Mohammad Aris Widodo

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

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.

Ganoderma Lucidum Subchronic Toxicity on The Liver As Anti-oxidant and Anti-inflamatory Agent for Cardivascular Disease

Background: Gonoderma lucidum is claimed to have beneficial health effects, and is developing into a comprehensive form of treatment against cardiovascular disease. Previous studies have successfully proven Ganoderma lucidum polysaccharides peptide ability as an antioxidant and anti-inflammatory agent whereby reducing levels of MDA, hs-CRP, H2O2, total cholesterol, foam cells as well as increasing the levels of HDL in experimental testing using Wistar rat (Rattus norvegicus strain wistar) fed with a high-fat diet. In order to develop Gonaderma lucidum polysaccharides peptide as an integral and comprehensive form of treatment against cardiovascular disease, further research regarding the subchronic toxicity on the liver was performed. Objective: To determine the safety profile of liver function in the use of Ganoderma lucidum polysaccharides peptide through subchronic toxicity studies on experimental animals. Method: The study of subchronic Ganoderma lucidum toxicity was performed using Wistar rat (Rattus novergicus strain wistar). 6 rats/sex/group were given a pure, freeze dried solution of Ganoderma lucidum with dosage ranging from 0,300, 600, 1200 mg/per kg body weight administered via gavage once a day for 90 days. Result : 90 days after the administration of pure, freeze dried Ganoderma lucidum solution with dosages ranging from 300 mg–1200 mg/per kg body weight, there were no observable toxic symptoms in male and female rats. There was no adverse effect on liver function with the administration of the maximum dosage (1200 mg/ per kg body weight). Gross pathology examinations of the rats liver after the maximal dosage of Ganoderma lucidum extract proved to be unremarkable. These findings are supported by the results of clinical pathology and histopathology of liver cells which do not indicate a change in morphology and histopathology of the liver. Conclusion: The result of this study shows that oral administration of Ganoderma lucidum polysaccharides peptide until the maximum dose of 1200 mg/per kg body weight/day does not cause toxic effects in the liver.

Subchronic Toxicity Effect of Cardioprotective Potential of Ganodermalucidum for the Heart

Background: The heart is a vital organ of the body. Although it is not a common target organ, this organ can be damaged by various chemical substances. Ganodermalucidumis a polysaccharide peptide which has antioxidant and anti-inflammatory properties to inhibit the progressivity of atherosclerosis as a cardiovascular disease related to oxidative stress and inflammatory process. In many cases, it is still contradictive with recommendations provided in guidelines. Objective: To study the subchronic toxicity effect of Ganodermalucidumas polysaccharide peptide to the heart of the studied animals. Methods: This study was an in vivo laboratory experiment using post test with control group approach and used 48 Rattusnovergicus Wistar strain. The dose of PSP used was 300 mg/kg, 600 mg/kg, and 1200 mg/kg. Thesubacute toxicity test was aimed to observe the anatomical and histopathological changes as the consequence of substance administration in various dose. Result: At day 90 after the administration of pure extract of Ganodermallucidum(freeze dried) with the dose of 300 mg/kg, 600 mg/kg, and 1200 mg/kg in male and female rats, no significant toxic symptoms was found. This finding was supported with the result of histopathological examination of the cardiac cells which shown no morphological or histopathological changes. Conclusion: The conclusion of this study showed that oral administration of polysaccharide peptide (Ganodermalucidum) at a dose of 300 mg/kg, 600 mg/kgand up to a dose of 1200 mg/kg was not found signs of toxicity to the heart.

Subchronic Toxicity Effect on Lung Organ Using Polysaccharide Peptide (Ganoderma lucidum) As Comprehensive Management Efforts for Atherosclerotic Heart Disease

