Metabolic Profiling, Antioxidant, and Anti-lipase Activity from Combined Leaves Extracts of Tamarindus indica and Murraya paniculata: A Simplex Lattice Design Approach
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Keywords:
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Anti-Lipase , Triglyceride Lowering , Combined Extract , Simplex-Lattice-Design
Abstract
Tamarindus indica leaves are recognized for their potent antioxidant and hypolipidemic properties, whereas Murraya paniculata leaves are known for their abilities to lower lipids and glucose levels. This study aimed to assess the combined extract of both leaves against pancreatic lipase inhibition and analyze their metabolomic profiles as an initial step toward developing a polyherbal treatment for hypertriglyceridemia. The extracts were subjected to Liquid Chromatography-High Resolution Mass Spectrometer (LC-HRMS) untargeted system coupled with Compounds Discoverer software to reveal their metabolomic profile. Subsequently, both individual extracts and their combination were evaluated for anti-lipase activity using pancreatic lipase enzyme with p-nitrophenyl butyrate as the substrate. The combination of the two extracts (0-300 μg/mL, 300 μg/mL in total) was prepared following the Simplex Lattice Experimental Design with 5 different composition variations. Results: The findings indicated that Tamarindus indica leaf extract (TIE) predominantly exhibited lipase inhibitory activity. Interestingly, the addition of Murraya paniculata extract (MPE) diminished this enzyme inhibitory effect. TIE was found to be rich in polyhydroxy flavonoids followed by fatty amides, whereas MPE contained mainly polymethoxy flavonoids, fatty amides, and coumarins. The presence of fatty amides in both extracts was identified as a potential cause for this incompatibility. In summary, Tamarindus indica leaf extract demonstrated strong lipase inhibition; however, its effectiveness was reduced when combined with Murraya paniculata extract, possibly due to primary fatty amides. Further research is necessary to explore strategies for eliminating these compounds and confirming their impact in vivo.
References
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Nuri, N., Fitriyah, T., Puspitasari, E., Triatmoko, B., & Dianasari, D. (2024). Anti-Lipase Activity of Kemuning (Murraya paniculata) Leaves Extract and Its Fractions. Journal of Agromedicine and Medical Sciences, 10(1), 53.
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Sumarni, W., Sudarmin, S., & Sumarti, S. S. (2019). The Scientification of Jamu: A Study of Indonesian’s Traditional Medicine. Journal of Physics: Conference Series, 1321, 032057.
Susanti, N., Mustika, A., Khotib, J., Muti’ah, R., & Rochmanti, M. (2023). Phytochemical, Metabolite Compound, and Antioxidant Activity of Clinacanthus nutans Leaf Extract from Indonesia. Science and Technology Indonesia, 8(1), 38–44.
Valaparla, G. R., Sai, G. V., & Kumar, D. (2022). Assessment of Anti-Obesity Activity of Tamarindus Leaves on Butter Induced Hyperlipidemia in Mice. Asian Journal of Pharmacy and Pharmacology, 8(3), 100–103.
Vo, Q. V., Nam, P. C., Thong, N. M., Trung, N. T., Phan, C.-T. D., & Mechler, A. (2019). Antioxidant Motifs in Flavonoids: O–H versus C–H Bond Dissociation. ACS Omega, 4(5), 8935–8942.
Wardani, E., Harahap, Y., Mun’im, A., & Bahtiar, A. (2021). Evaluation of the Combination of Kemuning Leaves Extracts and Simvastatin on Blood Fatty Acids and Amino Acids of Hyperlipidemic Model Rats. Research Journal of Pharmacy and Technology, 2076–2080.
Wiyono, T., Frediansyah, A., Sholikhah, E. N., & Pratiwi, W. R. (2022). UHPLC-ESI-MS Analysis of Javanese Tamarindus indica Leaves from Various Tropical Zones and Their Beneficial Properties in Relation to Antiobesity. Journal of Applied Pharmaceutical Science, 12(8), 137–147.
Yuk, T., Kim, Y., Yang, J., Sung, J., Jeong, H. S., & Lee, J. (2018). Nobiletin Inhibits Hepatic Lipogenesis via Activation of AMP-Activated Protein Kinase. Evidence-Based Complementary and Alternative Medicine, 2018, 1–8.
Zeng, S., Li, S., Lai, C., Wei, M., Chen, B., Li, P., Zheng, G., & Liu, E. (2018). Evaluation of Anti-Lipase Activity and Bioactive Flavonoids in the Citri Reticulatae Pericarpium from Different Harvest Time. Phytomedicine, 43, 103–109.
Ali, A., Amin, M. J., Ahmed, M. U., Taj, A., Aasim, M., & Tabrez, E. (2021). Frequency of Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Associated Risk Factors among Type-2 Diabetics. Pakistan Journal of Medical Sciences, 38(1).
