Medical Research Terpenes (general)

Terpenes as Drug Potentiators

Written by Sabina Pulone

Terpenes are the primary constituents of the essential oils of many type of plants and flowers, and are

capable of mediating various ecological interactions essential for a plant’s growth, such as engaging the attention of the pollinators, defending the plants from herbivores or attracting them, protecting the plants from diseases, and potentially participating in plant-plant interactions among other things. [1] These aromatic compounds are formed by a “head-to-tail” junction of isoprene units to form cyclic or acyclic structures. Depenging on the number of carbon atoms, terpenes can be classified into monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), triterpenes (C30), etc.

Terpenes and their functionalized counterparts, terpenoids, are pharmacologically versatile: they are lipophilic molecules and are capable of interacting with cell membranes, neuronal and muscle ion channels, neurotransmitter receptors, G-protein coupled receptors, and enzymes. [2] Exploited since ancient times in folk medicine and agro-food applications, terpenes are well-known for their antiseptic and medicinal effects such as analgesic, sedative, anti-inflammatory, antioxidant, spasmolytic, local anesthetic, and anti-carcinogenic properties. Low molecular weight terpenes such as limonene, geraniol, menthol, etc. can act as penetration enhancers for skin products by disrupting the stratum corneum lipid structure, thereby facilitating the transport of drugs through skin. [3]

With the increasing demand of reducing chemicals in the field of nutrition and defeating more aggressive multidrug resistent (MDR) microorganisms, terpenes attained great interest in the scientific community for their antimicrobial and antifungal properties. Combination therapy with terpenes is widely used in current therapeutic practices and there is nowadays a large array of in vitro and in vivo studies reporting increased and synergistic activity against MDR microorganisms combining various kind of these natural compounds with existing antifungals and antibiotics. [4] Moreover, structural modifications of terpenes either synthetically or via biotransformation may offer another method to face antimicrobial resistent (AMR) pathogens. [5]

Nevertheless, the precise mode of action of terpenes as antibiotics has yet to be clarified and more studies should be done regarding their toxicity and structure-activity relationships to develop these natural potentiators in combination with currently used antimicrobials.

Interestingly, various terpenes and derivatives have been recently investigated as potential sources for antiviral agents against the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), to be used as treatments or adjuvants to current COVID-19 therapies. [6] (See article by Susan Trapp, Ph.D., here.) The pharmacokinetic and the pharmacodynamic of these compounds are still arguments of research and more studies have to be done to highlight the most promising molecular scaffolds for the development of effective therapeutic alternatives anti SARS-CoV-2. [7]



[1] Omar J, Olivares M, Alonso I, Vallejo A, Aizpurua-Olaizola O, Etxebarria N. Quantitative analysis of bioactive compounds from aromatic plants by means of dynamic headspace extraction and multiple headspace extraction-gas chromatography-mass spectrometry. J Food Sci. 2016;81(4):C867-C873. [journal impact factor = 3.167; times cited =17] [2] Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology. 2011;163(7):1344-1364. doi:10.1111/j.1476-5381.2011.01238.x [journal impact factor = 8.740; times cited = 1379] [3] Varman RM, Singh S. Investigation of effects of terpene skin penetration enhancers on stability and biological activity of lysozyme. AAPS PharmSciTech. 2012;13(4):1084-1090. doi:10.1208/s12249-012-9840-1 [journal impact factor = 3.246; times cited = 27] [4] Cappiello F, Loffredo MR, Del Plato C, et al. The Revaluation of plant-derived terpenes to fight antibiotic-resistant infections. Antibiotics (Basel). 2020;9(6):325. [journal impact factor = 4.36; times cited = 14] [5] Mahizan NA, Yang SK, Moo CL, et al. Terpene derivatives as a potential agent against antimicrobial resistance (AMR) pathogens. Molecules. 2019;24(14):2631. [journal impact factor = 4.411; times cited = 130] [6] Chatow L, Nudel A, Nesher I, et al. In Vitro Evaluation of the activity of terpenes and cannabidiol against human coronavirus E229. Life (Basel). 2021;11(4):290. [journal impact factor = 3.817; times cited = 2] [7] Diniz LRL, Perez-Castillo Y, Elshabrawy HA, Filho CDSMB, de Sousa DP. Bioactive terpenes and their derivatives as potential SARS-CoV-2 proteases inhibitors from molecular modeling studies. Biomolecules. 2021;11(1):74. [journal impact factor = 4.69; times cited = 14]



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Sabina Pulone

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