Goniothalamus macrophyllus: A Comprehensive Review of Its Phytochemistry, Pharmacological Activities, and Therapeutic Potential
Main Article Content
Abstract
Goniothalamus macrophyllus, a tropical species belonging to the Annonaceae family, has long been utilized in traditional Southeast Asian medicine for treating fevers, infections, and various other health conditions. This review provides a thorough examination of the plant’s ethnomedicinal significance, phytochemical constituents, and pharmacological potential. A systematic review of the literature was conducted to collect data on its bioactive components, such as styryl-lactones, flavonoids, alkaloids, and acetogenins. Among these, goniothalamin, a major styryl-lactone, has been notably investigated for its cytotoxic effects, primarily through mechanisms like cell cycle arrest and apoptosis induction. Pharmacological investigations have highlighted the plant’s notable anticancer, antimicrobial, antioxidant, anti-inflammatory, and antiparasitic activities. In vitro experiments have shown that both extracts and isolated constituents possess potent cytotoxic effects against various cancer cell lines, including those of breast, cervical, and hepatic origin. Moreover, antimicrobial assays have confirmed efficacy against both Gram-positive and Gram-negative bacterial strains. Antioxidant and anti-inflammatory activities further support its potential therapeutic versatility. However, its pharmacological promise is tempered by the scarcity of comprehensive toxicological studies and limited clinical data. Most findings are restricted to in vitro or preliminary in vivo models, and there is a lack of standardized protocols for extract formulation and compound isolation. In summary, G. macrophyllus represents a valuable natural resource for bioactive compounds with therapeutic potential, yet more extensive in vivo research and mechanistic studies are essential to substantiate its clinical applicability and safety.
Keywords:
Downloads
Article Details
Section

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
References
1. Sharma A, Talimarada D, Dhuri SN, Sundaram VNN, Palanimutu D, Holla H. Isolation, Structure Elucidation and in Vitro Anticancer Activity of Phytochemical Constituents of Goniothalamus wynaadensis Bedd. and Identification of α-Tubulin as a Putative Molecular Target by in Silico Study. Chem Biodivers. 2023;20(9):e202300371. DOI: https://doi.org/10.1002/cbdv.202300371
2. Phumthum M, Srithi K, Inta A, Junsongduang A, Tangjitman K, Pongamornkul W, Trisonthi C, Balslev H. Ethnomedicinal plant diversity in Thailand. J Ethnopharmacol. 2018;214:90–8. DOI: https://doi.org/10.1016/j.jep.2017.12.003
3. Wiart C. Ethnopharmacology of Medicinal Plants: Asia and the Pacific. Springer Science & Business Media; 2007. 236 p. DOI: https://doi.org/10.1201/9781420006803
4. Lúcio ASSC, Almeida JRG da S, Da-Cunha EVL, Tavares JF, Barbosa Filho JM. Alkaloids of the Annonaceae: occurrence and a compilation of their biological activities. Alkaloids Chem Biol. 2015;74:233–409. DOI: https://doi.org/10.1016/bs.alkal.2014.09.002
5. Neske A, Ruiz Hidalgo J, Cabedo N, Cortes D. Acetogenins from Annonaceae family. Their potential biological applications. Phytochemistry. 2020;174:112332. DOI: https://doi.org/10.1016/j.phytochem.2020.112332
6. Sophonnithiprasert T, Nilwarangkoon S, Nakamura Y, Watanapokasin R. Goniothalamin enhances TRAIL-induced apoptosis in colorectal cancer cells through DR5 upregulation and cFLIP downregulation. Int J Oncol. 2015;47(6):2188–96. DOI: https://doi.org/10.3892/ijo.2015.3204
7. Burkill IH, Birtwistle W, Foxworthy FW, Scrivenor JB, Watson JG. A dictionary of the economic products of the Malay peninsula. [2d ed.]. Kuala Lumpur, Malaysia: Published on behalf of the governments of Malaysia and Singapore by the Ministry of Agriculture and cooperatives; 1966. 2 p.
