Djanggan Sargowo

Bio: Djanggan Sargowo is an academic researcher from University of Brawijaya. The author has contributed to research in topics: Polysaccharide peptide & Medicine. The author has an hindex of 10, co-authored 94 publications receiving 293 citations.

Green tea polyphenols inhibit oxidized LDL-induced NF-KB activation in human umbilical vein endothelial cells.

Abstract: AIM To examine the anti-inflammatory effects of green tea polyphenols on oxLDL-mediated TNFalpha expression and NF-KB activation in the human umbilical vein endothelial cells (HUVECs). METHODS We postulate that green tea polyphenols regulate TNF-alpha gene expression by modulating NF-KB activation through their inhibition effect on IKB Kinase (IKK) activity and as scavenger of free radicals. Pretreatment of green tea polyphenols reduced oxLDL-induced production of proinflammatory cytokine TNF-alpha and NF-KB activation in dose dependent manner (p < 0.05). Post hoc comparison test with Mann Whitney between various dosage of green tea polyphenols in inhibition of NF-KB activation showed significant result (p < 0.05). RESULTS In TNF-alpha expression, there was also declined TNF-alpha productions (p 0.09; 0.2 vs 0.4mg/ml: ns). The effect of green tea polyphenols on TNF-alpha expression were determined by Mann-Whitney test. There is significant difference between the first dose (0.1mg/ml) vs 0.2mg/ml polyphenols (p=0.009); between 0.1 vs 0.4 mg/ml polyphenols (p=0.009). There was no difference when the dose was increased from 0.2 mg/ml to 0,4 mg/ml polyphenols (0.141). In this study, green tea polyphenols showed significant effects on the inhibition of TNF-alpha through NF-KB activation pathway in HUVECs with oxidized LDL. CONCLUSION Green tea polyphenol can be used to prevent the development of atherosclerosis.

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.

Abstract: BACKGROUND Oxidative stress in atherosclerosis produces H2O2 and triggers the activation of nuclear factor kappa beta (NF-κB) and increase of inducible nitric oxide synthase (iNOS). The formation of vasa vasorum occurs in atherosclerosis. Vasa vasorum angiogenesis is mediated by VEGFR-1 and upregulated by hypoxia-inducible factor-1α (HIF-1α). The newly formed vasa vasorum are fragile and immature and thus increase plaque instability. It is necessary to control vasa vasorum angiogenesis by using mangosteen pericarp antioxidant. This study aims to demonstrate that mangosteen pericarp ethanolic extract can act as vasa vasorum anti-angiogenesis through H2O2, HIF-1α, NF-κB, and iNOS inhibition in rats given a hypercholesterol diet. METHODS This was a true experimental laboratory, in vivo posttest with control group design, with 20 Rattus norvegicus Wistar strain rats divided into five groups (normal group, hypercholesterol group, and hypercholesterol groups with certain doses of mangosteen pericarp ethanolic extract: 200, 400, and 800 mg/kg body weight). The parameters of this study were H2O2 measured by using colorimetric analysis, as well as NF-κB, iNOS, and HIF-1α, which were measured by using immunofluorescence double staining and observed with a confocal laser scanning microscope in aortic smooth muscle cell. The angiogenesis of vasa vasorum was quantified from VEGFR-1 level in aortic tissue and confirmed with hematoxylin and eosin staining. RESULTS Analysis of variance test and Pearson's correlation coefficient showed mangosteen pericarp ethanolic extract had a significant effect (P<0.05) in decreasing vasa vasorum angiogenesis through H2O2, HIF-1α, NF-κB, and iNOS inhibition in hypercholesterol-diet-given R. norvegicus Wistar strain. CONCLUSION Mangosteen pericarp ethanolic extract 800 mg/kg body weight is proven to decrease vasa vasorum angiogenesis. Similar studies with other inflammatory parameters are encouraged to clarify the mechanism of vasa vasorum angiogenesis inhibition by mangosteen pericarp ethanolic extract.

The role of polysaccharide peptide of Ganoderma lucidum as a potent antioxidant against atherosclerosis in high risk and stable angina patients.

