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INNOSC Theranostics and
Pharmacological Sciences Therapeutic value of terpenes

of many cancers. 209,225,314,315 Other terpenes (e.g., menthol, ability to inhibit IL-6, a pro-inflammatory mediator. In
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β-caryophyllene, d-limonene, eugenol, and menthol) may addition, limonene reportedly inhibited the activation/
be used independently or with chemotherapeutic drugs phosphorylation of extracellular receptor kinase (ERK) that
to promote anticancer activity by inducing apoptosis is linked to oxidative stress and pro-inflammatory immune
or necrosis and inhibiting cell proliferation. Table 7 responses in the pathogenesis of Alzheimer’s disease. 348,349
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features several terpenes and terpenoids, as well as their The aforementioned sesquiterpenes have also
mechanisms of action against various cancers. displayed the inhibition of lipoxygenase (LOX), the
3.9. Neuroprotective properties of terpenes overactivity of which leads to synaptic dysfunction and
neuroinflammation. 117,344 In another study, 1,8-cineole,
Neurological disorders are those characterized by the bornyl acetate, terpinen-4-ol, and camphor (extracted
dysregulation of the neurons (nerve cells) in the brain or of the from essential oils of Rosmarinus officinalis L.) reportedly
central and peripheral nervous systems. Neurodegenerative inhibited LOX, while 1,8-cineole and 3-carene (also from
diseases (Alzheimer’s disease, amyotrophic lateral sclerosis, the same extract) reportedly inhibited AChE. The
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and Parkinson’s disease) are a subgroup of neurological inhibition of AChE and BChE increases acetylcholine
disorders characterized by progressive and inexorable levels to promote neural activity and regulate Alzheimer’s
damage to the nervous system and accompanied by loss disease, respectively. Similarly, the inhibition of LOX also
of neurological function. In 2019, it was estimated that ameliorated the inflammatory and immune responses in
10 million global deaths were attributed to neurological the brain tissue of patients with Alzheimer’s disease.
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disorders. Nonetheless, the increasing prevalence In a drosophila model of Aβ42-induced neurotoxicity
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of neurological disorders with the aging of the global in Alzheimer’s disease, ρ-cymene, (+)-limonene,
population has prompted the search for novel therapeutics. (-)-limonene, linalool, (+)-α-pinene, and (-)-β-pinene
Alzheimer’s disease is the most prevalent neurological demonstrated partial suppression of amyloid β42 (Aβ42)
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disorder, with an estimated 10 million global cases expression and accumulation in the flies.
diagnosed annually. 340,341 The WHO has estimated that Oxidative stress and the accumulation of ROS and
55 million people are currently suffering from dementia. reactive nitrogen species (RNS) are also characteristics of
It has also been predicted that the number of Alzheimer’s Alzheimer’s disease due to the decline in the antioxidant
cases will reach 75 million by 2030 and up to 135 million by activities of superoxide dismutase (SOD) and glutathione
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2050. 341,342 Dementia (of which 80% are due to Alzheimer’s peroxidase (GPx). In this context, monoterpenes, such
disease) alone accounted for US$1.3 trillion worldwide in as limonene and nerol, with strong antioxidant properties
2019 and is projected to exceed US$2.8 trillion by 2030. can also be considered neuroprotective agents. 117-119
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In the United States alone, this amount is estimated to Besides that, the regulation of inflammation may play an
surpass $800 billion annually. In addition, the increasing important role in ameliorating neurological disorders.
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prevalence of Parkinson’s disease and other neurological Likewise, non-degenerative neurological disorders
disorders (e.g., stroke and epilepsy) suggests that can be managed by terpenes in isolation or combination
neurological diseases will be a substantial health burden, with other agents. For example, caryophyllene and
and their management may not be affordable or accessible β-caryophyllene have been studied for treating somatic
to the less developed regions of the world. pain and migraine, respectively. In contrast, linalool may
Neuroprotective agents may increase the recovery and directly target GABAergic neurotransmission in epilepsy
regeneration or slow the rate of deterioration of nerve tissues and enhance the effects of other agents, similar to the
due to neurodegenerative diseases or other insults (e.g., entourage effect with cannabinoids.
ischemia or toxic injury). In one study, both monoterpenes 3.10. Antidiabetic properties of terpenes
and sesquiterpenes extracted from Citrus sinensis (orange)
by-products demonstrated the ability to cross the blood– Diabetes is another major health burden that affects
brain barrier, suggesting their potential as neuroprotective over 500 million people worldwide 252-354 with an
agents. Sesquiterpenes (e.g., δ-cadinene and nootkatone) estimated 6.7 million deaths annually. It is estimated
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and other more common terpenes (e.g., limonene, pulegone, that approximately 578 million people will be affected by
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carvone, and γ-terpinene) have demonstrated the capacity to diabetes by 2030 and up to 700 million people by 2045.
inhibit acetylcholinesterase (AChE) and butylcholinesterase Notably, the global health expenditure for diabetes is
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(BChE), both of which are involved in the formation of estimated at US$966 billion.
amyloid β plaques in Alzheimer’s disease. 117,344-347 The Diabetes mellitus is a chronic disease characterized by
terpenoids of the orange extract also demonstrated the impairment in the regulation of glucose in the blood (blood

Volume 7 Issue 3 (2024) 11 doi: 10.36922/itps.0332