Toxicological and pharmacologic effects of farnesol (C15H26O): A descriptive systematic review

Delmondes, Gyllyandeson de Araújo; Bezerra, Daniel Souza; Dias, Diógenes de Queiroz; Borges, Alex de Souza; Araújo, Isaac Moura; Cunha, Glacithane Lins da; Bandeira, Paulo Felipe Ribeiro; Barbosa, Roseli; Coutinho, Henrique Douglas Melo; Felipe, Cícero Francisco Bezerra; Barbosa-Filho, José Maria; Menezes, Irwin Rose Alencar de; Kerntopf, Marta Regina

doi:10.1016/j.fct.2019.04.037

Cited by 36 publications

(26 citation statements)

References 96 publications

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“…Terpenes such as monoterpenes and sesquiterpenes are compounds commonly found in essential oils [16]. The interest in the study of terpenes has been increasing because they have been shown to have multiple biological attributes that can be useful for the treatment of several diseases, including antifungal, antibacterial, antiviral, antitumor, antiparasitic, hypoglycemic, anti-inflammatory, and analgesic properties [16].…”

Section: Introductionmentioning

confidence: 99%

“…The interest in the study of terpenes has been increasing because they have been shown to have multiple biological attributes that can be useful for the treatment of several diseases, including antifungal, antibacterial, antiviral, antitumor, antiparasitic, hypoglycemic, anti-inflammatory, and analgesic properties [16]. Farnesol (molecular formula C 15 H 26 O; International Union of Pure and Applied Chemistry (IUPAC): 3,7,11-trimethyl-2,6,10-dodecatrien-1-ol), an alcohol found in essential oils, is a natural terpene formed by 15 carbos made in plant cells by farnesyl pyrophosphate dephosphorylation [16]. Farnesol has been shown to reduce serum triglyceride levels and prevent hyperglycemia and hepatic steatosis in obese animals with a high-fat diet [17].…”

Section: Introductionmentioning

confidence: 99%

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Structure–Activity Relationship Study of Acyclic Terpenes in Blood Glucose Levels: Potential α-Glucosidase and Sodium Glucose Cotransporter (SGLT-1) Inhibitors

2019

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Twelve terpenoids were evaluated in the treatment of type 2 diabetes mellitus: seven monoterpenes (geranyl acetate (1), geranic acid (2), citral (3), geraniol (4), methyl geranate (5), nerol (6), and citronellic acid (7)), three sesquiterpenes (farnesal (8), farnesol (9), and farnesyl acetate (10)), one diterpene (geranylgeraniol (11)), and one triterpene (squalene (12)) were selected to carry out a study on normoglycemic and streptozotocin-induced diabetic mice. Among these, 2, 3, 7, 8, 9, and 10 showed antihyperglycemic activity in streptozotocin-induced diabetic mice. They were then selected for evaluation in oral sucrose and lactose tolerance tests (OSTT and OLTT) as well as in an oral glucose tolerance test (OGTT). In the OSTT and OLTT, compounds 3, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a sucrose or lactose load (comparable to acarbose). In the case of the OGTT, 2, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a glucose load (comparable to canagliflozin). Our results suggest that the control of postprandial hyperglycemia may be mediated by the inhibition of disaccharide digestion, such as sucrose and lactose, and the regulation of the absorption of glucose. The first case could be associated with an ∝-glucosidase inhibitory effect and the second with an inhibition of the sodium–glucose type 1 (SGLT-1) cotransporter. Finally, five acyclic terpenes may be candidates for the development and search for new α-glucosidase and SGLT-1 cotransporter inhibitors.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structure–Activity Relationship Study of Acyclic Terpenes in Blood Glucose Levels: Potential α-Glucosidase and Sodium Glucose Cotransporter (SGLT-1) Inhibitors

2019

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“…In other words, due to relatively high values of the K i´s , the inhibition observed most probably does not pose real harm to microsomal drug metabolism as the levels of sesquiterpenes in plasma (assuming the use of these compounds as spices or flavoring additives) do not usually exceed micromolar range (Yang et al 2012, de Araújo Delmondes et al 2019. Hence, the interaction of drugs metabolized by CYP3A4 is less probable and the compounds can be expected to be safe.…”

Section: Discussionmentioning

confidence: 99%

β‐caryophyllene Oxide and Trans-nerolidol Affect Enzyme Activity of CYP3A4 – In Vitro and In Silico Studies

