Immunomodulatory and Hepatoprotective Effects of Extract from Coffee-Like Product Derived from Rhizophora mucronata Fruit of Sangihe Islands in LPS-Treated Mice

Authors

DOI:

https://doi.org/10.36568/jone.v4i3.757

Keywords:

antioxidants, immunoglobulin G, inflammation, functional beverages, oxidative stress

Abstract

The mangrove fruit Rhizophora mucronata, native to Indonesia's Sangihe Islands, represents a promising functional food ingredient. This study evaluated the immunomodulatory and hepatoprotective potential of a coffee-like extract derived from this fruit in a lipopolysaccharide (LPS)-induced systemic inflammation mouse model. Thirty male BALB/c mice were randomly allocated into six groups (n=5/group): normal control, LPS control, LPS+vitamin E (500 mg/kg), and LPS+extract (500, 1000, or 1500 mg/kg). Extracts were administered orally for 14 consecutive days prior to LPS challenge (5 mg/kg). Phytochemical screening identified steroids (10.84 mg/kg), terpenoids (2.50 mg/kg), and saponins (0.52 mg/kg), alongside moderate antioxidant activity (IC₅₀=113.66 µg/mL). Proximate analysis revealed moisture (5.31%), ash (5.25%), protein (13.07%), fat (11.17%), carbohydrate (65.21%), energy value (413.61 kcal), and caffeine content (0.96%). LPS administration significantly reduced serum immunoglobulin G (IgG) concentrations from 2700 ± 29.42 µg/mL (normal) to 1890 ± 12.83 µg/mL. One-way ANOVA (F₍₅,₂₄₎ = 1368.34, p < 0.001) with Tukey's HSD post-hoc test demonstrated that the 500 mg/kg dose partially restored IgG levels (2600 ± 26.90 µg/mL, p < 0.05 vs. normal), while the 1000 and 1500 mg/kg doses achieved full restoration (2739 ± 18.53 and 2737 ± 2.55 µg/mL, respectively), statistically comparable to both normal and vitamin E groups (p > 0.05). At the higher doses, the extract also attenuated hepatic injury, evidenced by increased healthy hepatocyte counts and reduced nuclear abnormalities (pyknosis, karyorrhexis, karyolysis). These preliminary findings indicate that R. mucronata coffee-like extract exhibits notable immunomodulatory and hepatoprotective properties, warranting further translational investigation.

References

Dahibhate NL, Saddhe AA, Kumar K. Mangrove Plants as a Source of Bioactive Compounds: A Review. Nat Prod J. 2019;9(2):86-97. doi:10.2174/2210315508666180910125328

Arifin MZ, Mulalinda P, Kalesaran J, Tauladani SA, Asia. Study of the Level of Success of Mangrove Planting on the Coast of Dagho Village, Sangihe Islands Regency, Matahit Village, Talaud Islands Regency and Pasirpanjang Village, South Lembeh District, Bitung City. Frontiers (Boulder) [Internet]. 2019;2(1):21-33. Available from: https://garuda.kemdiktisaintek.go.id/documents/detail/1689806

Setyawan AD, Ragavan P, Basyuni M, Sarno S. Review: Rhizophora mucronata as Source of Foods and Medicines. Intl J Bonorowo Wetl. 2019;9(1):42-55. doi:10.13057/bonorowo/w090105

Hilmi E, Sari LK, Siregar AS, et al. Tannins in Mangrove Plants in Segara Anakan Lagoon, Central Java, Indonesia. Biodiversitas. 2021;22(8):3508-3516. doi:10.13057/biodiv/d220850

Rumengan AP, Mandiangan ES, Tanod WA, Paransa DSJ, Paruntu CP, Mantiri DMH. Identification of Pigment Profiles and Antioxidant Activity of Rhizophora mucronata Mangrove Leaves Origin Lembeh, North Sulawesi, Indonesia. Biodiversitas. 2021;22(7):2805-2816. doi:10.13057/biodiv/d220730

Das PS, Ashrafi S, Anjum J, Hossain MdE, Reza MdS, Ahsan M. Isolation of Terpenoids and Derivatives from a Bangladeshi Mangrove Plant, Rhizophora mucronata Lam., and Its Bioactivity Evaluation: In Vitro and In Silico Study. J Chem. 2024;2024(1):1-25. doi:10.1155/joch/8884812

