Nanotechnology-Based Nanopolymeric Polyherbal Formulation for Enhanced Antioxidant and Anti-Glycation Activity
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Keywords:
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Antiglycation, Antioxidant, Chitosan-Sodium Tripolyphosphate, Nanopolymeric Polyherbal
Abstract
Elevated oxidative stress and glycation give to the enhancement of degenerative condition such as diabetes and heart disease. Herbal extracts such as Apium graveolens, Centella asiatica, and Orthosiphon stamineus possess well-documented antioxidant and anti-glycation properties. However, their therapeutic effectiveness is measured by poor bioavailability, highlighting the need for innovative formulations. Nanotechnology presents a indicative of success approach by improving the solubility and distribution of active compounds. This study developed a nanopolymeric formulation by combining extracts of Apium graveolens, Centella asiatica, and Orthosiphon stamineus utilizing the ionic gelation method by chitosan, NaTPP, and Tween 80. The nanoparticles were characterized based on particle size, PDI, zeta capability, TEM, and FTIR. In vitro assays utilizing peripheral blood mononuclear cells (PBMCs) were conducted to analyze antioxidant activity through Nrf2 and GST expression, and anti-glycation capability by measuring AGEs. The nanopolyherbal particles had an average size of 186 ± 46.81 nm, by a PDI of 0.434 ± 0.04 and a zeta capability of -29.69 ± 1.54 mV. Both 1% and 3% nanopolyherbal treatments increased Nrf2 stages (66.77 ± 7.65 and 63.13 ± 2.75, respectively) and GST stages (87.97 ± 49.48 and 73.57 ± 4.61) compared to the control group (Nrf2: 54.1 ± 1.0; GST: 68.93 ± 2.28). The nanopolyherbal formulation also significantly decreased AGE itemion (1%: 1075.67 ± 107.51; 3%: 813.33 ± 117.05) compared to the control (1497.33 ± 161.58). These outcomes reveal that the nanopolyherbal formulation enhances antioxidant activity and inhibits glycation in PBMCs, suggesting its capability for managing oxidative stress-related condition.
References
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Guan, T., C. Bian, and Z. Ma (2023). In Vitro and In Silico Perspectives on the Activation of Antioxidant Responsive Element by Citrus-Derived Flavonoids. Frontiers in Nutrition, 10; 1–10.
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Hong Sheng, C., T. So Ha, and K. Khalid Abdul (2017). Therapeutic Agents Targeting at AGE-RAGE Axis for the Treatment of Diabetes and Cardiovascular Disease: A Review of Clinical Evidence. Clinical Diabetes and Research, 1(1); 16–34.
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Legiawati, L., F. Fadilah, K. Bramono, and A. I. Pratama (2023). In Silico Study of Centella asiatica Derivatives as Antioxidant: Enhancer of Superoxide Dismutase and Glutathione Peroxidase Activity. Research Journal of Pharmacy and Technology, 16(1); 399–403.
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López-León, T., E. L. S. Carvalho, B. Seijo, J. L. Ortega-Vinuesa, and D. Bastos-González (2005). Physicochemical Characterization of Chitosan Nanoparticles: Electrokinetic and Stability Behavior. Journal of Colloid and Interface Science, 283(3); 244–351.
Mardiyanto, R., Mohadi, N. A. Fithri, and G. Kurniawan (2024). Optimization of Nanoemulsion Formula Containing Erythromycin With VCO and Varying Concentrations of Tween-80 and PEG-400. Science and Technology Indonesia, 9(3); 697–709.
Masfria, Sumaiyah, H. Syahputra, and M. Witarman (2023). Formulation and Evaluation of Antibacterial and Anti-Inflammatory Capsules Containing Phyllanthus emblica L. Fruit Nanoparticles. Science and Technology Indonesia, 8(4); 607–615.
Németh, Z., I. Csóka, R. Semnani Jazani, B. Sipos, H. Haspel, G. Kozma, Z. Kónya, and D. G. Dobó (2022). Quality by Design-Driven Zeta Potential Optimisation Study of Liposomes With Charge Imparting Membrane Additives. Pharmaceutics, 14(9); 1798.
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Pahwa, S., R. Sharma, and B. Singh (2017). Role of Glutathione S-Transferase in Coronary Artery Disease Patients With and Without Type 2 Diabetes Mellitus. Journal of Clinical and Diagnostic Research, 11(1); BC05.
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Prasad, K. (2021). AGE-RAGE Stress and Coronary Artery Disease. International Journal of Angiology, 30(1); 4–14.
