QUALEN Bulletin of Marine and Fisheries Postharvest and Biotechnology Published Online: 31 May 2024 Page 55 of 69 1 Aquatic Product Processing and Storage, Department of Fisheries and Marine Technology Politeknik Negeri Nusa Utara, Jl. Kesehatan No. 1, Tahuna 95812, Sangihe Islands, North Sulawesi, Indonesia 2 Research Center of Ocean and Land Bioindustry, Indonesia National Research and Innovation Agency (BRIN), Teluk Kodek, Malaka, Pemenang 83352, North Lombok, West Nusa Tenggara. Indonesia * Corresponding Author: ekocahyono878@gmail.com Received: 8 November 2023 Accepted: 8 May 2024 Published: 31 May 2024 Academic Editor: Prof. Dr. Ing. Azis Sitanggang, S.TP, M.Sc. © Squalen Bulletin of Marine and Fisheries Postharvest and Biotechnology, 2024. Accreditation Number:148/M/KPT/2020. ISSN: 2089-5690, e-ISSN: 2406-9272. https://doi.org/ 10.15578/squalen.835 OPEN ACCESS SQUALEN BULLETIN The Ameliorating Effect of Artificial Coffee from Mangrove Fruits ( Rhizophora mucronata) on T Lymphocyte Cells and Renal Histopathology of BALB/c Mice Induced by Lipopolysaccharide Eko Cahyono 1 *, Wendy A. Tanod 1 , Frans G. Ijong 1 , Novalina M. S. Ansar 1 , Jefri A. Mandeno 1 , Ely J. Karimela 1 , Frets J. Rieuwpassa 1 , Jaka F. P. Palawe 1 , Yana Sambeka 1 , and Natalia P. Setiawati 2 Abstract The potential of Rhizophora mucronata mangrove fruits as antioxidants is noteworthy, with promising prospects as nutraceuticals, particularly in their role as immunomodulators for T lymphocyte cells. R. mucronata fruits have been utilized by household industries in Indonesia as a coffee-like drink (artificial coffee). This study aims to determine the ability of mangrove fruit artificial coffee R. mucronata to stimulate T lymphocyte cells and renal histopathology conditions in LPS-induced mice animal models. This study also characterizes proximate characteristics, antioxidant capacity, and Gas Chromatography-Mass Spectrometry (GC-MS) screening of mangrove fruit artificial coffee compounds. The stages of this research included the process of mangrove fruit artificial coffee; analysis of proximate and caffeine; compounds screening (GC-MS) and toxicity prediction (Pro-Tox II); antioxidant capacity (DPPH); T lymphocyte cell expression (flow cytometry); and renal histopathological evaluation. The results showed moisture content (5.22±0.20%); ash (5.17±0.27%); protein (13.74±0.24%); fat (11.63±0.32%); carbohydrate (64.23±0.15%), caffeine (1.09±0.04%). GC-MS analysis showed that the compounds contained in artificial coffee were derivatives of fatty aldehyde, fatty acid, and cycloalkanes compound classes. Predicted toxicity of artificial coffee LD 50 5000 mg/kg. Antioxidant capacity is classified as moderate (IC 50 119.41±0.99μg/mL). Mangrove fruit artificial coffee can increase the relative number of CD4 + CD62L + by 14.68-29.48% and CD8 + CD62L + T lymphocyte cells by 12.60-30.33%. Artificial coffee can also increase the number of healthy cells and reduce the cells that undergo necrosis in the renal of LPS-induced mice. This study concluded that mangrove fruit artificial coffee R. mucronata positively affects T lymphocyte activation and mice renal cells’ protection from necrosis due to LPS induction. Keywords: antioxidant, coffee, lymphocyte, North Sulawesi, Sangihe Introduction Mangroves thrive in tropical and subtropical coastal regions and exhibit robust growth in challenging environments characterized by daily tidal fluctuations (Dewanto et al., 2018). These plants demonstrate adaptability to low oxygen levels and brackish salinity conditions (Reef & Lovelock, 2015), often inhabiting waters with salinity conditions 100 times saltier (Santini et al., 2015). Their survival strategies encompass a range of chemo-physiological adaptations (Mitra et al., 2021), including salt secretion mechanisms that aid in coping with high-salinity habitats (Saiyed, 1992; Kathiresan & Bingham, 2001). Moreover, mangroves have evolved specialized root structures to thrive in oxygen-deprived conditions during inundation by high tides (Srikanth et al., 2016). Mangroves exhibit chemo-physiological adaptability by synthesizing unique compounds (Mitra et al., 2021). These compounds, derived from mangroves, have garnered attention for their potential applications in the pharmaceutical and nutraceutical sectors (Dahibhate et al., 2018; Sadeer et al., 2023). Research indicates that these mangrove-derived compounds possess a