Abstract: Objectives Antioxidants can reduce oxidative radicals that affect the early phase of atherogenesis, that is endothelial dysfunction. Polysaccharide Peptide (PsP) derived from Ganoderma lucidum has an active substance in the form of β-glucan. Previous studies have proven the PsP of Ganoderma lucidum as an effective antioxidant in atherosclerotic rats and shows no toxicity in animal model. This study aims to prove the effect of PsP as potent antioxidant in high risk and stable angina patients. Method This is a clinical trial conducted to 37 high risk and 34 stable angina patients, which were determined based on ESC Stable CAD Guidelines and Framingham risk score, with pre and post test design without control group. The parameters are superoxide dimustase (SOD) and malondialdehyde (MDA) concentration, circulating endothelial cell (CEC) and endothelial progenitor cell (EPC) counts. The patients were given PsP 750 mg/day in 3 divided dose for 90 days. Paired t-test was performed for normally distributed data, and Wilcoxon test for not normally distributed data, and significant level of p ≤ 0,05. Results SOD level in high risk patients slightly increased but not statistically significant with p = 0,22. Level of SOD in stable angina group significantly increased with p = 0,001. MDA concentration significantly reduced in high risk and stable angina patients with p = 0.000. CEC significantly reduced both in high risk and stable angina patients, with p = 0.000 in both groups. EPC count significantly reduced in high risk and stable angina with p = 0.000. Conclusion PsP of Ganoderma lucidum is a potent antioxidant against pathogenesis of atherosclerosis in stable angina and high risk patients

Endothelial progenitor cells proliferated via MEK-dependent p42 MAPK signaling pathway

Abstract: Endothelial progenitor cells (EPCs) clinical applications have been well reported. However, due to low number of EPCs that could be isolated, EPCs expansion study became one of the main focuses. Some optimized mediums to culture EPCs were currently available. However, the proliferation signaling pathway is not clearly disclosed yet. Peripheral blood was collected from eight healthy subjects, followed by mononuclear cells (MNCs) isolation. MNCs were then prepared and cultured for 2 days. After that, non-adherent cells were harvested and further cultured for 3 days. Resulted colony-forming unit (CFU)-Hill colonies were documented and enumerated under an inverted light microscope. To detect membrane markers, immunofluorescence was performed to detect CD34, VEGFR-2, and CD133. Cell documentation was conducted under a fluorescence microscope. To check cell proliferation, XTT Cell Proliferation Assay Kit was used according to kit insert. To detect possible activation of p44/42 MAPK, western blot was performed to detect p44/42 MAPK and phosphorylated p44/42 MAPK. All visualized bands were captured and quantified. Our results showed that EPCs markers (CD34, CD133 and VEGFR-2) were detected in 3 days culture. From XTT cell proliferation assay and CFU enumeration results, we found that EPCs proliferated significantly (p = 0.012) with addition of supplement. Phosphorylated-p42 MAPK expression of EPCs treated with supplement was significantly higher than the one of EPCs without treatment. Significant inhibition of p42 MAPK phosphorylation by U0126 was observed (p = 0.012). By pretreatment of U0126, number of viable cells and CFUs treated with supplement was significantly decreased (p = 0.012). Our results showed that MEK-dependent p42 MAPK pathway might play an important role in EPCs proliferation.

Extract of mangosteen increases high density lipoprotein levels in rats fed high lipid

