Neuropharmacological properties of farnesol in Murine model

Research on new compounds of therapeutic value for behavioral disorders has progressed recently. Several studies have reported neuropharmacological activities of plant derived terpenes. Farnesol is a sesquiterpene whose most popular source is fruits but the anxiolytic activity for farnesol is still unknown. The present study was conducted on 32 male Swiss Albino mice (8 in each group) to evaluate the neuropharmacological properties of farnesol and its effects on plasma cortisol levels. Farnesol was administered intraperitoneally at single doses of 50 and 100 mg/kg, while diazepam 2 mg/kg was used as standard anxiolytic. Thirty minutes after injections, open field test (OFT), elevated plus maze (EPM), a forced swimming test (FST), and a hot plate test (HPT) were performed for evaluation of anxiety-like behavior, depression and nociception. In OFT, farnesol at the dose of 100 mg/kg led to significant decrease in locomotor activity (P<0.01). In EPM, only farnesol 100 mg/kg led to significant increase in the number of entries to the open arms and the time spent in open arms (P<0.01). Increase in immobility time in FST was seen in farnesol 50 and 100 mg/kg (P<0.001). Farnesol 100 mg/kg exerts significant prolongation in the latency of responses to noxious heat stimuli in HPT. Like diazepam, farnesol decreased plasma levels of cortisol. Results revealed that farnesol had anxiolytic, anti-nociceptive and depressant effects in murine models. The present study provides pharmacological evidence supporting the use of farnesol as a sedative for anxiety disorders.

[1]  S. Vasconcelos,et al.  Anxiolytic-like effect of the monoterpene 1,4-cineole in mice , 2010, Pharmacology Biochemistry and Behavior.

[2]  S. Sultana,et al.  Farnesol attenuates 1,2-dimethylhydrazine induced oxidative stress, inflammation and apoptotic responses in the colon of Wistar rats. , 2011, Chemico-biological interactions.

[3]  Jéssica Pereira Costa,et al.  Farnesol: antinociceptive effect and histopathological analysis of the striatum and hippocampus of mice , 2013, Fundamental & clinical pharmacology.

[4]  M. C. Archer,et al.  Farnesol Decreases Serum Triglycerides in Rats: Identification of Mechanisms Including Up-Regulation of PPARα and Down-Regulation of Fatty Acid Synthase in Hepatocytes , 2008, Lipids.

[5]  C. Stevens,et al.  Aquaporin 4 and glymphatic flow have central roles in brain fluid homeostasis , 2021, Nature Reviews Neuroscience.

[6]  S. Vasconcelos,et al.  Central nervous system activity of acute administration of isopulegol in mice , 2007, Pharmacology Biochemistry and Behavior.

[7]  N. Lajis,et al.  Preliminary analysis of the antinociceptive activity of zerumbone. , 2009, Fitoterapia.

[8]  D. Vohora,et al.  Possible involvement of corticosterone and serotonin in antidepressant and antianxiety effects of chromium picolinate in chronic unpredictable mild stress induced depression and anxiety in rats. , 2015, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[9]  Qiyang Shou,et al.  Therapeutic effects of propolis essential oil on anxiety of restraint-stressed mice , 2012, Human & experimental toxicology.

[10]  Lorne M. Isabelle,et al.  Association of 24-hour cortisol production rates, cortisol-binding globulin, and plasma-free cortisol levels with body composition, leptin levels, and aging in adult men and women. , 2004, The Journal of clinical endocrinology and metabolism.

[11]  D. P. de Sousa,et al.  Antinociceptive effect of citronellal in mice , 2010, Pharmaceutical biology.

[12]  Jéssica Pereira Costa,et al.  Evaluation of acute toxicity of a natural compound (+)-limonene epoxide and its anxiolytic-like action , 2012, Brain Research.

[13]  Jéssica Pereira Costa,et al.  Anxiolytic-like effects of phytol: Possible involvement of GABAergic transmission , 2014, Brain Research.

[14]  A. Jetten,et al.  Molecular mechanisms involved in farnesol-induced apoptosis. , 2010, Cancer letters.

[15]  C. Marsden,et al.  Acute effects of bergamot oil on anxiety‐related behaviour and corticosterone level in rats , 2011, Phytotherapy research : PTR.

