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Husnul Khotimah
Departement of Pharmacology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
Neuroscience

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NEUROPROTECTIVE EFFECT OF CINNAMON ACTIVE COMPOUNDS VIA ACTIVATION OF SIRT1: A MOLECULAR DOCKING APPROACH Umi Kalsum; Husnul Khotimah; Nurfaizah Titisari Sulihah; Theakirana Firdaus; Fitrah Aulia Lisabilla; Editya Fukata; Happy Kurnia Permatasari; Sri Andarini
MNJ (Malang Neurology Journal) Vol. 8 No. 2 (2022): July
Publisher : PERDOSSI (Perhimpunan Dokter Spesialis Saraf Indonesia Cabang Malang) - Indonesian Neurological Association Branch of Malang cooperated with Neurology Residency Program, Faculty of Medicine Brawijaya University, Malang, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.mnj.2022.008.02.9

Abstract

Background: Neurodegenerative diseases are the main cause of morbidity and disability in the elderly. SIRT1 activation has been gaining popularity as novel treatment target. Cinnamon is known to possess neuroprotective abilities, however the mechanism in which it protects the brain is still limited. Objective: This research aimed to determine the interaction between several cinnamon active compounds with SIRT1 Methods: We used in-silico method to determine the molecular interactions between cinnamon main compounds as the ligands to target protein SIRT1. SIRT1 3D structure was retrieved from the Protein Data Bank and 4 ligands (Cinnamaldehyde, Caffeic Acid, Epicatechin, and Trigonelline) structures were obtained from PubChem web server, and we used Resveratrol as positive control ligand. SwissADME, Pyrx, Pymol, and Biovia Discovery Studio software were utilized in this research Results: All four ligands fulfilled Lipinski Rule of 5 criteria therefore they are suitable for oral administration. It was discovered in this study that epicathecin had higher binding affinity than the control ligand Resveratrol and interacted with SIRT1 in the similar amino acid residue as Resveratrol did. The binding pocket interaction between all ligands and SIRT1 are the same. Conclusion: Epicathecin, as one of the main cinnamon compounds, may possess neuroprotective properties by interacting with SIRT1. We pproposed that further research be implemented to investigate epicathecin biological effects on SIRT1 in vitro or in vivo.
Cinnamomum burmannii EXTRACT AMELIORATES HIGH GLUCOSE-INDUCED BRAIN APOPTOSIS IN ZEBRAFISH EMBRYOS THROUGH INHIBITION OF PROCASPASE-9 : IN SILICO AND IN VIVO STUDY Umi Kalsum; Husnul Khotimah; Theakirana Firdaus; Editya Fukata; Nurfaizah Titisari Sulihah; Fitrah Aulia Lisabilla; Happy Kurnia Permatasari; Sri Andarini
MNJ (Malang Neurology Journal) Vol. 8 No. 2 (2022): July
Publisher : PERDOSSI (Perhimpunan Dokter Spesialis Saraf Indonesia Cabang Malang) - Indonesian Neurological Association Branch of Malang cooperated with Neurology Residency Program, Faculty of Medicine Brawijaya University, Malang, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.mnj.2022.008.02.10