8. Mu Q, Tang WD, Liu RY, Li CM, Lou LG, Sun HD, Hu CQ. Constituents from the stems of Goniothalamus griffithii. Planta Med. 2003;69(9):826–830. DOI: https://doi.org/10.1055/s-2003-43219
9. Abd Wahab NZ, Ibrahim N. Styrylpyrone Derivative (SPD) Extracted from Goniothalamus umbrosus Binds to Dengue Virus Serotype-2 Envelope Protein and Inhibits Early Stage of Virus Replication. Mol Basel Switz. 2022;27(14):4566. DOI: https://doi.org/10.3390/molecules27144566
10. Blázquez MA, Bermejo A, Zafra-Polo MC, Cortes D. Styryl-lactones from Goniothalamus species— A review. Phytochem Anal. 1999;10(4):161–170. DOI: https://doi.org/10.1002/(SICI)1099-1565(199907/08)10:4<161::AID-PCA453>3.3.CO;2-U
11. Khaw-On P, Pompimon W, Banjerdpongchai R. Goniothalamin Induces Necroptosis and Anoikis in Human Invasive Breast Cancer MDA-MB-231 Cells. Int J Mol Sci. 2019;20(16):3953. DOI: https://doi.org/10.3390/ijms20163953
12. Meirelles MA, Braga CB, Ornelas C, Pilli RA. Synthesis of Nitrogen-Containing Goniothalamin Analogues with Higher Cytotoxic Activity and Selectivity against Cancer Cells. ChemMedChem. 2019;14(15):1403–1417. DOI: https://doi.org/10.1002/cmdc.201900281
13. Seyed MA, Jantan I, Bukhari SNA. Emerging Anticancer Potentials of Goniothalamin and Its Molecular Mechanisms. BioMed Res Int. 2014;2014:536508. DOI: https://doi.org/10.1155/2014/536508
14. Abd El-Kaream SA, Hussein NGA, El-Kholey SM, Elhelbawy AMAEI. Microneedle Combined with Iontophoresis and Electroporation for Assisted Transdermal Delivery of Goniothalamus Macrophyllus for Enhancement Sonophotodynamic Activated Cancer Therapy. Sci Rep. 2024;14(1):7962. DOI: https://doi.org/10.1038/s41598-024-58033-7
15. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009;6(7):e1000097. DOI: https://doi.org/10.1371/journal.pmed.1000097
16. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D. The PRISMA 2020 Statement: an Updated Guideline for Reporting Systematic Reviews. BMJ. 2021;372:n71. DOI: https://doi.org/10.1136/bmj.n71
17. Siddaway AP, Wood AM, Hedges LV. How to Do a Systematic Review: A Best Practice Guide for Conducting and Reporting Narrative Reviews, Meta-Analyses, and Meta-Syntheses. Annu Rev Psychol. 2019;70:747–770. DOI: https://doi.org/10.1146/annurev-psych-010418-102803
18. Heyne K. Useful Plants of Indonesia. Yayasan Sarana Wana Jaya: Distributed by the Employee Cooperative, Department of Forestry; 1988. 632 p.