Dewanto DK, Hermawan R, Muliadin, Riyadi PH, Aisiah S, Tanod WA. GC-MS Profile of Rhizophora apiculata Leaf Extract from The Coast of Tomini bay, Central Sulawesi with Antibacterial and Antioxidant Activity. J Kelautan: Indo J Mar Sci Technol. 2021;14(1):30-42. doi:10.21107/jk.v14i1.8904

Kalasuba K, Miranti M, Rahayuningsih SR, et al. Red Mangrove (Rhizophora stylosa Griff.)—A Review of Its Botany, Phytochemistry, Pharmacological Activities, and Prospects. Plants. 2023;12(11):2196. doi:10.3390/plants12112196

Suganthy N, Pandima Devi K. In vitro Antioxidant and Anti-cholinesterase Activities of Rhizophora mucronata. Pharm Biol. 2016;54(1):118-129. doi:10.3109/13880209.2015.1017886

Basyuni M, Yusraini E, Susilowati A, et al. Bioprospecting of Selected Mangrove Fruits Based-Nutritional, Antioxidant, and Element Properties to Support Functional Food Materials for Pulau Sembilan Coastal Communities, Indonesia. Int J Adv Sci Eng Inf Technol. 2021;11(4):1661-1667. doi:10.18517/ijaseit.11.4.13643

Miranti DI, Ichiura H, Ohtani Y. The Bioactive Compounds and Antioxidant Activity of Food Products of Rhizophora stylosa Fruit (Coffee and Tea Mangrove). Int J For Res. 2018;2018:1-6. doi:10.1155/2018/2315329

Sukma RN, Zahro M. Effect Utilization Mangrove Rhizophora sp. Fruit Extract in Production of Coffee Powder in Perspective of Water Content and Organoleptic Test. Aquasains [Internet]. 2020;9(1):881-886. Available from: https://jurnal.fp.unila.ac.id/index.php/JPBP/article/view/4747

Mandeno JA, Tanod WA, Cahyono E, et al. Characteristics of Analog Coffee from The Mangrove Fruit Rhizophora mucronata Origin Sangihe Islands. IOP Conf Ser Earth Environ Sci. 2023;1260(1):1-11. doi:10.1088/1755-1315/1260/1/012055

Cahyono E, Tanod WA, Ijong FG, et al. 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. Squalen Bull Mar Fish Postharvest Biotechnol. 2024;19(1):55-69. doi:10.15578/squalen.835

Roşian ŞH, Boarescu I, Boarescu PM. Antioxidant and Anti-Inflammatory Effects of Bioactive Compounds in Atherosclerosis. Int J Mol Sci. 2025;26(3):1379. doi:10.3390/ijms26031379

Shekhova E. Mitochondrial Reactive Oxygen Species as Major Effectors of Antimicrobial Immunity. PLoS Pathog. 2020;16(5):e1008470. doi:10.1371/journal.ppat.1008470

Iddir M, Brito A, Dingeo G, et al. Strengthening the Immune System and Reducing Inflammation and Oxidative Stress through Diet and Nutrition: Considerations during the COVID-19 Crisis. Nutrients. 2020;12(6):1562. doi:10.3390/nu12061562

Skrzypczak-wiercioch A. Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use. Molecules. 2022;27:5481. doi:10.3390/molecules27175481

Yin R, Zhang K, Li Y, et al. Lipopolysaccharide-Induced Depression-Like Model in Mice: Meta-analysis and Systematic Evaluation. Front Immunol. 2023;14(1181973):1-15. doi:10.3389/fimmu.2023.1181973

Ozawa A, Nakano T, Tanaka T, Hozumi Y, Iseki K, Goto K. Diacylglycerol Kinase ε Depletion Suppresses LPS-Stimulated NF-κB Activation and Reduces Free Radical-Induced DNA Damage. FEBS Lett. 2025;599(24):3629-3641. doi:10.1002/1873-3468.70164

Chen S nan, Tan Y, Xiao X chan, et al. Deletion of TLR4 Attenuates Lipopolysaccharide-Induced Acute Liver Injury by Inhibiting Inflammation and Apoptosis. Acta Pharmacol Sin. 2021;42(10):1610-1619. doi:10.1038/s41401-020-00597-x

