Antioxidant, Anti-Inflammatory, and Cytotoxic Activities Against Drug-Sensitive and Drug-Resistant Cancer Cells of the Extracts of Clausena excavata, Millettia pachycarpa, and Uvaria grandiflora
Abstract
Objective: This study aimed to analyze the chemical profiles of bioactive compounds in extracts from different parts of Clausena excavata (C. excavata), Millettia pachycarpa (M. pachycarpa), and Uvaria grandiflora (U. grandiflora), and to examine their antioxidant, anti-inflammatory, and cytotoxic effects on drug-sensitive and -resistant cancer and normal cells.
Material and Methods: Ethyl acetate extracts from C. excavata fruits (FCE), M. pachycarpa roots and leaves (RMP and LMP), and U. grandiflora twigs and leaves (TUG and LUG) were analyzed for total phenolic and flavonoid content and the chemical profiles of bioactive compounds. Antioxidant activities were determined using various methods. Anti-inflammatory properties were investigated in lipopolysaccharide-stimulated RAW264.7 cells, and cytotoxicity was evaluated in doxorubicin-sensitive and -resistant leukemic cells (K562 and K562/adr), breast cancer cells (MCF-7 and MCF-7/adr), and normal cells (peripheral blood mononuclear cells; PBMCs).
Results: The extracts contained bioactive compounds, including carbazole alkaloids, xanthones, and coumarins in FCE; isoflavonoids, coumarins, and rotenoids in RMP and LMP; and alkaloids, cyclohexenes, and flavonoids in TUG and LUG. TUG, RMP, and LMP exhibited the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, whereas RMP demonstrated the most potent 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and superoxide radical scavenging activities. LUG showed strong metal-chelating activity (MCA), and LMP showed superior ferric ion reducing antioxidant power (FRAP). FCE exhibited notable anti-inflammatory activity, whereas RMP showed significant cytotoxicity against MCF-7 and MCF-7/adr cells, with minimal toxicity to PBMCs. TUG also proved effective against drug-resistant leukemia cells.
Conclusion: These findings highlight the potential of these plants for use in dietary supplements and cancer treatments, especially for drug-resistant cancers.
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Abdel-Aziz SM, Aeron A, Kahil TA. Health benefits and possible risks of herbal medicine. In: Garg N, Abdel-Aziz S, Aeron A, editor. Microbes in Food and Health: Springer, Cham; 2016.
Li AN, Li S, Zhang YJ, Xu XR, Chen YM, Li HB. Resources and biological activities of natural polyphenols. Nutrients 2014;6:6020-47.
Liga S, Paul C, Peter F. Flavonoids: overview of biosynthesis, biological activity, and current extraction techniques. Plants (Basel) 2023;12.
Aminah NS, Thant TM, Kristanti AN, Ramadhan R, Aung HT, Takaya Y. Carbazomarin: a new potential of α-glucosidase inhibitor from clausena excavata roots. Nat Prod Commun 2019;14:1934578X19894076.
Sharif NM, Mustahil NA, Noor NM, Sukari MA, Rahmani M, Taufiq-Yap YH, et al. Cytotoxic constituents of Clausena excavata. Afr J Biotechnol 2011;10:16337-41.
Suthiphasilp V, Maneerat T, Laphookhieo S, Songkerdthong J, Harding DJ, Charoensup R. Bioactive compounds from the fruit extract of Clausena excavata Burm. f. (Rutaceae). S Afr J Bot 2022;151:538-48.
Thant TM, Aminah NS, Kristanti AN, Ramadhan R, Aung HT, Takaya Y. Antidiabetes and Antioxidant agents from Clausena excavata root as medicinal plant of Myanmar. Open Chem 2019;17:1339–44.
Tu YB, Xiao T, Gong GY, Bian YQ, Li YF. A new isoflavone with anti-inflammatory effect from the seeds of Millettia pachycarpa. Nat Prod Res 2020;34:981-7.
Ye H, Fu A, Wu W, Li Y, Wang G, Tang W, et al. Cytotoxic and apoptotic effects of constituents from Millettia pachycarpa Benth. Fitoterapia 2012;83:1402-8.
Suthiphasilp V, Rujanapun N, Kumboonma P, Chaiyosang B, Tontapha S, Maneerat T, et al. Antidiabetic and Cytotoxic Activities of Rotenoids and Isoflavonoids Isolated from Millettia pachycarpa Benth. ACS Omega 2022;7:24511-21.
Quimque MTJ, Magsipoc RJY, Llames LCJ, Flores AIG, Garcia KYM, Ratzenbock A, et al. Polyoxygenated Cyclohexenes from Uvaria grandiflora with Multi-Enzyme Targeting Properties Relevant in Type 2 Diabetes and Obesity. ACS Omega 2022;7:36856-64.
Seangphakdee P, Pompimon W, Meepowpan P, Panthong A, Chiranthanut N, Banjerdpongchai R, et al. Anti-inflammatory and anticancer activities of (-)-zeylenol from stems of Uvaria grandiflora. ScienceAsia 2013;39 610–4.
Kongkum N, Thanasansurapong S, Surapanich N, Kumutanat W, Sukkum C, Kuhakarn C, et al. Antioxidant and antimicrobial alkaloids isolated from twigs of Uvaria grandiflora Roxb. ScienceAsia 2021;47S:14–8.