19. Shakri NM, Salleh WMNHW, Khamis S, Ali NAM. Chemical Characterization of Goniothalamus macrophyllus and Goniothalamus malayanus leaves’ essential oils. Z Für Naturforschung C. 2020;75(11–12):485–488. DOI: https://doi.org/10.1515/znc-2020-0090
20. Leeratiwong C, Chalermglin P, Saunders RMK. Goniothalamusroseipetalus and G.sukhirinensis (Annonaceae): Two new species from Peninsular Thailand. PhytoKeys. 2021;184:1–17. DOI: https://doi.org/10.3897/phytokeys.184.73210
21. Saunders R. The genus Goniothalamus (Annonaceae) in Sumatra. Bot J Linn Soc. 2002;139(3):225–254. DOI: https://doi.org/10.1046/j.1095-8339.2002.00061.x
22. Adhya I, Hendrayana Y, Supartono T, Ismail AY, Nurdin. Vegetation Structure and Species Composition of Habitat Types Goniothalamus macrophyllus (Blume) Hook.f. and Thomson in Lowland Forest, Kuningan Regency, West Java. IOP Conf Ser Earth Environ Sci. 2021;819(1):012063. DOI: https://doi.org/10.1088/1755-1315/819/1/012063
23. Bluden G, Kyi A, Jewers K. The Comparative Stem and Root Anatomy of Goniothalamus andersonii, G. macrophyllus, G. malayanus and G. velutinus (Annonaceae) from the Peat Swamps of Sarawak. Bot J Linn Soc. 1974;68(3):209–225. DOI: https://doi.org/10.1111/j.1095-8339.1974.tb01759.x
24. Saunders R, Chalemgein P. A Synopsis of Goniothalamus Species (Annonaceae) in Thailand, with Descriptions of Three New Species. Bot J Linn Soc. 2008;156(3):355–384. DOI: https://doi.org/10.1111/j.1095-8339.2007.00762.x
25. Evans Schultes R. Medicinal plants of East and Southeast Asia: Attributed properties. Econ Bot. 1980;34(4):361–361. DOI: https://doi.org/10.1007/BF02858311
26. Chen PC. Traditional and modern medicine in Malaysia. Am J Chin Med. 1979;7(3):259–275. DOI: https://doi.org/10.1142/S0192415X79000222
27. Prakash S, Elavarasan N, Subashini K, Kanaga S, Dhandapani R, Sivanandam M, Kumaradhas P, Thirunavukkarasu C, Sujatha V. Isolation Of Hesperetin - A Flavonoid from Cordia Sebestena Flower Extract through Antioxidant Assay Guided Method and Its Antibacterial, Anticancer Effect on Cervical Cancer via In Vitro and In Silico Molecular Docking Studies. J Mol Struct. 2020;1207:127751. DOI: https://doi.org/10.1016/j.molstruc.2020.127751
28. Teruna HY, Rullah K, Hendra R, Utami R, Islami D, Mohd Faudzi SM, Mohd Aluwi MFF, Lam KW. Inhibitory Effect of (2S)-Pinocembrin From Goniothalamus macrophyllus on the Prostaglandin E2 Production in Macrophage Cell Lines: In Vitro and In Silico Studies. Adv Pharmacol Pharm Sci. 2024;2024:8811022. DOI: https://doi.org/10.1155/2024/8811022
29. Orlikova B, Schumacher M, Juncker T, Yan CC, Inayat-Hussain SH, Hajjouli S, Cerella C, Dicato M, Diederich M. Styryl-lactone goniothalamin inhibits TNF-α-induced NF-κB activation. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc. 2013;59:572–8. DOI: https://doi.org/10.1016/j.fct.2013.06.051
30. Sangrueng K, Sanyacharernkul S, Nantapap S, Nantasaen N, Pompimon W. Bioactive Goniothalamin from Goniothalamus tapis with Cytotoxic Potential. Am J Appl Sci. 2015;12(9):650–653. DOI: https://doi.org/10.3844/ajassp.2015.650.653