Kim K, Hong HL, Kim GM, Leem J, Kwon HH. Eupatilin Ameliorates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting Inflammation, Oxidative Stress, and Apoptosis in Mice. Curr Issues Mol Biol. 2023;45(9):7027-7042. doi:10.3390/cimb45090444

Maheshwari S, Kumar V, Bhadauria G, Mishra A. Immunomodulatory Potential of Phytochemicals and Other Bioactive Compounds of Fruits: A Review. Food Front. 2022;3(2):221-238. doi:10.1002/fft2.129

Colomeu TC, de Figueiredo D, de Matos da Silva P, Fernandes LGR, Zollner R de L. Antiproliferative and Pro-Oxidant Effect of Polyphenols in Aqueous Leaf Extract of Passiflora alata Curtis on Activated T Lymphocytes from Non-Obese Diabetic (NOD SHILT/J) Mice. Antioxidants. 2022;11(8):1503. doi:10.3390/antiox11081503

Rodda LB, Netland J, Shehata L, et al. Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19. Cell. 2021;184(1):169-183. doi:10.1016/j.cell.2020.11.029

Hematianlarki M, Nimmerjahn F. Immunomodulatory and Anti‐Inflammatory Properties of Immunoglobulin G Antibodies. Immunol Rev. 2024;328(1):372-386. doi:10.1111/imr.13404

Zhou Y, Hu X, Zhong S, et al. Effects of Continuous LPS Induction on Oxidative Stress and Liver Injury in Weaned Piglets. Vet Sci. 2022;10(1):22. doi:10.3390/vetsci10010022

Haruna HMS, Umar H, Zakari A, Baba G. Toxicological Assessment of Aqueous Leaf Extract of Anisopus mannii: Acute and Sub-Acute Studies in Albino Rats. Sahel J of Life Sci FUDMA. 2024;2(4):40-46. doi:10.33003/sajols-2024-0204-07

Olukanni AT, Omotosho D, Olalekan DT, et al. Hepatoprotective and Nephroprotective Effects of Leea guineensis Leaf Extract Against Paracetamol-Induced Toxicity: Combined Mouse Model-Integrated in Silico Evidence. Int J Mol Sci. 2025;26(13):6142. doi:10.3390/ijms26136142

Aliyu A, Shaari MR, Ahmad Sayuti NS, et al. Subacute Oral Administration of Clinacanthus nutans Ethanolic Leaf Extract Induced Liver and Kidney Toxicities in ICR Mice. Molecules. 2020;25(11):2631. doi:10.3390/molecules25112631

Wagner H, Bladt S. Plant Drug Analysis: A Thin Layer Chromatography Atlas. Second. Springer Berlin Heidelberg; 1996. doi:10.1007/978-3-642-00574-9

Harborne JB. Phytochemical Methods; A Guide to Modern Techniques of Plant Analysis. Vol 3. Chapman and Hall; 1998. doi:10.1017/CBO9781107415324.004

Sasidharan S, Chen Y, Saravanan D, Sundram KM, Yoga Latha L. Extraction, Isolation and Characterization of Bioactive Compounds from Plants’ Extracts. Afr J Tradit Complement Altern Med [Internet]. 2011;8(1):1-10. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC3218439/

Alara OR, Abdurahman NH, Ukaegbu CI, Kabbashi NA. Extraction and Characterization of Bioactive Compounds in Vernonia amygdalina Leaf Ethanolic Extract Comparing Soxhlet and Microwave-Assisted Extraction Techniques. J Taibah Univ Sci. 2019;13(1):414-422. doi:10.1080/16583655.2019.1582460

Shai LJ, Masoko P, Mokgotho MP, et al. Yeast Alpha Glucosidase Inhibitory and Antioxidant Activities of Six Medicinal Plants Collected in Phalaborwa, South Africa. S Afr J Bot. 2010;76(3):465-470. doi:10.1016/j.sajb.2010.03.002

Pillai JR, Wali AF, Al-Azzawi AM, Akhter R, El-Serehy HA, Akbar I. Phytochemical Analysis and Antimicrobial Activity of Enicostemma littorale. J King Saud Univ Sci. 2020;32(8):3279-3285. doi:10.1016/j.jksus.2020.09.011

Hossain MA. Biological and Phytochemicals Review of Omani Medicinal Plant Dodonaea viscosa. J King Saud Univ Sci. 2019;31(4):1089-1094. doi:10.1016/j.jksus.2018.09.012