Background: Polysaccharide Peptide (Ganoderma lucidum) are antioxidants and anti-inflammatory that is effective in inhibiting the progression of atherosclerosis as cardiovascular disease are very closely linked to the incidence of oxidative stress and inflammatory processes. Research before this proved the ability to significantly reduce the levels of MDA, hs-CRP, H2O2, total cholesterol and foam cells and to increase HDL levels in experimental animals Rattus novergicus Wistar strain were given a high-fat diet. Furthermore, to develop their potential in a comprehensive treatment of cardiovascular disease, then further research subkronik toxicity of polysaccharide peptide. Objective: To determine whether the polysaccharide peptide (Ganoderma lucidum) has subchronic toxicity effects on pulmonary organs experimental animals. Methods: Subchronic toxicity test Rattus novergicus Wistar strain, 6 rats/sex/group given pure solution (freeze dried) Ganoderma lucidum doses of 0, 300, 600, 1200 mg/kg personde once daily for 90 days. Results: Until the 90th day after the administration of pure extract of Ganoderma lucidum (freeze dried) dose of 300 mg/kg, 600 mg/kg and 1200 mg/kg in male and female rats, observed no significant toxic symptoms. Giving pure solution Ganoderma lucidum (freeze dried) to rank dose of 1200 mg/kg did not affect the respiratory system. Similarly, gross pathologic examination of the pulmonary organs up to a dose of 1200 mg/kg body weight change was not obtained. This finding is supported by the results of histopathological examination of the lung cells showed no morphological changes and histopathology. In contrast, administration of Ganoderma lucidum dose of 1200 mg/kg body weight can improve granulomas due to chronic inflammation. Conclusion: The results of this study showed that oral administration of polysaccharide peptide (Ganoderma lucidum) up to a dose of 1200 mg/kg/day was not found signs of toxicity in the lung. Instead it was found that oral administration of polysaccharide peptide dose of 1200 mg/kg/day may improve due to chronic inflammatory granuloma.

Effect Of Antioxidant And Anti Inflammation on Subchronic Toxicity Administration Of Ganoderma Lucidum Target Organ Kidney in Cardiovascular Diseases

Background: Ganodermalucidum was developed as a comprehensive approach for cardiovascular diseases. Efforts to develop polysaccharide peptide(Ganodermalucidum) as antioxidant and antiinflammation in previous studies had proved its ability to significantly reduce the level of MDA, hs-CRP, H2O2, total cholesterol, and foam cell and also increase the level of HDL in Rattusnovergicuswistar strain rats which was givenhigh fat diet. Furthermore, additional study has to be done to understandthe toxicity effect of subchronic administration of polysaccharide peptide (Ganodermalucidum). Objective: To understand the safety profile of renal function in the use of polysaccharide peptide (Ganodermalucidum) through subchronic toxicity test in animals. Methods: Subchronic toxicity test in RattusnovergicusWistar strain rats, with 6 rats/sex/group was given pure solution (freeze dried) of Ganodermalucidum with the dose of 0, 300, 600, 1200 mg/kgBB using feeding tubeonce a day for 90 days. Result: Until the 90th day after administration ofpure extract of Ganodermalucidum (freeze dried) with the dose of 300,600,1200 mg/kgBB in male and female rats, there was no toxic symptoms and did not affect the target organ kidney. The gross pathology and histopathology examination of the kidney showed no morfological and histopathology abnormality finding. Conclusion: There was no toxicity effect to the target organ kidney in subchronic oral administration of polysaccharide peptide(Ganodermalucidum) up to the dose of 1200 mg/kgBB/day.

Sub Chronic Toxicity Study of ovally administrated Ganoderma Lucidum on Aorta in Wistar Rats

Background: Ganoderma lucidum has been used as a traditional oriental medicine as a therapeutic treatment of cardiovascular diseases. It has been proved that in the study of development efforts of polysaccharide peptide (PsP) as an antioxidant and anti-inflammatory. Objective: To assess the safety profiles of PsP Ganoderma lucidum through testing the sub chronic toxicity in experimental animals in the aorta organ. Method: Sub chronic toxicity test of the Wistar Rats strain, 6 rats/sex/groups have given pure solution PsP doses of 0, 300, 600, 1200 mg/kg personde once daily for 90 days. Results: After the administration of pure extract of Ganoderma lucidum in the dose of 300 mg/kg, 600 mg/kg and 1200 mg/kg in male and female rats, was observed no significant toxic symptoms. Pure solution PsP until dose of 1200 mg/kg did not affect the morphology of the aorta tissue. Similarly in the gross pathologic examination of the aorta up to dose of 1200 mg/kg BW was not obtained any changes. This finding is supported by the results of histopathology examination of the aorta cells that did not show any changes in morphology and histopathology. Conclusion: The pure extract of Ganoderma Lucidum up to dose of 1200 mg/kg for 90 days in the aortic organ not giving any spectrum of significant toxicity effects, no changes in morphological in the both of the group.