31. Innajak S, Mahabusrakum W, Watanapokasin R. Goniothalamin Induces Apoptosis Associated with Autophagy Activation through MAPK Signaling in SK-BR-3 Cells. Oncol Rep. 2016;35(5):2851–8. DOI: https://doi.org/10.3892/or.2016.4655
32. Pilli RA, Toledo I de, Meirelles MA, Grigolo TA. Goniothalamin-Related Styryl Lactones: Isolation, Synthesis, Biological Activity and Mode of Action. Curr Med Chem. 2019;26(41):7372–7451. DOI: https://doi.org/10.2174/0929867325666181009161439
33. de Fátima A, Kohn LK, Antônio MA, de Carvalho JE, Pilli RA. (R)-Goniothalamin: Total Syntheses and Cytotoxic Activity Against Cancer Cell Lines. Bioorg Med Chem. 2005;13(8):2927–2933. DOI: https://doi.org/10.1016/j.bmc.2005.02.007
34. de Fátima A, Modolo LV, Conegero LS, Pilli RA, Ferreira CV, Kohn LK, de Carvalho JE. Styryl Lactones and Their Derivatives: Biological Activities, Mechanisms of Action and Potential Leads for Drug Design. Curr Med Chem. 2006;13(28):3371–3384. DOI: https://doi.org/10.2174/092986706779010298
35. Polbuppha I, Teerapongpisan P, Phukhatmuen P, Suthiphasilp V, Maneerat T, Charoensup R, Andersen RJ, Laphookhieo S. Alkaloids and Styryl lactones from Goniothalamus ridleyi King and Their α-Glucosidase Inhibitory Activity. Mol Basel Switz. 2023;28(3):1158. DOI: https://doi.org/10.3390/molecules28031158
36. Shao L, Shao Y, Yuan Y. Pinocembrin flavanone inhibits cell viability in PC-3 human prostate cancer by inducing cellular apoptosis, ROS production and cell cycle arrest. Acta Pharm Zagreb Croat. 2021;71(4):669–678. DOI: https://doi.org/10.2478/acph-2021-0042
37. Puranik NV, Swami S, Misar AV, Mamgain R, Gulawani SS, Dhiman null, Sarkar null, Srivastava P. The first synthesis of podocarflavone A and its analogs and evaluation of their antimycobacterial potential against Mycobacterium tuberculosis with the support of virtual screening. Nat Prod Res. 2022;36(15):3879–3886. DOI: https://doi.org/10.1080/14786419.2021.1893317
38. Kim C, Le D, Lee M. Diterpenoids Isolated from Podocarpus macrophyllus Inhibited the Inflammatory Mediators in LPS-Induced HT-29 and RAW 264.7 Cells. Mol Basel Switz. 2021;26(14):4326. DOI: https://doi.org/10.3390/molecules26144326
39. Khan Z, Nath N, Rauf A, Emran TB, Mitra S, Islam F, Chandran D, Barua J, Khandaker MU, Idris AM, Wilairatana P, Thiruvengadam M. Multifunctional roles and pharmacological potential of β-sitosterol: Emerging evidence toward clinical applications. Chem Biol Interact. 2022;365:110117. DOI: https://doi.org/10.1016/j.cbi.2022.110117
40. Lailaty IQ, Peniwidiyanti, Ismaini L, Normasiwi S, Fajriah S, Hariri MR, Dewi AP, Martiansyah I, Hutabarat PWK, Munawir A. Ethnopharmacology properties of Medicinal plants used by the community in Gunung Halimun Salak National Park, West Java, Indonesia. Res J Pharm Technol. 2024;17(5):2121–2132. DOI: https://doi.org/10.52711/0974-360X.2024.00336
41. Choo CY, Abdullah N, Diederich M. Cytotoxic activity and mechanism of action of metabolites from the Goniothalamus genus. Phytochem Rev. 2014;13(4):835–851. DOI: https://doi.org/10.1007/s11101-014-9372-2
