Terpenes are structurally diverse natural compounds synthesized by plants, fungi, and marine organisms, exhibiting critical ecological functions and remarkable pharmacological potential. Their wide-ranging bioactivities include antimicrobial, anti-inflammatory, antioxidant, anticancer, and neuroprotective effects, making them promising leads for therapeutic development. However, their clinical utility is limited by low aqueous solubility, instability, and poor bioavailability. This review systematically integrates the structural subclasses of terpenes, monoterpenes, sesquiterpenes, diterpenes, triterpenes, tetraterpenes, and marine-derived analogues, with innovative formulation approaches that enhance pharmacokinetics and therapeutic performance. Emphasis is placed on nanotechnology-based delivery systems, such as nanoemulsions, liposomes, polymeric nanoparticles, and nanostructured lipid carriers, which have demonstrated substantial improvements in solubility, stability, and bioavailability. Clinical trial outcomes and pharmacokinetic data highlight significant gains, with several terpenes achieving enhanced oral bioavailability, reduced dosage requirements, and improved safety profiles. Structure–activity relationship analyses further elucidate how functional groups, stereochemistry, and conjugation length critically influence biological activity and therapeutic outcomes. Beyond pharmacology, this review underscores the ecological and industrial significance of terpenes, ranging from plant defense and pollination to their use in cosmetics, food, and biotechnology. Looking forward, interdisciplinary strategies such as synthetic biology, CRISPR-based genome editing, metabolic engineering, and AI-driven drug discovery are expected to revolutionize terpene research by enabling sustainable production, rational design of derivatives, and advanced targeted delivery. Collectively, these advances position terpenes as multifunctional biomolecules with the potential to bridge natural product chemistry, nanomedicine, and clinical therapeutics, thereby opening new avenues for drug discovery, biotechnology, and sustainable healthcare innovations.
Anjali KM, Raghav A, Chauhan AS, Kumar P. Natural terpenes: An overview of structural diversity and multifunctional applications. J Appl Pharm Sci. 2025. Article in Press. http://doi.org/10.7324/JAPS.2026.274026
1. Jahangeer M, Fatima R, Ashiq M, Basharat A, Qamar SA, Bilal M, et al. Therapeutic and biomedical potentialities of terpenoids-a review. J Pure Appl Microbiol. 2021;15(2):471–83. doi: https://doi.org/10.22207/JPAM.15.2.04
2. Del Prado-audelo ML, Cortés H, Caballero-Florán IH, González- Torres M, Escutia-Guadarrama L, Bernal-Chávez SA, et al. Therapeutic applications of terpenes on inflammatory diseases. Front Pharmacol. 2021;12:704197. doi: https://doi.org/10.3389/FPHAR.2021.704197
3. Proshkina E, Plyusnin S, Babak T, Lashmanova E, Maganova F, Koval L, et al. Terpenoids as potential geroprotectors. Antioxidants. 2020;9:529. doi: https://doi.org/10.3390/ANTIOX9060529
4. Yamada Y, Kuzuyama T, Komatsu M, Shin-Ya K, Omura S, Cane DE, et al. Terpene synthases are widely distributed in bacteria. Proc Natl Acad Sci U S A. 2015;112:857–62. doi: https://doi.org/10.1073/PNAS.1422108112
5. Elshafie HS, Camele I. An overview of the biological effects of some mediterranean essential oils on human health. Biomed Res Int. 2017;2017:9268468. doi: https://doi.org/10.1155/2017/9268468
6. Bunse M, Daniels R, Gründemann C, Heilmann J, Kammerer DR, Keusgen M, et al. Essential oils as multicomponent mixtures and their potential for human health and well-being. Front Pharmacol. 2022;13:956541. doi: https://doi.org/10.3389/fphar.2022.956541.
