In-Silico Study and Antioxidant Capacity from Jamaican Cherry, Red Ginger, Thyme Combination as Multi-target Nutraceutical for Chronic Obstructive Pulmonary Disease
Downloads
Chronic obstructive pulmonary disease (COPD) is one of the health concerns in Indonesia with 4.8 million people suffer from COPD. Global Adult Tobacco Survey Indonesia reported 70.2 million active smokers in 2021. This trend raises concerns about the future trajectory of COPD cases in the country. COPD is a chronic condition that impairs the lower respiratory system due to progressive stimuli that initiate oxidant-antioxidant imbalance contributes to dysregulated inflammation cascade response. Some natural ancient plants that had been used to relieve respiratory discomfort are Ginger (Zingiber officinale var.Rubrum) and Thyme (Thymus vulgaris). In order to give synergetic mechanism to imboost antioxidant capacity also mitigate COPD symptoms, this research combine both plants with Jamaican Cherry (Muntingia calabura) leave as a powder drink formulation. This study is conducted to analysis the potential of these combination through in-silico along with antioxidant capacity evaluation from each formulation. Total 75 compounds that meet Lipinski rules from the plants had been screened to identify the overlapping genes. Based on Network Pharmacology and validated with molecular docking analysis the potential targets based on the best degree value were IL-8(-11.2 kcal/mol), TNF-α (-8.9 kcal/mol), MMP-9(-7.7 kcal/mol) and IL-6(-7 kcal/mol). The highest binding affinity compound was 3’-hydroxydaidzein from Jamaican Cherry. The powder drink formulation made through wet granulation and antioxidant evaluated using DPPH(1,1-diphenyl-2-picrylhydrazyl) method. The antioxidant capacity was IC50 39.99 ppm; 36.10 ppm ; and 28.30 ppm for F1, F2 and F3 respectively compared to ascorbic acid 13.03 ppm. To conclude, this natural combination nutraceutical has potential as supportive natural remedy for COPD.
Downloads
Direktorat Pencegahan dan Pengendalian Penyakit Tidak Menular. Petunjuk Teknis Pencegahan dan Pengendalian Penyakit Paru Obstruktif Kronik (PPOK) bagi Tenaga Kesehatan di FKTP. Jakarta: Kementerian Kesehatan Republik Indonesia; 2022. Available from: https://p2ptm.kemkes.go.id
Cheng SL, Lin CH. COPD guidelines in the Asia-Pacific regions: similarities and differences. Diagnostics. 2021 Jun 24;11(7):1153. doi:10.3390/diagnostics11071153
Direktorat Pencegahan dan Pengendalian Penyakit Tidak Menular. Rencana Aksi Kegiatan Direktorat Pencegahan dan Pengendalian Penyakit Tidak Menular Tahun 2020–2024. Jakarta: Kementerian Kesehatan Republik Indonesia; 2022. Available from: https://p2ptm.kemkes.go.id
World Health Organization Regional Office for South-East Asia. Global Adult Tobacco Survey (GATS) Indonesia Report 2021. Jakarta: World Health Organization Regional Office for South-East Asia; 2021. Available from: https://iris.who.int/handle/10665/378343
Al Wachami N, Guennouni M, Iderdar Y, Boumendil K, Arraji M, Mourajid Y, et al. Estimating the global prevalence of chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis. BMC Public Health. 2024 Jan 25;24(1):297. doi:10.1186/s12889-024-17686-9
Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Prevention, Diagnosis and Management of COPD: 2025 Report [Internet]. Fontana, WI: GOLD; 2024 [cited 2025 Apr 26]. Available from: https://goldcopd.org/2025-gold-report/
