Lipid Peroxidation Inhibition of Three Choline Chloride-based NADES Extracts from Pluchea indica Leaves: Ex vivo and in silico Approach
Keywords:
beluntas, phenolic acid, natural antioxidant, molecular docking, malondyaldehyde
Abstract
Pluchea indica (L.) Less leaves contain chlorogenic acid, which has antioxidant activity. This study aims to evaluate the ability to inhibit lipid peroxidation of P. indica leaf extract obtained from three natural deep eutectic solvents (NADES) based on choline chloride (ChCl). Chlorogenic acid content in the extracts was determined by RP-HPLC. Evaluation of lipid peroxidation inhibitory activity (LPOI) was carried out using the Thiobarbituric Acid Reactive Substances (TBARS) method on rat liver homogenates ex vivo. In silico studies was carried out against three enzymes, namely cyclooxygenase-2, lipoxygenase, and cytochrome P450. The ChCl-Urea (1:2) extract of P. indica leaves contains the highest levels of chlorogenic acid (0.404%, w/w). The extract at 12.5% (v/v) gave the best LPOI value of 22.5%. Chlorogenic acid as an antioxidant in inhibiting lipid peroxidation could be influenced by interaction with cyclooxygenase-2 and cytochrome P450 inhibition in silico with binding energy values of -7.27 and -6.47 Kcal/mol, respectively. Thus, chlorogenic acid, one of the active compounds from P. indica leaves, is responsible for inhibiting lipid peroxidation. However, in the future, it is necessary to investigate other phenolic chemical components from the NADES extract of P. indica leaves that play a role in this activity.
References
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Kudłak, B., Owczarek, K., & Namieśnik, J. (2015). Selected issues related to the toxicity of ionic liquids and deep eutectic solvents—a review. Environmental Science and Pollution Research, 22, 11975–11992. https://doi.org/10.1007/s11356-015-4794-y
Kumar, S., Chashoo, G., Saxena, A. K., & Pandey, A. K. (2013). Parthenium hysterophorus: A probable source of anticancer, antioxidant and anti-HIV agents. BioMed Research International, 2013. https://doi.org/10.1155/2013/810734
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Mansinhos, I., Gonçalves, S., Rodríguez-Solana, R., Ordóñez-Díaz, J. L., Moreno-Rojas, J. M., & Romano, A. (2021). Ultrasonic-assisted extraction and natural deep eutectic solvents combination: A green strategy to improve the recovery of phenolic compounds from Lavandula pedunculata subsp. lusitanica (Chaytor) Franco. Antioxidants, 10(582), 1–21. https://doi.org/10.3390/antiox10040582
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Meyer, B. N., Ferrigni, N. R., Putnam, J. E., Jacobsen, L. B., Nichols, D. E., & McLaughlin, J. L. (1982). Brine shrimp: A convenient general bioassay for active plant constituents. Planta Medica, 45(1), 31–34. https://doi.org/10.1055/s-2007-971236
Ministry of Health Republic of Indonesia. (2017). Farmakope Herbal Indonesia II (Indonesian Herbal Pharmacopoeia II) (2nd ed.). Kementerian Kesehatan RI, Direktorat Jenderal Bina Kefarmasian dan Alat Kesehatan.
Murador, D. C., de Souza Mesquita, L. M., Vannuchi, N., Braga, A. R. C., & de Rosso, V. V. (2019). Bioavailability and biological effects of bioactive compounds extracted with natural deep eutectic solvents and ionic liquids: advantages over conventional organic solvents. Current Opinion in Food Science, 26, 25–34. https://doi.org/10.1016/j.cofs.2019.03.002
Noridayu, A. R., Hii, Y. F., Faridah, A., Khozirah, S., & Lajis, N. (2011). Antioxidant and antiacetylcholinesterase activities of Pluchea indica Less. International Food Research Journal, 18(3), 925–929.