Abstract: BACKGROUND In cardiovascular medicine, Garcinia mangostana has been used as an antioxidant to inhibit oxidation of low density lipoproteins and as an antiobesity agent. The effect of Garcinia mangostana on hyperlipidemia is unknown. The aim of this study was to evaluate the effect of an ethanolic extract of Garcinia mangostana pericarp on lipid profile in rats fed a high lipid diet. METHODS A total of 40 rats were divided into five groups control, high lipid diet, and high lipid diet + ethanolic extract of Garcinia mangostana pericarp at dosages of 200, 400, and 800 mg/kg body weight. The control group received a standard diet for 60 days. The high lipid diet group received standard diet plus egg yolk, goat fat, cholic acid, and pig fat for 60 days with or without ethanolic extract of Garcinia mangostana pericarp by the oral route. After 60 days, rats were anesthesized with ether for collection of blood by cardiac puncture. Analysis of blood lipid profile comprised colorimetric determination of cholesterol, triglyceride, low density lipoprotein (LDL), and high density lipoprotein (HDL). RESULTS From the results of one-way ANOVA it was concluded that there were significant between-group differences in cholesterol, trygliceride, LDL, and HDL levels (p=0.000). Ethanolic extract of Garcinia mangostana pericarp significantly decreased cholesterol, trygliceride, and LDL levels, starting at 400 mg/kg body weight (p=0.000). Ethanolic extract of Garcinia mangostana pericarp significantly increased HDL level starting at 200 mg/kg body weight (p=0.000). CONCLUSION Ethanolic extract of Garcinia mangostana pericarp has a beneficial effect on lipid profile in rats on a high lipid diet.

Pathologic Basis of Disease

Abstract: Pathologic Basis of Diseaseby Stanley L. Robbins is really the fourth edition of hisPathology. Appropriate updating and addition enhance the otherwise identical format, sequence, writing, and illustrations. So many medical students have benefited from this source that it may be the best known general book in the field. I recommend it even more now. Like his former texts, this will be enjoyed for its readability. He clearly lays out a great deal of information. When he includes minutiae, the reasons are clear and one feels that all the material is pertinent. Robbins keeps the whole field in perspective—that is, he does not dwell so long or so heavily on pathologic anatomy or pathogenesis as to tempt the reader to overlook clinical presentation or prognosis. A great strength of the subject of pathology is that it bonds strongly with many other medical sciences and specialties and thus occupies the

Rheumatic heart disease

Abstract: RESEARCH into rheumatic heart disease has progressively yielded a series of important facts and a good deal that is still speculative. It has been shown that many tissues, especially vascular structures, throughout the body are injured in attacks of rheumatic fever, and that the most serious damage occurs in the heart, to the myocardium and to its valves. It is generally considered now to have been conclusively shown that infections of body tissues with type A hsemolytie streptococci play a causative and key role in the pathogenesis of this disease, but only a small proportion of human beings infected with type A streptococci develop rheumatic heart disease. It is also widely held that the rheumatic lesions in the myocardium, including the so-called Aschoff bodies, are non-myogenic lesions of the connective tissue and do not involve the heart muscle fibres. However, G. E. Murphy,' in a long and very detailed paper, subsequently reprinted as a monograph,\" has set out to demonstrate that this last-mentioned interpretation is not correct, and that it is the heart muscle and plain muscle fibres which are affected. He was able to produce typical cardiac changes in a small proportion of rabbits with multiple focal infections due to type A heemolytie streptococci, and these gave material for study at various stages of the cardiac changes. In addition, he made a detailed microscopic study of the hearts of over 100 patients who had died with active rheumatic heart disease and of the left atrial appendages removed from 150 other patients at the time of mitral commissurotomy. The histopathological findings are presented in considerable detail with 162 beautiful reproductions of coloured sections of cardiac tissue illustrating the points made in the text. A study of the text and the slides makes clear the author's claims that the changes in the myocardium, both in man and in rabbits, are really in the muscle cells and not in the fibrous tissue.

Angiogenesis in the atherosclerotic plaque

Abstract: Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving inflammation. Atherothrombotic complications are the leading cause of disability and mortality in western countries. Neovascularization in atherosclerotic lesions plays a major role in plaque growth and instability. The angiogenic process is mediated by classical angiogenic factors and by additional factors specific to atherosclerotic angiogenesis. In addition to its role in plaque progression, neovascularization may take part in plaque destabilization and thromboembolic events. Anti-angiogenic agents are effective to reduce atherosclerosis progression in various animal models. However, clinical trials with anti-angiogenic drugs, mainly anti-VEGF/VEGFR, used in anti-cancer therapy show cardiovascular adverse effects, and require additional investigations.