Terapi Adjuvan Polisakarida Peptida Ekstrak Miselia Ganoderma Lucidum untuk Penurunan Kondisi Hiperglikemia, Stres Oksidatif, dan Disfungsi Endotel pada Pasien Sindrom Metabolik

NADLIROH, KHILMI AINUN and Prof. Dr. dr. Djanggan Sargowo,, Sp. PD, Sp. JP (K) and dr. Anna Fuji Rahimah,, Sp.JP (K) (2023) Terapi Adjuvan Polisakarida Peptida Ekstrak Miselia Ganoderma Lucidum untuk Penurunan Kondisi Hiperglikemia, Stres Oksidatif, dan Disfungsi Endotel pada Pasien Sindrom Metabolik. Magister thesis, Universitas Brawijaya.

Abstract

Sindrom metabolik menurut National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) 2005 ditandai dengan adanya 3 dari 5 kelainan klinis berikut : hipertrigliserida; penurunan kadar High Density Lipoprotein (HDL) serum; obesitas sentral; hipertensi arteri sistemik; dan hiperglikemia. Hiperglikemia ditandai dengan adanya kadar glukosa dalam darah melebihi batas normal yang dapat diketahui melalui pemeriksaan glukosa darah sewaktu dan glukosa darah puasa (GDP), dan HbA1c. Kondisi hiperglikemia dapat mengarah pada kejadian stres oksidatif. Stres oksidatif terjadi dikarenakan ketidakseimbangan antara produksi reactive oxygen species (ROS) dan antioksidan dalam tubuh. Superoxyde dismutase (SOD) merupakan salah satu antioksidan enzimatik endogen untuk menangkal radikal bebas dalam tubuh. Jumlah radikal bebas yang berlebihan dapat menyebabkan peningkatan peroksidasi lipid dengan produk akhir berupa Malondialdehyde (MDA). ROS dapat memodifikasi fungsi endotel melalui berbagai mekanisme diantaranya efek langsung pada gangguan ketersediaan Nitric Oxide (NO). Ekstrak miselia Ganoderma Lucidum mengandung bioaktif yang sangat baik, salah satunya β-D-Glukans Polisakarida Peptida yang dilaporkan memiliki efek antioksidan, anti-inflamasi, anti-tumor, anti-hipertensi, antihistamin, dan antihepatotoksik, antihiperglikemik. Penelitian ini dilakukan untuk menentukan pengaruh pemberian β-1,3/1,6-D-Glukan Polisakarida Peptida ekstrak miselia Ganoderma Lucidum sebagai terapi adjuvan terhadap parameter hiperglikemia (GDP, HbA1c), stres oksidatif (SOD, MDA), dan disfungsi endotel (NO) pada pasien sindrom metabolik serta menentukan hubungan perubahan parameter hiperglikemia (GDP, HbA1c) dengan perubahan parameter stres oksidatif (SOD, MDA) dan disfungsi endotel (NO) pada pasien sindrom metabolik dengan terapi adjuvan β-1,3/1,6-D-Glukan Polisakarida Peptida ekstrak miselia Ganoderma Lucidum. Penelitian ini merupakan Uji Klinis Randomisasi Tersamar Ganda dengan pengambilan populasi menggunakan metode acak terkontrol diambil dari pasien sindrom metabolik di RSSA dan RSUB, kemudian data yang akan diambil pre-test dan post-test, untuk mengetahui adanya pengaruh pemberian terapi adjuvan β-1,3/1,6-D-Glukan Polisakarida Peptida dari ekstrak miselia Ganoderma Lucidum. Subjek sindrom metabolik diobati dengan kapsul plasebo atau PsP selama 60 hari. Serum darah dikumpulkan dari masing-masing subjek sebelum konsumsi kapsul pertama dan satu hari setelah konsumsi kapsul terakhir. Kadar GDP diukur menggunakan metode enzimatik glukosa oksidase. Kadar HbA1c, SOD, MDA, dan NO diukur dengan menggunakan enzyme-linked