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All Journal Journal of Food and Pharmaceutical Science Jurnal Tumbuhan Obat Indonesia Biology, Medicine, & Natural Product Chemistry Jurnal Biologi Tropis JURNAL FARMASIMED (JFM) ad-Dawaa : Journal of Pharmaceutical Sciences Acta Chimica Asiana Current Research on Biosciences and Biotechnology Journal of Multidisciplinary Applied Natural Science Sasambo Journal of Pharmacy Journal of Health Science Sinteza Scientica: Jurnal Ilmiah Sains dan Teknologi Journal of Food and Pharmaceutical Sciences Indonesian Journal of Cosmetics Medical Sains : Jurnal Ilmiah Kefarmasian
Arif Setiawansyah
Akademi Farmasi Cendikia Farma Husada
Religion Agriculture, Biological Sciences & Forestry Humanities Biochemistry, Genetics & Molecular Biology Chemical Engineering, Chemistry & Bioengineering Chemistry Civil Engineering, Building, Construction & Architecture Computer Science & IT Decision Sciences, Operations Research & Management Economics, Econometrics & Finance Energy Environmental Science Health Professions Immunology & microbiology Industrial & Manufacturing Engineering Materials Science & Nanotechnology Mathematics Medicine & Pharmacology Neuroscience Nursing Physics Public Health Social Sciences Other

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Furosemide Increases GABAA Receptor Activity via Antagonism to Sodium-Potassium-Chloride Cotransporter 1 In Silico and In Vivo Siregar, Marsintauli Hasudungan; Nurdiana, Nurdiana; Bal’afif, Farhad; Djajalaksana, Susanthy; Setiawansyah, Arif
Journal of Multidisciplinary Applied Natural Science Articles in Press
Publisher : Pandawa Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.47352/jmans.2774-3047.365

Abstract

GABAA receptor dysfunction and altered chloride homeostasis significantly contribute to seizure pathophysiology, with the sodium-potassium-chloride cotransporter 1 (NKCC1) playing a crucial role in regulating neuronal excitability. This study investigated furosemide's capacity to enhance GABAA receptor activity through NKCC1 antagonism and evaluated its therapeutic profile in combination with diazepam for seizure management. Comprehensive molecular docking analyses were conducted to assess binding affinities of furosemide and diazepam to NKCC1, followed by in vivo experiments using pentylenetetrazol-induced seizure models to evaluate GABAA receptor expression, seizure duration, and multiple pathophysiological biomarkers. Molecular analysis revealed that furosemide demonstrated measurable NKCC1 binding capacity (binding energy: -7.09 kcal/mol; Ki: 6.34 µM), though significantly lower affinity compared to diazepam (binding energy: -7.83 kcal/mol; Ki: 1.81 µM). The furosemide-diazepam combination exhibited complex competitive binding interactions, with furosemide substantially reducing diazepam's NKCC1 binding affinity. NKCC1 antagonism by furosemide effectively enhanced GABAA receptor expression by 29.8 ± 1.60% when used alone and 37.60 ± 2.0% in combination with diazepam. However, combination therapies resulted in significantly longer seizure durations (80 ± 3.0 s) compared to diazepam monotherapy (42.5 ± 2.10 s), suggesting antagonistic interactions on acute seizure suppression that may reflect altered chloride gradients or competitive pharmacokinetic effects. Despite reduced efficacy in seizure termination, combination therapy demonstrated selective advantages in other pathophysiological domains, including superior blood-brain barrier protection (reduced albumin level to 90.90 ± 2.70 µg/mL) and reduced excitotoxic damage. These findings indicate that furosemide-diazepam combination therapy presents a complex therapeutic profile characterized by trade-offs between acute seizure control and neuroprotective mechanisms. The data suggest potential utility in maintenance therapy or prevention of seizure-related complications rather than acute seizure termination, warranting further investigation into temporal optimization strategies and dose modifications.
Fermentation Driven Enhancement of Flavonoid, Phenolic, and Antioxidant Activity in Melastoma malabathricum Fruit Maharani, Maharani; Setiawansyah, Arif; Marpaung, Mauritz Pandapotan; Pratamarta, Meliasi Nora
Jurnal Biologi Tropis Vol. 26 No. 1 (2026): Januari-Maret
Publisher : Biology Education Study Program, Faculty of Teacher Training and Education, University of Mataram, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.29303/jbt.v26i1.11393