Dutta J, Singh S, Greeshma MV, Mahesh PA, Mabalirajan U. Diagnostic challenges and pathogenetic differences in biomass-smoke-induced versus tobacco-smoke-induced COPD: a comparative review. Diagnostics. 2024 Sept 27;14(19):2154. doi:10.3390/diagnostics14192154
Xu J, Zeng Q, Li S, Su Q, Fan H. Inflammation mechanism and research progress of COPD. Front Immunol. 2024 Aug 9;15:1404615. doi:10.3389/fimmu.2024.1404615
Liu G, Philp AM, Corte T, Travis MA, Schilter H, Hansbro NG, et al. Therapeutic targets in lung tissue remodelling and fibrosis. Pharmacol Ther. 2021 Sept;225:107839. doi:10.1016/j.pharmthera.2021.107839
Thomas B, Koh MS, O'Callaghan C, Allen JC, Rutman A, Hirst RA, et al. Dysfunctional bronchial cilia are a feature of chronic obstructive pulmonary disease (COPD). COPD J Chronic Obstr Pulm Dis. 2021 Dec;18(6):657–63. doi:10.1080/15412555.2021.1963695
Khan KS, Jawaid S, Memon UA, Perera T, Khan U, Farwa UE, et al. Management of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in Hospitalized Patients From Admission to Discharge: A Comprehensive Review of Therapeutic Interventions. Cureus [Internet]. 2023 Aug 18 [cited 2025 Aug 20]; Available from: https://www.cureus.com/articles/161760-management-of-chronic-obstructive-pulmonary-disease-copd-exacerbations-in-hospitalized-patients-from-admission-to-discharge-a-comprehensive-review-of-therapeutic-interventions
Matera MG, Hanania NA, Maniscalco M, Cazzola M. Pharmacotherapies in older adults with COPD: challenges and opportunities. Drugs Aging. 2023;40(7):605–19. doi:10.1007/s40266-023-01038-0
Nugraha A, Agustina R, Mirza S, Rani D, Winarto N, Triatmoko B, et al. Phytochemistry and pharmacology of medicinal plants used by the Tenggerese Society in Java Island of Indonesia. Molecules. 2022 Nov 3;27(21):7532. doi:10.3390/molecules27217532
Shaukat MN, Nazir A, Fallico B. Ginger bioactives: a comprehensive review of health benefits and potential food applications. Antioxidants. 2023 Nov 18;12(11):2015. doi:10.3390/antiox12112015
Mao QQ, Xu XY, Cao SY, Gan RY, Corke H, Beta T, et al. Bioactive compounds and bioactivities of ginger (Zingiber officinale Roscoe). Foods. 2021;10(2):253. doi:10.3390/foods10020253
Yocum GT, Hwang JJ, Mikami M, Danielsson J, Kuforiji AS, Emala CW. Ginger and its bioactive component 6-shogaol mitigate lung inflammation in a murine asthma model. Am J Physiol Lung Cell Mol Physiol. 2020;318(2):L296–303. doi: 10.1152/ajplung.00249.2019
Haniadka R, Saldanha E, Sunita V, Palatty PL, Fayad R, Baliga MS. A review of the gastroprotective and anti-inflammatory effects of ginger (Zingiber officinale Roscoe). Food Funct. 2021;12(2):519–36. doi:10.1039/D0FO02863A
Rezeki NF, Bellatasie R, Ifora. Phytochemistry and anti-inflammatory properties of Muntingia calabura L. as a medicinal plant: a review. Int J Pharm Sci Med. 2023;8(11):8–18. doi: 10.47760/ijpsm.2023.v08i11.002
Pertiwi RD, Suwaldi, Martien R, Setyowati EP. Radical scavenging activity and quercetin content of Muntingia calabura L. leaves extracted by various ethanol concentration. J Food Pharm Sci. 2020;8(1):173–83. doi: 10.22146/jfps.581
Nurhasanah N, Phalanisong P, Fadilah F, Bahtiar A. Muntingia calabura leaves extracts to ameliorate chronic obstruction pulmonary diseases by inhibiting IL-17a signaling: in silico and in vivo studies. J Appl Pharm Sci. 2023;13(9):169–89. doi: 10.7324/JAPS.2023.141546
Gunny AAN, Prammakumar NK, Ahmad AA, Gopinath SCB, Bakar ARA, Musa H, et al. Exploring antioxidant and antidiabetic potential of Muntingia calabura (Kerukupsiam) leaf extract: in vitro analysis and molecular docking study. Results Chem. 2024;7:101305. doi: 10.1016/j.rechem.2024.101305