Peng, X., Duan, M. H., Yao, X. H., Zhang, Y. H., Zhao, C. J., Zu, Y. G., & Fu, Y. J. (2016). Green extraction of five target phenolic acids from Lonicerae japonicae Flos with deep eutectic solvent. Separation and Purification Technology, 157, 249–257. https://doi.org/https://doi.org/10.1016/j.seppur.2015.10.065
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Rahman, M. M., Islam, M. B., Biswas, M., & Khurshid Alam, A. H. M. (2015). In vitro antioxidant and free radical scavenging activity of different parts of Tabebuia pallida growing in Bangladesh. BMC Research Notes, 8(621), 1–9. https://doi.org/10.1186/s13104-015-1618-6
Salehi, B., Azzini, E., Zucca, P., Varoni, E. M., Kumar, N. V. A., Dini, L., Panzarini, E., Rajkovic, J., Fokou, P. V. T., Peluso, I., Mishra, A. P., Nigam, M., Rayess, Y. El, Beyrouthy, M. El, Setzer, W. N., Polito, L., Iriti, M., Sureda, A., Quetglas-Llabrés, M. M., … Sharifi-Rad, J. (2020). Plant-derived bioactives and oxidative stress-related disorders: A key trend towards healthy aging and longevity promotion. Applied Sciences (Switzerland), 10(3), 947. https://doi.org/10.3390/app10030947
Singh, S., & Singh, R. P. (2008). In vitro methods of assay of antioxidants: An overview. Food Reviews International, 24(4), 392–415. https://doi.org/10.1080/87559120802304269
Solomons, T. W. G., & Fryhle, C. B. (2011). Organic chemistry (Tenth). John Wiley & Sons, Inc.
Upadhyay, R., & Rao, L. J. R. (2013). An Outlook on Chlorogenic Acids-Occurrence, Chemistry, Technology, and Biological Activities. Critical Reviews in Food Science and Nutrition, 53(9), 968–984. https://doi.org/10.1080/10408398.2011.576319
Vongsak, B., Kongkiatpaiboon, S., Jaisamut, S., & Konsap, K. (2018). Comparison of active constituents, antioxidant capacity, and α-glucosidase inhibition in Pluchea indica leaf extracts at different maturity stages. In Food Bioscience (Vol. 25, pp. 68–73). https://doi.org/10.1016/j.fbio.2018.08.006
Ali, D. E., Gedaily, R. A. E., Ezzat, S. M., Sawy, M. A. E., Meselhy, M. R., & Abdel-Sattar, E. (2023). In silico and in vitro anti-inflammatory study of phenolic compounds isolated from Eucalyptus maculata resin. Scientific Reports, 13(2093), 1–12. https://doi.org/10.1038/s41598-023-28221-y
Andarwulan, N., Batari, R., Sandrasari, D. A., Bolling, B., & Wijaya, H. (2010). Flavonoid content and antioxidant activity of vegetables from Indonesia. Food Chemistry, 121(4), 1231–1235. https://doi.org/10.1016/j.foodchem.2010.01.033
Ayala, A., Muñoz, M. F., & Argüelles, S. (2014). Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Medicine and Cellular Longevity, 2014. https://doi.org/10.1155/2014/360438
Benvenutti, L., Zielinski, A. A. F., & Ferreira, S. R. S. (2019). Which is the best food emerging solvent: IL, DES or NADES? Trends in Food Science and Technology, 90, 133–146. https://doi.org/10.1016/j.tifs.2019.06.003
Braguini, W. L., Pires, N. V., & Alves, B. B. (2018). Phytochemical analysis, antioxidant properties and Brine Shrimp lethality of unripe fruits of Solanum viarum. Journal of Young Pharmacists, 10(2), 159–163. https://doi.org/10.5530/jyp.2018.10.36
Dai, J., & Mumper, R. J. (2010). Plant phenolics: Extraction, analysis and their antioxidant and anticancer properties. Molecules, 15, 7313–7352. https://doi.org/10.3390/molecules15107313
Dai, Y., van Spronsen, J., Witkamp, G. J., Verpoorte, R., & Choi, Y. H. (2013). Natural deep eutectic solvents as new potential media for green technology. Analytica Chimica Acta, 766, 61–68. https://doi.org/10.1016/j.aca.2012.12.019
Devasagayam, T. P. A., Boloor, K. K., & Ramasarma, T. (2003). Methods for estimating lipid peroxidation: An analysis of merits and demerits. Indian Journal of Biochemistry and Biophysics, 40(5), 300–308.