Ravelliani A, Nisrina H, Komala Sari L, Marisah M, Riani R. Identification and Isolation of Saponin Glycosides from Several Plants in Indonesia. J sos sains. 2021;1(8):786-799. doi:10.59188/jurnalsosains.v1i8.176

Thatipelli S, Shanmugam M, Ramachandran S, Pushparathinam G. Screening and Validated Semi - Quantification High-Performance Thin Layer Chromatography Method Development for Lupeol, Lupeol Acetate, β-sitosterol, ρ-Coumaric Acid and Proto-Catechuic Acid in The Root Extracts of Hemidesmus indicus (L.) R.Br. & Decalepis hamiltonii Wight & Arn. J Appl Res Med Aromat Plants. 2023;36:100510. doi:10.1016/j.jarmap.2023.100510

Barwant MM, Satyannarayana B, Mahalaxmi SmtK. Phytochemical Insights: Techniques and Applications Volume I. First. Bhumi Publishing; 2025. doi:10.5281/zenodo.17876298

Blois M. Antioxidant Determinations by The Use of a Stable Free Radical. Nature. 1958;181(4617):1199-1200. doi:10.1038/1811199a0

Festing MFW, Altman DG. Guidelines for the Design and Statistical Analysis of Experiments Using Laboratory Animals. ILAR J. 2002;43(4):244-258. doi:10.1093/ilar.43.4.244

Kang H. Sample Size Determination and Power Analysis Using The G*Power Software. J Educ Eval Health Prof. 2021;18:17. doi:10.3352/jeehp.2021.18.17

Balcombe JP, Barnard ND, Sandusky C. Laboratory Routines Cause Animal Stress. Contemp Top Lab Anim Sci [Internet]. 2004;43(6):42-51. Available from: https://pubmed.ncbi.nlm.nih.gov/15669134/

National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals, 8th Edition. 8th ed. National Academies Press; 2011. doi:10.17226/12910

Percie du Sert N, Hurst V, Ahluwalia A, et al. The ARRIVE guidelines 2.0: Updated Guidelines for Reporting Animal Research. PLoS Biol. 2020;18(7):e3000410. doi:10.1371/journal.pbio.3000410

Muhammad-Azam F, Nur-Fazila SH, Ain-Fatin R, Noordin MM, Yimer N. Histopathological Changes of Acetaminophen-Induced Liver Injury and Subsequent Liver Regeneration in BALB/C and ICR Mice. Vet World. 2019;12(11):1682-1688. doi:10.14202/vetworld.2019.1682-1688

Zambrano MV, Dutta B, Mercer DG, MacLean HL, Touchie MF. Assessment of Moisture Content Measurement Methods of Dried Food Products in Small-Scale Operations in Developing Countries: A Review. Trends Food Sci Technol. 2019;88(April):484-496. doi:10.1016/j.tifs.2019.04.006

Ashihara H, Crozier A. Caffeine: A Well Known But Little Mentioned Compound in Plant Science. Trends Plant Sci. 2001;6(9):407-413. doi:10.1016/S1360-1385(01)02055-6

Gawborisut S, Ketkaew C, Buasook T. Production of Biocalcium from Fermented Fish Bone Residue for Fish Emulsion Sausage Fortification. Foods. 2024;13(6):882. doi:10.3390/foods13060882

Yamagishi K, Ike M, Guan D, Tokuyasu K. Washing Lime-Pretreated Rice Straw with Carbonated Water Facilitates Calcium Removal and Sugar Recovery in Subsequent Enzymatic Saccharification. J Appl Glycosci. 2019;66(1):11-19. doi:10.5458/jag.jag.JAG-2018_0003

Titisari PW, Elfis, Zen IS, et al. The Potential of Mangrove as a Food Source in Riau. Future Food: J Food Agric Soc. 2023;11(5):1-18. doi:10.17170/kobra-202307218420

About Coffee. Is coffee acidic? [Internet] 2024. Available from: https://www.aboutcoffee.org/health/faq/is-coffee-acidic/. 2024. Accessed July 31, 2026.

