Phytochemical Analysis, Antioxidant Activity and Bioassay-Guided Isolation of Acetylcholinesterase and Butyrylcholinesterase Inhibitors from Horsfieldia polyspherula Bark (Myristicaceae)
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Abstract
Alzheimer’s disease (AD) is a neurodegenerative condition brought on by aging and characterised by progressive decline in cognitive function and abnormalities in the central cholnergic system. ?-amyloid deposits, neurofibril tangle aggregation, oxidative stress or reduced level of acetylcholine are a few causes that have been linked to AD. In this study, the bioassay-guided isolation from ethyl acetate (EtOAc) extract of Horsfieldia polyspherula bark led to the isolation of nine compounds namely, 16-phenylhexadecanoic acid (1), undecylbenzene (2), 3,4-dihydroxybenzoic acid (3), dodecanoic acid (4), tetradecanoic acid (5), pentadecanoic acid (6), 1-tridecene (7), stigmasterol (8) and trimyristin (9). Phytochemical analysis revealed the presence of flavonoids, steroids, lignin, alkaloids, phytosterol and triterpenoids. The DPPH scavenging activity of EtOAc extract was related to the phenolic content (116.67 ± 16.98 GAE mg/g) and other non-phenolics such as lower fatty acids. Meanwhile, the DPPH scavenging activity was found to be concentration-dependent and correlated with both flavonoid and phenolic content. Furthermore, EtOAc and methanol (MeOH) extracts of H. polyspherula bark showed significant inhibitory activity at 100 ?g/mL on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), with EtOAc extract showing 77.2% and 64.1% inhibition and MeOH extract showing 37.5% and 39.2% inhibition, respectively. Additionally, the IC50 for BuChE and AChE of the EtOAc extract were found to be effective, with 15.41 ± 0.78 ?g/mL and 7.67 ± 0.13 ?g/mL, respectively. Compound 1 exhibited dual inhibition of 40.99 ± 1.99 ?M (BuChE) and 46.83 ± 2.44 ?M (AChE), while compounds 2 and 3 showed IC50 values above 200 ?M. This study revealed that this plant shows a significant potential as anti-cholinesterase focusing on acetylcholinesterase (AchE) and butyrylcholinesterase (BuChE). This is the first report on Horsfieldia polyspherula and their biological activity.
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References
Al-Mekhlafi N A, Shaari K, Abas F, Jeyaraj E J, Stanslas J, Khalivulla S I and Lajis N H. (2013). New flavan and alkyl α,β-lactones from the stem bark of Horsfieldia superba. Natural Product Communications 8: 447–451. https://doi.org/10.1177/1934578x1300800409
Alzheimer’s Association Report. (2023). Alzheimer’s disease facts and figures. Alzheimer’s & Dementia 19(4): 1598–1695. https://doi.org/10.1002/alz.13016
Anwal L A. (2021). Comprehensive review on Alzheimer’s disease. World Journal of Pharmaceutical Sciences 10: 1170. https://doi.org/10.20959/wjpps20217-19427
Aran K R and Singh S. (2023). Mitochondrial dysfunction and oxidative stress in Alzheimer’s disease: A step towards mitochondria based therapeutic strategies. Aging and Health Research 3(4): 100169. https://doi.org/10.1016/j.ahr.2023.100169
Armstrong J E and Wilson T K. (1978). Floral morphology of Horsfieldia (Myristicaceae). American Journal of Botany 65: 441–449. https://doi.org/10.1002/j.1537-2197.1978.tb06091.x
Batsika C S, Koutsilieris C, Koutoulogenis G S, Kokotou M G, Kokotos C G and Kokotos G. (2022). Light-promoted oxidation of aldehydes to carboxylic acids under aerobic and photocatalyst-free conditions. Green Chemistry 24: 6224–6231. https://doi.org/10.1039/d2gc02074b
Beura S K, Dhapola R, Panigrahi A R, Yadav P, Reddy D H and Singh S K. (2022). Redefining oxidative stress in Alzheimer’s disease: Targeting platelet reactive oxygen species for novel therapeutic options. Life Sciences 306: 120855. https://doi.org/10.1016/j.lfs.2022.120855
