Abstract
We analyzed here the in silico biological activities of caffeine, (+)-catechin, and theobromine. For this, the PubChem database of the NIH (National Institutes of Health) was used to obtain the SMILE canonical form of the bioactive molecules, and the free software PASS Online (Prediction of Activity Spectra for Substances) from the Way2Drug portal. Also, we conducted an in vitro experiment using a chronic myeloid leukemia (CML) cell line (K562) to confirm some results found in in silico investigation. These cells were exposed to different concentrations of caffeine, (+)-catechin, and theobromine for 72 h. The results found in this in silico study suggested that caffeine, (+)-catechin, and theobromine showed excellent biological properties, such as antioxidant, anti-inflammatory, and anticarcinogenic, as well as protection against cardiovascular, diabetes, neurological, allergic, respiratory, and other therapeutic activities. These findings can be elucidated through the modulation exerted by these bioactive molecules in many biochemical pathways involved in organism homeostasis, such as free radical scavenger action, oxidoreductase inhibitor, membrane permeability inhibitor, and lipid peroxidase inhibitor. In addition, we have found here that caffeine, (+)-catechin, and theobromine have a remarkable anti-inflammatory activity which plays an important role in the therapeutic approach of COVID-19. Moreover, our in vitro findings confirmed the in silico results regarding anticancer activity since these molecules reduce cell proliferation at all tested concentrations. Therefore, since these molecules exhibit important medicinal activities, further investigations should be conducted to reveal new therapies to improve the treatments and prevention of numerous disorders and, consequently, promote human health.
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References
Almasi F, Dang W, Mohammadipanah F, Li N (2022) Neurological disorders of COVID-19: insights to applications of natural products from plants and microorganisms. Arch Pharmacal Res. https://doi.org/10.1007/s12272-022-01420-
Amer MG, Mazen NF, Mohamed AM (2017) Caffeine intake decreases oxidative stress and inflammatory biomarkers in experimental liver diseases induced by thioacetamide: biochemical and histological study. Int J Immunopathol Pharmacol 30(1):13–24. https://doi.org/10.1177/0394632017694898
Arif MN (2020) Catechin derivatives as inhibitor of COVID-19 main protease (Mpro): molecular docking studies unveil an opportunity against CORONA. Comb Chem High Throughput Screening 25(1):197–203. https://doi.org/10.2174/1871520620666201123101002
Bae J, Kim N, Shin Y, Kim S-Y, Kim Y-J (2020) Activity of catechins and their applications. Biomed Dermatol. https://doi.org/10.1186/s41702-020-0057-8
Bhat JA, Kumar M (2022) Neuroprotective Effects of Theobromine in permanent bilateral common carotid artery occlusion rat model of cerebral hypoperfusion. Metab Brain Dis 37(6):1787–1801. https://doi.org/10.1007/s11011-022-00995-6
Cadoná FC, Rosa JL, Schneider T, Cubillos-Rojas M, Sánchez-Tena S, Azzolin VF, da Cruz IBM (2017) Guaraná, a highly caffeinated food, presents in vitro antitumor activity in colorectal and breast cancer cell lines by inhibiting AKT/mTOR/S6K and MAPKs pathways. Nutr Cancer 69(5):800–810. https://doi.org/10.1080/01635581.2017.1324994
Cadoná FC, Dantas RF, de Mello GH, Silva-Jr FP (2021) Natural products targeting into cancer hallmarks: an update on caffeine, theobromine, and (+)-catechin. Crit Rev Food Sci Nutr. https://doi.org/10.1080/10408398.2021.1913091
