Pengembangan Polisakarida Peptida Ekstrak Miselia Ganoderma lucidum Sebagai Anti-Inflamasi Dalam Memperbaiki Fungsi Ginjal Pada Pasien Sindrom Kardiometabolik

Wardhani, Syanindita Puspa and : Prof. Dr. dr. Djanggan Sargowo,, Sp.PD, Sp.JP(K) and dr. Anna Fuji Rahimah, Sp.JP(K) (2023) Pengembangan Polisakarida Peptida Ekstrak Miselia Ganoderma lucidum Sebagai Anti-Inflamasi Dalam Memperbaiki Fungsi Ginjal Pada Pasien Sindrom Kardiometabolik. Magister thesis, Universitas Brawijaya.

Abstract

Sindrom kardiometabolik merupakan suatu kumpulan kondisi yang menjadi faktor risiko penyakit kardiovaskuler. Sindrom kardiometabolik ditandai dengan adanya disfungsi metabolik yang meliputi resistensi insulin, hiperglikemia, dislipidemia, hipertensi, dan obesitas sentral. Sindrom kardiometabolik dapat memunculkan suatu proses inflamasi dengan patomekanisme spesifik pada masing-masing komponen. Dari segala patomekanisme tersebut, jalur proses inflamasi melibatkan nuclear factor kappa-b (NF-κΒ) yang melibatkan beberapa sitokin inflamasi. Beberapa mediator inflamasi yang terlibat dalam pengaruh sindrom kardiometabolik terhadap fungsi ginjal antara lain interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), dan high sensitivity C-reactive protein (hsCRP). Inflamasi yang disebabkan oleh sindrom kardiometabolik dapat menyebabkan disfungsi endotel. Disfungsi endotel adalah kegagalan vaskuler dalam melakukan fungsi fisiologis, di mana endotel berperan penting dalam regulasi tonus vaskuler, adhesi seluler, migrasi sel otot polos vaskuler, dan resistensi terhadap trombosis. Disfungsi endotel pada vaskuler sistemik tentunya akan memengaruhi vaskularisasi ginjal dan berdampak pada fungsi ginjal yang dipantau dari kadar urea serum, kreatinin serum, dan estimated glomerulus filtration rate (eGFR). Studi sebelumnya menunjukkan bahwa Polisakarida Peptida (PsP) ekstrak miselia Ganoderma lucidum memiliki fungsi anti-inflamasi pada vaskuler serta mengurangi risiko disfungsi endotel. PsP atau β-1,3/1,6-D-glukan berinteraksi dengan berbagai reseptor membrane sel imun seperti Dectin-1, Complement receptor 3 (CR3), toll-like receptor (TLR), reseptor scavenger, dan reseptor lactocylseramide Ikatan β-1,3/1,6-D-glukan dengan reseptor tersebut akan menimbulkan modulasi respon imun baik respon imun bawaan maupun adaptif sehingga β-1,3/1,6-D-glukan berperan dalam mengatur atau menyeimbangkan proses inflamasi sehingga dapat digunakan sebagai terapi ajuvan pada beberapa macam penyakit pada pasien kardiometabolik. Penelitian klinis randomisasi tersamar ganda dilakukan untuk mengetahui dan membuktikan efek pemberian β-1,3/1,6-D-Glukan (Polisakarida Peptida) dari ekstrak miselia Ganoderma lucidum sebagai berperan sebagai anti-inflamasi dalam memperbaiki atau mempertahankan fungsi ginjal yang diukur melalui kadar urea-kreatinin serum dan eGFR pada pasien dengan