Evaluation of Ophiocephalus striatus, Citrus sinensis (Fructus), and Curcuma domestica (Rhizoma) for Hypoalbuminemia Used Network Pharmacology

Tri Diana Puspita Rini, Yusril Izzamaulana, Rofiudin Ahmad, Sulistyaningsih Sulistyaningsih, Sri Suwarni

Abstract


Hypoalbuminemia is a clinical condition defined by serum albumin levels below 3.5 g/dL and is associated with poor health outcomes. Natural products such as snakehead fish (Ophiocephalus striatus), Citrus sinensis (fructus), and Curcuma domestica(rhizoma) have traditionally been used to improve albumin levels; however, their molecular mechanisms remain unclear. This study aimed to elucidate the pharmacological mechanisms of active compounds from these sources in the context of hypoalbuminemia using a network pharmacology approach. Active compounds were identified through the Knapsack database and literature, with molecular structures obtained from PubChem. ADMET and drug-likeness properties were evaluated using SwissADME. Target prediction was performed using SwissTargetPrediction and GeneCards, and overlapping targets were identified with Venny 2.1.0. Protein–protein interaction networks were constructed using STRING-DB and visualized with Cytoscape, followed by GO and KEGG pathway enrichment analyses. A total of 17 compounds from O. striatus, 7 from C. sinensis, and 7 from C. domestica were identified, of which 17, 4, and 7 compounds, respectively, met Lipinski’s criteria. Intersection analysis revealed 41, 74, and 45 hypoalbuminemia-related targets. Enrichment analysis indicated involvement in pathways such as the renin–angiotensin system, colorectal cancer signaling, and EGFR tyrosine kinase inhibitor resistance, which are implicated in hepatic albumin regulation.


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Moramarco, Stefania., et al. (2020). Epidemiology of Hypoalbuminemia in Hospitalized Patients: A Clinical Matter or an Emerging Public Health Problem?Nutrients MDPI Journal, 12 (3656): 1-15.

Wahyuni, D., Van Der Kooy, F., Klinkhamer, P., Verpoorte, R., Leiss, K. (2013). The Use of Bio-Guided Fractionation to Explore the Use of Leftover Biomass in Dutch Flower Bulb Production as Alleloc he m ica ls against W eeds. Molecules 18. 4510–4525. 10.3390/molecules18044510

Evi, R., & Ika, S. (2013). Manfaat Albumin pada Penderita Hipoalbuminemia dan Penyembuhan Pasca Operasi. Jurnal Kesehatan dan Kedokteran, 5(2), 112-120.

Ferry Erdani et al. 2022. Perbandingan Efektivitas Terapi Ekstrak Ikan Gabus Dengan Putih Telur Dan Human Albumin 20% Terhadap Peningkatan Kadar Albumin Pasien Hipoalbuminemia Di RSUD dr. Zainoel Abidin. Journal of Medical Science. 2, 2 (Mar. 2022), 123–129. DOI:https://doi.org/10.55572/jms.v2i2.49.

Mulyana, R, et al. 2017. The Effect of Ophiocephalus striatus Extract on The Levels of igf- 1 and Albumin in Elderly Patients With Hypoalbuminemia. The Indonesian Journal of Internal Medicine, Vol. 49 (4): 324-329

Khairunnisa, J., Rahman, M., & Ahadi, R. (2021). Korelasi Suhu Terhadap Aktivitas bekicot (Achatina fulica) Di Kawasan Kampus UIN AR-RANIRY Banda Aceh. Prosiding Seminar Nasional Biotik, 3(6), 83–85.

Zuraini A, Somchit MN, Solihah MH, et al. (2016). Fatty Acid and Amino Acid Composition of Three Local Malaysian Channa spp. Fish Food Chem 97: 674 - 678.

Wu XM, Wu CF. Network pharmacology: a new approach to unveiling Traditional Chinese Medicine. Chin J Nat Med. 2015 Jan;13(1):1-2. doi: 10.1016/S1875-5364(15)60001-2. PMID: 25660283.

Jeyabaskar Suganya, G. Rajesh Kumar, Mahendran Radha, Sagolsem Mandaly Devi. A Computational approach in identifying the herbal compounds as Lactation inducer. Research Journal of Pharmacy and Technology. 2022; 15(8):3345-0. doi: 10.52711/0974-360X.2022.00559

Rangga Adhi Prastika, Suhailah Hayaza, Azka Muhammad Nurrahman, Raden Joko Kuncoroningrat Susilo. Research Journal of Pharmacy and Technology. 2025;18(9):4215-4. doi: 10.52711/0974-360X.2025.00606

Tri Diana Puspita Rini, Frangky Sangande, Kurnia Agustini, Anton Bahtiar. Identification and Analysis of Ardisia humilis as Potential Antihyperlipidemic by Network Pharmacology Followed by Molecular Docking. Research Journal of Pharmacy and Technology. 2024; 17(5):2009-7. doi: 10.52711/0974-360X.2024.00318