42. Lekphrom R, Kanokmedhakul S, Kanokmedhakul K. Bioactive styryllactones and alkaloid from flowers of Goniothalamus laoticus. J Ethnopharmacol. 2009;125(1):47–50. DOI: https://doi.org/10.1016/j.jep.2009.06.023
43. Fang XP, Anderson JE, Chang CJ, McLaughlin JL, Fanwick PE. Two new styryl lactones, 9-deoxygoniopypyrone and 7-epi-goniofufurone, from Goniothalamus giganteus. J Nat Prod. 1991;54(4):1034–1043. DOI: https://doi.org/10.1021/np50076a017
44. Nogueira da Silva Avelino Oliveira Rocha G, Dutra LM, Pinheiro Paz WH, Araujo da Silva FM, Costa EV, Guedes da Silva Almeida JR. Chemical constituents from the leaves and branches of Annona coriacea Mart. (Annonaceae). Biochem Syst Ecol. 2021;97:104297. DOI: https://doi.org/10.1016/j.bse.2021.104297
45. Mereyala HB, Joe M. Cytotoxic activity of styryl lactones and their derivatives. Curr Med Chem Anti-Cancer Agents. 2001;1(3):293–300. DOI: https://doi.org/10.2174/1568011013354606
46. Xie F, Zhang ZL, Zheng XQ, Li YM, Wang R, Li WY. A Comprehensive Review of Phytochemistry and Anticancer of the Genus Goniothalamus. Chem Biodivers. 2025;e202402461. DOI: https://doi.org/10.1002/cbdv.202402461
47. Li LK, Rola AS, Kaid FA, Ali AM, Alabsi AM. Goniothalamin induces cell cycle arrest and apoptosis in H400 human oral squamous cell carcinoma: A caspase-dependent mitochondrial-mediated pathway with downregulation of NF-κβ. Arch Oral Biol. 2016;64:28–38. DOI: https://doi.org/10.1016/j.archoralbio.2015.12.002
48. Vendramini-Costa DB, de Castro IBD, Ruiz ALTG, Marquissolo C, Pilli RA, de Carvalho JE. Effect of goniothalamin on the development of Ehrlich solid tumor in mice. Bioorg Med Chem. 2010;18(18):6742–6747. DOI: https://doi.org/10.1016/j.bmc.2010.07.053
49. Abdullah N, Sahibul-Anwar H, Ideris S, Hasuda T, Hitotsuyanagi Y, Takeya K, Diederich M, Choo C. Goniolandrene A and B from Goniothalamus macrophyllus. Fitoterapia. 2013;88:1–6. DOI: https://doi.org/10.1016/j.fitote.2013.03.028
50. de Fátima Â, Zambuzzi WF, Modolo LV, Tarsitano CAB, Gadelha FR, Hyslop S, Carvalho JE de, Salgado I, Ferreira CV, Pilli RA. Cytotoxicity of goniothalamin enantiomers in renal cancer cells: Involvement of nitric oxide, apoptosis and autophagy. Chem Biol Interact. 2008;176(2):143–150. DOI: https://doi.org/10.1016/j.cbi.2008.08.003
51. Sophonnithiprasert T, Mahabusarakam W, Nakamura Y, Watanapokasin R. Goniothalamin induces mitochondria-mediated apoptosis associated with endoplasmic reticulum stress-induced activation of JNK in HeLa cells. Oncol Lett. 2017;13(1):119–28. DOI: https://doi.org/10.3892/ol.2016.5381
52. Sharma T, Paidesetty SK. Altholactone: A Natural Lead Scaffold As A Potential Anticancer Agent. Int J Pharm Sci Res. 2021;12(6):3010–3018.
53. Fátima A de, Kohn LK, Carvalho JE de, Pilli RA. Cytotoxic activity of (S)-goniothalamin and analogues against human cancer cells. Bioorg Med Chem. 2006;14(3):622–631. DOI: https://doi.org/10.1016/j.bmc.2005.08.036