Lawan MZ, Muhammad IM, Ahmed IS, Olu OO, Yusuf AA, Maryam I. Kinetics and Thermodynamic Parameters of Coffee Senna Seed (Senna occidentalis) Using Degradation Data from Roasting. Mikailalsys J Adv Eng Int. 2025;2(2):238-261. doi:10.58578/mjaei.v2i2.6277

Azizah DR, Sunarharum WB, Mahatmanto T, Kartika AA, Hakim L. Exploring the Impact of Various Manual Brewing Techniques on the Physicochemical and Sensory Characteristics of Brewed Coffee. IOP Conf Ser Earth Environ Sci. 2024;1299(1):012011. doi:10.1088/1755-1315/1299/1/012011

Iriondo-DeHond M, Iriondo-DeHond A, Herrera T, et al. Sensory Acceptance, Appetite Control and Gastrointestinal Tolerance of Yogurts Containing Coffee-Cascara Extract and Inulin. Nutrients. 2020;12(3):627. doi:10.3390/nu12030627

Batali ME, Cotter AR, Frost SC, Ristenpart WD, Guinard JX. Titratable Acidity, Perceived Sourness, and Liking of Acidity in Drip Brewed Coffee. ACS Food Sci Technol. 2021;1(4):559-569. doi:10.1021/acsfoodscitech.0c00078

Nooshkam M, Varidi M, Bashash M. The Maillard Reaction Products as Food-Born Antioxidant and Antibrowning Agents in Model and Real Food Systems. Food Chem. 2019;275:644-660. doi:10.1016/j.foodchem.2018.09.083

Rout P, Singh S, Kumar N, Basak UC. Nutritional and Antioxidant Potential of Some Selected Edible Mangrove Fruits of Odisha Coast. Int J Adv Sci Res. 2015;1(9):349-355. doi:10.7439/ijasr

Budiyanto F, Alhomaidi EA, Mohammed AE, et al. Exploring the Mangrove Fruit: From the Phytochemicals to Functional Food Development and the Current Progress in the Middle East. Mar Drugs. 2022;20(5):303. doi:10.3390/md20050303

Analuddin K, Septiana A, Nasaruddin, Sabilu Y, Sharma S. Mangrove Fruit Bioprospecting: Nutritional and Antioxidant Potential as a Food Source for Coastal Communities in the Rawa Aopa Watumohai National Park, Southeast Sulawesi, Indonesia. Int J Fruit Sci. 2019;19(4):423-436. doi:10.1080/15538362.2018.1555507

Ardiansyah PR, Wonggo D, Dotulong V, et al. Proximate Analysis of Sonneratia alba Mangrove Fruit Flour. Media Teknologi Hasil Perikanan. 2020;8(3):82. doi:10.35800/mthp.8.3.2020.27526

Ernawati, Suprayitno E, Hardoko, Yanuhar U. Extraction of Bioactive Compounds Fruit from Rhizophora mucronata Using Sonication Method. IOP Conf Ser Earth Environ Sci. 2019;236(1):012122. doi:10.1088/1755-1315/236/1/012122

Sungkar OF, Fahmi AS, Romadhon. Enrichment of Skin Lotion with Antioxidant from Rhizophora mucronata Fruit Extract. IOP Conf Ser Earth Environ Sci. 2019;246:012065. doi:10.1088/1755-1315/246/1/012065

Karimi A, Krähmer A, Herwig N, Schulz H, Hadian J, Meiners T. Variation of Secondary Metabolite Profile of Zataria multiflora Boiss. Populations Linked to Geographic, Climatic, and Edaphic Factors. Front Plant Sci. 2020;11:969. doi:10.3389/fpls.2020.00969

Chaaban H, Ioannou I, Chebil L, et al. Effect of Heat Processing on Thermal Stability and Antioxidant Activity of Six Flavonoids. J Food Process Preserv. 2017;41(5):e13203. doi:10.1111/jfpp.13203

Sebestyén Z, Jakab E, Badea E, Barta-Rajnai E, Şendrea C, Czégény Zs. Thermal Degradation Study of Vegetable Tannins and Vegetable Tanned Leathers. J Anal Appl Pyrolysis. 2019;138:178-187. doi:10.1016/j.jaap.2018.12.022

Tanod WA, Cahyono E, Rieuwpassa FJ, et al. Enhancing Functional Rice Crackers with Rhizophora mucronata Leaves Origin Sangihe Islands: A Novel Approach to Boost Nutritional and Antioxidant Properties. Adv Food Sci Sustain Agric Agroind Eng (AFSSAAE). 2025;8(4):362-373. doi:10.21776/ub.afssaae.2025.008.04.3