7. Koyama S, Heinbockel T. The effects of essential oils and terpenes in relation to their routes of intake and application. Int J Mol Sci. 2020;21:1558. doi: https://doi.org/10.3390/IJMS21051558
8. Sharifi-Rad J, Sureda A, Tenore G, Daglia M, Sharifi-Rad M, Valussi M, et al. Biological activities of essential oils: from plant chemoecology to traditional healing systems. Molecules. 2017;22:70. doi: https://doi.org/10.3390/MOLECULES22010070
9. Marshall B, Amritkar K, Wolfe M, Kaçar B, Landick R. Evolutionary flexibility and rigidity in the bacterial methylerythritol phosphate (MEP) pathway. Front Microbiol. 2023;14:1286626. doi: https://doi.org/10.3389/FMICB.2023.1286626/FULL
10. Bergman ME, Davis B, Phillips MA. Medically useful plant terpenoids: biosynthesis, occurrence, and mechanism of action. Molecules. 2019;24:3961. doi: https://doi.org/10.3390/MOLECULES24213961
11. Mosquera MEG, Jiménez G, Tabernero V, Vinueza-Vaca J, García- Estrada C, Kosalková K, et al. Terpenes and terpenoids: building blocks to produce biopolymers. Sustain Chem. 2021;2:467–92. doi: https://doi.org/10.3390/SUSCHEM2030026
12. Ninkuu V, Zhang L, Yan J, Fu Z, Yang T, Zeng H. Biochemistry of terpenes and recent advances in plant protection. Int J Mol Sci. 2021;22:5710. doi: https://doi.org/10.3390/IJMS22115710
13. Kasahara H, Hanada A, Kuzuyama T, Takagi M, Kamiya Y, Yamaguchi S. Contribution of the mevalonate and methylerythritol phosphate pathways to the biosynthesis of Gibberellins in Arabidopsis. J Biol Chem. 2002;277:45188–494. doi: https://doi.org/10.1074/jbc.M208659200
14. Masyita A, Mustika Sari R, Dwi Astuti A, Yasir B, Rahma Rumata N, Emran TB, et al. Terpenes and terpenoids as main bioactive compounds of essential oils, their roles in human health and potential application as natural food preservatives. Food Chem X. 2022;13:100217. doi: https://doi.org/10.1016/J.FOCHX.2022.100217
15. Siddiqui T, Khan MU, Sharma V, Gupta K. Terpenoids in essential oils: Chemistry, classification, and potential impact on human health and industry. Phytomed Plus. 2024;4:100549. doi: https://doi.org/10.1016/J.PHYPLU.2024.100549
16. Brock NL, Dickschat JS. Biosynthesis of terpenoids. In: Ramawat K, Mérillon JM, editors. Natural products. Berlin, Heidelberg: Springer; 2013:2693–732. doi: https://doi.org/10.1007/978-3-642-22144-6_121
17. Li C, Zha W, Li W, Wang J, You A. Advances in the biosynthesis of terpenoids and their ecological functions in plant resistance. Int J Mol Sci. 2023;24:11561. doi: https://doi.org/10.3390/IJMS241411561
18. Coca-Ruíz V, Suárez I, Aleu J, Collado IG. Structures, occurrences and biosynthesis of 11,12,13-Tri-nor-sesquiterpenes, an intriguing class of bioactive metabolites. Plants. 2022;11:769. doi: https://doi.org/10.3390/PLANTS11060769
19. Singh A, Singh L. Acyclic sesquiterpenes nerolidol and farnesol: mechanistic insights into their neuroprotective potential. Pharmacol Rep. 2025;77: 31–42. doi: https://doi.org/10.1007/S43440-024-00672-8
20. Chemistry LibreTexts. n.d. Chirality and Stereoisomers. [cited 2025 March 7] Available from: https://chem.libretexts.org/Bookshelves/OrganicChemistry/SupplementalModules(OrganicChemistry)/Chirality/ChiralityandStereoisomers
