Phytochemical investigation and cancer chemopreventive potential of selected medicinal plants from Thailand

Khuniad, C (2025) Phytochemical investigation and cancer chemopreventive potential of selected medicinal plants from Thailand. Doctoral thesis, Liverpool John Moores University.

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Abstract

Cancer is a significant public health issue globally, as indicated by its incidence and mortality rates. Undoubtedly, cancer chemoprevention is an effective strategy for cancer control aiming to prevent, delay or reverse the process of cancer development. Natural products are significant resources for the discovery of potential cancer chemopreventive and anticancer drugs. Thailand, a biodiversity-rich country in Southeast Asia, has a flora of around 11,000 plant species, many of which have medicinal properties and could be a source for cancer chemopreventive agents. Based on traditional uses and literature reviews, Amesiodendron chinense (Sapindaceae), Claoxylon longifolium (Euphorbiaceae) and Rhodomyrtus tomentosa (Myrtaceae) were selected and collected from Phatthalung, southern Thailand. A bioassay-guided approach was adopted to investigate the phytochemicals and cancer chemopreventive activity of these plants. Dried plant materials were ground and sequentially Soxhlet-extracted with n-hexane, dichloromethane (DCM) and methanol (MeOH). The chemopreventive effects of crude extracts, fractions and isolated compounds at non-cytotoxic concentrations were evaluated for Nrf2 induction potential using a cell-based luciferase assay in the AREc32 cell line. The MeOH extracts of C. longifolium stems, C. longifolium leaves and R. tomentosa fruits along with the DCM extract of R. tomentosa fruits were the most active with 38.9, 24.9, 7.1 and 6.7-fold induction of Nrf2 activity compared to the control. The active DCM extract was fractionated using vacuum liquid chromatography and the active MeOH extracts were fractionated using solid-phase extraction. GC-MS analysis revealed that the major compounds present in the seed oil of A. chinense were long-chain alkanes and fatty acids, while fatty acid methyl esters were the main compounds in the active fractions of C. longifolium stems. Analytical, semi-preparative and preparative reversed-phase HPLC were used for the isolation and purification of compounds from the active fractions. The structural elucidation of isolated compounds was achieved by extensive 1D and 2D NMR spectroscopy and mass spectrometry. Bioassay-guided isolation led to the identification of fourteen known compounds including four C-glycosyl flavones: isovitexin (124) and vicenins 1-3 (125-127); a fatty acid methyl ester: hexadecanoic acid methyl ester (128); two phenolic acids: caffeic acid (111) and 3-O-methylellagic acid 3′-O-α-rhamnopyranoside (136); three polymethoxyflavones: combretol (129), myricetin 3,3',4',5'-tetramethyl ether (130) and 3',5‐dihydroxy‐3,4',5’,7‐tetramethoxyflavone (131); four triterpenes: 3-O-cis-p-coumaroyl maslinic acid (132), 3-O-trans-p-coumaroyl maslinic acid (133), 3β-O-cis-p-coumaroyl-2α,23-dihydroxyolean-12-en-28-oic acid (134) and 3β-O-trans-p-coumaroyl-2α,23-dihydroxyolean-12-en-28-oic acid (135). Among them, compounds 136, 131 and 125 were considered potent chemopreventive compounds with 4.0, 3.1 and 2.3-fold induction of Nrf2 activation, respectively. In silico studies on the C-glycosyl flavones revealed the potential of these compounds as cancer chemopreventive and chemotherapeutic agents. This study generated the first phytochemical investigation on C. longifolium leaves. Moreover, this is also the first report on the chemopreventive properties through the Nrf2-ARE signalling pathway of A. chinense, C. longifolium and R. tomentosa. These findings highlight the promising use of these medicinal plants in cancer prevention. Future work should investigate the mechanism of action of active compounds and evaluate chemopreventive effect of isolated compounds in other cancer-related molecular signalling pathways.

Item Type:	Thesis (Doctoral)
Uncontrolled Keywords:	Bioassay-guided isolation; Cancer chemoprevention; Cytotoxicity; Nrf2 activation; AREc32 cell line; HPLC; NMR; LC-MS; GC-MS; Thai medicinal plants
Subjects:	R Medicine > R Medicine (General)
Divisions:	Pharmacy and Biomolecular Sciences
Date of acceptance:	21 August 2025
Date Deposited:	29 Aug 2025 16:00
Last Modified:	29 Aug 2025 16:01
DOI or ID number:	10.24377/LJMU.t.00026991
Supervisors:	Sarker, S, Ritchie, K and Nahar, L
URI:	https://researchonline.ljmu.ac.uk/id/eprint/26991

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