Zeena Fernandes, Dattatreya K S, Sahana D Kulkarni. Integration of the Computational Tools to Decode the Mode of Action of Citrus limon against Alzheimer’s Disease. Research Journal of Pharmacy and Technology. 2024; 17(6):2863-8. doi: 10.52711/0974-360X.2024.00449

Shweta Padher, Vinayak Walhekar, Ravindra Kulkarni, Varsha Pokharkar. Computational based in-silico and molecular docking approach for screening of phyto-constituents on PPAR targets in the treatment of NAFLD. Research Journal of Pharmacy and Technology. 2025;18(1):232-8. doi: 10.52711/0974-360X.2025.00036

Aisyah, Marselina Irasonia Tan, Azzania Fibriani. Molecular Docking Study of Natural Compounds from Indonesian Medicinal plants as AKT and KRAS G12D Inhibitors Candidates. Research Journal of Pharmacy and Technology. 2024; 17(8):3777-5. doi: 10.52711/0974-360X.2024.00587

Subhan Rullyansyah, Idha Kusumawati, Djoko Agus Purwanto. Molecular Docking and Secondary Metabolite ADMET Studies from Curcuma longa Linn. as an Antithrombotic. Research Journal of Pharmacy and Technology. 2025;18(1):152-8. doi: 10.52711/0974-360X.2025.00023

Fenita Shoviantari, Tristiana Erawati Munandar, Widji Soeratri, Mahardian Rahmadi, Inayah Dian Wulandari. Molecular Docking Anti Melanogenesis Activity of Anthocyanins from Butterfly Pea (Clitoria ternatea) Flower Water Extract. Research Journal of Pharmacy and Technology. 2025;18(5):2043-8. doi: 10.52711/0974-360X.2025.00292

Pires DE, Blundell TL, Ascher DB. (2015). pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity-Properties Using Graph-Based Signatures. J Med Chem, 58(9): 4066-4072.

Daina, A. (2017). SwissADME: a free web tool to evaluate ADME properties of small molecules. Scientific reports, 7(1), 42717.

Daina A, Michielin O, Zoete V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019 Jul 2;47(W1):W357-W364. doi: 10.1093/nar/gkz382. PMID: 31106366; PMCID: PMC6602486.

Farahani, Farzad & Karwowski, Waldemar & Lighthall, Nichole. (2019). Application of Graph Theory for Identifying Connectivity Patterns in Human Brain Networks: A Systematic Review. Frontiers in Neuroscience. 13. 585. 10.3389/fnins.2019.00585.

Akter, Most Shornale & Uddin, Md Helal & Rahman, Sheikh & Hossain, Md & Ashik, Md. Ashiqur & Zaman, Nurun & Faruk, Omar & Hossain, M Sanwar & Parvin, Anzana & Rahman, Md Habibur. (2024). Transcriptomic analysis revealed potential regulatory biomarkers and repurposable drugs for breast cancer treatment. Cancer Reports. 7. 10.1002/cnr2.2009.

Brosnihan, K.B., Neves, L.A., & Chappell, M.C. (2005). Does the angiotensin-converting enzyme (ACE)/ACE2 balance contribute to the fate of angiotensin peptides in programmed hypertension? Hypertension, 46 5, 1097-9 .

Wiedermann CJ, Wiedermann W, Joannidis M. Causal relationship between hypoalbuminemia and acute kidney injury. World J Nephrol 2017; 6(4): 176-187 PMID: 28729966 DOI: 10.5527/wjn.v6.i4.176

Chojkier, M. (2005). Inhibition of albumin synthesis in chronic diseases: molecular mechanisms. Journal of clinical gastroenterology, 39 4 Suppl 2, S143-6

Manning, B.D., & Cantley, L.C. (2007). AKT/PKB Signaling: Navigating Downstream. Cell, 129, 1261-1274. https://doi.org/10.1016/j.cell.2007.06.009

Liao, Y., & Hung, M. (2010). Physiological regulation of Akt activity and stability. American journal of translational research, 2 1, 19-42 .

Sianipar I. R., Andraini T., Santoso D. I. S., Ujianti, I., Antoni M. (2021). Ekspresi Protein FoxO1 dan Gen Glukosa 6 Fosfatase pada Tikus dengan Diet Restriksi Vitamin B12. J Kdokt Meditek, 28(2), 133–140.

Don, B.R., & Kaysen, G.A. (2004). Poor Nutritional Status And Inflammation: Serum Albumin: Relationship to Inflammation and Nutrition. Seminars in Dialysis, 17. https://doi.org/10.1111/j.0894-0959.2004.17603.x

Christina, N.M., Tjahyanto, T., Lie, J., Santoso, T.A., Albertus, H., Octavianus, D., Putri, D.A., Andrew, J.L., Jatinugroho, Y.D., Shiady, C., & Wijaya, J.H. (2023). Hypoalbuminemia and colorectal cancer patients: Any correlation?: A systematic review and meta-analysis. Medicine, 102. https://doi.org/10.1097/MD.0000000000032938