21. Kvittingen L, Sjursnes BJ, Schmid R. Limonene in citrus: a string of unchecked literature citings?. J Chem Educ. 2021;98:3600–7. doi: https://doi.org/10.1021/ACS.JCHEMED.1C00363/SUPPL_FILE/ED1C00363_SI_002.DOCX
22. Trepa M, Su?kowska-Ziaja K, Ka?a K, Muszy?ska B. Therapeutic potential of fungal terpenes and terpenoids: application in skin diseases. Molecules. 2024;29:1183. doi: https://doi.org/10.3390/MOLECULES29051183
23. Rodrigues ACJ, Carloto ACM, Gonçalves MD, Concato VM, Detoni MB, Santos YMD, et al. Exploring the leishmanicidal potential of terpenoids: a comprehensive review on mechanisms of cell death. Front Cell Infect Microbiol. 2023;13:1260448. doi: https://doi.org/10.3389/FCIMB.2023.1260448
24. Pattanaik B, Lindberg P. Terpenoids and their biosynthesis in cyanobacteria. Life. 2015;5:269. doi: https://doi.org/10.3390/LIFE5010269
25. Vavitsas K, Fabris M, Vickers C. Terpenoid metabolic engineering in photosynthetic microorganisms. Genes. 2018;9:520. doi: https://doi.org/10.3390/GENES9110520
26. Yang J, Lee SY, Jang SK, Kim KJ, Park MJ.Anti-inflammatory effects of essential oils from the peels of citrus cultivars. Pharmaceutics. 2023;15:1595. doi: https://doi.org/10.3390/PHARMACEUTICS15061595
27. Hou CY, Hazeena SH, Hsieh SL, Li BH, Chen MH, Wang PY, et al. Effect of D-limonene nanoemulsion edible film on banana (Musa sapientum Linn.) post-harvest preservation. Molecules. 2022;27: :6157. doi: https://doi.org/10.3390/MOLECULES27196157
28. Wei J, Yang Y, Peng Y, Wang S, Zhang J, Liu X, et al. Biosynthesis and the transcriptional regulation of terpenoids in tea plants (Camellia sinensis). Int J Mol Sci. 2023;24:6937. doi: https://doi.org/10.3390/IJMS24086937
29. Klawitter J, Weissenborn W, Gövon I, Walz M, Klawitter J, Jackson M, et al. B-caryophyllene inhibits monoacylglycerol lipase activity and increases 2-arachidonoyl glycerol levels in vivo: a new mechanism of endocannabinoid-mediated analgesia?. S Mol Pharmacol. 2024;105:75–83. doi: https://doi.org/10.1124/MOLPHARM.123.000668/-/DC1
30. Amalraj A, Jacob J, Varma K, Gopi S. Preparation and characterization of liposomal β-caryophyllene (rephyll) by nanofiber weaving technology and its effects on delayed onset muscle soreness (DOMS) in humans: a randomized, double-blinded, crossover-designed, and placebo-controlled study. ACS Omega. 2020;5:24045. doi: https://doi.org/10.1021/ACSOMEGA.0C03456
31. Nicolaou KC, Riemer C, Kerr MA, Rideout DR, Wrasidlo WW. Design, synthesis and biological activity of protaxols. Nature. 1993;364:464–6. doi: https://doi.org/10.1038/364464a0
32. Palumbo R, Sottotetti F, Trifirò G, Piazza E, Ferzi A, Gambaro A, et al. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer patients: prospective evaluation of activity, safety, and quality of life. Drug Des Devel Ther. 2015;9:2189. doi: https://doi.org/10.2147/DDDT.S79563
33. Xie C, Gu J, Zhu S. Progress in research on terpenoid biosynthesis and terpene synthases of Lauraceae species. Forests. 2024;15:1731. doi: https://doi.org/10.3390/F15101731
34. Cox-Georgian D, Ramadoss N, Dona C, Basu C. Therapeutic and medicinal uses of terpenes. Med Plants. 2019;2019:333. doi: https://doi.org/10.1007/978-3-030-31269-5_15