Raulf, M. (2020). T Cell: Primary Culture From Peripheral Blood. In Methods in Molecular Biology.
Rungratanawanich, W., Y. Qu, X. Wang, M. M. Essa, and B.-J. Song (2021). Advanced Glycation End Products (AGEs) and Other Adducts in Aging-Related Diseases and Alcohol-Mediated Tissue Injury. Experimental & Molecular Medicine, 53(2); 168–188.
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Sinha, S., S. K. Singh, N. Jangde, R. Ray, and V. Rai (2021). p32 Promotes Melanoma Progression and Metastasis by Targeting EMT Markers, Akt/PKB Pathway, and Tumor Microenvironment. Cell Death & Disease, 12(11); 1012.
Siska, S., A. Mun’im, A. Bahtiar, and F. D. Suyatna (2018). Effect of Apium graveolens Extract Administration on the Pharmacokinetics of Captopril in the Plasma of Rats. Scientia Pharmaceutica, 86(1); 6.
Sugunabai, J., M. Jeyaraj, and T. Karpagam (2015). Analysis of Functional Compounds and Antioxidant Activity of Centella asiatica. Journal of Pharmacy and Pharmaceutical Sciences, 4(8); 1982–1993. Available at: www.wjpps.com
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Tabana, Y. M., F. S. R. Al-Suede, M. B. K. Ahamed, S. S. Dahham, L. E. A. Hassan, S. Khalilpour, M. Taleb-Agha, D. Sandai, A. S. A. Majid, and A. M. S. A. Majid (2016). Cat’s Whiskers Orthosiphon stamineus Tea Modulates Arthritis Pathogenesis via the Angiogenesis and Inflammatory Cascade. BMC Complementary and Alternative Medicine, 16(1); 1–11.
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Andira, R. H., W. Yuniati, A. Tjitraresmi, R. Isolasi, A. Farmakologi, and D. Toksisitas (2024). Review: Isolation, Analysis, Pharmacological Activity, and Toxicity of Sinensetin. Indonesian Journal of Biological Pharmacy, 4(1); 53–61.
Auliya Putri, E. F., E. Indahyanti, D. Mardiana, M. L. A. D. Lestari, and Z. Ningsih (2023). Okra Mucilage Extract as a Co-Surfactant Increased the Curcumin Nanoemulsion Stability and Encapsulation Efficiency. Science and Technology Indonesia, 8(3); 509–515.
Ayala-Fuentes, J. C. and R. A. Chavez-Santoscoy (2021). Nanotechnology as a Key to Enhance the Benefits and Improve the Bioavailability of Flavonoids in the Food Industry. Foods, 10(11); 2701.
Bandopadhyay, S., S. Mandal, M. Ghorai, N. K. Jha, M. Kumar, Radha, A. Ghosh, J. Proćków, J. M. Pérez de la Lastra, and A. Dey (2023). Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review. Journal of Cellular and Molecular Medicine, 27(5); 593–608.
Bansal, S., A. Burman, and A. K. Tripathi (2023). Advanced Glycation End Products: Key Mediator and Therapeutic Target of Cardiovascular Complications in Diabetes. World Journal of Diabetes, 14(8); 1146.
Bilia, A. R., C. Guccione, B. Isacchi, C. Righeschi, F. Firenzuoli, and M. C. Bergonzi (2014). [Retracted] Essential Oils Loaded in Nanosystems: A Developing Strategy for a Successful Therapeutic Approach. Evidence-Based Complementary and Alternative Medicine, 2014(1); 651593.
Chen, J., B. Arshi, K. Waqas, T. Lu, D. Bos, M. A. Ikram, A. G. Uitterlinden, M. Kavousi, and M. C. Zillikens (2023a). Advanced Glycation End Products Measured by Skin Autofluorescence and Subclinical Cardiovascular Disease: The Rotterdam Study. Cardiovascular Diabetology, 22(1); 326.
Chen, P., F. Chen, Z. L. Guo, J. Lei, and B. Zhou (2023b). Recent Advancement in Bioeffect, Metabolism, Stability, and Delivery Systems of Apigenin, a Natural Flavonoid Compound: Challenges and Perspectives. Frontiers in Nutrition, 10; 1–14.
Danaei, M., M. Dehghankhold, S. Ataei, F. Hasanzadeh Davarani, R. Javanmard, A. Dokhani, S. Khorasani, and M. R. Mozafari (2018). Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics, 10(2); 1–17.
