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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.
Co-Authors Agnesia, Agnesia Aliefman Hakim Alrayan, Reza Amanda, Putri Fadillah Amelia, Nanda Arsul, Muhammad Ikhlas 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 Fong, Siau Friardi Ismed Gita Susanti Gita Susanti, Gita Hadi, Ismanurrahman Hakim, Aditia Rahman Hengki Adi. P Herlina, Santi Ibnu Fadilah Ikhlas Arsul, Muhammad Indah Indah Jaya, Farrel Septian Khairunnisa Khairunnisa Khairunnisa Lanang Rachmadi Luthfiana, Dewi maha rani Maharani Maharani, Maharani Maharani, Andi Rani Gustia 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 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 Yufri Aldi Yulius Evan Christian