54. Yen CY, Chiu CC, Haung RW, Yeh CC, Huang KJ, Chang KF, Hseu YC, Chang FR, Chang HW, Wu YC. Antiproliferative effects of goniothalamin on Ca9-22 oral cancer cells through apoptosis, DNA damage and ROS induction. Mutat Res. 2012;747(2):253–8. DOI: https://doi.org/10.1016/j.mrgentox.2012.06.003
55. Barcelos RC, Pelizzaro-Rocha KJ, Pastre JC, Dias MP, Ferreira-Halder CV, Pilli RA. A new goniothalamin N-acylated aza-derivative strongly downregulates mediators of signaling transduction associated with pancreatic cancer aggressiveness. Eur J Med Chem. 2014;87:745–758. DOI: https://doi.org/10.1016/j.ejmech.2014.09.085
56. Wiart C. Goniothalamus Species: A Source of Drugs for the Treatment of Cancers and Bacterial Infections? Evid-Based Complement Altern Med ECAM. 2007;4(3):299–311. DOI: https://doi.org/10.1093/ecam/nem009
57. Mosaddik MA, Haque ME. Cytotoxicity and antimicrobial activity of goniothalamin isolated from Bryonopsis laciniosa. Phytother Res PTR. 2003;17(10):1155–1157. DOI: https://doi.org/10.1002/ptr.1303
58. Humeirah AS, Azah MN, Mastura M, Mailina J, Saiful JA, Muhajir H, Puad AM. Chemical constituents and antimicrobial activity of Goniothalamus macrophyllus (Annonaceae) from Pasoh Forest Reserve, Malaysia. Afr J Biotechnol. 2010;9(34):234-247
59. Jantan I bin, Ahmad ,Fasihuddin bin, and Din L bin. Chemical Constituents of the Bark Oil of Goniothalamus macrophyllus Hook. f. from Malaysia. J Essent Oil Res. 2005;17(2):181–183. DOI: https://doi.org/10.1080/10412905.2005.9698868
60. Kurniawan D, Kustiawan PM, Pramaningsih V, Yuliawati R, Ismiati R. Antibacterial and biolarvicidal activity of extracts of ethanol of Goniothalamus macrophyllus leaves and roots. IOP Conf Ser Earth Environ Sci. 2023;1282(1):012005. DOI: https://doi.org/10.1088/1755-1315/1282/1/012005
61. de Souza LES, Santos KA, Raspe DT, da Silva C, Silva EA da. Application of ultrasound-assisted extraction to obtain antioxidant compounds from leaves of Echinodorus macrophyllus. Sustain Chem Pharm. 2023;32:101031. DOI: https://doi.org/10.1016/j.scp.2023.101031
62. Tan WN, Ali R, Tong WY, Leong CR, Khaw KY. Essential Oils from Traditional Medicinal Plants in Malaysia: A Review on Their Traditional Uses, Bioactive Constituents and Therapeutic Potential. Pharm Chem J. 2023;57(5):703–711. DOI: https://doi.org/10.1007/s11094-023-02941-x
63. Halagarda M, Groth S, Popek S, Rohn S, Pedan V. Antioxidant Activity and Phenolic Profile of Selected Organic and Conventional Honeys from Poland. Antioxid Basel Switz. 2020;9(1):44. DOI: https://doi.org/10.3390/antiox9010044
64. Rasul A, Millimouno FM, Ali Eltayb W, Ali M, Li J, Li X. Pinocembrin: a novel natural compound with versatile pharmacological and biological activities. BioMed Res Int. 2013;2013:379850. DOI: https://doi.org/10.1155/2013/379850
65. Li X, Zhai Y, Xi B, Ma W, Zhang J, Ma X, Miao Y, Zhao Y, Ning W, Zhou H, Yang C. Pinocembrin Ameliorates Skin Fibrosis via Inhibiting TGF-β1 Signaling Pathway. Biomolecules. 2021;11(8):1240. DOI: https://doi.org/10.3390/biom11081240
66. Yang X, Wang X, Chen XY, Ji HY, Zhang Y, Liu AJ. Pinocembrin−Lecithin Complex: Characterization, Solubilization, and Antioxidant Activities. Biomolecules. 2018;8(2):41. DOI: https://doi.org/10.3390/biom8020041