Aly, S. H., El-Hassab, M. A., Elhady, S. S., & Gad, H. A. (2022). Comparative Metabolic Study of Tamarindus indica L.’s Various Organs Based on GC/MS Analysis, In Silico and In Vitro Anti-Inflammatory and Wound Healing Activities. Plants, 12(1), 87.
Amado, J. R. R., Prada, A. L., Arranz, J. C. E., Rosés, R. P., Quevedo, H. M., Keita, H., Zapata, E. P., Fernandes, C. P., & Carvalho, J. C. T. (2016). Antioxidant and Hepatoprotective Activity of a New Tablets Formulation from Tamarindus indica L. Evidence-Based Complementary and Alternative Medicine, 1–7.
Berim, A., & Gang, D. R. (2016). Methoxylated Flavones: Occurrence, Importance, Biosynthesis. Phytochemistry Reviews, 15(3), 363–390.
Bessone, F., Razori, M. V., & Roma, M. G. (2019). Molecular Pathways of Nonalcoholic Fatty Liver Disease Development and Progression. Cellular and Molecular Life Sciences, 76(1), 99–128.
Chandra, S., Khan, S., Avula, B., Lata, H., Yang, M. H., El-Sohly, M. A., & Khan, I. A. (2014). Assessment of Total Phenolic and Flavonoid Content, Antioxidant Properties, and Yield of Aeroponically and Conventionally Grown Leafy Vegetables and Fruit Crops: A Comparative Study. Evidence-Based Complementary and Alternative Medicine, 1–9.
Dosoky, N., Satyal, P., Gautam, T., & Setzer, W. (2016). Composition and Biological Activities of Murraya paniculata (L.) Jack Essential Oil from Nepal. Medicines, 3(1), 7.
Elfita, E., Oktiansyah, R., Mardiyanto, M., Setiawan, A., & Widjajanti, H. (2024). Combination Effect of Extracts and Pure Compounds of Endophytic Fungi Isolated from Sungkai (Peronema canescens) Leaves on Antioxidant Activity. Science and Technology Indonesia, 9(1), 69–76.
Gao, X., Li, X., Zhang, C., & Bai, C. (2024). Scopoletin: A Review of Its Pharmacology, Pharmacokinetics, and Toxicity. Frontiers in Pharmacology, 15, 1268464.
Guo, H., Chen, Y., Song, N., Yang, X., Yao, S., & Qian, J. (2020). Screening of Lipase Inhibitors from Bamboo Leaves Based on the Magnetic Ligand Fishing Combined with HPLC/MS. Microchemical Journal, 153, 104497.
Hasim, H., Faridah, D. N., Afandi, F. A., & Qomaliyah, E. N. (2021). Evaluation of Indonesian Anti-Obesity Traditional Medicinal Plants: A Systematic Review and Meta-Analysis on Pancreatic Lipase Inhibition Activity. Research Square, PREPRINT (Version 1), 1–16.
Hofmann, A. F., & Borgström, B. (1963). Hydrolysis of Long-Chain Monoglycerides in Micellar Solution by Pancreatic Lipase. Biochimica et Biophysica Acta (BBA) - Specialized Section on Lipids and Related Subjects, 70, 317–331.
Karole, S., Shrivastava, S., Thomas, S., Soni, B., Khan, S., Dubey, J., Dubey, S. P., Khan, N., & Jain, D. K. (2019). Polyherbal Formulation Concept for Synergic Action: A Review. Journal of Drug Delivery and Therapeutics, 9(1-s), 453–466.
Kuddus, S. A., Bhuiyan, M. I., Subhan, N., Shohag, M. H., Rahman, A., Hossain, M. M., Alam, M. A., & Khan, F. (2020). Antioxidant-Rich Tamarindus indica L. Leaf Extract Reduced High-Fat Diet-Induced Obesity in Rat through Modulation of Gene Expression. Clinical Phytoscience, 6(1), 68.
Lahamado, O. T., Sabang, S. M., & Mustapa, K. (2017). Ekstrak Daun Asam Jawa (Tamarindus Indica L.) Sebagai Antidiabetes. Jurnal Akademika Kimia, 6(1), 1–6.
Laufs, U., Parhofer, K. G., Ginsberg, H. N., & Hegele, R. A. (2020). Clinical Review on Triglycerides. European Heart Journal, 41(1), 99–109c.
Li, Y., Chen, B., Cao, H.-Y., Li, J., Chen, L., & Zhang, Q. (2021). Pancreatic Lipase Inhibitory Activity of Bambusa multiplex Cv. Fernleaf Leaf Extract in Vitro and in Vivo. Food & Function, 12(16), 7440–7447.