Sibero MT, Sabdono A, Pribadi R, et al. Study of Biomedical Properties of Rhizophora mucronata Fruit from Rembang, Central Java. IOP Conf Ser Earth Environ Sci. 2020;584(1):012001. doi:10.1088/1755-1315/584/1/012001

Hardoko, Suprayitno E, Puspitasari YE, Amalia R. Study of Ripe Rhizophora mucronata Fruit Flour as Functional Food for Antidiabetic. Int Food Res J [Internet]. 2015;22(3):953-959. Available from: https://www.ifrj.upm.edu.my/22%20(03)%202015/(11).pdf

Sadeer NB, Rocchetti G, Senizza B, et al. Untargeted Metabolomic Profiling, Multivariate Analysis and Biological Evaluation of the True Mangrove (Rhizophora mucronata Lam.). Antioxidants. 2019;8(10):489. doi:10.3390/antiox8100489

Mhada M, Metougui ML, El Hazzam K, El Kacimi K, Yasri A. Variations of Saponins, Minerals and Total Phenolic Compounds Due to Processing and Cooking of Quinoa (Chenopodium quinoa Willd.) Seeds. Foods. 2020;9(5):660. doi:10.3390/foods9050660

Yang M, Hou CY, Hsu HY, et al. Enhancing Bioactive Saponin Content of Raphanus sativus Extract by Thermal Processing at Various Conditions. Molecules. 2022;27(23):8125. doi:10.3390/molecules27238125

Vittaya L, Charoendat U, Janyong S, Ui-eng J, Leesakul N. Comparative Analyses of Saponin, Phenolic, and Flavonoid Contents in Various Parts of Rhizophora mucronata and Rhizophora apiculata and Their Growth Inhibition of Aquatic Pathogenic Bacteria. J Appl Pharm Sci. 2022;12(11):111-121. doi:10.7324/JAPS.2022.121113

Vo Q V., Tam NM, Hieu LT, et al. The Antioxidant Activity of Natural Diterpenes: Theoretical Insights. RSC Adv. 2020;10(25):14937-14943. doi:10.1039/D0RA02681F

Hunyadi A. The Mechanism(s) of Action of Antioxidants: From Scavenging Reactive Oxygen/Nitrogen Species to Redox Signaling and The Generation of Bioactive Secondary Metabolites. Med Res Rev. 2019;39(6):2505-2533. doi:10.1002/med.21592

Somjai C, Siriwoharn T, Kulprachakarn K, Chaipoot S, Phongphisutthinant R, Wiriyacharee P. Utilization of Maillard Reaction in Moist-Dry-Heating System to Enhance Physicochemical and Antioxidative Properties of Dried Whole Longan Fruit. Heliyon. 2021;7(5):e07094. doi:10.1016/j.heliyon.2021.e07094

Langner E, Rzeski W. Biological Properties of Melanoidins: A Review. Int J Food Prop. 2014;17(2):344-353. doi:10.1080/10942912.2011.631253

Molina-Cortés A, Quimbaya M, Toro-Gomez A, Tobar-Tosse F. Bioactive Compounds as an Alternative for The Sugarcane Industry: Towards an Integrative Approach. Heliyon. 2023;9(2):e13276. doi:10.1016/j.heliyon.2023.e13276

Sadeer NB, Zengin G, Mahomoodally MF. Biotechnological Applications of Mangrove Plants and Their Isolated Compounds in Medicine-A Mechanistic Overview. Crit Rev Biotechnol. 2023;43(3):393-414. doi:10.1080/07388551.2022.2033682

den Brok MH, Büll C, Wassink M, et al. Saponin-Based Adjuvants Induce Cross-Presentation in Dendritic Cells by Intracellular Lipid Body Formation. Nat Commun. 2016;7(1):13324. doi:10.1038/ncomms13324

Huis in ’t Veld LG, Cornelissen LA, van den Bogaard L, Ansems M, Ho NI, Adema GJ. Saponin-Based Adjuvant Uptake and induction of Antigen Cross-Presentation by CD11b+ Dendritic Cells and Macrophages. NPJ Vaccines. 2025;10(1):15. doi:10.1038/s41541-024-01056-y