67. Anatachodwanit A, Promnart P, Deachathai S, Maneerat T, Charoensup R, Duangyod T, Laphookhieo S. Chemical Composition of the Essential Oils from Goniothalamus tortilipetalus M.R.Hend. and Their Antioxidant and Antibacterial Activities. Chemistry. 2024;6(2):264–271. DOI: https://doi.org/10.3390/chemistry6020013
68. Vendramini-Costa DB, Francescone R, Posocco D, Hou V, Dmitrieva O, Hensley H, de Carvalho JE, Pilli RA, Grivennikov SI. Anti-inflammatory natural product goniothalamin reduces colitis-associated and sporadic colorectal tumorigenesis. Carcinogenesis. 2017;38(1):51–63. DOI: https://doi.org/10.1093/carcin/bgw112
69. Qian J, Xue M. Pinocembrin Relieves Mycoplasma pneumoniae Infection‑Induced Pneumonia in Mice Through the Inhibition of Oxidative Stress and Inflammatory Response. Appl Biochem Biotechnol. 2022;194(12):6335–6348. DOI: https://doi.org/10.1007/s12010-022-04081-6
70. Wu YL, Hu T, Zheng H, Feng J, Huang C, Zhou X, Wang W, Jiang CL. Pinocembrin alleviates LPS-induced depressive-like behavior in mice via the NLRP3/DCC signaling pathway. Biochem Biophys Res Commun. 2024;736:150870. DOI: https://doi.org/10.1016/j.bbrc.2024.150870
71. Zhou LT, Wang KJ, Li L, Li H, Geng M. Pinocembrin inhibits lipopolysaccharide-induced inflammatory mediators production in BV2 microglial cells through suppression of PI3K/Akt/NF-κB pathway. Eur J Pharmacol. 2015;761:211–216. DOI: https://doi.org/10.1016/j.ejphar.2015.06.003
72. Soromou LW, Jiang L, Wei M, Chen N, Huo M, Chu X, Zhong W, Wu Q, Baldé A, Deng X, Feng H. Protection of mice against lipopolysaccharide-induced endotoxic shock by pinocembrin is correlated with regulation of cytokine secretion. J Immunotoxicol. 2014;11(1):56–61. DOI: https://doi.org/10.3109/1547691X.2013.792886
73. Gu X, Zhang Q, Du Q, Shen H, Zhu Z. Pinocembrin attenuates allergic airway inflammation via inhibition of NF-κB pathway in mice. Int Immunopharmacol. 2017;53:90–95. DOI: https://doi.org/10.1016/j.intimp.2017.10.005
74. Duque C, Vizoto NL, Nunes GP, Peres GR, Feiria SNB, Hofling JF, Regasini LO. Metabolic regulation and oxidative stress attenuation in LPS-stimulated macrophages by flavonoids. Odontology.2025;63:80–89. DOI: https://doi.org/10.1007/s10266-025-01085-6
75. Soromou LW, Chu X, Jiang L, Wei M, Huo M, Chen N, Guan S, Yang X, Chen C, Feng H, Deng X. In vitro and in vivo protection provided by pinocembrin against lipopolysaccharide-induced inflammatory responses. Int Immunopharmacol. 2012;14(1):66–74. DOI: https://doi.org/10.1016/j.intimp.2012.06.009
76. Rullah K, Mohd Aluwi MFF, Yamin BM, Abdul Bahari MN, Wei LS, Ahmad S, Abas F, Ismail NH, Jantan I, Wai LK. Inhibition of prostaglandin E(2) production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation. Bioorg Med Chem Lett. 2014;24(16):3826–3834. DOI: https://doi.org/10.1016/j.bmcl.2014.06.061
77. Noor Rain A, Khozirah S, Mohd Ridzuan M a. R, Ong BK, Rohaya C, Rosilawati M, Hamdino I, Badrul A, Zakiah I. Antiplasmodial properties of some Malaysian medicinal plants. Trop Biomed. 2007;24(1):29–35.