David, J. A., W. J. Rifkin, P. S. Rabbani, and D. J. Ceradini (2017). The Nrf2/Keap1/ARE Pathway and Oxidative Stress as a Therapeutic Target in Type II Diabetes Mellitus. Journal of Diabetes Research, 2017(1); 4826724.
de Silva, W. N. D., A. P. Attanayake, L. D. A. M. Arawwawala, D. N. Karunaratne, and G. K. Pamunuwa (2023). In Vitro Antioxidant Activity of Alginate Nanoparticles Encapsulating the Aqueous Extract of Coccinia grandis L. Turkish Journal of Chemistry, 47(4); 715–725.
Doney, A. S. F., S. Lee, G. P. Leese, A. D. Morris, and C. N. A. Palmer (2005). Increased Cardiovascular Morbidity and Mortality in Type 2 Diabetes Is Associated With the Glutathione S Transferase Theta-Null Genotype: A Go-DARTS Study. Circulation, 111(22); 2927–2934.
Fan, W., W. Yan, Z. Xu, and H. Ni (2012). Formation Mechanism of Monodisperse, Low Molecular Weight Chitosan Nanoparticles by Ionic Gelation Technique. Colloids and Surfaces B: Biointerfaces, 90; 21–27.
Feng, M., Y. Hu, L. Yang, I. Wu, G. Yang, S. Jian, B. Hu, and C. Wen (2023). GST-Mu of Cristaria plicata Is Regulated by Nrf2/Keap1 Pathway in Detoxification Microcystin and Has Antioxidant Function. Aquatic Toxicology, 263; 106708.
García-Sánchez, A., A. G. Miranda-Díaz, and E. G. Cardona-Muñoz (2020). The Role of Oxidative Stress in Physiopathology and Pharmacological Treatment With Pro- and Antioxidant Properties in Chronic Diseases. Oxidative Medicine and Cellular Longevity; 1–13.
Guan, T., C. Bian, and Z. Ma (2023). In Vitro and In Silico Perspectives on the Activation of Antioxidant Responsive Element by Citrus-Derived Flavonoids. Frontiers in Nutrition, 10; 1–10.
Hassanein, E. H. M., H. S. Althagafy, M. A. Baraka, E. K. Abd-alhameed, I. M. Ibrahim, M. S. Abd El-Maksoud, N. M. Mohamed, and S. A. Ross (2024). The Promising Antioxidant Effects of Lignans: Nrf2 Activation Comes Into View. Naunyn-Schmiedeberg’s Archives of Pharmacology, 397(9); 6439–6458.
Hong Sheng, C., T. So Ha, and K. Khalid Abdul (2017). Therapeutic Agents Targeting at AGE-RAGE Axis for the Treatment of Diabetes and Cardiovascular Disease: A Review of Clinical Evidence. Clinical Diabetes and Research, 1(1); 16–34.
Jiang, T., Z. Huang, Y. Lin, Z. Zhang, D. Fang, and D. D. Zhang (2010). The Protective Role of Nrf2 in Streptozotocin-Induced Diabetic Nephropathy. Diabetes, 59(4); 850–860.
Krysa, M., M. Śmigielski, and A. Zdunek (2022). FT-IR and FT-Raman Fingerprints of Flavonoids – A Review. Food Chemistry, 393; 133430.
Legiawati, L., F. Fadilah, K. Bramono, and A. I. Pratama (2023). In Silico Study of Centella asiatica Derivatives as Antioxidant: Enhancer of Superoxide Dismutase and Glutathione Peroxidase Activity. Research Journal of Pharmacy and Technology, 16(1); 399–403.
Liu, D., X. Cao, Y. Kong, T. Mu, and J. Liu (2021). Inhibitory Mechanism of Sinensetin on ????-Glucosidase and Non-Enzymatic Glycation: Insights From Spectroscopy and Molecular Docking Analyses. International Journal of Biological Macromolecules, 166; 259–267.
López-León, T., E. L. S. Carvalho, B. Seijo, J. L. Ortega-Vinuesa, and D. Bastos-González (2005). Physicochemical Characterization of Chitosan Nanoparticles: Electrokinetic and Stability Behavior. Journal of Colloid and Interface Science, 283(3); 244–351.
Mardiyanto, R., Mohadi, N. A. Fithri, and G. Kurniawan (2024). Optimization of Nanoemulsion Formula Containing Erythromycin With VCO and Varying Concentrations of Tween-80 and PEG-400. Science and Technology Indonesia, 9(3); 697–709.
Masfria, Sumaiyah, H. Syahputra, and M. Witarman (2023). Formulation and Evaluation of Antibacterial and Anti-Inflammatory Capsules Containing Phyllanthus emblica L. Fruit Nanoparticles. Science and Technology Indonesia, 8(4); 607–615.