Ernawati, Suryadi, H., & Mun’im, A. (2021). Effect of gamma irradiation on the caffeoylquinic acid derivatives content, antioxidant activity, and microbial contamination of Pluchea indica leaves. Heliyon, 7(8), e07825. https://doi.org/10.1016/j.heliyon.2021.e07825
Gulcin, İ. (2020). Antioxidants and antioxidant methods: an updated overview. Archives of Toxicology, 94(3), 651–715. https://doi.org/10.1007/s00204-020-02689-3
Hikmawanti, N. P. E., Ramadon, D., Jantan, I., & Mun’im, A. (2021). Natural Deep Eutectic Solvents (NADES): Phytochemical Extraction Performance Enhancer for Pharmaceutical and Nutraceutical Product Development. Plants, 10(2091). https://doi.org/https://doi.org/10.3390/plants10102091
Hikmawanti, N. P. E., Saputri, F. C., Yanuar, A., Jantan, I., Ningrum, R. A., Juanssilfero, A. B., & Mun’im, A. (2024). Choline chloride-urea-based natural deep eutectic solvent for highly efficient extraction of polyphenolic antioxidants from Pluchea indica (L.) Less leaves. Arabian Journal of Chemistry, 17(2), 105537. https://doi.org/10.1016/j.arabjc.2023.105537
Ivanović, M., Grujić, D., Cerar, J., Razboršek, M. I., Topalić-Trivunović, L., Savić, A., Kočar, D., & Kolar, M. (2022). Extraction of Bioactive Metabolites from Achillea millefolium L. with Choline Chloride Based Natural Deep Eutectic Solvents: A Study of the Antioxidant and Antimicrobial Activity. Antioxidants, 11(724). https://doi.org/10.3390/antiox11040724
Kongkiatpaiboon, S., Chewchinda, S., & Vongsak, B. (2018). Optimization of extraction method and HPLC analysis of six caffeoylquinic acids in Pluchea indica leaves from different provenances in Thailand. Revista Brasileira de Farmacognosia, 28(2), 145–150. https://doi.org/10.1016/j.bjp.2018.03.002
Kritsi, E., Tsiaka, T., Ioannou, A. G., Mantanika, V., Strati, I. F., Panderi, I., Zoumpoulakis, P., & Sinanoglou, V. J. (2022). In Vitro and In Silico Studies to Assess Edible Flowers’ Antioxidant Activities. Applied Sciences, 12(14), 7331. https://doi.org/10.3390/app12147331
Kudłak, B., Owczarek, K., & Namieśnik, J. (2015). Selected issues related to the toxicity of ionic liquids and deep eutectic solvents—a review. Environmental Science and Pollution Research, 22, 11975–11992. https://doi.org/10.1007/s11356-015-4794-y
Kumar, S., Chashoo, G., Saxena, A. K., & Pandey, A. K. (2013). Parthenium hysterophorus: A probable source of anticancer, antioxidant and anti-HIV agents. BioMed Research International, 2013. https://doi.org/10.1155/2013/810734
Lu, H., Tian, Z., Cui, Y., Liu, Z., & Ma, X. (2020). Chlorogenic acid: A comprehensive review of the dietary sources, processing effects, bioavailability, beneficial properties, mechanisms of action, and future directions. Comprehensive Reviews in Food Science and Food Safety, 1–29. https://doi.org/10.1111/1541-4337.12620
Mansinhos, I., Gonçalves, S., Rodríguez-Solana, R., Ordóñez-Díaz, J. L., Moreno-Rojas, J. M., & Romano, A. (2021). Ultrasonic-assisted extraction and natural deep eutectic solvents combination: A green strategy to improve the recovery of phenolic compounds from Lavandula pedunculata subsp. lusitanica (Chaytor) Franco. Antioxidants, 10(582), 1–21. https://doi.org/10.3390/antiox10040582
Martínez, G. M., Townley, G. G., & Martínez-Espinosa, R. M. (2022). Controversy on the toxic nature of deep eutectic solvents and their potential contribution to environmental pollution. Heliyon, 8(12), e12567. https://doi.org/10.1016/j.heliyon.2022.e12567
Meyer, B. N., Ferrigni, N. R., Putnam, J. E., Jacobsen, L. B., Nichols, D. E., & McLaughlin, J. L. (1982). Brine shrimp: A convenient general bioassay for active plant constituents. Planta Medica, 45(1), 31–34. https://doi.org/10.1055/s-2007-971236
Ministry of Health Republic of Indonesia. (2017). Farmakope Herbal Indonesia II (Indonesian Herbal Pharmacopoeia II) (2nd ed.). Kementerian Kesehatan RI, Direktorat Jenderal Bina Kefarmasian dan Alat Kesehatan.