Bitwell C, Sen S I, Luke C and Kakoma M K. (2023). UHPLC-MS/MS phytochemical screening, polyphenolic content and antioxidant potential of Diplorhynchus condylocarpon (Müll.Arg.) Pichon (Apocynaceae), a medicinal plant. Scientific African 20: e01712. https://doi.org/10.1016/j.sciaf.2023.e01712
Chua L S, Rahaman N L A, Adnan N A and Eddie Tan T T. (2013). Antioxidant activity of three honey samples in relation with their biochemical components. Journal of Analytical Methods in Chemistry 2013: 313798. https://doi.org/10.1155/2013/313798
Du S Z, Wang Z C, Liu Y, Zhan R and Chen Y G. (2017). Diarylpropanes and lignans from Horsfieldia tetratepala. Phytochemistry Letters 19: 98–100. https://doi.org/10.1016/j.phytol.2016.12.018
Ellman G L, Courtney K D, Andres V and Featherstone R M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology 7: 88–95. https://doi.org/10.1016/0006-2952(61)90145-9
Gonfa T, Temesgen A, Erba O, Mengesha E T and Sivasubramanian M. (2023). Phytochemicals analysis, in vitro antibacterial activities of extracts, and molecular docking studies of the isolated compounds from Melhania zavattarii Cufod leaves. Journal of Tropical Medicine 2023: 8820543. https://doi.org/10.1155/2023/8820543
Jemain M M, Nik Musa’adah M, Rohaya A, Abdul Rashid L and Nor Hadiani I. (2011). In vitro antihyperglycemic effects of some Malaysian plants. Journal of Tropical Forest Science 23: 467–472. https://www.jstor.org/stable/23617061
Jiangseubchatveera N, Saechan C, Petchsomrit A, Treeyaprasert T, Leelakanok N and Prompanya C. (2023). Phytochemicals and antioxidant activities of red oak, red coral and butterhead. Tropical Life Sciences Research 34(1): 1–17. https://doi.org/10.21315/tlsr2023.34.1.1
Jumina, Nurmala A, Fitria A, Pranowo D, Sholikhah E N, Kurniawan Y S and Kuswandi B. (2018). Monomyristin and monopalmitin derivatives: Synthesis and evaluation as potential antibacterial and antifungal agents. Molecules 23: 3141. https://doi.org/10.3390/molecules23123141
Kaneria M and Chanda S. (2013). Evaluation of antioxidant and antimicrobial capacity of Syzygium cumini L. leaves extracted. Journal of Food Biochemistry 37: 168–176. https://doi.org/10.1111/j.1745-4514.2011.00614.x
Kumar C, Akhter S, Satti N K, Gupta V K, Meena S R, Vishwakarma R, Hassan Q P and Verma M K. (2023). Dereplication approach for the first time isolation of tatarinowin a and pentadecanoic acid from Acorus calamus L. by using GC-MS. Natural Product Research 37: 2632–2637. https://doi.org/10.1080/14786419.2022.2061482
Kurniasih N, Supriadin A, Harneti D, Abdulah R, Taib M N A M and Supratman U. (2021). Ergosterol peroxide and stigmasterol from the stembark of Aglaia simplicifolia (Meliaceae) and their cytotoxic against HeLa cervical cancer cell lines. Jurnal Kimia Valensi 7: 46–51. https://doi.org/10.15408/jkv.v7i1.20068
Lai W H, Hon Y K, Pang G M H, Chong E M G, Nordin N, Tiong L L, Tan S H, Sapian R A, Lee Y F and Rosli N. (2022). Dementia of the ageing population in Malaysia: A scoping review of published research. Aging and Health Research 2: 100077. https://doi.org/10.1016/j.ahr.2022.100077
Lei H and Rovis T. (2019). Ir-catalyzed intermolecular branch-selective allylic C-H amidation of unactivated terminal olefins. Journal of American Chemical Society 141: 2268–2273. https://doi.org/10.1021/jacs.9b00237
Liu W, Su Z H and Wan Q J. (2024). Proteinuria selectivity index in renal disease. Clinica Chimica Acta 552: 117675. https://doi.org/10.1016/j.cca.2023.117675
Martins G R, Monteiro A F, do Amaral F R L and da Silva A S. (2021). A validated Folin-Ciocalteu method for total phenolics quantification of condensed tannin-rich açaí (Euterpe oleracea Mart.) seeds extract. Journal of Food Science and Technology 58: 4693–4702. https://doi.org/10.1007/s13197-020-04959-5
