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Journal : Narra J

Exploring the anti-inflammatory and anti-apoptotic properties of phloroglucinol on pancreatic cells in diabetic models: In silico and in vivo study Puspitasari, Renny N.; I'tishom, Reny; Kurnijasanti, Rochmah; Mustafa, Mohammad R.; Sudjarwo, Sri A.
Narra J Vol. 4 No. 3 (2024): December 2024
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v4i3.1211

Abstract

Pancreatic cell damage in diabetes mellitus is closely linked to inflammation and apoptosis. This study aimed to investigate the protective effects of phloroglucinol on pancreatic cells in a streptozotocin-induced diabetic model by assessing its anti-inflammatory and anti-apoptotic mechanisms. Phloroglucinol ligand and the structures of Bax, Bcl-2, and caspase-3 proteins were sourced from the PubChem database. Molecular docking was performed using Autodock Tools and docking results were analyzed with PyRx software. In addition, during the in vivo study, the BALB/c mice were grouped into four categories: healthy control, untreated streptozotocin-induced diabetic, and streptozotocin-induced diabetic treated with two doses of oral phloroglucinol at 100 mg/kg and 200 mg/kg body weight. After 28 days, pancreatic tissues were collected for flow cytometric analysis of NF-κB, IL-6, TNF-α, and apoptotic markers (Bax, Bcl-2, and caspase-3). The docking simulations revealed specific binding interactions: phloroglucinol interacted with Bcl-2 via amino acid residues of ALA90 and TYR139, with Bax via ALA42, LEU45, ALA46, LEU47, PRO130, and ILE133, and with caspase-3 through ARG64, SER120, GLN161, CYS163, and ARG207. The binding affinities for Bax, Bcl-2, and caspase-3 were -5.0, -4.7, and -4.9 kcal/mol, respectively. In vivo, results showed that streptozotocin significantly elevated inflammatory cytokines NF-κB, TNF-α, and IL-6, along with apoptotic markers in pancreatic cells (p<0.05) compared to healthy controls. Phloroglucinol administration at 200 mg/kg significantly reduced TNF-α, NF-κB and IL-6 levels. Phloroglucinol also prevented streptozotocin-induced pancreatic cell damage through anti-apoptotic effects by downregulating Bax and caspase-3 and upregulating Bcl-2. These findings suggest that phloroglucinol may offer protective benefits in diabetic conditions by modulating apoptotic and inflammatory pathways.
Co-Authors Agustina, Firanda Aisyafalah, Salma Aksono HP., Eduardus Bimo Al Arif, M Anam Al Arif, Moh. Anam Annette d’Arqom, Annette Anugrah, Alvyan Lantang Arimbi Azzahra, Farah Nabila Boedi Setiawan Budi Utomo BUDI UTOMO Cholifah, Siti Chusnul Citagami, Salsabila Dadik Rahardjo, Dadik Darmawan, Moch. Rizky Dewi, Aprilia Kurnia Dwi Puspa Sukma Viranda Eka Pramyrtha Hestianah, Eka Pramyrtha Endang Suprihati Epy Muhammad Luqman Erma Safitri Firnanda, Ferian Fitriati, Mariza Hana Eliyani Hani Plumeriastuti Harijani, Nenny Hermin Ratnani Hernanda, Ary Setya Herry Agoes Hermadi Hidajati, Nove Hidayatik, Nanik Hisyam, Mirza Atikah Madarina I'tishom, Reny IMAM MUSTOFA Indah Norma Triana, Indah Norma Indri Safitri Mukono, Indri Safitri Ira Sari Yudaniayanti Iwan Sahrial Hamid Jusak Nugraha Kadek Rachmawati Kadek Rachmawati Khairullah, Aswin Rafif Khoirunnisa, Itrah Legowo, Djoko Lilik Maslachah Lucia Tri Suwanti, Lucia Tri Ma'ruf, Anwar Mafruchati, Maslichah Maryana Siska Silviani Mas'ad, Khasmawati Meles, Dewa Ketut Meta Aprilia Mochamad Lazuardi Moh. Sukmanadi Mohammad Sukmanadi Mono Pratiko Gustomi Mubarok, Muhammad Syahrul Muhammad Faizal Adiutomo Mustafa, Mohammad R. Mustofa Helmi Effendi Nunuk Dyah Retno Lastuti Oski Illiandri Panggabean, Rosenna Tiara Paramita, Chici Ayu Poedji Hastutiek Prastyaningtyas, Kukuh Pratama, Fahrul Andika Pratama, Ricki Primarizky, Hardany Pudji Srianto Purwitasari, Neny Puspitasari, Renny N. Putri, Arninda Alfiani Rahmaniabdi, El Roy Achmad Rahmawati, Kadek Rahmi Sugihartuti, Rahmi Raindra Daksina Ramadhani, Fifi Fauziah Rimayanti Rimayanti Rohmah, Etik Ainun ROHMAH, LAILATUL Rr. Juni Triastuti Sabdoningrum, Emy Koestanti Saputra, Rakan Mahiid Soeharsono Soeharsono Sri Agus Sudjarwo Sri Mulyati Sri Pantja Madyawati Sri Pantja Madyawati, Sri Pantja Subagyo Yotopranoto Sudjarwo, Sri A. Suherni Susilowati Sukmanadi, Mohammad Sunarso, Agus Supriyadi Supriyadi Supriyadi Suwanto Suwanto Suzanita Utama Swari, Wahyu Retno Tatik Hernawati Tita Damayanti Lestari Tjuk Imam Restiadi Tri Wahyu Suprayogi Tyasningsih, Wiwiek Vladika, Maulinda Agchirilia Warsito, Sunaryo Hadi Widiyatno, Thomas Valentinus Widjiati Widjiati, Widjiati Widya Paramita Lokapirnasari Wurlina, W Yuani Setiawati Yuliani, Gandul Atik Yulianna Puspitasari Yustinasari, Lita Rakhma