Murador, D. C., de Souza Mesquita, L. M., Vannuchi, N., Braga, A. R. C., & de Rosso, V. V. (2019). Bioavailability and biological effects of bioactive compounds extracted with natural deep eutectic solvents and ionic liquids: advantages over conventional organic solvents. Current Opinion in Food Science, 26, 25–34. https://doi.org/10.1016/j.cofs.2019.03.002
Noridayu, A. R., Hii, Y. F., Faridah, A., Khozirah, S., & Lajis, N. (2011). Antioxidant and antiacetylcholinesterase activities of Pluchea indica Less. International Food Research Journal, 18(3), 925–929.
Peng, X., Duan, M. H., Yao, X. H., Zhang, Y. H., Zhao, C. J., Zu, Y. G., & Fu, Y. J. (2016). Green extraction of five target phenolic acids from Lonicerae japonicae Flos with deep eutectic solvent. Separation and Purification Technology, 157, 249–257. https://doi.org/https://doi.org/10.1016/j.seppur.2015.10.065
Rael, L. T., Thomas, G. W., Craun, M. L., Curtis, C. G., Bar-or, R., & Bar-or, D. (2004). Lipid Peroxidation and the Thiobarbituric Acid Assay : Standardization of the Assay When Using Saturated and Unsaturated Fatty Acids. Biochemistry and Moluecular Biology, 37(6), 749–752. https://doi.org/10.5483/bmbrep.2004.37.6.749
Rahman, M. M., Islam, M. B., Biswas, M., & Khurshid Alam, A. H. M. (2015). In vitro antioxidant and free radical scavenging activity of different parts of Tabebuia pallida growing in Bangladesh. BMC Research Notes, 8(621), 1–9. https://doi.org/10.1186/s13104-015-1618-6
Salehi, B., Azzini, E., Zucca, P., Varoni, E. M., Kumar, N. V. A., Dini, L., Panzarini, E., Rajkovic, J., Fokou, P. V. T., Peluso, I., Mishra, A. P., Nigam, M., Rayess, Y. El, Beyrouthy, M. El, Setzer, W. N., Polito, L., Iriti, M., Sureda, A., Quetglas-Llabrés, M. M., … Sharifi-Rad, J. (2020). Plant-derived bioactives and oxidative stress-related disorders: A key trend towards healthy aging and longevity promotion. Applied Sciences (Switzerland), 10(3), 947. https://doi.org/10.3390/app10030947
Singh, S., & Singh, R. P. (2008). In vitro methods of assay of antioxidants: An overview. Food Reviews International, 24(4), 392–415. https://doi.org/10.1080/87559120802304269
Solomons, T. W. G., & Fryhle, C. B. (2011). Organic chemistry (Tenth). John Wiley & Sons, Inc.
Upadhyay, R., & Rao, L. J. R. (2013). An Outlook on Chlorogenic Acids-Occurrence, Chemistry, Technology, and Biological Activities. Critical Reviews in Food Science and Nutrition, 53(9), 968–984. https://doi.org/10.1080/10408398.2011.576319
Vongsak, B., Kongkiatpaiboon, S., Jaisamut, S., & Konsap, K. (2018). Comparison of active constituents, antioxidant capacity, and α-glucosidase inhibition in Pluchea indica leaf extracts at different maturity stages. In Food Bioscience (Vol. 25, pp. 68–73). https://doi.org/10.1016/j.fbio.2018.08.006
Published
2025-04-22
How to Cite
Ni Putu Ermi Hikmawanti, Bariroh, T., Yumita, A., Saputri, F. C., Yanuar, A., Mun’im, A., Zikriyah, L., Fitriyani, A. N., Mulyati, R., & Sekar, L. A. D. (2025). Lipid Peroxidation Inhibition of Three Choline Chloride-based NADES Extracts from Pluchea indica Leaves: Ex vivo and in silico Approach. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.12197
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Research Article