Špičáková

Bazgier²,

Skálová³

et al. 2019

Physiol Res

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Evaluation of possible interactions with enzymes of drug metabolism is an important part of studies on safety and, in general, on the properties of any drug or biologically active compound. Here, focus is given on interactions of three sesquiterpenes (β-caryophyllene oxide (CAO), trans-nerolidol (tNER) and farnesol (FAR)) with CYP3A4. To determine the CYP3A4 activity, specific substrates testosterone (TES) and midazolam (MDZ) were used. In human liver microsomes, the CAO inhibited the MDZ 1´-hydroxylation by mixed type inhibition and Ki 46.6 μM; TES 6-hydroxylation was inhibited more strongly by tNER by the same mechanism and with Ki of 32.5 μM. Results indicated a possibility of different mode of interaction of both compounds within the active site of CYP3A4 and this was why the molecular docking study was done. The docking experiments showed that the studied sesquiterpenes (CAO and tNER) bound to the CYP3A4 active site cause a significant decrease of binding affinity of substrates tested which corresponded well to the inhibition studies. The inhibition observed, however, most probably does not pose a real harm to microsomal drug metabolism as the levels of sesquiterpenes in plasma (assuming the use of these compounds as spices or flavoring additives) does not usually exceed micromolar range. Hence, the interaction of drugs metabolized by CYP3A4 with sesquiterpenes is less probable.

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“…Mass spectrometry has been used for their identification (26) and, within the methodological limitations, for quantification as well. De Araújo Delmondes et al (27) recently summarized the toxicological and pharmacological effects of farnesol. In insects, farnesol is best known as a precursor of the six presently known JHs.…”

Section: Chemical Properties Of Farnesol and Mode Of Actionmentioning

confidence: 99%

Intraluminal Farnesol and Farnesal in the Mealworm's Alimentary Canal: An Unusual Storage Site Uncovering Hidden Eukaryote Ca2+-Homeostasis-Dependent “Golgicrine” Activities

Loof

Schoofs

2019

Front. Endocrinol.

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Farnesol, the sesquiterpenoid precursor of the six presently known insect juvenile hormones (JHs) was for the first time chemically identified in 1961, not in JH synthesizing glands or whole body extracts, but in excrements of the mealworm Tenebrio molitor. This finding was thought to be irrelevant and remained unexplored. In 1970, it was reported that the fall to zero of the JH titer in both prediapausing adults and in last instar larvae of the Colorado potato beetle causes severe malfunctioning of the Golgi system in the fat body, among various other effects. This endomembrane system in the cytoplasm resides at the intersection of the secretory, lysosomal, and endocytic pathways and is required for the processing of secretory proteins. Why the Golgi needs farnesol-like endogenous sesquiterpenoids (FLS) for its proper functioning has also never been further investigated. In 1999, farnesol was found to be a natural endogenous ligand for particular types of voltage-gated Ca 2+ channels in mammalian cells, a finding that also remained undervalued. Only since 2014 more attention has been paid to the functional research of the "noble unknown" farnesol, in particular to its Ca 2+-homeostasis-related juvenilizing and anti-apoptotic activities. Here, we introduce the term "Golgicrine activity" that addresses the secretory activity of the RER-Golgi system from its role in Ca 2+-homeostasis rather than from its conventional role in mere protein secretion. Golgicrine activity attributes the so far forgotten role of farnesol-like sesquiterpenoids in proper Golgi functioning, and unites the endocrine, exocrine and enterocrine functions of these sesquiterpenoids. This out of the box view may open novel perspectives for the better understanding of particular inflammatory bowel diseases and of neurodegenerative diseases as well, because the early initiation of Alzheimer's disease may possibly result from malfunctioning of the mevalonate-farnesol-cholesterol biosynthetic pathway and thus might be a farnesol-and Ca 2+-homeostasis-dependent Golgicrine issue.

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Toxicological and pharmacologic effects of farnesol (C15H26O): A descriptive systematic review

Cited by 36 publications

References 96 publications

Structure–Activity Relationship Study of Acyclic Terpenes in Blood Glucose Levels: Potential α-Glucosidase and Sodium Glucose Cotransporter (SGLT-1) Inhibitors

Structure–Activity Relationship Study of Acyclic Terpenes in Blood Glucose Levels: Potential α-Glucosidase and Sodium Glucose Cotransporter (SGLT-1) Inhibitors

β‐caryophyllene Oxide and Trans-nerolidol Affect Enzyme Activity of CYP3A4 – In Vitro and In Silico Studies

Intraluminal Farnesol and Farnesal in the Mealworm's Alimentary Canal: An Unusual Storage Site Uncovering Hidden Eukaryote Ca2+-Homeostasis-Dependent “Golgicrine” Activities

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