[16]  D. C. Weaver The effects of diazepam. , 1969, Anesthesiology.

[17]  R. Kuster,et al.  Antinociceptive activity of fractions from Couroupita guianensis Aubl. leaves. , 2010, Journal of ethnopharmacology.

[18]  J. Jordán,et al.  Anxiolytic-like effects and mechanism of (−)-myrtenol: A monoterpene alcohol , 2014, Neuroscience Letters.

[19]  D. Sousa Analgesic-like activity of essential oils constituents. , 2011 .

[20]  R. Lea,et al.  Anxiolytic effects of Lavandula angustifolia odour on the Mongolian gerbil elevated plus maze. , 2007, Journal of ethnopharmacology.

[21]  M. Dos Santos,et al.  Antinociceptive effect of extract of Emilia sonchifolia in mice. , 2011, Journal of ethnopharmacology.

[22]  Michel Bourin,et al.  Forced swimming test in mice: a review of antidepressant activity , 2004, Psychopharmacology.

[23]  Anti-anxiety activity of Amorphophallus paeoniifolius tuber in mice , 2013 .

[24]  G. Crescimanno,et al.  The effects of diazepam on the behavioral structure of the rat's response to pain in the hot-plate test: Anxiolysis vs. pain modulation , 2012, Neuropharmacology.

[25]  R. M. Freitas,et al.  Antioxidant Effects of Nerolidol in Mice Hippocampus After Open Field Test , 2013, Neurochemical Research.

[26]  L. Quintans-Júnior,et al.  Terpenes and derivatives as a new perspective for pain treatment: a patent review , 2014, Expert opinion on therapeutic patents.

[27]  G. Viana,et al.  Anxiolytic‐like effect of Carvacrol (5‐isopropyl‐2‐methylphenol) in mice: involvement with GABAergic transmission , 2009, Fundamental & clinical pharmacology.

[28]  H. Mo,et al.  Volatile isoprenoid constituents of fruits, vegetables and herbs cumulatively suppress the proliferation of murine B16 melanoma and human HL-60 leukemia cells. , 2002, Cancer letters.

[29]  G. Sudhandiran,et al.  Farnesol attenuates lipopolysaccharide-induced neurodegeneration in Swiss albino mice by regulating intrinsic apoptotic cascade , 2015, Brain Research.

[30]  G. Cerqueira,et al.  Anxiolytic-like effects of carvacryl acetate, a derivative of carvacrol, in mice , 2013, Pharmacology Biochemistry and Behavior.

[31]  Ayako Yamada,et al.  Aromatic amino acid-leucine dipeptides exhibit anxiolytic-like activity in young mice , 2013, Neuroscience Letters.

[32]  A. Tommasini,et al.  Natural isoprenoids inhibit LPS-induced-production of cytokines and nitric oxide in aminobisphosphonate-treated monocytes. , 2010, International immunopharmacology.

[33]  M. Hascöet,et al.  Anxiolytic-like effects of 5-HT2 ligands on three mouse models of anxiety , 2003, Behavioural Brain Research.

[34]  Â.,et al.  The Essential Oils , 1949, Nature.

[35]  D. P. de Sousa,et al.  Analgesic-like Activity of Essential Oils Constituents , 2011, Molecules.

[36]  M. F. Agra,et al.  Essential Oils and Their Constituents: Anticonvulsant Activity , 2011, Molecules.

[37]  H. Tsang,et al.  A systematic review on the anxiolytic effects of aromatherapy in people with anxiety symptoms. , 2011, Journal of alternative and complementary medicine.

[38]  K. Ressler,et al.  Chronic overexpression of corticotropin-releasing factor from the central amygdala produces HPA axis hyperactivity and behavioral anxiety associated with gene-expression changes in the hippocampus and paraventricular nucleus of the hypothalamus , 2012, Psychoneuroendocrinology.

[39]  E. Caramão,et al.  Effects of inhaled Linalool in anxiety, social interaction and aggressive behavior in mice. , 2010, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[40]  J. Flório,et al.  The GABAergic system contributes to the anxiolytic-like effect of essential oil from Cymbopogon citratus (lemongrass). , 2011, Journal of ethnopharmacology.