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INNOSC Theranostics and
Pharmacological Sciences Therapeutic value of terpenes

have gained significant interest in medicine, research, and Monoterpenes, such as linalool, myrcene, limonene,
drug discovery and development (e.g., cannabinergic, and 1,8-cineole in particular, are strong candidates for
cannabimimetic, and cannabinoid-based therapeutic the treatment of chronic pain (e.g., chronic muscle pain,
drugs) to inhibit the metabolic pathways and/or agonism cancer-related pain, chronic inflammatory pain, and
or antagonism of the ECS receptors. 165,166 Consequently, neuropathic pain). 139,182,188-191 Likewise, the combination
ECS regulation enables the treatment of a wide range of cannabinoids and flavonoids may be used to treat
of diseases, including (but not limited to) general pain, headaches and migraines. 64
headache, migraine, glaucoma, mood and anxiety The analgesic activity of terpenes involves stimulating
disorders, obesity/metabolic syndrome, osteoporosis, the release of anti-inflammatory cytokines, regulating
182
neuromotor, neuropsychological and neurodegenerative ion channels (e.g., transient receptor potential cation
diseases, respiratory diseases (i.e., asthma), and vascular channels), and directly acting on nociceptive afferent
192
diseases such as stroke, atherosclerosis, myocardial fibers through multiple receptors (e.g., opioid, adenosine
75
infarction, arrhythmias, and hypertension. 49,165-170
A1 and A2, and capsaicin). 151,191,193-196 The possible
3.3. Antimicrobial properties of terpenes mechanisms of analgesic and antinociceptive actions of
terpenes and their derivatives are displayed in Table 4.
The antimicrobial properties of essential oils are well
established and are primarily attributed to the presence Furthermore, terpenes can also enhance skin
of a complex mixture of terpenes and other secondary permeability and drug permeation by promoting
metabolites. 18,19,24,77,171-180 In a 2019 study, Guimarães et al. interactions with the lipid bilayer of the stratum corneum
investigated that the antibacterial activities of terpenes of the human skin. Therefore, terpenes are good candidates
and terpenoids present in essential oils against bacteria for transdermal and transmucosal drug delivery systems,
such as Salmonella enterica and Staphylococcus aureus. particularly for pain relief and management. 197
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Terpenes (i.e., eugenol and terpineol) demonstrated 3.5. Anti-inflammatory properties of terpenes
rapid bactericidal action against S. enterica serovar
Typhimurium and S. aureus, respectively, while other The pathological development of inflammatory
terpenes (i.e., carveol, citronella, and geraniol) exhibited diseases is regulated by NF-κB and is characterized
significant bactericidal activity against Escherichia coli. by an overproduction of inflammatory cytokines
77
Therefore, terpenes may serve as a suitable alternative to (e.g., interleukin-6 [IL-6, IL-1β, IL-4, IL-8, IL-17, and tumor
current antibiotics when antibiotic resistance becomes a necrosis factor-alpha [TNF-α]). Nonetheless, terpenes
critical issue. have demonstrated the ability to inhibit the inflammation-
associated signaling pathways by downregulating the
3.4. Analgesic and anti-nociceptive properties of expression of specific inflammatory cytokines. 208-213
terpenes
D-Limonene reportedly inhibited several pro-
The demand for analgesic drugs continues to increase due inflammatory cytokines, i.e., IL-1β, IL-4, IL-8, and
to the increasing prevalence of pain (of all sorts) affecting IL-17, 197,214-218 thereby suggesting a protective role
people worldwide, leading to a growing interest in novel against various inflammatory disorders, such as asthma,
therapeutic options. The analgesic potential of terpenes rheumatoid arthritis, inflammatory bowel disease,
181
is also well studied and documented, 75,182 particularly in skin inflammation, and psoriasis. 219-223 Artemisinin has
animals subjected to pain and nociceptive tests, such as reportedly treated inflammation-associated pain that is
hot-plate, formalin, tail-flick, and acetic acid-induced regulated by NF-κB signaling, promoted TNF-α-induced
writhing tests. apoptosis, inhibited ROS production, and blocked the
Plant species, such as Hyptis fruticosa Salzm. ex phosphorylation of p38 and ERK, both of which are pro-
Benth. (Lamiaceae), Hyptis pectinata Poit. (Lamiaceae), inflammatory processes. 208,221,224-226 In contrast, pinene,
Illicium lanceolatum A.C. Smith (Illiciaceae), Lippia linalool, and 1-octanol-inhibited COX-2 overexpression,
gracilis Schauer (Verbenaceae), Matricaria recutita L. inducible nitric oxide synthase (iNOS), and nociceptive
(Asteraceae), Mentha x villosa Huds (Labiatae), Pimenta stimulus-induced inflammatory infiltrate. 182,197,208,221,227
pseudocaryophyllus (Gomes) L.R. Landrum (Myrtaceae), Similarly, citral (geranial) and carvacrol activate the
and Erythrina velutina Willd. (Fabaceae), are known for peroxisome proliferator-activated receptors (PPAR) α
197
their therapeutic essential oils and are widely used in folk and γ. α-Terpineol reportedly inhibited the intracellular
147
medicine as analgesics and antinociceptives. 183-187 These formation of IL-6, while borneol, linalool, catalpol,
properties are primarily due to the presence of terpenoids carvacrol, citronellol, geniposide, paeoniflorin, and
(monoterpenes and sesquiterpenes) and phenylpropanoids. 1,8-cineole (eucalyptol) inhibited the expression of

Volume 7 Issue 3 (2024) 6 doi: 10.36922/itps.0332