| Description: |
(+)-Borneol is a bicyclic monoterpene used for analgesia and anaesthesia in traditional Chinese and Japanese medicine, it and its enantiomer (-)-borneol have a highly efficacious positive modulating action at GABA(A) receptors at human recombinant alpha1beta2gamma2L GABA(A) receptors. Borneol specifically inhibits the nicotinic acetylcholine receptor (nAChR)-mediated effects in a noncompetitive way, can depress P-glycoprotein function by a NF-κB signaling mediated mechanism in a blood brain barrier in vitro model. Borneol has neuroprotection through the inhibition of IκBα-NF-κB and translocation signaling pathway, it also has an anti-cerebral ischemia effects. It can suppresse inflammatory responses in LPS-induced acute lung injury through inhibition of the NF-κB and MAPKs signaling pathways. |
| Targets: |
P-gp | NF-kB | ROS | NO | NOS | JNK | p65 | IkB | p38MAPK | ERK | TNF-α | GABA Receptor | AChR | IKK |
| In vitro: |
| Neuroscience. 2011 Mar 10;176:408-19. | | Protection by borneol on cortical neurons against oxygen-glucose deprivation/reperfusion: involvement of anti-oxidation and anti-inflammation through nuclear transcription factor κappaB signaling pathway.[Pubmed: 21168474] |
Borneol, a terpene and bicyclic organic compound found in several species, can easily penetrate the blood-brain barrier (BBB) and helps the absorption of many agents through BBB in the brain, but there has been no study about its direct action on neurons in the CNS. In the present study, we used an in vitro ischemic model of oxygen-glucose deprivation followed by reperfusion (OGD/R) to investigate the neuroprotective effects of borneol and the related mechanisms.
METHODS AND RESULTS:
We demonstrated that borneol reversed OGD/R-induced neuronal injury, nuclear condensation, intracellular reactive oxygen species (ROS) generation, and mitochondrial membrane potential dissipation. The elevation of nitric oxide (NO), the increase of inducible nitric oxide synthase (iNOS) enzymatic activity and the upregulation of iNOS expression were also attenuated by borneol. The inhibition of caspase-related apoptotic signaling pathway was consistently involved in the neuroprotection afforded by borneol. Meanwhile, borneol inhibited proinflammatory factor release and IκBα degradation, and blocked nuclear transcription factor κappaB (NF-κB) p65 nuclear translocation induced by OGD/R. On the other hand, borneol did not show obvious effect on the inhibition of phospho-IKKα activation. Furthermore, it failed to affect the OGD/R-induced enhanced level of phospho-SAPK/JNK.
CONCLUSIONS:
In conclusion, our study indicated that borneol protects against cerebral ischemia/reperfusion injury through multifunctional cytoprotective pathways. The mechanisms of this reversal from OGD/R may be involved in the alleviation of intracellular ROS and iNOS/NO pathway, inhibition of inflammatory factor release and depression of caspase-related apoptosis. Among these effects, the inhibition of IκBα-NF-κB and translocation signaling pathway might play a significant role in the neuroprotection of borneol. | | Biochem Pharmacol. 2005 Apr 1;69(7):1101-11. | | (+)- And (-)-borneol: efficacious positive modulators of GABA action at human recombinant alpha1beta2gamma2L GABA(A) receptors.[Pubmed: 15763546 ] | (+)-Borneol is a bicyclic monoterpene used for analgesia and anaesthesia in traditional Chinese and Japanese medicine and is found in the essential oils of medicinal herbs, such as valerian. (+)-Borneol was found to have a highly efficacious positive modulating action at GABA(A) receptors, as did its enantiomer (-)-borneol.