35. Holopainen JK, Himanen SJ, Yuan JS, Chen F, Stewart CN. Ecological functions of terpenoids in changing climates. In: Ramawat K, Mérillon JM. editors, Natural products. Berlin, Heidelberg: Springer; 2013:2913–40. doi: https://doi.org/10.1007/978-3-642-22144-6_129
36. Al-Khayri JM, Rashmi R, Toppo V, Chole PB, Banadka A, Sudheer WN, et al. Plant secondary metabolites: the weapons for biotic stress management. Metabolites. 2023;13:716. doi: https://doi.org/10.3390/METABO13060716
37. Khwaza V, Aderibigbe BA. Antibacterial activity of selected essential oil components and their derivatives: a review. Antibiotics. 2025;14:68. doi: https://doi.org/10.3390/ANTIBIOTICS14010068
38. Rakoczy K, Szyma?ska N, Stecko J, Kisiel M, Maruszak M, Niedziela M, et al. Applications of limonene in neoplasms and non- neoplastic diseases. Int J Mol Sci. 2025;26:6359. doi: https://doi.org/10.3390/IJMS26136359
39. Huang AC, Osbourn A. Plant terpenes that mediate below-ground interactions: prospects for bioengineering terpenoids for plant protection. Pest Manag Sci. 2019;75:2368. doi: https://doi.org/10.1002/PS.5410
40. Boncan DAT, Tsang SSK, Li C, Lee IHT, Lam HM, Chan TF, et al. Terpenes and Terpenoids in Plants: interactions with Environment and Insects. Int J Mol Sci. 2020;21:7382. doi: https://doi.org/10.3390/IJMS21197382
41. Maffei ME. Sites of synthesis, biochemistry and functional role of plant volatiles. South Afr J Botany. 2010;76:612–31. doi: https://doi.org/10.1016/J.SAJB.2010.03.003
42. Liktor-Busa E, Keresztes A, Lavigne J, Streicher JM, Largent- Milnes TM. Analgesic potential of terpenes derived from Cannabis sativa. Pharmacol Rev. 2021;73:1269. doi: https://doi.org/10.1124/PHARMREV.120.000046
43. Wang Z, Chen Y, Huang A, Wen H, Wu Y, Xu X, et al. Design, synthesis and biological evaluation of novel β-caryophyllene derivatives as potential anti-cancer agents through the ROS-mediated apoptosis pathway. RSC Med Chem. 2025;16:3174–89. doi: https://doi.org/10.1039/D4MD00951G
44. Dahham S, Tabana Y, Iqbal M, Ahamed M, Ezzat M, Majid A, et al. The anticancer, antioxidant and antimicrobial properties of the sesquiterpene β-caryophyllene from the essential oil of Aquilaria crassna. Molecules. 2015;20:11808. doi: https://doi.org/10.3390/MOLECULES200711808
45. Mumu M, Das A, Emran TB, Mitra S, Islam F, Roy A, et al. Fucoxanthin: a promising phytochemical on diverse pharmacological targets. Front Pharmacol. 2022;13:929442. doi: https://doi.org/10.3389/FPHAR.2022.929442/FULL
46. Gammone MA, D’Orazio N. Anti-obesity activity of the marine carotenoid fucoxanthin. Mar Drugs. 2015;13:2196–4. doi: https://doi.org/10.3390/MD13042196
47. Huang Q, Chen H, Ren Y, Wang Z, Zeng P, Li X, et al. Anti-hepatocellular carcinoma activity and mechanism of chemopreventive compounds: ursolic acid derivatives. Pharm Biol. 2016;54:3189–96. doi: https://doi.org/10.1080/13880209.2016.1214742
48. Zhang DM, Tang PMK, Chan JYW, Lam HM, Au SWN, Kong SK, et al. Anti-proliferative effect of ursolic acid on multidrug resistant hepatoma cells R-HepG2 by apoptosis induction. Cancer Biol Therapy. 2007;6:1381–9. doi: https://doi.org/10.4161/cbt.6.9.4528
49. Mahizan NA, Yang SK, Moo CL, Song AAL, Chong CM, Chong CW, et al. Terpene derivatives as a potential agent against antimicrobial resistance (AMR) pathogens. Molecules. 2019;24:2631. doi: https://doi.org/10.3390/MOLECULES24142631