Liang, H., Zhao, M., Tu, P., & Jiang, Y. (2020). Polymethoxylated Flavonoids from Murraya paniculata (L.) Jack. Biochemical Systematics and Ecology, 93, 104162.
Menezes, C. D. A., de Oliveira Garcia, F. A., de Barros Viana, G. S., Pinheiro, P. G., Felipe, C. F. B., de Albuquerque, T. R., Moreira, A. C., Santos, E. S., Cavalcante, M. R., Garcia, T. R., Silva, T. F., Coutinho, H. D. M., & de Menezes, I. R. A. (2017). Murraya paniculata (L.) (Orange Jasmine): Potential Nutraceuticals with Ameliorative Effect in Alloxan-Induced Diabetic Rats. Phytotherapy Research, 31(11), 1747–1756.
Nuri, N., Fitriyah, T., Puspitasari, E., Triatmoko, B., & Dianasari, D. (2024). Anti-Lipase Activity of Kemuning (Murraya paniculata) Leaves Extract and Its Fractions. Journal of Agromedicine and Medical Sciences, 10(1), 53.
Palmer, T., & Bonner, P. L. (2011). Enzyme Inhibition. Woodhead Publishing, 126–152.
Park, N. W., Lee, E. S., Ha, K. B., Jo, S. H., Kim, H. M., Kwon, M.-H., & Chung, C. H. (2023). Umbelliferone Ameliorates Hepatic Steatosis and Lipid-Induced ER Stress in High-Fat Diet-Induced Obese Mice. Yonsei Medical Journal, 64(4), 243.
Sookying, S., Duangjai, A., Saokaew, S., & Phisalprapa, P. (2022). Botanical Aspects, Phytochemicals, and Toxicity of Tamarindus indica Leaf and a Systematic Review of Antioxidant Capacities of T. indica Leaf Extracts. Frontiers in Nutrition, 9, 977015.
Sumarni, W., Sudarmin, S., & Sumarti, S. S. (2019). The Scientification of Jamu: A Study of Indonesian’s Traditional Medicine. Journal of Physics: Conference Series, 1321, 032057.
Susanti, N., Mustika, A., Khotib, J., Muti’ah, R., & Rochmanti, M. (2023). Phytochemical, Metabolite Compound, and Antioxidant Activity of Clinacanthus nutans Leaf Extract from Indonesia. Science and Technology Indonesia, 8(1), 38–44.
Valaparla, G. R., Sai, G. V., & Kumar, D. (2022). Assessment of Anti-Obesity Activity of Tamarindus Leaves on Butter Induced Hyperlipidemia in Mice. Asian Journal of Pharmacy and Pharmacology, 8(3), 100–103.
Vo, Q. V., Nam, P. C., Thong, N. M., Trung, N. T., Phan, C.-T. D., & Mechler, A. (2019). Antioxidant Motifs in Flavonoids: O–H versus C–H Bond Dissociation. ACS Omega, 4(5), 8935–8942.
Wardani, E., Harahap, Y., Mun’im, A., & Bahtiar, A. (2021). Evaluation of the Combination of Kemuning Leaves Extracts and Simvastatin on Blood Fatty Acids and Amino Acids of Hyperlipidemic Model Rats. Research Journal of Pharmacy and Technology, 2076–2080.
Wiyono, T., Frediansyah, A., Sholikhah, E. N., & Pratiwi, W. R. (2022). UHPLC-ESI-MS Analysis of Javanese Tamarindus indica Leaves from Various Tropical Zones and Their Beneficial Properties in Relation to Antiobesity. Journal of Applied Pharmaceutical Science, 12(8), 137–147.
Yuk, T., Kim, Y., Yang, J., Sung, J., Jeong, H. S., & Lee, J. (2018). Nobiletin Inhibits Hepatic Lipogenesis via Activation of AMP-Activated Protein Kinase. Evidence-Based Complementary and Alternative Medicine, 2018, 1–8.
Zeng, S., Li, S., Lai, C., Wei, M., Chen, B., Li, P., Zheng, G., & Liu, E. (2018). Evaluation of Anti-Lipase Activity and Bioactive Flavonoids in the Citri Reticulatae Pericarpium from Different Harvest Time. Phytomedicine, 43, 103–109.
Authors
Sholikhah, E. N., Wiyono, T., & Pratiwi, W. R. (2024). Metabolic Profiling, Antioxidant, and Anti-lipase Activity from Combined Leaves Extracts of Tamarindus indica and Murraya paniculata: A Simplex Lattice Design Approach. Science and Technology Indonesia, 9(4), 828–839. https://doi.org/10.26554/sti.2024.9.4.828-839
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