Brain Targeting by Intranasal Drug Delivery: Effect of Different Formulations of the Biflavone “Cupressuflavone” from Juniperus sabina L. on the Motor Activity of Rats

Abstract

The polar fractions of the Juniperus species are rich in bioflavonoid contents. Phytochemical study of the polar fraction of Juniperus sabina aerial parts resulted in the isolation of cupressuflavone (CPF) as the major component in addition to another two bioflavonoids, amentoflavone and robustaflavone. Biflavonoids have various biological activities, such as antioxidant, anti-inflammatory, antibacterial, antiviral, hypoglycemic, neuroprotective, and antipsychotic effects. Previous studies have shown that the metabolism and elimination of biflavonoids in rats are fast, and their oral bioavailability is very low. One of the methods to improve the bioavailability of drugs is to alter the route of administration. Recently, nose-to-brain drug delivery has emerged as a reliable method to bypass the blood–brain barrier and treat neurological disorders. To find the most effective CPF formulation for reaching the brain, three different CPF formulations (A, B and C) were prepared as self-emulsifying drug delivery systems (SEDDS). The formulations were administered via the intranasal (IN) route and their effect on the spontaneous motor activity in addition to motor coordination and balance of rats was observed using the activity cage and rotarod, respectively. Moreover, pharmacokinetic investigation was used to determine the blood concentrations of the best formulation after 12 h. of the IN dose. The results showed that formulations B and C, but not A, decreased the locomotor activity and balance of rats. Formula C at IN dose of 5 mg/kg expressed the strongest effect on the tested animals.

Targeting inflammation and oxidative stress for protection against ischemic brain injury in rats using cupressuflavone

“…Flavonoids and their metabolites can penetrate the BBB, although their ability to do so depends on compound lipophilicity and/or transporters ( Faria et al, 2011 ). CUP, a naturally occurring bioflavonoid, has shown neuroprotective benefits, prevents neurodegeneration via inhibiting cyclin-dependent kinases, and is effective in cases of oxidative stress and amyloid β-peptide-induced cell death in brain ( Khafagy et al, 2023 ) .…”

“…The CUP used in this study was isolated from J. sabina and identified as previously described ( Khafagy et al, 2023 ). In brief t he lyophilized aqueous ethanol fraction of 1 kg of the dried aerial parts was reconstituted in water and filtered to yield 37.54 g of water insoluble fraction.…”

“…Yellow powder; mp 392 °C Decomp. ; UV λmax (MeOH) 329, 276, and 226 nm; 1 H- and 13 C NMR (CD 3 OD, δ): ( Khafagy et al, 2023 ). HRESIMS: m / z 539.0972.…”

“…The antimicrobial activity of the Essential oil of the plant reported to express antimicrobial activity correlated to the terpene contents ( Akimov et al, 1977 ). Our phytochemical study of the non-polar fractions of J. sabina resulted in the identification of trans -calamenene, cadalene, epi -cubenol, manool, calamenene-10 β -ol, calamenene-10α-ol, 4- epi -abietic acid, sandaracopimaric acid and isopimaric acid ( Abdel-Kader et al, 2019 ) The polar fraction afforded Cupressuflavone (CUP) as the major bioflavonoid in addition to amentoflavone and robustaflavone ( Khafagy et al, 2023 ). The present study aims to explore the neuroprotective benefits of CUP by improving behavioral imbalance, oxidant/antioxidant dysfunction, and histological abnormalities resulting from cerebral IR injury in rats.…”

Chemistry and Biological Activities of Cannflavins of the Cannabis Plant

“… 19 A pharmaceutical formula containing cupressuflavone isolated from Juniperus sabina aerial parts administered via the intranasal route markedly reduced the spontaneous motor activity, motor coordination, and balance of rats using the activity cage and rotarod, respectively. 20 These findings may indicate some role of flavonoids in cannabis activity. In this review, the isolation, biosynthesis, analysis, and biological activities of cannflavins from cannabis are discussed in detail.…”