Sueyoshi K, Ledderose C, Shen Y, Lee AH, Shapiro NI, Junger WG. Lipopolysaccharide Suppresses T cells by Generating Extracellular ATP that Impairs their Mitochondrial Function via P2Y11 Receptors. J Biol Chem. 2019;294(16):6283-6293. doi:10.1074/jbc.RA118.007188

Ogikubo Y, Norimatsu M, Sasaki Y, Yasuda A, Saegusa J, Tamura Y. Effect of Lipopolysaccharide (LPS) Injection on the Immune Responses of LPS-Sensitive Mice. J Vet Med Sci. 2004;66(10):1189-1193. doi:10.1292/jvms.66.1189

Hematianlarki M, Nimmerjahn F. Immunomodulatory and Anti‐inflammatory Properties of Immunoglobulin G Antibodies. Immunol Rev. 2024;328(1):372-386. doi:10.1111/imr.13404

Wheeler ML, DeFranco AL. Prolonged Production of Reactive Oxygen Species in Response to B Cell Receptor Stimulation Promotes B Cell Activation and Proliferation. J Immunol. 2012;189(9):4405-4416. doi:10.4049/jimmunol.1201433

Lewis ED, Meydani SN, Wu D. Regulatory Role of Vitamin E in The Immune System and Inflammation. IUBMB Life. 2019;71(4):487-494. doi:10.1002/iub.1976

Kilicarslan You D, Fuwad A, Lee KH, et al. Evaluation of the Protective Role of Vitamin E Against ROS-Driven Lipid Oxidation in Model Cell Membranes. Antioxidants. 2024;13(9):1135. doi:10.3390/antiox13091135

Câmara JS, Perestrelo R, Ferreira R, Berenguer C V., Pereira JAM, Castilho PC. Plant-Derived Terpenoids: A Plethora of Bioactive Compounds with Several Health Functions and Industrial Applications—A Comprehensive Overview. Molecules. 2024;29(16):3861. doi:10.3390/molecules29163861

Masyita A, Mustika Sari R, Dwi Astuti A, et al. Terpenes and Terpenoids as Main Bioactive Compounds of Essential Oils, Their Roles in Human Health and Potential Application as Natural Food Preservatives. Food Chem X. 2022;13:1-14. doi:10.1016/j.fochx.2022.100217

Jadon K, Padhi S. Comprehension of the Function of Antioxidants in Targeting Different Signaling Pathways to Cure Oxidative Stress-Induced Hepatotoxicity. Curr Top Med Chem. 2025;25. doi:10.2174/0115680266398364250811231140

Xu L, Yu Y, Sang R, Li J, Ge B, Zhang X. Protective Effects of Taraxasterol against Ethanol‐Induced Liver Injury by Regulating CYP2E1/Nrf2/HO‐1 and NF‐ κ B Signaling Pathways in Mice. Oxid Med Cell Longev. 2018;2018(1):8284107. doi:10.1155/2018/8284107

Jairaman C, Alehaideb ZI, Yacoob SAM, et al. Rhizophora mucronata Lam. (Mangrove) Bark Extract Reduces Ethanol-Induced Liver Cell Death and Oxidative Stress in Swiss Albino Mice: In Vivo and In Silico Studies. Metabolites. 2022;12(11):1021. doi:10.3390/metabo12111021

Thorgersen EB, Barratt‐Due A, Haugaa H, et al. The Role of Complement in Liver Injury, Regeneration, and Transplantation. Hepatology. 2019;70(2):725-736. doi:10.1002/hep.30508

OECD. Test No. 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents. OECD Publishing; 2025. doi:10.1787/9789264070707-en

Downloads

Published

2026-08-07

How to Cite

Mandeno, J. A., Tanod, W. A., Cahyono, E., Riyadi, P. H., Rieuwpassa, F. J., Ansar, N. M. S., … Palawe, J. F. P. (2026). Immunomodulatory and Hepatoprotective Effects of Extract from Coffee-Like Product Derived from Rhizophora mucronata Fruit of Sangihe Islands in LPS-Treated Mice . Journal of Nutrition Explorations, 4(3), 400–429. https://doi.org/10.36568/jone.v4i3.757

Issue

Section

Articles

Most read articles by the same author(s)