Wijaya, J.H., & Wong, E. (2021). 410P Preoperative hypoalbuminemia is associated with poor postoperative outcome in colorectal cancer patients: A systematic review and meta-analysis. Annals of Oncology. https://doi.org/10.1016/j.annonc.2021.08.931

Stares M, Swan A, Cumming K, Ding T-E, Leach J, Stratton C, Thomson F, Barrie C, MacLennan K, Campbell S, Evans T, Tufail A, Harrow S, MacKean M and Phillips I (2021) Hypoalbuminaemia as a Prognostic Biomarker of First-Line Treatment Resistance in Metastatic Non-small Cell Lung Cancer. Front. Nutr. 8:734735. https://doi.org/10.3389/fnut.2021.734735

Khalid, M.; Petroianu, G.; Adem, A. Advanced Glycation End Products and Diabetes Mellitus: Mechanisms and Perspectives. Biomolecules 2022, 12, 542. https:// doi.org/10.3390/biom12040542https://doi.org/10.3390/biom12040542

Zhao, jia; Randive, R.; Stewart, JA.(2014). Molecular Mechanism of AGE/RAGE-mediated fibrosis ini the diabetic heart. World J Diabeter. December 15; 5(6): 860-867. ISSN 1948-9358 https://doi.org/10.4239/wjd.v5.i6.860

Hudson, Barry I. and Lippan, Marc E. (2018). Targeting RAGE Signaling in Inflammatory Disease. Annual Review of Medicine. 69:349-64 https://doi.org/10.1146/annurev-med-041316-085215

Moshage, H., Janssen, J.A., Franssen, J.H., Hafkenscheid, J.C., & Yap, S.H. (1987). Study of the molecular mechanism of decreased liver synthesis of albumin in inflammation. The Journal of clinical investigation, 79 6, 1635-41 . https://doi.org/10.1172/JCI113000

Artigas, A., Wernerman, J., Arroyo, V., Vincent, J., & Levy, M.M. (2016). Role of albumin in diseases associated with severe systemic inflammation: Pathophysiologic and clinical evidence in sepsis and in decompensated cirrhosis. Journal of critical care, 33, 62-70 . https://doi.org/10.1016/j.jcrc.2015.12.019

Khalid, M.; Petroianu, G.; Adem, A. Advanced Glycation End Products and Diabetes Mellitus: Mechanisms and Perspectives. Biomolecules 2022, 12, 542. https:// doi.org/10.3390/biom12040542

Lee, M.R. (1981). The renin/angiotensin system. British journal of clinical pharmacology, 12 5, 605-12 . https://doi.org/10.1111/J.1365-2125.1981.TB01278.X

Hilgers, K.F., & Mann, J.F. (1996). Role of angiotensin II in glomerular injury: lessons from experimental and clinical studies. Kidney & blood pressure research, 19 5, 254-62 . https://doi.org/10.1159/000174085

Gansevoort, R.T., Zeeuw, D., & Jong, D.P. (1996). ACE inhibitors and proteinuria. Pharmacy World and Science, 18, 204-210. https://doi.org/10.1007/BF00735961

Shaiba, R. Al; McMillan, DC.; Angerson, WJ.; Leen, E.; McArdle, CS.; Horgan, P. 2004. The relationship between hypoalbuminaemia, tumour volume and the systemic inflammatory response in patients with colorectal liver metastases. British Journal of Cancer. https://doi.org/10.1038/sj.bjc.6601886

Ceciliani, F., Giordano, A., & Spagnolo, V. (2002). The systemic reaction during inflammation: the acute-phase proteins. Protein and peptide letters, 9 3, 211-23 . https://doi.org/10.2174/0929866023408779

Kaufmann, T., and Jost, P., 2010. Cancer coused by too apoptosis- An intriguing contradiction?. Hepatology. Vol. 51, No. 4. https://doi.org/10.1002/hep.23514

Inarah Fajriaty, Siti Nani Nurbaeti, Hariyanto IH, Hadi Kurniawan, Fajar Nugraha, Rizki Kurnia Agus Putra. Effectiveness of Tengkawang Fruit Extract (Shorea stenoptera Burck), Virgin Coconut Oil and Astaxanthin to Albumin, Total Protein and Hemoglobin in Malnourished Animal Model as Antistunting Supplement. Research Journal of Pharmacy and Technology.2025;18(2):585-3. doi: 10.52711/0974-360X.2025.00087

Sabilia, Maria and Komposch, K., 2015. EGFR Signaling in Liver Disease. International Journal of Molecular Sciences. Vol. 17.30.https://doi.org/10.3390/ijms17010030.

Moshage, H., Janssen, J.A., Franssen, J.H., Hafkenscheid, J.C., & Yap, S.H. (1987). Study of the molecular mechanism of decreased liver synthesis of albumin in inflammation. The Journal of clinical investigation, 79 6, 1635-41 . . https://doi.org/10.1172/JCI113000.

Suganya, J., T, V., Radha, M., and Marimuthu, N. In silico Molecular Docking studies to investigate interactions of natural Camptothecin molecules with diabetic enzymes. Research Journal of Pharmacy and Technology. 2017; 10(9), 2917–2922.


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