetic rats with polysaccharide peptides. Biomarkers Genomic Med 2015;7:31–7.10.1016/j.bgm.2014.09.020Search in Google Scholar
[19] Sargowo D, Andri WT, Heriansyah T, Prasetya I, Ashriyah R, Setyawati I. Anti inflammation and anti oxidant effect of active agent polysaccharide peptide (Ganoderma lucidum) in preventing atherosclerotic diseases. Biomed Pharmacol J 2015;8:27–33.10.13005/bpj/578Search in Google Scholar
[20] Valdés-Ramos R, Guadarrama-López A, Martínez-Carrillo B, Benítez-Arciniega AD. Vitamins and type 2 diabetes mellitus. Endocrine, Metab Immune Disord – Drug Targets 2015;15:54–63.10.2174/1871530314666141111103217Search in Google Scholar PubMed PubMed Central
[21] Wihastuti TA, Sargowo D, Tjokroprawiro A, Permatasari N, Widodo MA, Soeharto S. Vasa vasorum angiogenesis through increased levels of H2O2, HIF-1α, NF-κB and INOS: In vivo study of atherosclerosis. J Med Bioeng 2015;4:342–9.10.12720/jomb.4.5.342-349Search in Google Scholar
[22] Murwani S, Ali M, Muliartha K. Atherogenic diet of white-rat (Rattus novergicus strain Wistar) as atherosclerotic animal model. J Kedokt Univ Brawijaya 1997;22:6–9.10.21776/ub.jkb.2006.022.01.2Search in Google Scholar
[23] Heriansyah T, Adam AA, Wihastuti TA, Rohman MS. Elaborate evaluation of serum and tissue oxidized LDL level with darapladib therapy: a feasible diagnostic marker for early atherogenesis. Asian Pac J Trop Biomed 2017;7:134–8.10.1016/j.apjtb.2016.11.014Search in Google Scholar
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