50. El Fannassi Y, Gharsallaoui A, Khelissa S, El Amrani MA, Suisse I, Sauthier M, et al. Complexation of terpenes for the production of new antimicrobial and antibiofilm molecules and their encapsulation in order to improve their activities. Appl Sci. 2023;13:9854. doi: https://doi.org/10.3390/APP13179854
51. Kamran S, Sinniah A, Abdulghani MAM, Alshawsh MA. Therapeutic potential of certain terpenoids as anticancer agents: a scoping review. Cancers. 2022;14:1100. doi: https://doi.org/10.3390/CANCERS14051100/S1
52. Gonçalves ECD, Baldasso GM, Bicca MA, Paes RS, Capasso R, Dutra RC. Terpenoids, cannabimimetic ligands, beyond the cannabis plant. Molecules. 2020;25:1567. doi: https://doi.org/10.3390/MOLECULES25071567
53. De Cássia Da Silveira E Sá R, Andrade L, De Sousa D. A review on anti-inflammatory activity of monoterpenes. Molecules. 2013;18:1227. doi: https://doi.org/10.3390/MOLECULES18011227
54. Potocka W, Assy Z, Bikker FJ, Laine ML. Current and potential applications of monoterpenes and their derivatives in oral health care. Molecules. 2023;28:7178. doi: https://doi.org/10.3390/MOLECULES28207178
55. Meeran MFN, Al Taee H, Azimullah S, Tariq S, Adeghate E, Ojha S. Β-Caryophyllene, a natural bicyclic sesquiterpene attenuates doxorubicin-induced chronic cardiotoxicity via activation of myocardial cannabinoid type-2 (CB2) receptors in rats. Chem Biol Interact. 2019;304:158–67. doi: https://doi.org/10.1016/J.CBI.2019.02.028
56. Andrade-Silva M, Correa LB, Candéa ALP, Cavalher-Machado SC, Barbosa HS, Rosas EC, et al. The cannabinoid 2 receptor agonist β-caryophyllene modulates the inflammatory reaction induced by Mycobacterium bovis BCG by inhibiting neutrophil migration. Inflamm Res. 2016;65:869–79. doi: https://doi.org/10.1007/S00011- 016-0969-3
57. Schneider F, Pan L, Ottenbruch M, List T, Gaich T. The chemistry of nonclassical taxane diterpene. Acc Chem Res. 2021;54:2347–60. doi: https://doi.org/10.1021/ACS.ACCOUNTS.0C00873
58. Sati P, Sharma E, Dhyani P, Attri DC, Rana R, Kiyekbayeva L, et al. Paclitaxel and its semi-synthetic derivatives: comprehensive insights into chemical structure, mechanisms of action, and anticancer properties. Eur J Med Res. 2024;29:90. doi: https://doi.org/10.1186/S40001-024-01657-2
59. Kashyap D, Sharma AS, Tuli H, Punia SK, Sharma A. Ursolic acid and oleanolic acid: pentacyclic terpenoids with promising anti-inflammatory activities. Recent Pat Inflamm Allergy Drug Discov. 2016;10:21–33. doi: https://doi.org/10.2174/1872213X10666160711143904
60. Similie D, Minda D, Bora L, Kroškins V, Lugi?ina J, Turks M, et al. An update on pentacyclic triterpenoids ursolic and oleanolic acids and related derivatives as anticancer candidates. Antioxidants. 2024;13:952. doi: https://doi.org/10.3390/ANTIOX13080952
61. Wróblewska-?uczka P, Cabaj J, Bargie? J, ?uszczki JJ.Anticancer effect of terpenes: focus on malignant melanoma. Pharmacol Rep. 2023;75:1115. doi: https://doi.org/10.1007/S43440-023-00512-1
62. Lou J, Duan H, Qin Q, Teng Z, Gan F, Zhou X, et al. Advances in oral drug delivery systems: challenges and opportunities. Pharmaceutics. 2023;15:484. doi: https://doi.org/10.3390/PHARMACEUTICS15020484
63. Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol. 2018;16(1):1– 33. doi: https://doi.org/10.1186/S12951-018-0392-8