immunosorbent assay. Hasil penelitian ini menunjukkan pemberian β-1,3/1,6-D-Glukan Polisakarida Peptida dari ekstrak miselia Ganoderma Lucidum sebagai terapi adjuvan pada pasien sindrom metabolik dapat menurunkan kadar GDP, HbA1c, MDA secara tidak signifikan (p=0,789, p=0,693, p=0,062), meningkatkan NO secara tidak signifikan (p=0,107), serta dapat meningkatkan kadar SOD secara signifikan (p=0,012). Pengaruh yang tidak signifikan dipengaruhi oleh beberapa faktor meliputi usia subjek penelitian, adanya kemungkinan keterlambatan viii meminum kapsul PsP, kurang lamanya durasi pemberian kapsul PsP, kurang banyaknya subjek penelitian, dan beberapa faktor lain seperti stres, konsumsi makanan, pola hidup, dan tidak terkendalinya penyakit metabolik yang mendasari. Pada pasien sindrom metabolik dengan terapi adjuvan β-1,3/1,6-D-Glukan Polisakarida Peptida ekstrak miselia Ganoderma Lucidum didapatkan korelasi positif yang sangat rendah antara GDP dengan SOD (r=0,052, p=0,781), korelasi negatif yang sangat rendah antara HbA1c dengan SOD (r=-0,061, p=0,743), korelasi positif yang rendah antara GDP dengan MDA (r=-0,303, p=0,098), korelasi positif yang sangat rendah antara HbA1c dengan MDA (r=0,231, p=0,251), korelasi negatif yang sangat rendah antara GDP dengan NO (r=-0,007, p=0,969), korelasi positif yang rendah antara HbA1c dengan NO (r=0,314, p=0,085), korelasi negatif yang rendah antara SOD dengan NO (r=-0,291, p=0,113), dan korelasi negatif yang sangat rendah antara MDA dengan NO (r=-0,006, p=0,976). Pada kondisi kronik hiperglikemia dimana metabolisme glukosa melalui jalur glikolisis terganggu, maka akan mengaktifkan jalur lain dimana jalur-jalur ini telah diketahui menjadi kunci perubahan biokimia yang disebabkan oleh hiperglikemia dan kunci dari peran sentral stres oksidatif terhadap terjadinya komplikasi. Kondisi hiperglikemia dan resistensi insulin menyebabkan gangguan transduksi insulin pada endotelial sehingga terdapat ketidakseimbangan antara molekul vasodilator (NO) dan vasokontriktor (ET-1). Glukosa darah yang tinggi dapat meningkatkan produksi ROS. ROS dapat menurunkan produksi NO melalui penghambatan eNOS, yang mengarah pada kejadian disfungsi endotel, namun pada penelitian ini hubungan tersebut sangat rendah. Kesimpulan dari penelitian ini adalah pemberian β-1,3/1,6-D-Glukan Polisakarida Peptida dari ekstrak miselia Ganoderma Lucidum sebagai terapi adjuvan pada pasien sindrom metabolik tidak dapat menurunkan kondisi hiperglikemia (penurunan tidak signifikan kadar GDP dan HbA1c), dapat menurunkan kondisi stress oksidatif (peningkatan signifikan kadar SOD dan penurunan tidak signifikan kadar MDA), serta tidak dapat menurunkan kondisi disfungsi endotel (peningkatan tidak signifikan kadar NO). Pada pasien sindrom metabolik dengan terapi adjuvan β-1,3/1,6-D-Glukan Polisakarida Peptida ekstrak miselia Ganoderma Lucidum tidak ada hubungan antara perubahan parameter hiperglikemia (GDP, HbA1c) dengan perubahan parameter stres oksidatif (SOD, MDA) dan disfungsi endotel (NO) pada pasien sindrom metabolik dengan terapi adjuvan β-1,3/1,6-D-Glukan Polisakarida Peptida ekstrak miselia Ganoderma Lucidum