Abstract

Senggani (Melastoma malabathricum L.) is a fruit known for its high content of phenolic and flavonoid compounds, which contribute to its antioxidant properties and are highly affected by fermentation processes. This study investigated how aerobic and anaerobic fermentation influence the total phenolic content, total flavonoid content, and antioxidant activity of senggani fruit extracts. The experiment involved aerobic fermentation without yeast and anaerobic fermentation with yeast, both conducted for three days. Total phenolics were quantified using the Folin–Ciocalteu assay, total flavonoids were measured via the aluminum chloride colorimetric method, and antioxidant activity was evaluated through the DPPH radical scavenging assay using UV–Vis spectrophotometry. The findings indicated that aerobic fermentation resulted in greater total phenolic (16.45 mg GAE/g) and flavonoid levels (16.95 mg QE/g), along with stronger antioxidant activity (IC50 55.37 ppm), compared to anaerobic fermentation. In contrast, anaerobic treatment yielded lower phenolic (11.77 mg GAE/g) and flavonoid contents (11.53 mg QE/g) and reduced antioxidant capacity (IC₅₀ 59.86 ppm). Overall, the results suggest that fermentation conditions play a crucial role in shaping the bioactive composition and antioxidant performance of senggani extracts, with aerobic fermentation showing better potential for developing functional and nutraceutical products.
Network pharmacology and molecular docking simulation uncovered the potential of hexacyclinic acid as anti-osteoarthritis by regulating IL-17 signaling pathway Arif Setiawansyah
Acta Chimica Asiana Vol. 8 No. 1 (2025)
Publisher : The Indonesian Chemical Society, Chapter Nusa Tenggara and The University of Mataram

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.29303/aca.v8i1.238

Abstract

Hexacyclinic acid has shown promising pharmacological activities, yet its molecular mechanisms and therapeutic potential remain largely unexplored. This study aimed to identify potential disease targets and elucidate the mechanism of action of hexacyclinic acid using an integrated computational approach. We employed network pharmacology analysis to predict potential targets and pathways of hexacyclinic acid using SuperPred and Swiss Target server, followed by protein-protein interaction network construction via STRING database. Pathway enrichment analysis was performed using ShyniGO and DAVID databases. Molecular docking studies were conducted using AutoDock Vina to evaluate binding affinities between hexacyclinic acid and identified target proteins. Binding poses and interactions were visualized using Biovia Discovery Studio Visualizer. Disease prediction analysis identified osteoarthritis as the most promising target, with the IL-17 signaling pathway emerging as the most significant KEGG pathway. TNF-α and IL-1β were identified as key molecular targets within this pathway. Molecular docking simulations corroborated these findings, revealing favorable binding energies between hexacyclinic acid and TNF-α (-8.62 kcal/mol) and IL-1β (-8.76 kcal/mol). These results suggest that hexacyclinic acid may exert its anti-osteoarthritis effects by modulating the IL-17 signaling pathway, particularly through interactions with TNF-α and IL-1β. The strong binding affinities observed indicate a potentially high efficacy of hexacyclinic acid in targeting these inflammatory mediators. These results have significant clinical implications, potentially leading to the development of new therapeutic strategies for osteoarthritis management with reduced side effects compared to current treatments. Future research should focus on experimental validation through in vitro and in vivo models to confirm these computational predictions and establish hexacyclinic acid as a viable candidate for clinical development
Fermentation-Mediated Modulation of Nutraceutically Relevant Polyphenolic Compounds and Antioxidant Capacity of Red Spinach (Amaranthus tricolor L.) Leaf Extract Nur Amelia; Yovi Pranata; Arif Setiawansyah; Mauritz Pandapotan Marpaung; Fika Minata Wathan
Biology, Medicine, & Natural Product Chemistry Vol 15, No 1 (2026)
Publisher : Sunan Kalijaga State Islamic University & Society for Indonesian Biodiversity