Strategy and Planning Division MoPH. Public health statistics 2022 [monograph on the Internet] Nonthaburi: Ministry of Public Health; [cited 2025 Jan 26]. Available from: https://spd.moph.go.th/wp-content/uploads/2023/11/Hstatistic65.pdf
Amjad MT, Chidharla A, Kasi A. Cancer chemotherapy [homepage on the Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Mar 01]. Available from: https://www.statpearls.com/
Choiprasert W, Dechsupa N, Kothan S, Garrigos M, Mankhetkorn S. Quercetin, quercetrin except rutin potentially increased pirarubicin cytotoxicity by non-competitively inhibiting the P-glycoprotein and MRP1 function in living K562/adr and GLC4/adr cells. Am J Pharm Toxicol 2010;5:24-33.
Suttana W, Mankhetkorn S, Poompimon W, Palagani A, Zhokhov S, Gerlo S, et al. Differential chemosensitization of P-glycoprotein overexpressing K562/Adr cells by withaferin A and Siamois polyphenols. Mol Cancer 2010;9:99.
Suttana W, Singharachai C, Charoensup R, Rujanapun N, Suya C. Antiproliferative and apoptosis-inducing activities of Benchalokawichian remedy against doxorubicin-sensitive and -resistant erythromyelogenous leukemic cells. CMU J Nat Sci 2021;20:e2021056.
Menezes LR, Costa CO, Rodrigues AC, Santo FR, Nepel A, Dutra LM, et al. Cytotoxic Alkaloids from the Stem of Xylopia laevigata. Molecules 2016;21.
Rossi YE, Bohla LP, Vanden Braber NL, Ballatore MB, Escobar FM, Bodoira R, et al. Polyphenols of peanut (Arachis hypogaea L.) skin as bioprotectors of normal cells. Studies of cytotoxicity, cytoprotection and interaction with ROS. J Functional Foods 2020;67:103862.
Chanthasri W, Puangkeaw N, Kunworarath N, Jaisamut P, Limsuwan S, Maneenoon K, et al. Antioxidant capacities and total phenolic contents of 20 polyherbal remedies used as tonics by folk healers in Phatthalung and Songkhla provinces, Thailand. BMC Complement Altern Med 2018;18:73.
Sun J, Song YL, Zhang J, Huang Z, Huo HX, Zheng J, et al. Characterization and quantitative analysis of phenylpropanoid amides in eggplant (Solanum melongena L.) by high performance liquid chromatography coupled with diode array detection and hybrid ion trap time-of-flight mass spectrometry. J Agric Food Chem 2015;63:3426-36.
Zhu Z, Zhong B, Yang Z, Zhao W, Shi L, Aziz A, et al. LC-ESI-QTOF-MS/MS Characterization and Estimation of the Antioxidant Potential of Phenolic Compounds from Different Parts of the Lotus (Nelumbo nucifera) Seed and Rhizome. ACS Omega 2022;7:14630-42.
Rujanapun N, Jaidee W, Duangyod T, Phuneerub P, Paojumroom N, Maneerat T, et al. Special Thai Oolong Tea: Chemical Profile and In Vitro Antidiabetic Activities. Front Pharmacol 2022;13:797032.
Riss TL, Moravec RA, Niles AL, Duellman S, Benink HA, Worzella TJ, et al. Cell viability assays. Assay Guidance Manual. 2016.
Ito C, Itoigawa M, Kumagaya M, Okamoto Y, Ueda K, Nishihara T, et al. Isoflavonoids with antiestrogenic activity from Millettia pachycarpa. J Nat Prod 2006;69:138-41.
Shao W, Zhu Y, Chen F. Study on the chemical constituents of thickfruit millettia root (Millettia pachycarpa). Zhong Cao Yao 2001;30:3-5.
Tanruean K, Poolprasert P, Suwannarach N, Kumla J, Lumyong S. Phytochemical analysis and evaluation of antioxidant and biological activities of extracts from three clauseneae plants in Northern Thailand. Plants (Basel) 2021;10.
Azam S, Ansari P, Rashid MMU, Alam MN, Ahmed IH, Ibarahim MY, et al. In vitro anti-oxidant and in vivo anti-inflammatory activity determination of the methanolic leaves extract of Millettia pachycarpa. Biomed Res Ther 2015;2:366-73.
Zohmachhuana AM, Lalrinzuali K, Lalnunmawia F, Vabeiryureilai M, Kumar NS. The assessment of the free radical scavenging activity and flavonoid contents of selected medicinal plants of Mizoram. Current Trends Biotech Pharm 2021;15:34-43.
Abbas ASF, Abdullah R, Noorlidah A, Yusuf A. Methanolic extract of Clausena excavata promotes wound healing via antiinflammatory and anti-apoptotic activities. Asian Pacific J Trop Biome 2020;10:232-8.
Ye H, Xie C, Wu W, Xiang M, Liu Z, Li Y, et al. Millettia pachycarpa exhibits anti-inflammatory activity through the suppression of LPS-induced NO/iNOS expression. Am J Chin Med 2014;42:949-65.
Su XH, Li CY, Zhong YJ, Yuan ZP, Li YF, Liang B. A new prenylated chalcone from the seeds of Millettia pachycarpa. Chin J Nat Med 2012;10:222-5.
Macabeo APG, Flores AIG, Fernandez RAT, Budde S, Faderl C, Dahse HM, et al. Antitubercular and cytotoxic polyoxygenated cyclohexane derivatives from Uvaria grandiflora. Nat Prod Res 2021;35:5229-32.
Gottesman MM. Mechanisms of cancer drug resistance. Annu Rev Med 2002;53:615-27.
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