PEG-400 Nanoencapsulated Gotu Kola Leaf Extracts as an Alternative Treatment for Cognitive System Impairment: In-Vitro and In-Vivo Assays

Main Article Content

Brian Limantoro
Samuel
Aqillah N Naufaldy
Rita Anggraini
Servatia P Renatamagani
Michail F Sutami
Rachelle X Nyomanto
Nurul IM Apandi
Fatma Y Mahdani

Abstract

Cognitive impairment, a debilitating condition affecting over 60 million elderly individuals globally, remains inadequately addressed by current pharmacological therapies due to limitations in bioavailability and blood-brain barrier (BBB) penetration. This study aimed to investigate PEG-400 nanoencapsulated Gotu Kola (Centella asiatica) as a novel phytopharmacological intervention to enhance cognitive function in α-glycosidase-induced cognitive impairment models. Twenty male DDY strain mice (Mus musculus) were acclimatized, randomized into four groups (placebo, 1:1, 1:100, and 100:1 extract: PEG-400 ratios), and administered daily oral treatments for 10 days. Cognitive performance was evaluated using T-maze assays pre- and post-treatment, while inflammatory responses and acetylcholinesterase activity were quantified via TNF-α flow cytometry and Ellman’s assay, respectively. Advanced characterization techniques, including SEM-EDX and GC-MS, were employed to assess nanoparticle morphology and phytochemical composition. The 1:100 formulation demonstrated superior efficacy, reducing maze completion time by 1.44 ± 0.21 seconds (p < 0.05) and TNF-α levels by 19.9% compared to controls. SEM-EDX revealed homogeneous nanoparticles (5 - 7 nm, sphericity 0.8) with optimal BBB penetration potential, while GC-MS identified γ-sitosterol (7.22%) and β-sitosterol (7.22%) as primary bioactive constituents. Ellman’s assay confirmed 100% acetylcholinesterase inhibition for the 1:1 and 1:100 formulations, underscoring their neuroprotective potential. These findings position PEG-400 nanoencapsulated Centella asiatica as a promising candidate for mitigating age-related cognitive decline, aligning with SDG 3 (Good Health and Well-being). 


 


Keywords: 

Downloads

Download data is not yet available.

Article Details

Section

Articles

Author Biography

Fatma Y Mahdani, Faculty of Dental Medicine, Airlangga University, Surabaya, East Java, Indonesia 

Department of Oral Medicine, Faculty of Dental Medicine, Airlangga University, Surabaya, East Java, Indonesia       

How to Cite

PEG-400 Nanoencapsulated Gotu Kola Leaf Extracts as an Alternative Treatment for Cognitive System Impairment: In-Vitro and In-Vivo Assays. (2025). Tropical Journal of Natural Product Research , 9(7), 3097 – 3104. https://doi.org/10.26538/tjnpr/v9i7.22

References

Blazer DG, Yaffe K, Lieberman CT. Cognitive Aging: Process in Understanding and opportunities for Action. National Academic Press (US). Washington (DC). 2015: 1. Doi: 10.17226/21693 DOI: https://doi.org/10.17226/21693

World Health Organization. Geneva (SW): World failing to address dementia challenge; 2021 [cited 2025 Feb 11]. Available from: https://www.who.int/news/item/02-09-2021-world-failing-to-address-dementia-challenge2.

Indonesia Statistic Centre. Jakarta (ID): Elderly Population Statistics in 2021; 2021 [cited 2025 Feb 11].

Murman DL. The Impact of Age on Cognition. Seminars in Hearing. 2015; 36(03):111–121. Doi: 10.1055/s-0035-1555115 DOI: https://doi.org/10.1055/s-0035-1555115

Sanford AM. Mild cognitive impairment. Clin Ger Med. 2017; 33(3):325–337. Doi: 10.1016/j.cger.2017.02.005 DOI: https://doi.org/10.1016/j.cger.2017.02.005

Huang X, Zhao X, Li B, Cai Y, Zhang S, Wan Q, Yu F. Comparative efficacy of various exercise interventions on cognitive function in patients with mild cognitive impairment or dementia: A systematic review and network meta-analysis. J Sport Health Sci. 2022; 11(2):212–223. Doi: 10.1016/j.jshs.2021.05.003 DOI: https://doi.org/10.1016/j.jshs.2021.05.003

Wright KM, Wright KM, McFerrin J, Alcázar Magaña A, Roberts J, Caruso M, Kretzschmar D, Stevens JF, Maier CS, Quinn JF, Soumyanath A. Developing a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials: Real World Challenges. Front Nutr. 2022; 8:799137. Doi: 10.3389/fnut.2021.799137 DOI: https://doi.org/10.3389/fnut.2021.799137

Gray NE, Zweig JA, Caruso M, Martin MD, Zhu JY, Quinn JF, Soumyanath A. Centella asiatica Increases Hippocampal Synaptic Density and Improves Memory and Executive Function in Aged Mice. Brain Behav. 2018; 8(7):e01024. Doi: 10.1002/brb3.1024 DOI: https://doi.org/10.1002/brb3.1024