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14421/biomedich.2026.151.585-596

Abstract

Fermentation has emerged as a promising biotechnological approach to enhance the nutraceutical quality of plant-based materials through targeted modulation of bioactive compounds. This study investigated the effects of aerobic and anaerobic fermentation on total phenolic content (TPC), total flavonoid content (TFC), and antioxidant capacity of red spinach (Amaranthus tricolor L.) leaf extracts. Aerobic fermentation markedly enhanced the phytochemical profile, yielding a 1.87-fold increase in TPC (121.28 mg GAE/g extract) and a 1.66-fold increase in TFC (897.82 mg QE/g extract) compared with fresh leaves. These compositional improvements translated into superior functional activity, as evidenced by the lowest IC50 value (56.07 mg/L) and the highest antioxidant activity index (AAI = 0.713). In contrast, anaerobic fermentation provided limited phenolic enrichment and resulted in substantial flavonoid degradation, leading to inferior antioxidant performance. Strong correlations between polyphenolic contents and antioxidant parameters confirmed that phenolics and flavonoids are key contributors to radical scavenging activity. Overall, the findings demonstrate that aerobic fermentation is an effective, low-cost strategy to improve the nutraceutical value and antioxidant capacity of red spinach leaf extracts, highlighting its potential application in the development of functional foods and nutraceutical ingredients.
Co-Authors Agnesia, Agnesia Aliefman Hakim Alrayan, Reza Amanda, Putri Fadillah Amelia, Nanda Baiq Maylinda Gemantari Bal’afif, Farhad Bambang Hernawan Nugroho, Bambang Hernawan Daryono Hadi Tjahjono Dewantara, Jeisen Pajar Dewi Luthfiana Diah Ayu. S Dian Handayani Djajalaksana, Susanthy Doloking, Haeria Dwi Handayani Dyke Gita Wirasisya Enggy Erwansani Erwansani, Enggy Evifani, Dinda Silvia Fendi Fendi FIKA MINATA WATHAN Fong, Siau Friardi Ismed Gita Susanti Gita Susanti, Gita Hadi, Ismanurrahman Hakim, Aditia Rahman Hengki Adi. P Herlina, Santi Ibnu Fadilah Indah Indah Jaya, Farrel Septian Khairunnisa Khairunnisa Khairunnisa Lanang Rachmadi Luthfiana, Dewi maha rani Maharani Maharani, Maharani Maharani, Andi Rani Gustia Mauritz Pandapotan Marpaung MAURITZ PANDAPOTAN MARPAUNG Maya Ganda Ratna Meliasi Nora Pratamarta Muh Ikhlas Arsul Muhammad Andre Reynaldi Mutiara, Berkah Nanda Puspita. S Nugraheni Febrianti S Nur Adliani Nur Amelia Nurcahya, Salsabila Nurdiana Nurdiana Nurul Hasanah Nurul Hidayati Nweze, Leonard Chinecherem Nyimas Rahma. K Perdana Priya Haresmita Putra, Teguh Adiyas Putri Adelia. M Putri, Stella Anatasya Putri Reza Alrayan Rico Saputra RINA SE SITINDAON Rindi Permata.S Sadaqa, Ebrahim Salsabila, Salwa Salsabilla Nur. C Saputri, Aurya Sephia Panorama Setiawati, Diah Ayu Siregar, Marsintauli Hasudungan Siti Aminah Stevia, Tessa Sukrasno Susianti Susianti Sutopo Hadi Syaiful Bahri Valentina, Febriani Wilsya, Mayaranti Wismayani, Leni Yovi Pranata Yovi Pranata Yufri Aldi Yulius Evan Christian