sindrom kardiometabolik. Variabel bebas penelitian ini adalah ekstrak miselia Ganoderma lucidum, sedangkan variabel terikat yaitu kadar urea dan kreatinin serum serta eGFR yang dimediasi oleh variabel antara yaitu IL-6, TNF-α, dan hsCRP. Penelitian ini melibatkan dua kelompok yaitu kelompok perlakuan (diberi kapsul PsP) dan kelompok placebo (diberi kapsul netral). Selama penelitian berjalan, peneliti tidak mengetahui pasien manasaja yang masuk ke dalam kelompok perlakuan maupun placebo. Partisipan penelitian mengonsumsi kapsul tersebut tiga kali sehari viii selama 60 hari. Penelitian ini menggunakan analisis uji T berpasangan untuk mengetahui pengaruh pemberian kapsul PsP maupun placebo sebelum dan sesudah pemberian 60 hari. Uji T independen juga digunakan untuk mengetahui perbedaan antara kelompok perlakuan dan placebo. Selain itu, penelitian ini juga menggunakan Partial Least Square (PLS) menganalisis proses pendugaan yang dilakukan secara iteratif dengan melibatkan struktur keragaman variabel bebas dan variabel tak bebas yang terdiri atas diagram jalur, pengujian hipotesis pengaruh langsung dan tidak langsung, konversi diagram jalur ke dalam model struktural, dan pengaruh dominan. Hasil penelitian ini menunjukkan terdapat penurunan pada sitokin pro�inflamasi yaitu IL-6, TNF-α, dan hsCRP pada kelompok PsP dan placebo. Penurunan yang signifikan tersebut pada kedua kelompok tersebut tidak memberikan added value ekstrak Ganoderma lucidum sebagai anti-inflamasi pada pasien sindrom kardiometabolik. Hal ini disebabkan oleh beberapa faktor seperti proses anti-inflamasi yang diperantarai oleh TRAF dan obat rutin yang menginhibisi NF-κB secara langsung seperti metformin. Ekstrak PsP miselia Ganoderma lucidum memiliki pengaruh negatif terhadap kadar sitokin pro�inflamasi (TNF-α, IL-6, dan hsCRP) yang berarti ekstrak PsP dapat menurunkan kadar sitokin pro-inflamasi meskipun tidak signifikan yang dipengaruhi oleh beberapa faktor meliputi usia, adanya kemungkinan keterlambatan meminum ekstrak PsP, dan beberapa faktor lain seperti stres, konsumsi makanan, pola hidup, pengaruh hormonal, dan tidak terkendalinya penyakit metabolik yang mendasari. Penelitian ini juga menunjukkan bahwa terdapat penurunan urea dan kreatinin serum (p= 0,6040 dan p=0,8600) serta terdapat peningkatan eGFR (p=0,8260) pada kelompok PsP. Berdasarkan hasil penelitian yang telah dilakukan, peneliti menyarankan beberapa hal yaitu Perlu dilakukan penelitian serupa dengan durasi pengobatan yang lebih lama lagi dan jumlah partisipan yang lebih besar dan Perlu dilakukan pengambilan sampel yang lebih selektif dan terkontrol baik sebelum, saat, dan sesudah masa terapi untuk mendapatkan hasil yang signifikan (dengan kata lain agar dapat membuktikan bahwa ekstrak miselia Ganoderma lucidum memiliki added value sebagai anti-inflamasi pada pasien sindrom kardiometabolik)