Fan J, Chen Q, Wei L, Zhou X, Wang R, Zhang H. Asiatic Acid Ameliorates CCl4-Induced Liver Fibrosis in rats: Involvement of Nrf2/ARE, NF-κB/IκBα, and JAK1/STAT3 Signaling Pathways. Drug Des Dev Ther. 2018; 12:3595–3605. Doi: 10.2147/DDDT.S179876 DOI: https://doi.org/10.2147/DDDT.S179876

Wong JH, Barron AM, Abdullah JM. Mitoprotective Effects of Centella asiatica (L.) Urb.: Anti-Inflammatory and Neuroprotective Opportunities in Neurodegenerative Disease. Front Pharmacol. 2021; 12:687935. Doi: 10.3389/fphar.2021.687935 DOI: https://doi.org/10.3389/fphar.2021.687935

Asimakidou E, Tan JKS, Zeng J, Lo CH. Blood–Brain Barrier- Targeting Nanoparticles: Biomaterial Properties and Biomedical Applications in Translational Neuroscience. Pharmaceuticals. 2024; 17(5):612. Doi: 10.3390/ph17050612 DOI: https://doi.org/10.3390/ph17050612

Špadina M, Bohinc K, Zemb T, Dufrêche J. Synergistic Solvent Extraction Is Driven by Entropy. ACS Nano. 2019; 13(12):13745-13758. Doi: 10.1021/acsnano.9b07605 DOI: https://doi.org/10.1021/acsnano.9b07605

Wei X, Koo I, Kim S, Zhang X. Compound Identification in GC-MS by Simultaneously Evaluating the Mass Spectrum and Retention Index. The Analyst. 2014; 139(10):2507-2514. Doi: 10.1039/c3an02171h DOI: https://doi.org/10.1039/C3AN02171H

Olivia NU, Goodness UC, Obinna OM. Phytochemical Profiling and GC-MS Analysis of Aqueous Methanol Fraction of Hibiscus Asper Leaves. Futur J Pharm Sci. 2021; 7:59. Doi: 10.1186/s43094-021-00208-4 DOI: https://doi.org/10.1186/s43094-021-00208-4

Zinatloo-Ajabshir S. Advanced Rare Earth-Based Ceramic Nanomaterials at A Glance. Elsevier eBooks. 2022. 1–11 pp. Doi: 10.1016/B978-0-323-89957-4.00011-6 DOI: https://doi.org/10.1016/B978-0-323-89957-4.00011-6

Caputo F, Mehn D, Clogston J, Rosslein M, Prina-Mello S, Borgos S, Gioria S, Calzolai L. Asymmetric-Flow Field-Flow Fractionation for Measuring Particle Size, Drug Loading and (in)stability of Nanopharmaceuticals. The Joint View of European Union Nanomedicine Characterization Laboratory and National Cancer Institute Nanotechnology Characterization Laboratory. J Chromatogr. 2021; 1635:461767. Doi: 10.1016/j.chroma.2020.461767 DOI: https://doi.org/10.1016/j.chroma.2020.461767

Rades S, Hodoroaba VD, Salge T, Wirth T, Lobera MP, Labrador RH, Natte K, Behnke T, Gross T, Unger WES. High-resolution imaging with SEM/T-SEM, EDX and SAM as a combined methodical approach for morphological and elemental analyses of single engineered nanoparticles. RSC Adv. 2014; 4(91):49577–49578. Doi: 10.1039/C4RA05092D DOI: https://doi.org/10.1039/C4RA05092D

Różyk-Myrta A. In Search of Memory Tests Equivalent for Experiments on Animals and Humans. Med Sci Monit. 2014; 20:2733–2739. Doi: 10.12659/MSM.891056 DOI: https://doi.org/10.12659/MSM.891056

Decourt B, Lahiri DK, Sabbagh MN. Targeting Tumor Necrosis Factor Alpha for Alzheimer’s Disease. Cur Alzheimer Res. 2017; 14(4):412–425. Doi: 10.2174/1567205013666160930110551 DOI: https://doi.org/10.2174/1567205013666160930110551

Ambavade SD, Misar AV, Ambavade PD. Pharmacological, Nutritional, and Analytical Aspects of β-sitosterol: a review. Orient Pharm Exp Med. 2014; 14:193–211. Doi: 10.1007/s13596-014-0151-9 DOI: https://doi.org/10.1007/s13596-014-0151-9

Worek F, Eyer P, Thiermann H. Determination of Acetylcholinesterase Activity by the Ellman Assay: A Versatile Tool for In Vitro Research on Medical Countermeasures Against Organophosphate Poisoning. Drug Test Anal. 2011; 4(3-4):282–291. Doi: 10.1002/dta.337 DOI: https://doi.org/10.1002/dta.337

Dolled-Filhart M, Singh U, Wu D, Emancipator K. Implementation of immunohistochemistry Assays for Clinical Trial Sample Analyses. AAPS Adv Pharm Sci Series. 2016; 177–187 pp. Doi: 10.1186/s43094-021-00208-4. DOI: https://doi.org/10.1007/978-3-319-40793-7_16