64. Kurul F, Turkmen H, Cetin AE, Topkaya SN. Nanomedicine: how nanomaterials are transforming drug delivery, bio-imaging, and diagnosis. Next Nanotechnol. 2025;7:100129. doi: https://doi.org/10.1016/J.NXNANO.2024.100129
65. Montero AJ, Adams B, Diaz-Montero CM, Glück S. Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. Expert Rev Clin Pharmacol. 2011;4:329–4. doi: https://doi.org/10.1586/ECP.11.7
66. Rivera-Pérez E, Escobar-Ortiz A, Pérez-Ramírez IF, Regalado- González C, Zubieta-Otero LF, Rodríguez-García ME, et al. Encapsulation of spray-dried curcumin nanoemulsions to develop a supplement with ingredients for the control of osteoarthritis. J Drug Deliv Sci Technol. 2023;82:104299. doi: https://doi.org/10.1016/J.JDDST.2023.104299
67. Mumu M, Das A, Emran T Bin, Mitra S, Islam F, Roy A, et al. Fucoxanthin: a promising phytochemical on diverse pharmacological targets. Front Pharmacol. 2022;13:929442. doi: https://doi.org/10.3389/FPHAR.2022.929442
68. Hosseini M, Pereira DM. The chemical space of terpenes: insights from data science and AI. Pharmaceuticals. 2023;16:202. doi: https://doi.org/10.3390/PH16020202
69. Yadav H, Mahalvar A, Pradhan M, Yadav K, Kumar Sahu K, Yadav R. Exploring the potential of phytochemicals and nanomaterial: a boon to antimicrobial treatment. Med Drug Discov. 2023;17:100151. doi: https://doi.org/10.1016/J.MEDIDD.2023.100151
70. Jadhav LA, Mandlik SK. Nanocarriers in skin cancer treatment: emerging drug delivery approaches and innovations. Nano TransMed. 2025;4:100068. doi: https://doi.org/10.1016/J.NTM.2024.100068
71. Chehelgerdi M, Chehelgerdi M, Allela OQB, Pecho RDC, Jayasankar N, Rao DP, et al. Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation. Mol Cancer. 2023;22:169. doi: https://doi.org/10.1186/S12943-023-01865-0
72. Markovic M, Ben-Shabat S, Dahan A. Prodrugs for improved drug delivery: lessons learned from recently developed and marketed products. Pharmaceutics. 2020;12:1031. doi: https://doi.org/10.3390/pharmaceutics12111031
73. Elbouzidi A, Haddou M, Baraich A, Taibi M, El Hachlafi N, Pareek A, et al. Biochemical insights into specialized plant metabolites: advancing cosmeceutical applications for skin benefits. J Agric Food Res. 2025;19:101651. doi: https://doi.org/10.1016/J.JAFR.2025.101651
74. Vaou N, Stavropoulou E, Voidarou C, Tsigalou C, Bezirtzoglou E. Towards advances in medicinal plant antimicrobial activity: a review study on challenges and future perspectives. Microorganisms. 2021;9:2041. doi: https://doi.org/10.3390/MICROORGANISMS9102041
75. Kim YW, Kim MJ, Chung BY, Bang DY, Lim SK, Choi SM, et al. Safety evaluation and risk assessment of D-limonene. J Toxicol Environ Health B Crit Rev. 2013;16:17–38. doi: https://doi.org/10.1080/10937404.2013.769418
76. Ricardi C, Barachini S, Consoli G, Marazziti D, Polini B, Chiellini G. Beta-caryophyllene, a cannabinoid receptor type 2 selective agonist, in emotional and cognitive disorders. Int J Mol Sci. 2024;25:3203. doi: https://doi.org/10.3390/IJMS25063203
77. Muradian K, Vaiserman A, Min KJ, Fraifeld VE. Fucoxanthin and lipid metabolism: a minireview. Nutr Metab Cardiovasc Dis. 2015;25:891– 7. doi: https://doi.org/10.1016/J.NUMECD.2015.05.010
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