Abstract

Background: Brain is an organ that is prone to oxidative stress and subsequent apoptosis due to high aerobic metabolism and relatively low antioxidants, especially under hyperglycemic condition. Cinnamomum burmanii (CB) is a species that is abundant in Indonesia, therefore it is of special concern for researchers to identify the anti-apoptotic effect of CB. Objective: This study was initiated to determine the effect of CB extract on the inhibition of brain apoptosis in zebrafish embryos exposed to high glucose and to investigate its anti-apoptosis mechanism by molecular docking approach. Methods: Molecular docking was conducted to determine the interaction between several CB extracts main constituents with target protein procaspase-9, compared to control ligand Saxagliptin. Zebrafish embryos were used to assess the effect of 4% glucose exposure and three doses of CB extract treatment (1.25, 5, and 10 µg/ml) on apoptosis in brain region. High-glucose condition in zebrafish embryo was confirmed with overexpression of Phosphoenolpyruvate carboxykinase (PEPCK). Apoptosis was evaluated by performing acridine orange (AO) staining and quantified by ImageJ software. Results: Molecular docking study indicated that main CB compounds, namely epicatechin, displayed stronger molecular interactions with procaspase-9 compared to control ligand Saxagliptin. There were increased numbers of apoptotic cells seen around brain region in glucose-treated group. Meanwhile, supplementation of CB extract at dose of 10 µg/ml resulted in decreased amount of apoptotic cells in brain region. Conclusion: The results suggest that CB extract protects from hyperglycemic-induced apoptosis in zebrafish embryos brain by modulating procaspase-9.
LIGHT EXPOSURE’S EFFECTS ON INACTIVE STATE DURATION AND SLEEP LATENCY IN ZEBRAFISH (DANIO RERIO) LARVAE INSOMNIA MODEL Zamroni Afif; Mochammad Istiadjid Eddy Santoso; Husnul Khotimah; Irawan Satriotomo; Edi Widjajanto; Masruroh Rahayu; Shahdevi Nandar Kurniawan; Dheka Sapti Iskandar; Annisatul Hakimah; Syafiatul Azizah; Nurvia Andriani; Kartika Agustina
MNJ (Malang Neurology Journal) Vol. 8 No. 2 (2022): July
Publisher : PERDOSSI (Perhimpunan Dokter Spesialis Saraf Indonesia Cabang Malang) - Indonesian Neurological Association Branch of Malang cooperated with Neurology Residency Program, Faculty of Medicine Brawijaya University, Malang, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.mnj.2022.008.02.11

Abstract

Background: Insomnia is defined as difficulty falling or staying asleep or a sleep state that cannot restore the body's condition. The zebrafish (Danio rerio) is a vertebrate model that has been extensively studied to study sleep and neurological disorders. One of the most widely used methods to examine the effect of the light-dark cycle on the circadian system is by exposing animals and humans to pulse wave light. Objective: To see the effect of light exposure on zebrafish larvae by looking at inactive state duration and sleep latency in zebrafish (Danio rerio) larvae insomnia model. Methods: This study used four groups of zebrafish larvae i.e : (1) normal group (2) minutes of light exposure and 2 minutes off (2/2)), (3) Four minutes of light exposure and 1 minute off (4/1), and (4)  24 hours on (24/0). Observation of larval movement was carried out on 5, 6, and 7 dpf (day post fertilization). Observation time was 30 minutes before and after turned off of light exposure. Results: There were significant differences on days 5, 6, and 7 between the normal group and the three light treatment groups on inactive state duration and sleep latency in dark and light conditions with p-values (p<0.05) and (p< 0.031), but there was no significant difference among groups of light exposure 2 minutes on 2 minutes off, 4 minutes on 1 minute off, and 24 hours on. The 24-hour on treatment showed the most inactive state duration among the light treatments, while the sleep latency was found in the 24-hour treatment. Conclusion: Light treatment of 2 minutes on 2 minutes off, 4 minutes on 1 minute off, and 24 hours on can cause insomnia, but the most substantial insomnia effect is obtained from the 24-hour treatment.
Co-Authors Annisatul Hakimah Dheka Sapti Iskandar Edi Widjajanto Editya Fukata Fitrah Aulia Lisabilla Happy Kurnia Permatasari Irawan Satriotomo Kalsumy, Umi Kartika Agustina Masruroh Rahayu Mochammad Istiadjid Eddy Santoso Nurfaizah Titisari Sulihah Nurvia Andriani Shahdevi Nandar Kurniawan, Shahdevi Nandar Sri Andarini Syafiatul Azizah Theakirana Firdaus Zamroni Afif