Borneol

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]

Neuroscience. 2011 Mar 10;176:408-19.

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.

(+)- And (-)-borneol: efficacious positive modulators of GABA action at human recombinant alpha1beta2gamma2L GABA(A) receptors.[Pubmed: 15763546 ]

Biochem Pharmacol. 2005 Apr 1;69(7):1101-11.

(+)-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.

Borneol Depresses P-Glycoprotein Function by a NF-κB Signaling Mediated Mechanism in a Blood Brain Barrier in Vitro Model.[Pubmed: 26593909 ]

Int J Mol Sci. 2015 Nov 18;16(11):27576-88.

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.

Study on the anti-cerebral ischemia effect of borneol and its mechanism.[Pubmed: 24653571 ]

Afr J Tradit Complement Altern Med. 2013 Nov 2;11(1):161-4.

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.

Inhibition of acetylcholine-mediated effects by borneol.[Pubmed: 12473382]

Biochem Pharmacol. 2003 Jan 1;65(1):83-90.

We previously reported that the aqueous extract from a medicinal plant Dryobalanops aromatica specifically inhibits the nicotinic acetylcholine receptor (nAChR) (Oh et al. Pharmacol Res 2000;42(6):559-64). Here, the effect of Borneol, the main constituent of D. aromatica, on nAChR activity was investigated in bovine adrenal chromaffin cells.
METHODS AND RESULTS:
Borneol inhibited a nAChR agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP)-induced calcium increase with a half maximal inhibitory concentration (IC(50)) of 56+/-9 microM. In contrast, Borneol did not affect the calcium increases induced by high K+, veratridine, and bradykinin. The sodium increase induced by DMPP was also inhibited by Borneol with similar potency (49+/-12 microM), suggesting that the activity of nAChRs is inhibited by Borneol. Borneol inhibited DMPP-induced secretion of [3H]norepinephrine with an IC(50) of 70+/-12 microM. Carbon-fiber amperometry also confirmed the inhibition of DMPP-induced exocytosis by Borneol in single chromaffin cells. [3H]nicotine binding, however, was not affected by Borneol. The inhibitory effect by Borneol is more potent than the effect by lidocaine, a commonly used local anesthetic.
CONCLUSIONS:
The data suggest that Borneol specifically inhibits the nAChR-mediated effects in a noncompetitive way.

Modulation of LPS-stimulated pulmonary inflammation by Borneol in murine acute lung injury model.[Pubmed: 24566873]

Inflammation. 2014 Aug;37(4):1148-57.

The object of our study is to investigate the protective effects of Borneol on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.
METHODS AND RESULTS:
To determine the effects of Borneol on the histopathological changes in mice with ALI, inflammatory cell count in bronchoalveolar lavage fluid (BALF) and lung wet/dry weight ratio were measured in LPS-challenged mice, and lung histopathologic changes observed via paraffin section were assessed. Next, cytokine production induced by LPS in BALF and RAW 264.7 cells was measured by enzyme-linked imunosorbent assay (ELISA). To further study the mechanism of Borneol-protective effects on ALI, nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) pathways were investigated. In the present study, Borneol obviously alleviated pulmonary inflammation by reducing inflammatory infiltration, histopathological changes, descended cytokine production, and pulmonary edema initiated by LPS. Furthermore, Borneol significantly suppressed phosphorylation of NF-κB/P65, IκBa, p38, JNK, and ERK.
CONCLUSIONS:
Taken together, our results suggest that Borneol suppressed inflammatory responses in LPS-induced acute lung injury through inhibition of the NF-κB and MAPKs signaling pathways. Borneol may be a promising potential preventive agent for acute lung injury treatment.