Megawati, Ariani N, Minarti, Darmawan A and Eka Prastya M. (2023). Investigations of antibacterial, antioxidant, and antidiabetic potential of extract and its active fractions from the leaves of Horsfieldia spicata (Roxb.) J. Sinclair. Chemistry and Biodiversity 20(6): e202300113. https://doi.org/10.1002/cbdv.202300113
Mohamed Yusoff N, Osman H, Katemba V, Abd Ghani M S, Supratman U, Che Omar M T, Murugaiyah V, ren X, Six Y and Azmi M N. (2022). Design, synthesis and cholinesterase inhibitory activity of new dispiro pyrrolidine derivatives. Tetrahedron 128: 133115. https://doi.org/10.1016/j.tet.2022.133115
Omidpanah S, Vahedi-Mazdabadi Y, Manayi A, Rastegari A, Hariri R, Mortazavi-Ardestani E and Saeedi M. (2020). Phytochemical investigation and anticholinesterase activity of ethyl acetate fraction of Myristica fragrans Houtt. seeds. Natural Products Research 36(2): 610–616. https://doi.org/10.1080/14786419.2020.1788555
Ourhzif E M, Ricelli A, Stagni V, Cirigliano A, Rinaldi T, Bouissane L, Saso L, Chalard P, Troin Y, Khouili M and Akssira M. (2022). Antifungal and cytotoxic activity of diterpenes and bisnorsesquiterpenoides from the latex of Euphorbia resinifera Berg. Molecules 27: 5253. https://doi.org/10.3390/molecules27165234
Pohanka M. (2014). Inhibitors of acetylcholinesterase and butyrylcholinesterase meet immunity. International Journal of Molecular Sciences 15: 9809–9825. https://doi.org/10.3390/ijms15069809
Pourparizi A, Nadri H, Naghsh N, Eider A R and Pourrajab F. (2023). Synthesis of aurone sulfonate derivatives: Evaluation of their cholinesterase inhibition, neuroprotective effects, and expression of oxidative stress-related genes. Journal of Molecular Structure 1294: 136334. https://doi.org/10.1016/j.molstruc.2023.136334
Ramadhan R and Phuwapraisirisan P. (2015). Arylalkanones from Horsfieldia macrobotrys are effective antidiabetic agents achieved by α-glucosidase inhibition and radical scavenging. Natural Product Communications 10(2): 325–328. https://doi.org/10.1177/1934578x1501000230
Ramadhan R, Kusuma I W, Amirta R, Worawalai W and Phuwapraisirisan P. (2018). A new 4-arylflavan from the pericarps of Horsfieldia motleyi displaying dual inhibition against α-glucosidase and free radicals. Natural Products Research 32(22): 2676–2682. https://doi.org/10.1080/14786419.2017.1378204
Sedem C, Mawunyo F, Kpodo K and Asante-donyinah D. (2024). The influence of Morinda citrifolia fruit maturity level, parts and storage length on total phenols, ascorbic acid, antioxidant activity and ethylene gas emission. Food Chemistry Advances 4: 100599. https://doi.org/10.1016/j.focha.2023.100599
Sardar B, Biswas N and Srimani D. (2022). Ruthenium pincer-catalyzed selective synthesis of alkanes and alkenes via deoxygenative coupling of primary alcohols. Organometallics 42: 55–61. https://doi.org/10.1021/acs.organomet.2c00519
Shraim A M, Ahmed T A, Rahman M M and Hijji Y M. (2021). Determination of total flavonoid content by aluminum chloride assay: A critical evaluation. LWT – Food Science and Technology 150: 111932. https://doi.org/10.1016/j.lwt.2021.111932
Tillekeratne L M V, Jayamanne D T, Weerasuria K D V and Gunatilaka A A L. (1982). Lignans of Horsfieldia iryaghedhi. Phytochemistry 21: 476–478. https://doi.org/10.1016/S0031-9422(00)95299-3
Widowati W, Ginting C N, Lister I N E, Girsang E, Amalia A, Wibowo S H B and Kusuma H S W. (2020). Anti-aging effects of mangosteen peel extract and its phytochemical compounds: Antioxidant activity, enzyme inhibition and molecular docking simulation. Tropical Life Sciences Research 31(3): 127–144. https://doi.org/10.21315/tlsr2020.31.3.9
Yang J N, Zhou X Q, Nong X H, Cao J, Hui Y, Wen M and Chan W H. (2021). Phytochemical investigation of the flowers of Praxelis clematidea (Griseb.) R.M. King & H. Rob. Natural Product Research 35: 3504–3508. https://doi.org/10.1080/14786419.2019.1709189