English Abstract

Cardiometabolic syndrome is a collection of conditions that are risk factors for cardiovascular disease. Cardiometabolic syndrome is characterized by the presence of metabolic dysfunction which includes insulin resistance, hyperglycemia, dyslipidemia, hypertension, and central obesity. The cardiometabolic syndrome can give rise to an inflammatory process with specific pathomechanisms for each component. Of all the pathomechanisms, the pathway of the inflammatory process involves nuclear factor kappa-b (NF-κΒ) which involves several inflammatory cytokines. Several inflammatory mediators involved in the effect of cardiometabolic syndrome on kidney function include interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high sensitivity C-reactive protein (hsCRP). Inflammation caused by cardiometabolic syndrome can cause endothelial dysfunction. Endothelial dysfunction is vascular failure in carrying out physiological functions, in which endothelium plays an important role in the regulation of vascular tone, cellular adhesion, migration of vascular smooth muscle cells, and resistance to thrombosis. Endothelial dysfunction in the systemic vasculature will certainly affect renal vascularization and impact on kidney function which is monitored from serum urea levels, serum creatinine, and estimated glomerular filtration rate (eGFR). Previous studies have shown that the polysaccharide peptide (PsP) of Ganoderma lucidum mycelia extract has an anti-inflammatory function in the vascular system and reduces the risk of endothelial dysfunction. PsP or β-1,3/1,6- D-glucan interacts with various immune cell membrane receptors such as Dectin�1, Complement receptor 3 (CR3), toll-like receptor (TLR), scavenger receptor, and lactocylseramide receptor β binding -1,3/1,6-D-glucan with these receptors will lead to modulation of the immune response both innate and adaptive immune responses so that β-1,3/1,6-D-glucan plays a role in regulating or balancing the inflammatory process so that it can be used as adjuvant therapy in various diseases in cardiometabolic patients. A double-blind randomized clinical study was conducted to determine and prove the effect of giving β-1,3/1,6-D-Glucan (Polysaccharide Peptides) from the mycelia extract of Ganoderma lucidum as acting as an anti-inflammatory in improving or maintaining kidney function as measured by levels Serum urea�creatinine and eGFR in patients with cardiometabolic syndrome. The independent variable in this study was the mycelia extract of Ganoderma lucidum, while the dependent variable was serum urea and creatinine levels and eGFR which were mediated by intermediate variables, namely IL-6, TNF-α, and hsCRP. This study involved two groups: the treatment group (given PsP capsules) and the placebo group (given neutral capsules). During the study, researchers did not know which patients were in the treatment or placebo groups. Study participants took the capsules three times daily for 60 days. This study used paired t-test analysis to x determine the effect of PsP capsules and placebo before and after 60 days of administration. An independent T test was also used to determine differences between the treatment and placebo groups. In addition, this study also uses Partial Least Square (PLS) to analyze the estimation process which is carried out iteratively by involving the structure of the diversity of independent variables and dependent variables consisting of path diagrams, testing the hypothesis of direct and indirect effects, converting path diagrams into models. structural, and dominant influences. This study used paired t-test analysis to determine the effect of PsP capsules and placebo before and after 60 days of administration. An independent T test was also used to determine differences between the treatment and placebo groups. In addition, this study also uses Partial Least Square (PLS) to analyze the estimation process which is carried out iteratively by involving the structure of the diversity of independent variables and dependent variables consisting of path diagrams, testing the hypothesis of direct and indirect effects, converting path diagrams into models. structural, and dominant influences. This study used paired t-test analysis to determine the effect of PsP capsules and placebo before and after 60 days of administration. An independent T test was also used to determine differences between the treatment and placebo groups. In addition, this study also uses Partial Least Square (PLS) to analyze the estimation process which is carried out iteratively by involving the structure of the diversity of independent variables and dependent variables consisting of path diagrams, testing the hypothesis of direct and indirect effects, converting path diagrams into models. structural, and dominant influences. The results of this study show there was a decrease in pro-inflammatory cytokines, namely IL-6, TNF-α, and hsCRP in the PsP and placebo groups. This significant decrease in the two groups did not provide added value to Ganoderma lucidum extract as an anti-inflammatory in patients with cardiometabolic syndrome. This is due to several factors such as the anti-inflammatory process mediated by TRAF and the inhibitory routine drugsNF-κB is directly like metformin. PsP of Ganoderma lucidum mycelial extract has a negative effect on pro-inflammatory cytokine levels (TNF-α, IL-6, and hsCRP) which means that PsP extract can reduce pro-inflammatory cytokine levels although not significantly influenced by several factorsincluding age, the possibility of delay in drinking PsP extract, and several other factors such as stress, food consumption, lifestyle, hormonal influences, and uncontrolled underlying metabolic disease. This research also shows thatthere was a decrease in serum urea and creatinine (p = 0.6040 and p = 0.8600) and there was an increase in eGFR (p = 0.8260) in the PsP group. Based on the results of the research, the researchers suggest a number of things, namely the need to conduct similar studies with a longer duration of treatment and a larger number of participants and the need for more selective and controlled sampling both before, during and after the therapy period to obtain significant results (in other words to be able to prove that Ganoderma lucidum mycelia extract has added value as an anti-inflammatory in cardiometabolic syndrome patients)

Item Type:	Thesis (Magister)
Identification Number:	0423060111
Subjects:	600 Technology (Applied sciences) > 610 Medicine and health > 610.28 Auxiliary techniques and procedures; apparatus, equipment, materials / Biomedical engineering
Divisions:	S2/S3 > Magister Ilmu Biomedis, Fakultas Kedokteran
Depositing User:	Endang Susworini
Date Deposited:	14 Dec 2023 03:26
Last Modified:	14 Dec 2023 03:26
URI:	http://repository.ub.ac.id/id/eprint/205393

Text (DALAM MASA EMBARGO) Syanindita Puspa Wardhani.pdf Restricted to Registered users only until 31 December 2025. Download (7MB)

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