78. Caballero-George C, Gupta MP. A quarter century of pharmacognostic research on Panamanian flora: a review. Planta Med. 2011;77(11):1189–1202. DOI: https://doi.org/10.1055/s-0030-1271187
79. Boyom FF, Kemgne EM, Tepongning R, Ngouana V, Mbacham WF, Tsamo E, Zollo PHA, Gut J, Rosenthal PJ. Antiplasmodial activity of extracts from seven medicinal plants used in malaria treatment in Cameroon. J Ethnopharmacol. 2009;123(3):483–88. DOI: https://doi.org/10.1016/j.jep.2009.03.008
80. Rakotomanga M, Razakantoanina V, Raynaud S, Loiseau PM, Hocquemiller R, Jaureguiberry G. Antiplasmodial activity of acetogenins and inhibitory effect on Plasmodium falciparum adenylate translocase. J Chemother Florence Italy. 2004;16(4):350–356. DOI: https://doi.org/10.1179/joc.2004.16.4.350
81. Melaku Y, Worku T, Tadesse Y, Mekonnen Y, Schmidt J, Arnold N, Dagne E. Antiplasmodial Compounds from Leaves of Dodonaea angustifolia. Curr Bioact Compd. 2017;13(3):268–273. DOI: https://doi.org/10.2174/1573407213666170403121222
82. Melaku Y, Solomon M, Eswaramoorthy R, Beifuss U, Ondrus V, Mekonnen Y. Synthesis, antiplasmodial activity and in silico molecular docking study of pinocembrin and its analogs. BMC Chem. 2022;16(1):36. DOI: https://doi.org/10.1186/s13065-022-00831-z
83. AL-Ishaq RK, Abotaleb M, Kubatka P, Kajo K, Büsselberg D. Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels. Biomolecules. 2019;9(9):430. DOI: https://doi.org/10.3390/biom9090430
84. Sarian MN, Ahmed QU, Mat So’ad SZ, Alhassan AM, Murugesu S, Perumal V, Syed Mohamad SNA, Khatib A, Latip J. Antioxidant and Antidiabetic Effects of Flavonoids: A Structure-Activity Relationship Based Study. BioMed Res Int. 2017;2017:8386065. DOI: https://doi.org/10.1155/2017/8386065
85. Teerapongpisan P, Suthiphasilp V, Kumboonma P, Maneerat T, Duangyod T, Charoensup R, Promnart P, Laphookhieo S. Aporphine alkaloids and a naphthoquinone derivative from the leaves of Phaeanthus lucidus Oliv. and their α-glucosidase inhibitory activity. Phytochemistry. 2024;220:114020. DOI: https://doi.org/10.1016/j.phytochem.2024.114020
86. Antunes C, Arbo MD, Konrath EL. Hepatoprotective Native Plants Documented in Brazilian Traditional Medicine Literature: Current Knowledge and Prospects. Chem Biodivers. 2022;19(6):e202100933. DOI: https://doi.org/10.1002/cbdv.202100933
87. Tran LTT, Pham LHD, Dang NYT, Nguyen Le NT, Nguyen HB, Nguyen TK. Phytochemicals Derived from Goniothalamus elegans Ast Exhibit Anticancer Activity by Inhibiting Epidermal Growth Factor Receptor. Nat Prod Commun. 2022;17(11):1934578X221138435. DOI: https://doi.org/10.1177/1934578X221138435
88. Alkofahi A, Rupprecht JK, Smith DL, Chang CJ, McLaughlin JL. Goniothalamicin and annonacin: bioactive acetogenins from Goniothalamus giganteus (Annonaceae). Experientia. 1988;44(1):83–85. DOI: https://doi.org/10.1007/BF01960258
89. Tip-pyang S, Limpipatwattana Y, Khumkratok S, Siripong P, Sichaem J. A new cytotoxic 1-azaanthraquinone from the stems of Goniothalamus laoticus. Fitoterapia. 2010;81(7):894–896. DOI: https://doi.org/10.1016/j.fitote.2010.05.019
90. Lan YH, Chang FR, Liaw CC, Wu CC, Chiang MY, Wu YC. Digoniodiol, Deoxygoniopypyrone A, and Goniofupyrone A: Three New Styryllactones from Goniothalamus amuyon. Planta Med. 2005;71(2):153–159. DOI: https://doi.org/10.1055/s-2005-837783
91. Pérez Zamora CM, Torres CA, Nuñez MB. Antimicrobial Activity and Chemical Composition of Essential Oils from Verbenaceae Species Growing in South America. Mol J Synth Chem Nat Prod Chem. 2018;23(3):544. DOI: https://doi.org/10.3390/molecules23030544
92. Magnani RF, Volpe HXL, Luvizotto RAG, Mulinari TA, Agostini TT, Bastos JK, Ribeiro VP, Carmo-Sousa M, Wulff NA, Peña L, Leal WS. α-Copaene is a potent repellent against the Asian Citrus Psyllid Diaphorina citri. Sci Rep. 2025;15(1):3564. DOI: https://doi.org/10.1038/s41598-025-86369-1