METHODS AND RESULTS:
The effects of these bicyclic monoterpenes alone and with GABA were evaluated at recombinant human alpha(1)beta(2)gamma(2L) GABA(A) receptors expressed in Xenopus laevis oocytes using two-electrode voltage-clamp electrophysiology. (+)-Borneol (EC(50) 248microM) and (-)-borneol (EC(50) 237microM) enhanced the action of low concentrations of GABA by more than 1000%. These enhancing effects were highly dependent on the relative concentrations of the borneol enantiomer and GABA, and were insensitive to flumazenil indicating that (+)- and (-)-borneol were not acting at classical benzodiazepine sites. The maximal responses to GABA were enhanced 19% by (+)-borneol and reduced 21% by (-)-borneol. The borneol analogues isoborneol, (-)-bornyl acetate and camphor, produced less marked effects. At high concentrations (>1.5mM) (+)- and (-)-borneol directly activated GABA(A) receptors producing 89% and 84%, respectively, of the maximal GABA response indicative of a weak partial agonist action. Although of lower potency, the highly efficacious positive modulatory actions of (+)- and (-)-borneol on GABA responses were at least equivalent to that of the anaesthetic etomidate and much greater than that of diazepam or 5alpha-pregnan-3alpha-ol-20-one.
CONCLUSIONS:
The relatively rigid cage structure of these bicyclic monoterpenes and their high efficacy may aid in a greater understanding of molecular aspects of positive modulation of the activation of GABA(A) receptors. |
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| In vivo: |
| Int J Mol Sci. 2015 Nov 18;16(11):27576-88. | | Borneol Depresses P-Glycoprotein Function by a NF-κB Signaling Mediated Mechanism in a Blood Brain Barrier in Vitro Model.[Pubmed: 26593909 ] | P-glycoprotein (P-gp) on brain microvascular endothelial cells (BMECs) that form the blood brain barrier (BBB), influences transportation of substances between blood and brain. The objective of this study was to characterize the effects of borneol on P-gp efflux function on BBB and explore the potential mechanisms.
METHODS AND RESULTS:
We established an in vitro BBB model comprised of rat BMECs and astrocytes to measure the effects of borneol on the known P-gp substrates transport across BBB, and examined the function and expression of P-gp in BMECs and the signaling pathways regulating P-gp expression. Borneol increased intracellular accumulation of Rhodamine 123, enhanced verapamil and digoxin across the BBB in vitro model, and depressed mdr1a mRNA and P-gp expression. Borneol could activate nuclear factor-κB (NF-κB) and inhibition of NF-κB with MG132 (carbobenzoxy-Leu-Leu-leucinal) and SN50 (an inhibitory peptide) obscuring the P-gp decreases induced by borneol.
CONCLUSIONS:
These data suggested that borneol depresses P-gp function in BMECs by a NF-κB signaling medicated mechanism in a BBB in vitro model. | | Afr J Tradit Complement Altern Med. 2013 Nov 2;11(1):161-4. | | Study on the anti-cerebral ischemia effect of borneol and its mechanism.[Pubmed: 24653571 ] | Borneol is the processed item from resin of Dryobalanops aromatica Gaertn. f. It can enhance the activity of antioxidant enzymes in brain tissue and reduce inflammatory response by improving the energy metabolism of ischemic brain regions, and thereby reduces brain tissue damage. The objective of this paper was to study the anti-cerebral ischemia effect of borneol and its mechanism.
METHODS AND RESULTS:
The anti-cerebral ischemia effect of borneol was studied by ligation of bilateral common carotid arteries (CCA), and vagus nerves in mice and the acute cerebral ischemia-reperfusion experiment in rats.
Compared with the blank and solvent control groups, the borneol low-; medium-; and high-dose groups can significantly prolong the gasping time of mice after decapitation, and extend the survival time of mice after ligation of bilateral CCA, and vagus nerves.
Compared with the Xueshuantong injection group, the prolongation of survival time of mice after ligation of bilateral CCA, and vagus nerves was more apparent in the high-dose borneol experimental group; each experimental group can significantly reduce the number of leukocyte infiltration, the number of ICAM-1-positive vessels, as well as the number of TNF-α-positive cells.
CONCLUSIONS:
Borneol has an anti-cerebral ischemia effect. |
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