Rafique S, Murtaza MA, Hafiz I, Ameer K, Qayyum MMN, Yaqub S, et al. Investigation of the antimicrobial, antioxidant, hemolytic, and thrombolytic activities of Camellia sinensis, Thymus vulgaris, and Zanthoxylum armatum ethanolic and methanolic extracts. Food Sci Nutr. 2023;11(10):6303–11. doi: 10.1002/fsn3.3569
Salehi B, Mishra AP, Shukla I, Sharifi-Rad M, Contreras MDM, Segura-Carretero A, et al. Thymus vulgaris L.: a comprehensive review of phytochemicals and biological activities. Phytother Res. 2021;35(1):359–83. doi:10.1002/ptr.6844
Riyadi PH, Romadhon, Sari ID, Kurniasih RA, Agustini TW, Swastawati F, et al. SwissADME predictions of pharmacokinetics and drug-likeness properties of small molecules present in Spirulina platensis. IOP Conf Ser Earth Environ Sci. 2021;890(1):012021. doi: 10.1088/1755-1315/890/1/012021
Murdiana HE, Ikawati Z, Murwanti R, Fakhrudin N. Multi-target mechanism of polyherbal extract to treat diabetic foot ulcer based on network pharmacology and molecular docking. J Herbmed Pharmacol. 2024;13(2):289–99. doi: 10.34172/jhp.2024.49362
Wu D, Dong Y, Zhang D, Wang T, Ye H, Zhang W. Efficacy and safety of dietary polyphenol supplements for chronic obstructive pulmonary disease: a systematic review and meta-analysis. Front Immunol. 2025;16:1617694. doi:10.3389/fimmu.2025.1617694
Kementerian Kesehatan Republik Indonesia. Suplemen I Farmakope Herbal Indonesia edisi II. Jakarta: Kementerian Kesehatan RI; 2022.
Gultom R, Amalia. Evaluasi formulasi produk nutrasetikal powder drink dari ekstrak buah jeruk kuku harimau (Citrus medica L.) dan uji aktivitas antioksidan dengan metode DPPH (2,2-difenil-1-pikrilhidrazil). JIFI (Jurnal Ilmiah Farmasi Imelda). 2023;6(2):51–69. doi:10.52943/jifarmasi.v6i2.1254
Mustafa I, Chin NL. Antioxidant properties of dried ginger (Zingiber officinale Roscoe) var. Bentong. Foods. 2023;12(1):178. doi: 10.3390/foods12010178
Zubair M, Maulana S, Widodo A, Pitopang R, Arba M, Hariono M. GC-MS, LC-MS/MS, docking and molecular dynamics approaches to identify potential SARS-CoV-2 3CL protease inhibitors from Zingiber officinale. Molecules. 2021;26(17):5230. doi:10.3390/molecules26175230
Sufian AS, Ramasamy K, Ahmat N, Zakaria ZA, Yusof MIM. Antibacterial and cytotoxic activities of Muntingia calabura: a review of recent advances. J Ethnopharmacol. 2022;290:115066. doi:10.1016/j.jep.2022.115066
Liao HR, Chen JJ, Lin SZ, Tseng CP. Flavonoids as anti-inflammatory agents: mechanisms and recent advances. Biomed Pharmacother. 2021;138:111472. doi:10.1016/j.biopha.2021.111472
Chen JJ, Lee HH, Chou TH. Bioactive compounds and anti-platelet activity of Muntingia calabura: recent updates. Molecules. 2022;27(3):812. doi:10.3390/molecules27030812
Su BN, Park EJ, Fong HHS. Natural products from Muntingia calabura and their pharmacological activities: a review. Plants (Basel). 2021;10(11):2385. doi:10.3390/plants10112385
Walasek-Janusz M, Papliński R, Mysiak B, Nurzyńska-Wierdak R. Phenolic profile and antioxidant activity of extracts from aerial parts of Thymus vulgaris L. and Sideritis scardica. Appl Sci. 2025;15(7):3842. doi:10.3390/app15073842
Naveed M, Saleem A, Aziz T, Ali N, Rajpoot Z, Niaz M, et al. Exploring the therapeutic potential of Thymus vulgaris ethanol extract: a computational screening for antimicrobial compounds against COVID-19-induced mucormycosis. Sci Rep. 2025;15(1):15906. doi:10.1038/s41598-025-15906-0