English Abstract

Khilmi Ainun Nadliroh. NIM 226070101111010. Postgraduate Program, Faculty of Medicine, University of Brawijaya Malang. Adjuvant Therapy of Mycelia Lucidum Extract Polysaccharide Peptides for Reducing Hyperglycemia, Oxidative Stress, and Endothelial Dysfunction in Patients with Metabolic Syndrome. Advisory Commission Chairman: Djanggan Sargowo, Member: Anna Fuji Rahimah. Sanarto Santoso's examiner, Maimun Zulhaidah Arthamin. According to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) 2005, metabolic syndrome is characterized by the presence of 3 of the following 5 clinical abnormalities: hypertriglycerides; decrease in serum High Density Lipoprotein (HDL) levels; central obesity; systemic arterial hypertension; and hyperglycemia. Hyperglycemia is characterized by the presence of glucose levels in the blood that exceed normal limits which can be determined by examining fasting blood glucose (GDP) and HbA1c. Conditions of hyperglycemia can lead to the occurrence of oxidative stress. Oxidative stress occurs due to an imbalance between the production of reactive oxygen species (ROS) and antioxidants in the body. Superoxyde dismutase (SOD) is one of the endogenous enzymatic antioxidants to counteract free radicals in the body. Excessive amounts of free radicals can cause increased lipid peroxidation with the end product being Malondialdehyde (MDA). ROS can modify endothelial function through various mechanisms including a direct effect on impaired availability of Nitric Oxide (NO). Ganoderma Lucidum mycelia extract contains excellent bioactives, one of which is β-D-Glucans Polysaccharide Peptide which is reported to have antioxidant, anti-inflammatory, anti-tumor, anti-hypertensive, antihistamine, and anti-hepatotoxic, anti-hyperglycemic effects. This study was conducted to determine the effect of giving β-1,3/1,6-D-Glucan Polysaccharide Peptides from mycelial extract of Ganoderma Lucidum as adjuvant therapy on parameters of hyperglycemia (GDP, HbA1c), oxidative stress (SOD, MDA), and endothelial dysfunction ( NO) in patients with metabolic syndrome and determine the relationship between changes in hyperglycemia parameters (GDP, HbA1c) with changes in parameters of oxidative stress (SOD, MDA) and endothelial dysfunction (NO) in patients with metabolic syndrome with β-1,3/1,6-adjuvant therapy D-Glucan Polysaccharide Peptide Mycelia Extract of Ganoderma Lucidum. This study is a double-blind randomized clinical trial with population sampling using a randomized controlled method taken from patients with metabolic syndrome in RSSA and RSUB, then the data will be taken pre-test and post-test, to determine the effect of adjuvant therapy β-1,3 /1,6-D-Glucan Polysaccharide Peptide from Ganoderma Lucidum mycelia extract. Metabolic syndrome subjects were treated with placebo or PsP capsules for 60 days. Blood serum was collected from each subject before consuming the first capsule and one day after consuming the last capsule. GDP levels were measured using the glucose oxidase enzymatic method. HbA1c, SOD, MDA, and NO levels were measured using an enzyme-linked immunosorbent assay. The results of this study showed that administration of β-1,3/1,6-D-Glucan Polysaccharide Peptides from Ganoderma Lucidum mycelia extract as adjuvant therapy in patients with metabolic syndrome could not significantly reduce GDP, HbA1c, MDA levels (p=0.789, p= 0.693, p=0.062), did not significantly increase NO (p=0.107), and significantly increased SOD levels (p=0.012). The insignificant effect was influenced by several factors including the age of the study subjects, the possibility of delay in taking PsP capsules, the lack of duration of PsP capsule x administration, the lack of a large number of research subjects, and several other factors such as stress, food consumption, lifestyle, and uncontrolled metabolic diseases which underlie. In metabolic syndrome patients with adjuvant therapy of β-1,3/1,6-D-Glucan Polysaccharide Peptides of mycelial extract of Ganoderma Lucidum, a very low positive correlation was found between GDP and SOD (r=0.052, p=0.781), a very low negative correlation. low between HbA1c and SOD (r=-0.061, p=0.743), low positive correlation between GDP and MDA (r=-0.303, p=0.098), very low positive correlation between HbA1c and MDA (r=0.231, p =0.251), very low negative correlation between GDP and NO (r=-0.007, p=0.969), low positive correlation between HbA1c and NO (r=0.314, p=0.085), low negative correlation between SOD and NO (r=-0.291, p=0.113), and a very low negative correlation between MDA and NO (r=-0.006, p=0.976). In chronic conditions of hyperglycemia where glucose metabolism through the glycolysis pathway is disrupted, it will activate other pathways where these pathways are known to be the key to the biochemical changes caused by hyperglycemia and the key to the central role of oxidative stress in the occurrence of complications. Conditions of hyperglycemia and insulin resistance lead to impaired insulin transduction in the endothelium so that there is an imbalance between vasodilator (NO) and vasoconstrictor (ET-1) molecules. High blood glucose can increase ROS production. ROS can reduce NO production through inhibition of eNOS, which leads to endothelial dysfunction, but in this study the relationship was very low. The conclusion of this study is that the administration of β-1,3/1,6-D-Glucan Polysaccharide Peptides from Ganoderma Lucidum mycelia extract as adjuvant therapy in patients with metabolic syndrome cannot reduce hyperglycemia (not significant decrease in GDP and HbA1c levels), can reduce hyperglycemia. conditions of oxidative stress (significant increase in SOD levels and insignificant decrease in MDA levels), and could not reduce conditions of endothelial dysfunction (not significant increase in NO levels). In metabolic syndrome patients with adjuvant therapy of β-1,3/1,6-D-Glucan Polysaccharide Peptides of Ganoderma Lucidum mycelia extract, there is no relationship between changes in hyperglycemia parameters (GDP, HbA1c) with changes in oxidative stress parameters (SOD, MDA) and dysfunction. Endothelial (NO) in patients with metabolic syndrome with adjuvant therapy β-1,3/1,6-D-Glucan Polysaccharide Peptides Mycelia Extract of Ganoderma Lucidum

Item Type:	Thesis (Magister)
Identification Number:	042306
Uncontrolled Keywords:	Volatile Organic Compounds, Leukotrien B4, Neutrofil, PPOK, Leukotriene B4, Neutrophil, COPD
Divisions:	S2/S3 > Magister Ilmu Biomedis, Fakultas Kedokteran
Depositing User:	Unnamed user with username ihwan
Date Deposited:	12 Jan 2024 02:40
Last Modified:	12 Jan 2024 02:40
URI:	http://repository.ub.ac.id/id/eprint/208864

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