Chen XQ, Hu T, Han Y, Huang W, Yuan HB, Zhang YT, Jiang YW (2016) Preventive effects of catechins on cardiovascular disease. Molecules. https://doi.org/10.3390/molecules21121759
Demir EO, Demirtaş CY, Paşaoğlu ÖT (2016) Ratlarda böbrek antioksidan aktivitesi üzerine kafeinin etkileri. Turk J Biochem 41(3):216–222. https://doi.org/10.1515/tjb-2016-0032
Dutra RC, Campos MM, Santos ARS, Calixto JB (2016) Medicinal plants in Brazil: pharmacological studies, drug discovery, challenges and perspectives. Pharmacol Res. https://doi.org/10.1016/j.phrs.2016.01.021
Eissa IH, Yousef RG, Elkaeed EB, Alsfouk AA, Husein DZ, Ibrahim IM, Metwaly AM (2023) Anticancer derivative of the natural alkaloid, theobromine, inhibiting EGFR protein: computer-aided drug discovery approach. PLoS ONE. https://doi.org/10.1371/journal.pone.0282586
Fikrika H, Ambarsari L, Sumaryada T (2016) Molecular docking studies of catechin and its derivatives as anti-bacterial inhibitor for glucosamine-6-phosphate synthase. IOP Conf Ser: Earth Environ Sci. https://doi.org/10.1088/1755-1315/31/1/012009
Filippini T, Malavolti M, Borrelli F, Izzo AA, Fairweather-Tait SJ, Horneber M, Vinceti M (2020) Green tea (Camellia sinensis) for the prevention of cancer. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD005004.pub3
Gajalakshmi D, Kavitha E (2022) Caffeine docking studies with keratin: implications for its cosmetic applications. Mater Today: Proc 69:1408–1412. https://doi.org/10.1016/j.matpr.2022.09.206
Grosso G, Godos J, Galvano F, Giovannucci EL (2017) Coffee, caffeine, and health outcomes: an umbrella. Review. https://doi.org/10.1146/annurev-nutr-071816
Halberstein RA (2005) Medicinal plants: historical and cross-cultural usage patterns. Ann Epidemiol 15(9):686–699. https://doi.org/10.1016/j.annepidem.2005.02.004
Isemura M (2019) Catechin in human health and disease. Molecules. https://doi.org/10.3390/molecules24030528
Jang YJ, Koo HJ, Sohn EH, Kang SC, Rhee DK, Pyo S (2015) Theobromine inhibits differentiation of 3T3-L1 cells during the early stage of adipogenesis via AMPK and MAPK signaling pathways. Food Funct 6(7):2365–2374. https://doi.org/10.1039/c5fo00397k
Kang P, Liao M, Wester MR, Leeder JS, Pearce RE (2010) NIH public access. Ratio 36(3):490–499. https://doi.org/10.1124/dmd.107.016501.CYP3A4-Mediated
Kolahdouzan M, Hamadeh MJ (2017) The neuroprotective effects of caffeine in neurodegenerative diseases. CNS Neurosci Therap. https://doi.org/10.1111/cns.12684
Kovács EG, Alatshan A, Budai MM, Czimmerer Z, Bíró E, Benkő S (2021) Caffeine has different immunomodulatory effect on the cytokine expression and nlrp3 inflammasome function in various human macrophage subpopulations. Nutrients. https://doi.org/10.3390/nu13072409
Ladio AH, Acosta M (2019) Urban medicinal plant use: do migrant and non-migrant populations have similar hybridisation processes? J Ethnopharmacol. https://doi.org/10.1016/j.jep.2019.01.013
Langeder J, Grienke U, Chen Y, Kirchmair J, Schmidtke M, Rollinger JM (2020) Natural products against acute respiratory infections: strategies and lessons learned. J Ethnopharmacol. https://doi.org/10.1016/j.jep.2019.112298
Martínez-Pinilla E, Oñatibia-Astibia A, Franco R (2015) The relevance of theobromine for the beneficial effects of cocoa consumption. Front Pharmacol. https://doi.org/10.3389/fphar.2015.00030
Mazumder A, Cerella C, Diederich M (2018) Natural scaffolds in anticancer therapy and precision medicine. Biotechnol Adv. https://doi.org/10.1016/j.biotechadv.2018.04.009