Németh, Z., I. Csóka, R. Semnani Jazani, B. Sipos, H. Haspel, G. Kozma, Z. Kónya, and D. G. Dobó (2022). Quality by Design-Driven Zeta Potential Optimisation Study of Liposomes With Charge Imparting Membrane Additives. Pharmaceutics, 14(9); 1798.
Nomi, A. G., H. Handayani, R. H. Khuluk, A. H. Karomah, L. Wulansari, N. D. Yuliana, E. Rohaeti, and M. Rafi (2024). Antioxidant Activity and Metabolite Changes in Centella asiatica With Different Drying Methods Using FTIR- and Quantitative HPLC-Based Metabolomics. International Food Research Journal, 31(1); 228–238.
Pahwa, S., R. Sharma, and B. Singh (2017). Role of Glutathione S-Transferase in Coronary Artery Disease Patients With and Without Type 2 Diabetes Mellitus. Journal of Clinical and Diagnostic Research, 11(1); BC05.
Patel, V. and Y. Agrawal (2011). Nanosuspension: An Approach to Enhance Solubility of Drugs. Journal of Advanced Pharmaceutical Technology & Research, 2(2); 81.
Perrone, A., A. Giovino, J. Benny, and F. Martinelli (2020). Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects. Oxidative Medicine and Cellular Longevity, 2020(Cml); 1–18.
Prasad, K. (2021). AGE-RAGE Stress and Coronary Artery Disease. International Journal of Angiology, 30(1); 4–14.
Raulf, M. (2020). T Cell: Primary Culture From Peripheral Blood. In Methods in Molecular Biology.
Rungratanawanich, W., Y. Qu, X. Wang, M. M. Essa, and B.-J. Song (2021). Advanced Glycation End Products (AGEs) and Other Adducts in Aging-Related Diseases and Alcohol-Mediated Tissue Injury. Experimental & Molecular Medicine, 53(2); 168–188.
Satta, S., A. M. Mahmoud, F. L. Wilkinson, M. Y. Alexander, and S. J. White (2017). The Role of Nrf2 in Cardiovascular Function and Disease. Oxidative Medicine and Cellular Longevity, 2017; 9237263.
Siam, N. H., N. N. Snigdha, N. Tabasumma, and I. Parvin (2024). Diabetes Mellitus and Cardiovascular Disease: Exploring Epidemiology, Pathophysiology, and Treatment Strategies. Reviews in Cardiovascular Medicine, 25(12); 436.
Singhal, S. S., S. P. Singh, P. Singhal, D. Horne, J. Singhal, and S. Awasthi (2016). Antioxidant Role of Glutathione S-Transferases: 4-Hydroxynonenal, a Key Molecule in Stress-Mediated Signaling. Toxicology and Applied Pharmacology, 289(3); 361–370.
Sinha, S., S. K. Singh, N. Jangde, R. Ray, and V. Rai (2021). p32 Promotes Melanoma Progression and Metastasis by Targeting EMT Markers, Akt/PKB Pathway, and Tumor Microenvironment. Cell Death & Disease, 12(11); 1012.
Siska, S., A. Mun’im, A. Bahtiar, and F. D. Suyatna (2018). Effect of Apium graveolens Extract Administration on the Pharmacokinetics of Captopril in the Plasma of Rats. Scientia Pharmaceutica, 86(1); 6.
Sugunabai, J., M. Jeyaraj, and T. Karpagam (2015). Analysis of Functional Compounds and Antioxidant Activity of Centella asiatica. Journal of Pharmacy and Pharmaceutical Sciences, 4(8); 1982–1993. Available at: www.wjpps.com
Syahputra, R. A., A. Dalimunthe, Z. D. Utari, P. Halim, M. A. Sukarno, S. Zainalabidin, E. Salim, M. Gunawan, F. Nurkolis, M. N. Park, J. A. Luckanagul, H. Bangun, B. Kim, and U. Harahap (2024). Nanotechnology and Flavonoids: Current Research and Future Perspectives on Cardiovascular Health. Journal of Functional Foods, 120; 106355.
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Authors
Astuti, F., Mustofa, Arif Budi Setianto, & Akrom. (2025). Nanotechnology-Based Nanopolymeric Polyherbal Formulation for Enhanced Antioxidant and Anti-Glycation Activity. Science and Technology Indonesia, 10(3), 972–981. https://doi.org/10.26554/sti.2025.10.3.972-981
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