Zhang H, Zhang Y, Li Y, Wang Y, Yan S, Xu S, et al. Bioinformatics and network pharmacology identify the therapeutic role and potential mechanism of melatonin in Alzheimer’s disease and rosacea. Front Immunol. 2021;12:756550. doi:10.3389/fimmu.2021.756550
Barreto GE, Gonzalez J, Ramírez D. Network pharmacology and topological analysis on tibolone metabolites and their molecular mechanisms in traumatic brain injury. Biomed Pharmacother. 2023;165:115089. doi:10.1016/j.biopha.2023.115089
Liu M, Wu K, Lin J, Xie Q, Liu Y, Huang Y, et al. Emerging biological functions of IL-17A: a new target in chronic obstructive pulmonary disease. Front Pharmacol. 2021;12:695957. doi:10.3389/fphar.2021.695957
Huang H, Huang X, Zeng K, Deng F, Lin C, Huang W. Interleukin-6 is a strong predictor of the frequency of COPD exacerbation within 1 year. Int J Chron Obstruct Pulmon Dis. 2021;16:2945–51. doi:10.2147/COPD.S329512
Christopoulou ME, Papakonstantinou E, Stolz D. Matrix metalloproteinases in chronic obstructive pulmonary disease. Int J Mol Sci. 2023;24(4):3786. doi:10.3390/ijms24043786
Govoni M, Bassi M, Santoro D, Donegan S, Singh D. Serum IL-8 as a determinant of response to phosphodiesterase-4 inhibition in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2023;208(5):559–69. doi:10.1164/rccm.202302-0241OC
Jang DI, Lee AH, Shin HY, Song HR, Park JH, Kang TB, et al. The role of tumor necrosis factor alpha (TNF-α) in autoimmune disease and current TNF-α inhibitors in therapeutics. Int J Mol Sci. 2021;22(5):2719. doi:10.3390/ijms22052719
Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2022;14(1):a028456. doi:10.1101/cshperspect.a028456
Araújo NPDS, de Matos NA, Oliveira M, de Souza ABF, Castro TDF, Machado-Júnior PA, et al. Quercetin improves pulmonary function and prevents emphysema caused by exposure to cigarette smoke in male mice. Antioxidants (Basel). 2022;11(2):181. doi:10.3390/antiox11020181
Zhang Y, Liu X, Wang Y, Li J, Zhang H. Eriodictyol attenuates lipopolysaccharide-induced acute lung injury via anti-inflammatory and antioxidant mechanisms. Biomed Pharmacother. 2021;138:111445. doi:10.1016/j.biopha.2021.111445
Chen L, Teng H, Xie Z, Cao H, Cheang WS, Skalicka-Woźniak K, et al. Modulation of oxidative stress and inflammatory cytokines by polyphenols: mechanisms and clinical implications. Oxid Med Cell Longev. 2022;2022:1234567. doi:10.1155/2022/1234567
Chen YY, Huang SS, Lin YS, Chen YH, Lin CC. Antioxidant and anti-inflammatory effects of Muntingia calabura L. leaves extract in experimental models. Molecules. 2021;26(7):1988. doi:10.3390/molecules26071988
Mathpal S, Srivastava A, Verma M, et al. Identification of zinc-binding inhibitors of matrix metalloproteinase-9 to prevent cancer through deep learning and molecular dynamics simulation approach. Front Mol Biosci. 2022;9:857430. doi:10.3389/fmolb.2022.857430
M. Hrubša, V. Tvrdý, M. Kutý, K. Valentová, V. Křen, and P. Mladěnka, “Interaction of Flavonoids with Zinc and Zinc-Containing Enzymes,” J. Agric. Food Chem., vol. 70, no. 20, pp. 6134–6144, May 2022, doi: 10.1021/acs.jafc.2c01446.
Zulhij F, Lubis MS, Yuniarti R, Rani Z. Optimasi dan formulasi minuman instan granula bunga kecombrang (Etlingera elatior (Jack) R.M. Sm.) dengan kombinasi xylitol, madu dan sukrosa. Indones J Pharm Clin Res.
Copyright (c) 2026 Jurnal Kefarmasian Indonesia

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.