Monji F, Siddiquee A, Hashemian F (2020) Potential role of methylxanthines as an adjuvant to COVID-19 treatment: a review of pentoxifylline and caffeine as the case of any port in the storm. Authorea. https://doi.org/10.22541/au.159015270.02586731
Montazersaheb S, Hosseiniyan Khatibi SM, Hejazi MS, Tarhriz V, Farjami A, Ghasemian Sorbeni F, Ghasemnejad T (2022) COVID-19 infection: an overview on cytokine storm and related interventions. Virol J. https://doi.org/10.1186/s12985-022-01814-1
Monteiro J, Alves MG, Oliveira PF, Silva BM (2019) Pharmacological potential of methylxanthines: Retrospective analysis and future expectations. Crit Rev Food Sci Nutr. https://doi.org/10.1080/10408398.2018.1461607
Newman DJ, Cragg GM (2016) Natural products as sources of new drugs from 1981 to 2014. J Nat Prod. https://doi.org/10.1021/acs.jnatprod.5b01055
Nishimura H, Okamoto M, Dapat I, Katsumi M, Oshitani H (2021) Inactivation of SARS-CoV-2 by catechins from green tea. Jpn J Infect Dis 74(5):421–423. https://doi.org/10.7883/yoken.JJID.2020.902. (Epub 2021 Jan 29 PMID: 33518628)
Paiva CLRS, Beserra BTS, Reis CEG, Dorea JG, da Costa THM, Amato AA (2019) Consumption of coffee or caffeine and serum concentration of inflammatory markers: a systematic review. Crit Rev Food Sci Nutr. https://doi.org/10.1080/10408398.2017.1386159
Rolta R, Salaria D, Sharma B, Awofisayo O, Fadare OA, Sharma S, Dev K (2022) Methylxanthines as potential inhibitor of SARS-CoV-2: an in silico approach. Curr Pharmacol Rep. https://doi.org/10.1007/s40495-021-00276-3
Romero-Martínez BS, Montaño LM, Solís-Chagoyán H, Sommer B, Ramírez-Salinas GL, Pérez-Figueroa GE, Flores-Soto E (2021) Possible beneficial actions of caffeine in sars-cov-2. Int J Mol Sci. https://doi.org/10.3390/ijms22115460
TangL-Q, Wei W, Wang X-Y (2017) Effects and mechanisms of catechin for adjuvant arthritis in rats
Ulvia B, Andarwulan N, Hunaefi D (2020) Profile of bioactive compounds and antioxidant capacity of Indonesian cocoa powder: a case of food processing authentication. Scitepress, pp 97–105. https://doi.org/10.5220/0009977300970105
van Dam RM, Hu FB (2022) Caffeine consumption and cardiovascular health. Nat Rev Cardiol. https://doi.org/10.1038/s41569-022-00719-4
Vieira AJSC, Gaspar EM, Santos PMP (2020) Mechanisms of potential antioxidant activity of caffeine. Radiat Phys Chem. https://doi.org/10.1016/j.radphyschem.2020.108968
Yang N, Shen H-M (2020) Targeting the endocytic pathway and autophagy process as a novel therapeutic strategy in COVID-19. Int J Biol Sci 16(10):1724–1731. https://doi.org/10.7150/ijbs.45498
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The authors would like to express their gratitude to the Franciscan University research team for all their help and support.
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Data curation: NRD, CMSA, TCS, TOM, ICL, ACZB, FKS, FCC. Formal analysis: NRD, CMSA, TCS, FCC. Investigation: NRD, CMSA, TCS, TOM, ICL, ACZB, FKS, FCC. Methodology: FCC. Project administration: FCC. Supervision: FCC. Roles/writing—original draft: NRD, CMSA, TCS, TOM, ICL, ACZB, FKS, FCC. Writing—review and editing: NRD, CMSA, TCS, TOM, ICL, ACZB, FKS, FCC.
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Dutra, N.S., da Silva D’Ávila, C.M., da Silva, T.C. et al. Biological properties of caffeine, (+)-catechin, and theobromine: an in silico study. 3 Biotech 14, 94 (2024). https://doi.org/10.1007/s13205-024-03934-7
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DOI: https://doi.org/10.1007/s13205-024-03934-7