Borneol, a messenger agent, improves central nervous system drug delivery through enhancing blood–brain barrier permeability: a preclinical systematic review and meta-analysis

Abstract

To achieve sufficient blood–brain barrier (BBB), penetration is one of the biggest challenges in the development of diagnostic and therapeutic for central nervous system (CNS) disorders. Here, we conducted a systematic review and meta-analysis to assess the preclinical evidence and possible mechanisms of borneol for improving co-administration of CNS drug delivery in animal models. The electronic literature search was conducted in six databases. Fifty-eight studies with 63 comparisons involved 1137 animals were included. Among 47 studies reporting the assessments of CNS drug concentration, 45 studies showed the significant effects of borneol for improving CNS drug delivery (p<.05), whereas 2 studies showed no difference (p>.05). Nineteen comparisons showed borneol up-regulated BBB permeability (p<.05) using brain EB content (n = 8), Rh 123 content (n = 4), brain imaging agent content (n = 2), brain water content (n = 1) and observing ultrastructure of BBB (n = 4), whereas three studies showed no difference or unclear results. Seven studies reported the safety, in which one study showed borneol was reversible changes in the BBB penetration; six studies showed borneol did not increase co-administration of blood drugs concentration of peripheral tissues (p > .05). Effects of borneol are closely associated with inhibition of efflux protein function, releasement of tight junction protein, increasement of vasodilatory neurotransmitters, and inhibition of active transport by ion channels. In conclusion, borneol is a promising candidate for CNS drug delivery, mainly through mediating a multi-targeted BBB permeability.

Bornyl Diphosphate Synthase From Cinnamomum burmanni and Its Application for (+)-Borneol Biosynthesis in Yeast

“…The monoterpene borneol is a highly desirable natural product widely used in medicine, spice, and chemical fields since ancient times ( Wojtunik-Kulesza et al, 2019 ). It has a broad spectrum of bidirectional regulation on the central nervous system ( Zhang et al, 2017 ; Zheng et al, 2018 ); anti-inflammatory ( Zou et al, 2017 ; Ji et al, 2020 ) and antimicrobial activities ( Xin et al, 2020 ); and increases biofilm barrier permeability ( Song et al, 2018 ; Chen et al, 2019 ). Borneol is divided into (+)-borneol and (−)-borneol according to optical rotations.…”

Neuroprotective Effect for Cerebral Ischemia by Natural Products: A Review

“…In addition, curcumin was proven to suppress the release of inflammatory cytokines via NF-κB, signal transducer and activator of transcription (STAT), Akt/mTOR, ERK signaling pathways ( Huang et al, 2018 ; Li et al, 2015 ; Mukherjee et al, 2019 ; Xu, H. et al, 2018 ). Moreover, Bax, Bcl 2, caspase 3, LC3 II activity and other autophagy and apoptosis cytokines were also reversed by curcumin ( Hou et al, 2019 ; Huang et al, 2018 ; Wang et al, 2005 ; Xie, C. J. et al, 2018 ; Xu, L. et al, 2019 ; Zhang et al, 2018a ). Furthermore, curcumin promoted neuron survival in vitro to exert neuroprotective effects against ischemia injury ( Lu et al, 2018 ; Xie, W. et al, 2018 ; Zhang, X. et al, 2018 ).…”

“…Borneol ( Figure 5E ) is a terpene and bicyclic organic compound, a resin from Cinnamomum camphora (L.) Presl , a traditional Chinese medicine ( Yin et al, 2017 ; Zheng et al, 2018a ). As a traditional Chinese medicine, borneol has been used for thousands of years in the treatment of cardiovascular and cerebrovascular diseases.…”

<p>Nanoparticle Drug Delivery System for Glioma and Its Efficacy Improvement Strategies: A Comprehensive Review</p>

“…The mechanism of borneol passing through BBB may be inhibition of transporters to increase the vasodilatory neurotransmitters and inhibit active transport of ion channels. 165,166 P-glycoprotein (P-gp) is an efferent protein on the BBB. It can easily bind with a variety of substrates and expel them from brain tissues to reduce the therapeutic drug effects.…”